“Experience is the name everyone gives to their mistakes”Oscar Wilde Whilst this may be true for the liberal use of systemic corticosteroids in an attempt to minimise the risk of developing chronic neonatal lung disease [CNLD]/bronchopulmonary dysplasia [BPD] and the risk of adverse neurodevelopmental outcomes, it can be persuasively argued that the evolution of neonatal intensive care and the results achieved for increasingly preterm infants are truly staggering when one considers the progress made over 50 years. Comparing the original survivors in Northway's “old BPD” cohort from 1967 with those with the “New BPD” of the 1990s, one can only marvel at the contribution antenatal corticosteroids, better ventilatory strategies, improved nutritional approaches and a more measured use of supplemental oxygen to the outcomes of extremely low birth weight infants born today. more >>
Summary: The following review focuses on the normal development of the lung from conception to birth. The defined periods of lung development–Embryonic, Pseudoglandular, Canalicular, Saccular and Alveolar–will be explored in detail in relation to gestational age. Cellular differentiation, formation of the conducting airways and respiratory zone and development of the alveoli will be reviewed. Pulmonary vascular development will also be examined within these periods to relate the formation of the blood-air barrier to the lungs for their essential function of gas exchange after birth. The development of the surfactant and cortisol systems will also be discussed as these need to be mature before the lungs are able to take on their role of respiration following birth. It is clear that premature birth interrupts normal lung development so the effect of preterm birth on lung development will be examined and the respiratory consequences of very preterm birth will be briefly explored. more >>
Summary: Bronchopulmonary dysplasia (BPD) is associated with increased mortality and significant long-term cardiorespiratory and neurodevelopmental sequelae. Treatment of evolving BPD in the neonatal intensive care unit (NICU) is challenging due to the complex interplay of contributing risk factors which include preterm birth per se, supplemental oxygen, positive pressure ventilation, patent ductus arterious, and pre- and postnatal infection. Management of evolving BPD requires a multimodal approach including adequate nutrition, careful fluid management, effective and safe pharmacotherapy, and respiratory support aiming at minimal lung injury. Among pharmacological interventions, caffeine has the best risk-benefit profile. Systemic postnatal corticosteroids should be reserved to ventilated infants at highest risk of BPD who cannot be weaned from the ventilator. Several ongoing randomised trials are evaluating optimal oxygen saturation targets in preterm infants. The most beneficial respiratory support strategy to minimise lung injury remains unclear and requires further investigation. more >>
Summary: Pulmonary hypertension is an uncommon but significantly challenging complication of chronic neonatal lung disease [CNLD] as it occurs in the “new bronchopulmonary dysplasia [BPD]”. The presence of pulmonary hypertension may be sub-clinical and is often overlooked as it is not considered in all but the more severe cases of children with CNLD. Whilst the mainstays of therapy are supplemental oxygen and time and the majority of children will have resolution of their pulmonary hypertension with lung growth, the advent of newer pharmacological treatments has offered stability and perhaps a better prognosis for more severe cases of pulmonary hypertension. more >>
Summary: The history of oxygen therapy in neonatology has been littered with error. Controversies remain in a number of areas of oxygen therapy, including targets and strategies in supplemental oxygen therapy in Chronic Neonatal Lung Disease (CNLD). This article reviews some of these controversies, and makes some recommendations based on the available evidence. In graduates of neonatal units who are left with CNLD, oxygen saturation should be kept above 93-95%, with levels below 90% being avoided as far as possible. Titration of oxygen should be done using oximetry recordings which include periods of different activities. Weaning of oxygen supplementation should only be done based on satisfactory recordings during a trial of a lower flow. There is insufficient evidence to say whether weaning for increasing hours a day or stepwise weaning to a continuous lower flow is a better method. more >>
Summary: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Chest imaging is important in making the diagnosis of BPD, and in assessing for complications. More recently computerised tomography (CT) scanning has provided insights in to the pathophysiology of BPD. Studies in infants, young and school age children as well as young adults have consistently demonstrated abnormalities in the peripheral lung, possibly related either to small airway or alveolar disease. Advances in CT scanning may increase the clinical role for this modality, in addition newer techniques such as hyperpolarised gas magnetic resonance imaging are likely to provide further insights in to the nature of BPD and its effects on the developing lung. more >>
Summary: Respiratory morbidity and mortality remain common in preterm infants. The immature preterm lung is especially prone to injury. This process often starts in-utero due to maternal chorioamnionitis, priming the lung for further injury in response to post-natal ventilation, oxygen and nosocomial infection. Pulmonary inflammation has been strongly implicated in the pathway leading to lung injury in this population of infants. Several therapeutic approaches have been attempted to prevent acute lung injury or to limit its progress. The mechanisms of acute lung injury in preterm infants; their clinical correlates and available therapeutic approaches are reviewed here. more >>
Summary: Acute lung injury(ALI) is an important condition in critically ill children, contributing to overall mortality and morbidity. ALI represents the severe spectrum of lower airways disease in children. It is the pathological culmination of diseases such as pneumonia and sepsis. These conditions elicit a host response, which results in a clinically and radiologically defined pulmonary syndrome, leading to additional physiological burden. Despite ALI being well described in the paediatric age group, its management has been largely based on adult studies. Ventilatory support with low tidal volumes, positive end expiratory pressure(PEEP) and permissive hypercapnoea are the pillars of management – derived from adult studies. For those caring for critically unwell children, this review outlines recent paediatric studies, current therapies in the context of available literature and novel emerging approaches. more >>
Abstract: Pseudomonas aeruginosa (Pa) is the predominant organism infecting the airways of patients with cystic fibrosis (CF). This organism has an armamentarium of survival mechanisms that allows it to survive in the CF airway. Since colonization and chronic infection with Pa is associated with poorer lung function and increased morbidity and mortality, therapies that can prevent infection could significantly improve the lives of patients with CF. Numerous studies have examined the effects of treatment on the eradication of Pa as a means to ameliorate disease. This article outlines the pathophysiology and clinical implication of Pa acquisition, and reviews the existing treatment regimens aimed at early eradication of Pa in patients with CF. more >>
Summary: ‘Paediatric asthma: everything that seemed to be certain no longer is’, holds the promise of leaving you with more questions than answers at the end of this review of paediatric asthma 2008–2009. This has often been true for asthma research, in particular over the past few years. Research with direct consequences for a clinician managing children with wheezing or asthma is discussed such as limitations in the characterisation of asthma phenotypes and the influence of early viral infections on asthma and the development of atopic sensitisation. It appears that wheezing in preschool children with specific viral pathogens confers differential rates of asthma risk. Viruses and day-care shift respiratory morbidity to an early age when it is more troublesome than at a later age but are not protective for sensitisation or asthma. What needs to be further explored is the relationship between viruses and recurrent wheeze or asthma in studies with stringently defined phenotypes including personal atopic status, timing of infection, and severity of infection. A modification of preschool wheeze phenotypes or replacement by other phenotypes that have been defined with the application of different methods is needed. Oral corticosteroids should not be prescribed in preschool children with acute mild to moderate viral wheeze, unless a severe outcome is anticipated or if the child has a classic atopic phenotype. Despite initial high expectations, FeNO was proven not to be beneficial for routine monitoring of asthma treatment. more >>
Spontaneous pneumomediastinum (SPM), while rare, is probably underestimated in children. Treatment targets on the underlying disease and trigger factors. The study aimed in analysis different etiology in different age groups.
Patients and Methods
Total 37 children with SPM were analyzed from two medical centers in middle Taiwan from 1994 to 2007.
Results
Incidence of SPM in children was 1:11,726 patients at Department of Pediatric Emergency in middle Taiwan. Bimodal peak in incidence occurred in those under 7 and in those aged 15–18 years old. The Characteristic symptoms were dyspnea (64.9%), followed by chest pain (62.2%) and neck pain (40.5%); common specific physical signs were subcutaneous emphysema (SCE) (67.6%) and Hammer's sign (13.5%). Trigger factors were infection (43.2%), asthma (21.0%), esophageal rupture (5.4%), foreign body aspiration (2.7%), and diabetic ketoacidosis (2.7%). Idiopathic SPM accounted for 35.1% of patients with mean age 14.1 years. In age distribution, preschoolers (<7 years old) got SPM mostly due to lower respiratory tract infection. In adolescents, the most common etiologies were asthma and upper respiratory tract infection. Mean hospitalization was 6.4 days. Although 17 (46.0%) patients needed intensive care, nearly all had complete resolution in chest radiography before discharge.
Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction.
Patients and Methods
One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T0), and at 3 (T1), 6 (T2), 9 (T3), and 12 (T4) months of follow-up. Eighteen patients were excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6–11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis.
Results
After 1 year of follow-up, there was significant improvement in respiratory symptoms (T4 − T0 = 8.1; 95% confidence interval (95% CI) = [2.1;14.0]; effect size (ES) = 0.35; P < 0.001), Emotional Functioning (T4 − T0 = 5.6; 95% CI = [1.1;10.1]; ES = 0.31; P < 0.05), Social Functioning (T4 − T0 = 6.0; 95% CI = [1.3;11.7]; ES = 0.31; P < 0.05), Body Image (T4 − T0 = 11.9; 95% CI = [4.1;19.7]; ES = 0.42; P < 0.05), and Treatment Burden (T4 − T0 = 5.3; 95% CI = [0.3;10.3]; ES = 0.24; P < 0.05) domains in the younger group. A significant improvement in Role Functioning (T4 − T0 = 6.1; 95% CI = [1.1;11.1]; ES = 0.40; P < 0.05), Body Image (T4 − T0 = 12.6; 95% CI = [3.5;21.7]; ES = 0.46; P < 0.05), and Weight (T4 − T0 = 11.7; 95% CI = [1.8;21.6]; ES = 0.40; P < 0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T4 − T0 = 5.5; 95% CI = [1.5;9.4]; ES = 0.30; P < 0.05), Respiratory Symptoms (T4 − T0 = 7.6; 95% CI = [3.9;11.4]; ES = 0.48; P < 0.05), and Weight (T4 − T0 = 10.1; 95% CI = [1.6;18.6]; ES = 0.26; P < 0.05) domains.
Invasive community acquired (CA) Staphylococcus aureus (SA) disease has been endemically observed in Hawaiian children. We wanted to evaluate the clinical, laboratory findings, and outcomes of methicillin-resistant SA (MRSA) and methicillin-susceptible SA (MSSA) associated pneumonia admissions.
Methods
We performed retrospective chart reviews of 38 culture proven SA pneumonia patients admitted to a pediatric tertiary medical center in Hawaii between January 1996 to December 2007.
Results
Twenty-six patients (68%) had MRSA and 12 patients (32%) had MSSA infection. The mean age of MRSA patients was 2.8 and 6.7 years for MSSA patients (P < 0.05). Pacific Islander and Native Hawaiian patients were affected disproportionately compared to non-Pacific Islander and Hawaiian groups (P < 0.0001). Demographic data, days of fever, tachypnea, hypoxia, and length of stay (LOS) were not significantly different between MRSA and MSSA infected patients. The mean LOS was 26.2 days (range 6–138 days); mean length of fever was 12.4 days. Seventy five percent (15 of 20) of patients who required intubation had MRSA. Twenty-one of the 29 (72%) total patients with pleural effusions had MRSA infection and all required chest tube placements. Two (5%) patients died; both had MRSA infection.
Reliable interpretation of pulmonary function tests relies on appropriate reference data, which remain very limited for infants.
Objectives
This study aimed to assess the validity of published reference equations for forced expiratory flow-volume (FEFV) data in infants when using current, commercially available equipment, and how this could impact on interpretation of results from infants with lung disease.
Methods
The Jaeger Masterscreen BabyBody (v4.67) equipment was used to perform partial and raised volume FEFV maneuvers in healthy infants and those with cystic fibrosis (CF). Results were initially expressed as Z-scores using published reference equations. Multilevel modeling was used to calculate differences, if any, from predicted scores in healthy infants.
Results
Data were available from 66 healthy full term infants on 89 test occasions; [median (range) postnatal age 49.4 (12–101) weeks. All FEFV outcomes were significantly lower than predicted, with mean (SD) Z-score differences of −0.4 (1.1) for FVC; −0.6 (1.0) for FEV0.5; −1.0 (1.0) for FEF25–75 and −1.4 (1.1) for V'maxFRC. After adjustments using multilevel modeling, mean Z-scores were within 0.1 (SD∼1.0) predicted for all outcomes in healthy infants. Among 50 infants with CF, studied on 85 test occasions, results were “abnormal” (<−1.96 Z-scores) on 35 (41%) and 37 (45%) test occasions for FEV0.5 and FEF25–75, respectively, when using published equations. This fell to 24 (28%) and 20 (24%), respectively, after adjustment.
There is very limited information on how the risk of persistent asthma in recurrent wheezing (RW) infants modifies their lung function early in life. The aim of this study is to compare lung function of RW infants and young children with a positive or negative asthma predictive index (API), an index previously used to anticipate asthma persistence into childhood and adolescence.
Methods
Two groups of RW infants and young children were recruited in two centres in Spain (Palma de Mallorca and Murcia). Lung function was measured according to the thoracho-abdominal compression technique (RCT), and values of the maximal flow at functional residual capacity were expressed as Z-scores. Other variables included in the study, as independent factors, were: gender, age, length, weight, and parental smoking habits together with information regarding API.
Results
Expressed as mean ± SD, API+ RW infants (n = 50; age in months 11.9 ± 4.9) had a lower Z-score than API− RW ones (n = 41; age in months 12.3 ± 6.2; −2.01 ± 0.79 vs. −1.64 ± 0.77, P = 0.026, respectively). Centre and tobacco exposition did not have an effect on lung function.
Asthma therapy should be stepped up or stepped down in response to changes in asthma control. However, there is little evidence available on the optimal timing, sequence, and degree of medication reductions. In this study we analyzed clinically stable asthmatic children who underwent a medication reduction from a combination preparation consisting of an inhaled corticosteroid (ICS) and long acting beta2-agonist (LABA) to monotherapy with the same dose of the ICS. We hypothesized that the extent of exercise-induced bronchoconstriction (EIB) would not increase after the cessation of the LABA.
Methods
Nineteen children, aged 8–16 years, with clinically stable asthma, receiving LABA/ICS combination therapy, were analyzed in this open-label pilot study. Children performed an exercise challenge at baseline and 3 weeks after the medication reduction. Best values of spirometric measurements of the forced expiratory volume in 1 sec (FEV1) were used for statistical calculations.
Results
Maximum percent fall in FEV1 was significantly lower after 3 weeks of ICS monotherapy (P = 0.03). Eight of 19 children had a ≥15% fall in FEV1 after exercise at the initial exercise challenge. In this subgroup, maximum percent fall in FEV1 after the medication reduction was significantly lower (P < 0.01), and in six children it decreased to <15%, indicating they no longer had EIB.
The EPIC Observational Study is an ongoing prospective cohort study investigating risk factors for and clinical outcomes associated with early Pseudomonas aeruginosa (Pa) acquisition in young children with cystic fibrosis (CF).
Objectives and Hypothesis
To describe the baseline characteristics of the cohort and evaluate associations between potential risk factors and nutritional and respiratory characteristics at enrollment. We hypothesized that distinct demographic and environmental risk factors could be identified for poorer nutritional status and lung function at enrollment.
Methods
During 2004–2006, 1,700 children with CF were enrolled at 59 US CF centers. Children ≤12 years were eligible if they had no prior Pa infection (Pa-Never) or, if prior isolation of Pa from respiratory cultures, at least a 2-year history of Pa negative cultures (Pa-Past).
Results
One thousand one hundred seventeen participants (65.7%) were Pa-Never and 583 (34.3%) Pa-Past. Pa-never patients had a lower proportion of CFTR genotypes with both mutations in functional classes I, II, or III), higher lung function and less respiratory symptoms. Diagnosis after newborn or prenatal screening was associated with significantly higher mean weight, height, and FEV1 at enrollment, while maternal smoking during pregnancy appeared to worsen these parameters.
Summary: Haemothorax is a problem commonly encountered in medical practice and is most frequently related to open or closed chest trauma or to invasive procedures of the chest. Spontaneous haemothorax is less common and can have various causes, such as the use of anticoagulants, neoplasia, and rupture of pleural adhesions. Identification by radiography and thoracentesis is indicated and treatment of the underlying trauma should start immediately. After insertion of a large chest tube, antibiotic prophylaxis in trauma patients should be administered for 24 h.Further treatment depends on the haemodynamic stability of the patient, the volume of evacuated blood and the occurrence of persistent blood loss. Surgical exploration by VATS or thoracotomy is necessary if >1.500 ml of blood has accumulated and/or an ongoing production of >200 ml of blood per hour is observed. If the haemorrhage is less severe, careful investigation into the underlying cause must be performed and blood should be evacuated by tube thoracostomy. If clotted blood retained in spite of tube thoracostomy, intrapleural fibrinolytic therapy can be applied to breakdown clots and adhesions. If conservative treatment is insufficient, a surgical approach with VATS or thoracotomy is indicated to prevent subsequent complications. more >>
Summary: OBJECTIVE: The associations between air pollution and children’s respiratory health in the high pollution range have not yet been clearly characterized. We evaluated the effects of outdoor air pollution on respiratory morbidity in children selected from multiple sites in a heavy industrial province of northeastern China.METHODS: The study included 11,860 children aged 3–12 years, selected from 18 districts of 6 cities in Liaoning province, the participation rate is 89.9%. Informed consent and written responses to surveys about children’s historic and current health status, personal and household characteristics, and other information were obtained from parents. A two-stage regression approach was applied in data analyses.RESULTS: There were wide gradients for TSP (188–689 μg/m3), SO2 (14–140 μg/m3 and NO2 (29–94 μg/m3) across the 18 districts of 6 cities. The three air pollutants significantly increased the prevalence of persistent cough (21–28%), persistent phlegm (21–30%) and current asthma (39–56%) for each interquartile range increment (172 μg/m3 for TSP, 69 μg/m3 for SO2, 30 μg/m3 for NO2), showing larger between-city effects than within-city. Rates of respiratory symptoms were significantly higher for children with younger age, atopy, respiratory disease in early age, family history of asthma or chronic bronchitis, and tobacco smoke exposure.CONCLUSION: The high levels of outdoor air pollution in north China are positively associated with children’s respiratory symptoms, the associations with TSP appear to be stronger than SO2 and NO2. more >>
Summary: Rationale: There is a lack of consensus on factors that predict mortality in idiopathic pulmonary arterial hypertension (IPAH). Tests that can accurately predict prognosis are needed to guide treatment and counsel patients.Methods: We conducted a systematic review to identify factors that prognosticate mortality in IPAH. Study design, cohort size, comparison method, measured value, and statistical significance was extracted for eight pre-selected parameters [pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), mean right atrial pressure (mRAP), cardiac output, right ventricular end diastolic pressure, functional class, 6 min walk distance (6MWD), and diffusing capacity of carbon monoxide].Results: 107 factors have been associated with mortality in IPAH. A reproducible predictive association with mortality was demonstrated for only 10 factors: functional class (14 studies), heart rate (10 studies), 6MWD (8 studies), pericardial effusion (5 studies), mPAP (10 studies), mRAP (17 studies), cardiac index (13 studies), stroke volume index (4 studies), PVR (10 studies), mixed venous PaO2 or saturations (4 studies). Of the 8 factors chosen for detailed evaluation, there were at least half as many studies that evaluated the variable and did not find an association with mortality compared to those that did.Conclusions: There is a large body of literature describing numerous factors that predict mortality in IPAH. Most factors have been assessed in very few studies. There are conflicting reports on the prognostic value of many factors. These discrepancies highlight the need to evaluate the literature in total when considering the utility of variables as prognostic factors in IPAH. more >>
Summary: Background: Osteoporosis is common in advanced COPD and worsens rapidly after transplantation, potentially impairing quality of life. Increased high density lipoprotein cholesterol (HDLc) has been observed in COPD and linked with osteoporosis in the general population. This association has not been previously examined in COPD.Methods: We reviewed the records of 245 COPD patients referred for lung transplant evaluation. Osteoporosis was defined by either dual energy X-ray absorptiometry scan or use of osteoporosis medications. The presence or absence of osteoporosis could be ascertained in 152 subjects. Cholesterol values and other clinical variables were assessed for their association with osteoporosis.Results: Clinical factors associated with osteoporosis included lower BMI [OR 0.81, 95% CI 0.73–0.90], higher HDLc [OR 1.04, 95% CI 1.02 to 1.07], and worse lung function. HDLc was an independent predictor of OP and demonstrated an inverse linear correlation with T-scores (r = −0.21, p = 0.05), which was stronger amongst males (r = −0.45, p = 0.004).Conclusion: In COPD patients referred for lung transplantation, osteoporosis is highly prevalent. Raised HDLc levels are common in this group and are independently associated with OP. more >>
Summary: Introduction: Large-cell neuroendocrine carcinoma is an aggressive variant of large-cell carcinoma of the lung, which has poor survival in most series, resembling that of small-cell lung carcinoma. We report our retrospective assessment of surgically-resected cases of both tumours.Methods: 33 large-cell neuroendocrine carcinomas and 16 peripheral small-cell lung carcinomas were reassessed retrospectively. Survival rates of both tumours in surgically-resected cases were calculated and compared using Kaplan–Meier survival curves and Log Rank test, respectively.Results: In large-cell neuroendocrine carcinomas, there were 25 patients with pathologic stage I, 4 with pathologic stage II and 4 with pathologic stage III. In small-cell lung carcinomas, there were 6 patients with pathologic stage I, 3 with pathologic stage II and 7 with pathologic stage III. 12% of large-cell neuroendocrine carcinomas and 62.5% of small-cell lung carcinomas were of advanced disease. The mean follow-up was 89 months. The actuarial survival for the 2 groups was not significantly different.Conclusion: Large-cell neuroendocrine carcinomas of the lung have poor prognosis even in early stages, with survival rates similar to that of small-cell lung carcinomas. more >>
Summary: Background: It is documented that omalizumab treatment reduces the cell surface expression of immunoglobulin E high-affinity receptor (FcɛRI) on several cell types. This has not been investigated in patients with uncontrolled severe persistent allergic asthma.Methods: In a double-blind, randomized, placebo-controlled study, patients with severe allergic asthma uncontrolled by high dose inhaled corticosteroids and long-acting β2-agonist received either omalizumab (n = 20) or placebo (n = 11) over 16 weeks at appropriate doses and frequencies. Baseline and end of study (week 16) FcɛRI expression on basophils and plasmacytoid dendritic cells was determined by flow cytometry for the primary endpoint. Secondary efficacy endpoints included asthma control and lung function as part of an initial investigation into the use of FcɛRI expression as a marker of response.Results: In the omalizumab group, and with respect to placebo, FcɛRI expression was significantly reduced at end of study on basophils (−82.6%, p < 0.01) and plasmacytoid dendritic cells (−44.2%, p = 0.029). FcɛRI expression reduction was not found to be correlated with clinical response.Conclusions: Long-term omalizumab treatment induced reduction of FcɛRI expression on circulating basophils and plasmacytoid dendritic cells. These changes were not associated with those of clinical features related to severe asthma, which does not support further investigation into its use as a predictive marker of response.Trial registration: The study was registered with ClinicalTrials.gov (identifier: NCT00454051) and the European Clinical Trials Database, EudraCT (identifier: 2006-003591-35) more >>
Summary: We describe a new tool, the Physicians’ Practice Assessment Questionnaire (PPAQ), designed for the global self-assessment of implementation of asthma and COPD guidelines, as determined by the percentage of patients in whom physicians estimate that they implement guidelines key recommendations. Some of its properties were assessed by a group of 47 general practitioners (GPs), and test–retest data were obtained in repeating the questionnaire at a 5-week interval without intervention in a sub-group of 28 practitioners. Answers to the various questions were globally reproducible. The lowest scores (recommendations implemented in less than 50% of their patients) were: 1) for both asthma and COPD: referral for patient education, provision of a written action plan and regular assessment of inhaler technique, 2) for asthma: referral to a specialist for difficult to control asthma or uncertain diagnosis, and 3) for COPD: assessment of lung function and disability according to specific criteria and referral to a rehabilitation program. The analysis showed sufficient internal consistency for both questionnaires (Cronbach alphas 0.7617 for asthma and 0.8317 for COPD). Pearson’s correlations indicated good test–retest (r = 0.6421, p = 0.0002 for asthma; r = 0.6801, p < 0.0001 for COPD). In conclusion, the PPAQ is a new tool to assess implementation of asthma and COPD guidelines; it has the potential to identify care gaps that can be specifically targeted for intervention. more >>
Summary: Background: In patients with moderate to severe allergic asthma, clinical effectiveness of omalizumab, an approved anti-IgE-reacting substance, is usually assessed by pulmonary function testing (PFT), symptom scores and physicians judgement.Aims: We postulate that cardiopulmonary exercise testing (CPET) may provide an additional option to verify symptomatic changes in patients with allergic asthma.Methods: Ten consecutive patients with allergic asthma were treated with omalizumab. Prior to and after 16 weeks of treatment all patients underwent PFT and symptom-limited CPET. Results were compared to 10 asthmatic controls without omalizumab medication. Symptoms were assessed according to investigators judgement (IGETE).Results: All 20 patients showed a significantly impaired exercise capacity at baseline [peak oxygen uptake (VO2) 71 ± 16% predicted]. In patients with omalizumab, peakVO2 increased from 13.8 (8.4–21.4) to 16.8 (11.2–23.9) ml/kg/min (p < 0.05), VO2 at anaerobic threshold increased by 22% [9.8 (3.3–15.2) to 12.3 (6.7–14.4) ml/kg/min (p < 0.05)]. There was no improvement in the controls. The increase in VO2 was significantly correlated to the improvement in symptoms. All patients revealed dynamic hyperinflation under exercise with a decreasing extent with omalizumab treatment.Conclusion: This study suggests that CPET may provide additional and useful tools to assess and verify the individual clinical response to omalizumab treatment. An improvement in exercise capacity can reliably mirror changes in quality of life and IGETE. Patients with omalizumab experience significant improvements in their initially impaired exercise capacity. CPET can be safely accomplished in patients with severe asthma. more >>
Summary: We tested whether markers of systemic oxidant stress were detectable in 29 typical IPF patients, and whether these increased after low level exercise. We obtained resting plasma for measurement of amino terminal pro brain natriuretic peptide (NT-proBNP), and plasma and urine samples for isoprostanes and total nitrite. Total antioxidant capacity (TAC) was measured in plasma, and H2O2 was measured in urine. Subjects exercised at ˜50 W on a semi recumbent bicycle until limited by dyspnea. Samples were obtained immediately after exercise for measurement of the same variables.Plasma and urine samples were also obtained at rest from 6 normal individuals over 40 years of age solely to establish comparison values for NT-proBNP, nitrite, H2O2 and TAC assays.Plasma NT-proBNP was high at rest and after exercise, suggesting pulmonary arterial hypertension. IPF patients’ resting NT-proBNP concentrations apparently exceeded those of normal controls. IPF plasma isoprostanes at rest exceeded the normals. IPF urine isoprostanes increased significantly after exercise (P = 0.047 by signed rank test); and, plasma TAC decreased significantly after exercise (P < 0.001 by signed rank test). Neither plasma nor urine nitrite changed significantly after exercise. H2O2 concentration was quite high after exercise in some IPF subjects’ urine.IPF patients demonstrate systemic oxidant stress at rest detectable as increased isoprostanes in the circulation. An increase in urine isoprostanes and a decrease in plasma TAC after exercise suggest that reactive oxygen species (ROS) are produced during low level exercise done by IPF patients. more >>
Summary: Background: Increased expression of inducible nitric oxide synthase in inflamed tonsils has been reported. Our preliminary observation was the first to demonstrate that increased exhaled NO level may occur in patients with tonsillitis.Objective: To extend the observation scope, the same group of patients was examined for NO exhaled after tonsillectomy.Materials and Methods: Exhaled oral NO level was measured with Niox Mino® analyzer, six-seven months after tonsillectomy in 27 non-atopic patients who suffered from recurrent tonsillitis and in 35 healthy non-atopic subjects.Results: After tonsillectomy, exhaled NO levels were significantly reduced as compared to the preoperative period values and did not differ significantly from those of the healthy subjects.Conclusions: The results support a finding of the elevated exhaled NO consequent to NO production in chronically inflamed tonsils, but whether NO plays any role in the pathogenesis of tonsillitis or is merely a by-product of another process, needs to be determined. more >>
Summary: Whilst recent large-scale studies have provided much evidence on the natural history and therapeutic response in patients with chronic obstructive pulmonary disease (COPD), relatively little is known about the effect in younger patients.We report a pre-specified post-hoc analysis of 356 patients with COPD ≤ 50 years old from the four year randomised, double blind placebo controlled Understanding Potential Long Term Impact on Function with Tiotropium (UPLIFT) trial. Inclusion criteria included a post-bronchodilator forced expiratory volume in 1 s (FEV1) of ≤70%, FEV1/FVC < 0.70, age ≥40 years, and smoking history of ≥10 pack years.Younger patients had a mean FEV1 of 1.24 L (39% predicted) and an impaired health-related quality of life (St. George’s Respiratory Questionnaire (SGRQ)) compared to the entire UPLIFT population. There were 40.2% women and 51.1% current smokers in the younger age group. Tiotropium was associated with a sustained improvement in spirometry and SGRQ. Mean decline in post-bronchodilator FEV1 was 58 ml/year (placebo) vs. 38 ml/year (tiotropium) (p = 0.01). Corresponding values for pre-bronchodilator FEV1 were 41 ml/year (placebo) compared with 34 ml/year (tiotropium) (p = 0.34). The hazard ratio (95%CI) for an exacerbation in the younger age group was 0.87(0.68, 1.13)). The rate of exacerbations was reduced by tiotropium (rate ratio (95%CI) = 0.73(0.56, 0.95)).Tiotropium resulted in sustained bronchodilation, improved quality of life, and a decreased exacerbation rate in younger patients. Tiotropium also resulted in a significant reduction in the decline in post-bronchodilator FEV1, suggesting possible disease modification by tiotropium in younger patients with COPD. more >>
Summary: Background: Susceptibility to Chronic Obstructive Pulmonary Disease (COPD) has a genetic component. We undertook a study to determine if a genetic variant of the gene encoding the cyclooxygenase-2 gene influences the likelihood of developing COPD.Methods: In a case control study the frequency of a single nucleotide polymorphism in the promoter region of the cyclooxygenase-2 gene (-765 G → C) was determined in 205 subjects with COPD, 171 chronic smokers with normal lung function (resistant smokers) and 95 healthy blood donors using the polymerase chain reaction and restriction enzyme fragment length polymorphism.Results: The frequency of the C allele of the -765 cyclooxygenase-2 polymorphism was higher in resistant smokers (24.6%) compared with subjects with COPD (14.4%, OR = 1.98, 95% CI = 1.28–3.06, p = 0.003) and blood donors (14.7%, OR = 1.97, 95% CI = 1.14–3.41, p = 0.03).Conclusions: The -765C allele, which has been shown to be associated with decreased promoter activity of the cyclooxygenase-2 gene, is more common in resistant smokers. This raises the possibility that decreased activity of cyclooxygenase-2 may protect smokers against the development of COPD. more >>
Summary: Purpose: The aim of this retrospective study is to present data on clinical significance of lactate dehydrogenase (LDH) serum levels in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED).Patients and methods: From June 2004 to June 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed LD and ED SCLC. 397 cases were identified. We collected data on patient characteristics including clinical performance status and LDH serum levels, metastatic sites, efficacy of first line chemotherapy and survival.Results: In both limited and extensive disease SCLC, elevated LDH serum levels resulted in significantly shorter median survival. The effect was most pronounced if levels were 300 U/l or higher. In patients with limited disease and normal LDH levels, median survival was 18.0 months. If LDH was higher than 300 U/l, overall survival was reduced to 12 months. In cases with extensive disease, overall survival was significantly lower in patients with elevated LDH serum levels with an additional reduction in overall survival in patients with LDH levels above 300 U/l. (7.0 vs. 12.0 months, p = <0.001). Multivariate Cox regression analyses revealed LDH levels to be an independent predictor of mortality after adjustment for age and Performance Status in LD and ED SCLC (HR 1.003, p = 0.017; HR 1.001, p = 0.002 respectively). However, categorizing LDH levels revealed no significant difference in LD SCLC.Conclusion: In our contemporary comprehensive patient population, LDH is proved to be a strong, independent predictive factor of median survival in patients with LD and ED SCLC. more >>
Summary: Background: Multimorbidity is defined as two or more co-existing chronic conditions in an individual and is common in general practice. It is associated with poorer outcomes for patients. This study aimed to establish the prevalence of multimorbidity in patients with chronic respiratory disease in general practice and to describe its impact on health service use.Methods: Cross-sectional study based in general practice in Dublin. Drug and disease code searches were performed to identify adult patients with a diagnosis of chronic respiratory disease. Medical records were reviewed for chronic respiratory diagnosis, other chronic conditions, demographic characteristics, General Practitioner (GP) and practice nurse utilisation rates, and numbers of medications.Results: In a general practice population of 16,946 patients 3.9% had chronic respiratory disease and 60% of these had one or more co-existing chronic condition(s). GP and practice nurse utilisation rates, and number of medications were significantly higher among those with multimorbidity compared with those with respiratory disease alone. Multivariate analysis showed that increasing age and low socio-economic status were significantly associated with multimorbidity.Conclusion: The majority of patients with chronic respiratory disease have multimorbidity. Clinical guidelines based on single disease entities and outcomes are not as easy to implement and may not be as effective in this group. more >>
Summary: Background: The present study aimed to illustrate differences in characteristics and perception of dyspnea between young atopic adults who have no history of asthma (never-asthmatics) with or without asymptomatic airway hyperresponsiveness (AHR) and those who had childhood asthma and consider themselves to be grown out of the disease (past-asthmatics).Methods: Blood parameters, lung function and methacholine PC20 were measured in 88 never-asthmatics and 24 past-asthmatics. A perception score of dyspnea at 20% fall in FEV1 (PS20) was obtained by interpolation of the two last points on the perception (modified Borg scale)/fall in FEV1 curve during methacholine challenge.Results: Thirty-one of 88 never-asthmatics and eighteen of 24 past-asthmatics exhibited AHR (PC20 was <8 mg/ml). Higher levels of specific IgE to house dust mite in past-asthmatics were observed than never-asthmatics with and without AHR. Mean values of FEV1 and FEF25–75 (%predicted) were significantly lower in past-asthmatics than never-asthmatics without AHR, and the values in never-asthmatics with AHR were intermediate between never-asthmatics without AHR and past-asthmatics. PC20 was not significantly different between past-asthmatics and never-asthmatics with AHR. Of particular interest was that PS20 was significantly lower in never-asthmatics with AHR compared with past-asthmatics.Conclusion: The present findings suggest the possibilities that presence or absence of past history of outgrow of childhood asthma might be associated with airway narrowing, sensitization to house dust mite and perception of dyspnea in young asymptomatic adults with atopy and AHR. more >>
Summary: Background: Long-acting muscarinic antagonists (LAMA), long-acting β2-agonists (LABA) and fixed dose combinations (FDC) of inhaled corticosteroids (ICS) and LABA are used as inhaled maintenance therapies for COPD.Objective: To estimate persistence rates from dispensing patterns of long-acting inhaled drugs for COPD.Methods: From the PHARMO-database, COPD patients starting LAMA, LABA or LABA-ICS FDC between 2002 and 2006 were selected. Persistence with the initial as well as with any long-acting inhaled drug was determined, defined as time between start and stop of initial/any therapy, allowing ≤60-days gaps between refills. For patients who did not continue to receive dispensings of the initial therapy for at least one year, the first change in therapy was determined.Results: The study included 2201 LAMA, 1201 LABA and 4146 LABA-ICS FDC users. Persistence rates with initial therapy alone at 1, 2, and 3 years were 25%, 14%, 8% for LAMA, 21%, 10%, 6% for LABA and 27%, 14%, 8% for LABA-ICS FDC. Of patients who did not persist with LAMA alone for one year, 15% added and 13% switched therapy (both mostly LABA-ICS FDC). Of patients not persisting with LABA alone, 9% added therapy (mostly LAMA) and 31% switched therapy (mostly to LABA-ICS FDC). In patients not persisting with LABA-ICS FDC, add-on and switch occurred equally frequent (11%, mostly LAMA). Persistence rates with any long-acting drug at 1, 2 and 3 years were 36%, 23% and 17% respectively.Conclusion: Persistence with the initial as well as with any long-acting inhaled drug in COPD is low, with a substantial proportion of patients changing therapy. more >>
Summary: Background: The predictive factors for treatment response in patients with severe chronic obstructive pulmonary disease (COPD) are unknown. We investigated predictive factors for response to fluticasone propionate/salmeterol (FSC) in severe COPD patients.Methods: This prospective, open-label, non-comparative study included 921 adult patients with severe COPD (baseline forced expiratory volume in 1 s (FEV1) <50% of predicted), a history of repeated exacerbations, and symptoms despite bronchodilator treatment. FSC (500 μg/50 μg) was delivered via an inhaler, twice a day, for 12 weeks. The primary efficacy endpoint was the response rate for inspiratory capacity (IC), FEV1, or quality of life (QoL), assessed with the Saint George’s respiratory questionnaire, at week 6 and week 12.Results: The overall response rate to FSC at 6 and 12 weeks was 79%. The corresponding rates for FEV1, IC, and QoL were 38%, 55%, and 62%, respectively. More than 40% of patients showed a response for IC and/or QoL without being responders for FEV1. Overall lung function and QoL were improved. FSC was well tolerated with a safety profile consistent with that observed previously.Conclusion: Nearly 80% of patients responded to FSC treatment in this real-life study. Improvements in IC and QoL at 12 weeks revealed a clinically relevant response in patients with no improvement in FEV1. IC reversibility to salbutamol before treatment might represent, better than FEV1, a prognostic factor of response to FSC in severe COPD. Moreover these tests are easy to perform routinely and in large numbers of patients. more >>
Summary: Introduction: Respiratory symptoms in relationship to exercise, bronchial hyperresponsiveness (BHR), and exercise-induced asthma (EIA) are very common in elite winter athletes. Symptom-based screening for BHR would facilitate selection of athletes with possible EIA.Objectives: The aim of the present study was to evaluate the diagnostic accuracy of self-reported symptoms as predictors of BHR in an unselected population of adult elite cross-country skiers.Methods: Forty-six Swedish adult skiers competing at national or international level were included. They had a mean (SD) training volume in the past 12 months of 593 (122) hours. Twenty-four subjects had previous physician-diagnosed asthma. The European Community Respiratory Health Survey questionnaire was used to evaluate the presence of respiratory symptoms. BHR was defined as bronchoconstriction to either eucapnic voluntary hyperventilation, dry powder mannitol or methacholine provocation.Results: The “classical” EIA symptom of shortness of breath post-exercise was reported by 17% of all skiers. Eight subjects (17%) had BHR. None of the self-reported respiratory symptoms had high positive predictive values. However, symptoms caused by grass or pollen had high negative predictive values.Discussion: EIA in elite winter athletes cannot accurately be based only on self-reported symptoms but requires verification with objective testing of BHR. Bronchoprovocation of elite winter athletes reporting respiratory symptoms in rest or because of exercise will probably reveal a high proportion of athletes without BHR.Clinical trial: EUDRA-CT number 2006-005822-21. more >>
Summary: Background: The methacholine challenge test performed with the tidal breathing method induces a greater fall in FEV1 than the dosimeter method; however, the effect of the challenge method on methacholine-induced fall in FVC has not been investigated.Objective: To determine the influence of the challenge method on methacholine-induced changes in FEV1 and FVC.Methods: Airway responsiveness to methacholine was determined by dosimeter method and tidal breathing method in 37 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method and the same nebulizer model was used for the two challenges. The response was expressed by the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) and by the percent fall in FVC at the PC20 value relative to FVC after saline inhalation.Results: The PC20 values obtained with the tidal breathing method and the dosimeter method were similar, with geometric mean values of 3.15 (95%CI, 1.85–5.34 mg/mL) and 2.51 (1.37–4.61 mg/mL, P = 0.092), respectively. The percent fall in FVC at the PC20 value obtained with the dosimeter was significantly greater than that obtained with the tidal breathing method, with mean values of 11.8 (95%CI, 10.0–13.5%) and 9.4 (95%CI, 8.1–10.8, P = 0.002), respectively.Conclusions: Differences in methacholine PC20 values obtained with the two challenge methods recommended in guidelines may be overcome by introducing some technical modifications in the dosimeter method. However, the technical factors that affect methacholine sensitivity and air trapping are at least partially different. more >>
Summary: Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress.101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F2α and leukotriene E4 (LTE4) were measured.Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF2α was increased after exercise challenge, but not after mannitol challenge, while LTE4 was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF2α and LTE4 in individuals with a positive mannitol challenge.The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF2α and LTE4 indicate a pathophysiological role in both mannitol and exercise challenge. more >>
Summary: Background: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT) deficiency predispose to lung emphysema, especially in smokers. We hypothesized that multi-slice computed tomography (CT) might be superior to pulmonary function tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of 32 years.Methods: A subgroup of PiZZ and PiSZ individuals identified during the Swedish newborn screening programme in 1972–74 underwent multi-slice CT and PFT at the age of 32 years. From the CT scans the percentile density at 15% (PD15) and the relative area below –910 Hounsfield Units (RA−910 HU) were calculated. The results of PFT and CT were compared between the AAT-deficient individuals and an age-matched control group.Results: Twenty-five PiZZ, 11 PiSZ and 17 PiMM individuals participated in the study. All Pi subgroups had normal lung function. The mean PD15 was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in the PiSZ individuals and 79 (SD 17) g/L in the PiMM individuals (ns), and the RA-910 were 30 (SD 18)%, 24 (SD 20)%, and 32 (SD 18)%, respectively (ns). For the never-smoker subgroups, in the PiZZ (n = 23), PiSZ (n = 8) and PiMM (n = 12), the mean PD15 were 95 (SD 35) g/L, 81 (SD 22) g/L, and 75 (SD 12) g/L, respectively (ns). PD15 was significantly correlated to CT derived lung size (r = −0.72; p < 0.001).Conclusions: CT densitometry revealed no signs of emphysema and no differences between the AAT-deficient individuals identified by neonatal screening and age-matched control subjects. more >>
Summary: Objective: To evaluate patient characteristics and practice patterns in the management of acute asthma attack at tertiary care centers across Turkey.Methods: A total of 294 patients (mean age: 50.4 ± 15.1 years; females: 80.3%) diagnosed with persistent asthma were included in this retrospective study upon their admission to the hospital with an acute asthma attack. Patient demographics, asthma control level, asthma attack severity and the management of the attack were evaluated.Results: There was no influence of gender on asthma control and attack severity. In 57.5% of the patients, asthma attack was moderate. Most patients (78.9%) were hospitalized with longer duration evident in the severe attack. Spirometry and chest X-Ray were the most frequent tests (85.4%), while steroids (72.0% parenteral; 29.0% oral) and short-acting beta-agonists (SABA) + anticholinergics (45.5%) were the main drugs of choice in the attack management. Attack severity and pre-attack asthma control level was significantly correlated (p < 0.001). Pre-attack asthma was uncontrolled in 42.6% of the patients with severe attack. Most of the patients were on combination of more than one (two in 38.7% and 3–4 in 31.2%) controller drugs before the attack.Conclusion: Providing country specific data on practice patterns in the management of acute asthma attack in a representative cohort in Turkey, prescription of steroids and SABA + anticholinergics as the main drugs of choice was in line with guidelines while the significant relation of pre-attack asthma control to risk/severity of asthma attack and rate/duration of hospitalization seem to be the leading results of the present study. more >>
Summary: Introduction: BODE index comprises Body mass index, Obstruction of the airway [FEV1], Dyspnoea score [modified Medical Research Council questionnaire] and Exercise capacity [6 min walk test]. This study assessed the role of serial changes in BODE index in predicting mortality and readmissions of COPD patients.Methods: A prospective cohort study involving 243(208males) COPD patients hospitalized for acute exacerbations of COPD [AECOPD]. BODE index was assessed at 6 weeks(baseline), 6, 12, 18 and 24 months post hospital discharge. Mortality and readmissions in the subsequent 3 years were recorded. All the patients were managed by usual care without additional intervention.Results: The mean (SD) age and FEV1% predicted were 74.2(7.8) yrs and 51.7(21.6)% respectively. Over the 3 years, 25.1% died whereas 76.5% had at least 1 readmission for AECOPD. Baseline BODE index was predictive of both the survival and readmissions to hospital for AECOPD by Cox regression analysis (p 1point), no change, and decreased in BODE (>1point) index respectively. Serial changes in BODE index at 6 month was marginally associated with mortality, but not at 12-, 18- and 24-month. The 6-, 12- and 24-month BODE indices were predictive of the readmissions for AECOPD when compared to baseline.Conclusion: Baseline BODE index could predict both survival and readmissions for AECOPD, whereas serial BODE indices were not predictive of survival at 3 years. Single rather than serial measurements of BODE index is sufficient for prediction of survival and readmissions for patients treated with usual care. more >>
Summary: Background: Early diagnosis of Chronic Obstructive Pulmonary Disease (COPD) remains the cornerstone for effective management. In this study we compared an open spirometry programme and a case-finding programme providing spirometry to high-risk subjects selected by primary care physicians.Methods: A network of primary care physicians was created after invitation and all participants received training on COPD and spirometry. The study team visited 12 primary care settings in each programme in a 1-year period. Spirometry was performed in all eligible participants. COPD diagnosis and classification was based on GOLD guidelines and evaluation by a chest physician.Results:: Patients with acceptable spirometry were evaluated (n = 201 in the case-finding and n = 905 in the open spirometry programme). The proportion of newly diagnosed COPD was 27.9% in the case-finding programme compared to 8.4% in the open spirometry programme (p < 0.0001). The numberneeded-to-screen (NNS) for a new diagnosis of COPD was 3.6 in the case-finding programme compared to 11.9 in the open spirometry programme. The majority of newly diagnosed patients were classified in GOLD stages I an II. The average cost for a new diagnosis of COPD was 173€ in the open spirometry programme and 102€ in the case-finding programme.Conclusions: A case-finding programme involving primary care physicians was more cost-effective for the identification of new cases of COPD compared to an open spirometry programme. The development of networks of primary care physicians with access to good quality spirometry and specialist consultation for early diagnosis of COPD is justified. more >>
Summary: It is widely accepted that CF lung disease starts before clinical symptoms become apparent or spirometry deteriorates. Computed chest tomography (CT) is the reference method for identifying structural changes in CF; however, radiation exposure limits its use as a monitoring tool. It has been suggested that the Lung Clearance Index (LCI) measured by Multiple Breath Washout (MBW) for assessing ventilation inhomogeneity is a more sensitive surrogate marker than spirometry allowing non-invasive monitoring of CF lung disease.The aim of this study was to prospectively investigate the diagnostic accuracy of the LCI in comparison to CT in CF patients with early lung disease and normal FEV1 (>80% pred.).MBW and ultra-low-dose CT were performed in 34 patients (6–26 years). LCI was abnormal in 76.5% subjects. LCI and CT correlated significantly in 82.3%. LCI was related to presence and extent of structural lung changes observed on CT with a sensitivity of 88%.Diagnostic accuracy of the LCI for detecting CF lung disease in patients with normal FEV1 was good when compared to CT. Results indicate that structural changes are unlikely if a normal LCI is measured. We speculate that serial measurements of the LCI for assessing ventilation inhomogeneity may help to identify early structural lung disease and help to reduce the individual cumulative radiation dose. The LCI may be a suitable surrogate marker for monitoring progression of CF lung disease and effect of treatment in both, clinical care and research settings. more >>
Summary: The reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients’ lung function and airway hyperreactivity (AHR).Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by [35S]-sulphate-incorporation/ion chromatography.Patients’ FEV1% predicted and methacholine log PD20 negatively correlated with PICP synthesized by patients’ bronchial fibroblasts (r = −0.74 and r = −0.71, respectively). PICP and proteoglycan amounts positively correlated (0.8 ≤ r ≤ 0.9) with MMP-2 and MMP-3 activity. A positive correlation (r = 0.75) was also found between proteoglycan production and TIMP-1. There was no correlation between MMP-9 activity and PICP or proteoglycan production. MMP-9 activity positively correlated with patients’ FEV1% predicted (r = 0.97) and methacholine log PD20 (r = 0.86), whereas negative associations (−0.6 ≤ r ≤ −0.7) were observed for MMP-2 and MMP-3.In stable mild-to-moderate asthma, increased procollagen I synthesis and activity of MMP-2 and MMP-3 in bronchial fibroblasts may negatively affect patients’ lung function and AHR. In contrast, MMP-9 activity was not associated with procollagen or proteoglycan production, or worsening of patients’ lung function and AHR. An enhanced production of procollagen I and proteoglycans might be a result of a negative feedback from their degradation by MMP-2 and MMP-3. more >>
Summary: Ratio: Asthma is a major public health problem, with bronchial inflammation as the therapeutic target. The role of dietary fish oil derived polyunsaturated fatty acids (PUFAs) in allergic inflammation is controversial. Most asthmatics suffer from mild disease and non-pharmacologic interventions are attractive. This study investigates the anti-inflammatory potential of nutritional PUFAs in an experimentally induced bronchial inflammation.Methods: We examined 38 grass pollen allergic asthmatics and 19 controls. History of dietary PUFA intake was compared with levels of PUFAs in erythrocyte membranes, and stratified according to low (25th quartile; Q25) and high (75th quartile; Q75) ratios of omega-3 (n-3) to omega-6 (n-6) PUFAs as a surrogate for anti-inflammatory (Q75) or proinflammatory (Q25) effects. Bronchial inflammation was simulated with one-step inhalation of grass pollen. Bronchial response (exhaled nitric monoxide, eNO as surrogate for inflammation, decrease of FEV1) was correlated with levels of PUFAs in erythrocyte membranes.Results: Ratios of n-3/n-6 PUFA were significantly lower in asthmatics than in healthy controls. Levels of eNO were significantly higher in Q25 asthmatics than in Q75 asthmatics (p = 0.040). There was a trend of higher bronchial hyperreactivity in Q25 asthmatics (median PD20 0.27 vs. 0.14; n.s.), induced by specific bronchial challenge with grass pollen (FEV1 decrease 16.7 vs. 23.1%; n.s.).Conclusion: When stratifying for erythrocyte membrane PUFA content as a surrogate for alimentary intake, we found mild effects on bronchial allergic inflammation. Future intervention studies with pharmacological PUFA doses appear suitable to clarify dietary PUFA role as an adjunctive intervention to the established treatment of asthma.ClinicalTrials.gov No. NCT00519740. more >>
Summary: Objective: To evaluate the association of periodontal health and parameters of quality of life assessed in 306 Chinese patients with chronic obstructive pulmonary disease (COPD).Methods: Periodontal status and respiratory function in 306 COPD patients were clinically evaluated and their quality of life was assessed using the standardized St George’s Respiratory Questionnaire (SGRQ).Results: The SGRQ scores were all significantly correlated with major lung function parameters (r2 = −0.37 to −0.28; all p < 0.0001) and Medical Research Council dyspnoea scale (r2 = 0.23 to 0.30; all p < 0.0001). The SGRQ scores also correlated with the 6-min walk test (r2 = −0.15 to −0.13; all p < 0.05). Of periodontal health parameters, missing tooth number and plaque index appeared to be related to the scores of quality of life. The age- and gender-adjusted Pearson’s correlation coefficients between missing teeth and total score, symptoms score, and activity score were 0.09, 0.12, and 0.12, respectively (all p < 0.05). The Pearson’s correlation coefficients between plaque index and symptoms score and activity score were 0.09 and 0.09 (p < 0.05). After adjusting for age, gender, body mass index, and smoking status, missing teeth remained significantly associated with symptom score (p = 0.030) and activity score (p = 0.033) while plaque index was significantly associated with symptom score (p = 0.007).Conclusions: Poor periodontal health as reflected by missing teeth and plaque index was significantly associated with lower quality of life in COPD patients. Our findings indicate the importance of promoting dental care in current public health strategies to improve the quality of life in COPD patients. more >>
Summary: Background: Indacaterol is a novel, inhaled once-daily ultra-long-acting beta-2 agonist under development as a fixed-dose combination with an inhaled corticosteroid (ICS) for asthma treatment. This study evaluated the 24-h bronchodilator efficacy of indacaterol in Japanese patients with asthma.Methods: Randomised, placebo-controlled, 5-period crossover study. Patients with persistent asthma (18–75 years, FEV1 50–85% predicted, ≥12% and 200 mL FEV1 reversibility) receiving ICS were randomised to double-blind single dose indacaterol 150, 300, or 600 μg or placebo, with open-label salmeterol 50 μg twice-daily for one day in the 5th period. Primary endpoint was FEV1AUC22–24h.Results: Of 41 randomised patients (48.8% male; mean age: 47.8 years), 39 completed. All indacaterol doses showed significantly higher FEV1AUC22–24h than placebo (P<0.001), with treatment–placebo differences of 180, 220, and 260mL for indacaterol 150, 300, and 600 μg, respectively (salmeterol–placebo difference 170mL; P < 0.001). For individual time-point FEV1, all indacaterol doses were superior to placebo from 5min to 24h post-dose (P < 0.001). Compared with salmeterol, all indacaterol doses were superior from 5 to 30min (P < 0.05); in addition indacaterol 300 μg and 600 μg were superior at a number of subsequent time points. Changes in safety parameters with indacaterol were similar to placebo. All indacaterol doses were well tolerated.Conclusion: Single dose indacaterol provided sustained 24-h bronchodilation with a faster onset of action than salmeterol and a good overall safety and tolerability profile in Japanese patients with asthma. These results are consistent with data from Caucasian populations. more >>
Summary: Ambient air pollution is a contributing factor to respiratory morbidity and mortality and asthmatics are a particularly vulnerable population. The aim of the study was to investigate whether acute exposure to traffic related air pollution in a road tunnel would increase bronchial responsiveness in mild asthmatics, and if this would be accompanied by increased measures of inflammatory markers in the airways assessed by nasal lavage (NAL) and induced sputum.Fourteen mild asthmatics (7 treated with inhaled corticosteroids) were exposed for 2 h in a road tunnel and a control environment, respectively, separated by at least 3 weeks. Symptoms and peak expiratory flow (PEF) were recorded. Seven hours following exposure sessions, subjects underwent measurements of fraction of exhaled nitric oxide (FENO), spirometry, and a bronchial provocation test. NAL, induced sputum and blood samples were collected.The median PM2.5 and PM10 levels during the exposure occasions in the road tunnel were 80 (range 41–93) μg/m3 and 183 (72–213) μg/m3 respectively. Irritative symptoms from the airways increased and PEF decreased after road tunnel exposure. Increased levels of IL-10, IL-12 and TNF-α were observed in NAL fluid from subjects without ongoing inhaled corticosteroid treatment. Forced expiratory volume in 1 s (FEV1) and the degree of bronchial responsiveness in asthmatics did not change significantly after tunnel exposure.We conclude that asthmatics exhibit increased symptoms, decreased PEF and signs of inflammatory response in the upper airways, after a 2 h road tunnel exposure. Our findings may further emphasize asthmatics as a vulnerable group to common air pollutants. more >>
Summary: Objective: To evaluate the efficacy and safety of three doses of ciclesonide (with or without spacer) in children with persistent asthma.Patients and methods: This was a multicentre, double-blind, placebo-controlled, 12-week study of ciclesonide 40, 80 or 160 μg (once daily pm). Children (6–11 years) were randomised 1:1 to treatment via a metered dose inhaler (MDI) or MDI plus spacer. The primary variable was change from baseline in mean morning peak expiratory flow (PEF). Secondary variables included: time to first lack of efficacy (LOE), asthma control, forced expiratory volume in 1 s (FEV1), asthma symptom score and quality of life (QoL). Safety assessments included: adverse events (AEs), urinary cortisol excretion and body height.Results: In total, 1073 children received treatment. At endpoint, mean morning PEF significantly improved with all doses of ciclesonide vs. placebo. There was no difference over placebo in time to first LOE, but ciclesonide was superior to placebo on asthma control, symptom score, FEV1 and QoL. There were no differences between the spacer or non-spacer subgroups. The incidences of AEs were comparable between treatment groups (approximately 35%) and there were no between-group differences in body height or urinary cortisol.Conclusions: Ciclesonide 40–160 μg once daily is effective and well tolerated in children with persistent asthma; its efficacy and safety are unaffected by the use of a spacer.clinicaltrials.gov registration number: NCT00384189. more >>
Summary: Research on the peripheral effects of COPD has focused on physiological and structural changes. However, different from muscular weakness or decreased physical activity, mechanical abnormalities of the muscular system, e.g. walking, have yet to be investigated. Our purpose was to utilize the National Health and Nutritional Examination Survey (NHANES) dataset to determine whether walking abnormalities are associated with COPD severity. To determine if walking abnormalities were independently associated with COPD severity, our analysis aimed to investigate the association of physical activity levels with COPD severity and with walking abnormalities. The NHANES III dataset that contains data for 31,000 persons that were collected from 1988 to 1994, was used to explore the association of COPD severity on gross walking abnormalities, i.e. limp, shuffle, etc. Logistic regression models were created using FEV1/FVC ratio, age, gender, BMI, and smoking status as predictors of walking abnormalities and physical activity in persons aged 40 to 90 years old. Results demonstrated a significant correlation between the presence of walking abnormalities and severe COPD (odds ratio: 1.97; 95% CI: 1.1 to 3.5). This suggests that disease severity can contribute to mechanical outcomes of patients with COPD. In addition, decreased physical activity levels were significantly associated with all COPD severity levels with the exception of mild COPD. The association between altered gait and COPD status may be due to the presence of physical inactivity that is present in patients with COPD. Future research directions should include investigating more closely the mechanical outcomes of persons with COPD. more >>
Summary: Background: Computed tomography (CT) has been used for non-invasive quantitative assessment of airway dimensions, potentially showing airway remodeling, in asthma. However, most studies have examined either only one airway or only airways in anatomically unidentified cross-sections. Using software capable of precisely identifying the generation of airways and measuring airway dimensions perpendicular to the long axis of airways, we examined, in older patients with stable asthma, how inter-subject variation in airway dimensions correlated among the 3rd to 6th generation of airways, and then examined relationships between airway dimensions of each generation and indices of airflow limitation.Methods: Subjects aged ≥55 years old comprised 59 asthmatic patients who underwent CT and pulmonary function tests on the same day. We measured airway wall area (WA%) and inner luminal area (Ai) from the 3rd to the 6th generation of eight bronchi in the right lung.Results: Excellent correlations were identified for both WA% and Ai among the generations (r = 0.744–0.930 for WA%) when we took the average of all measured bronchi per generation as a personal representative value. Significant correlations of airflow limitation indices with both WA% and Ai/BSA were found at each of the 3rd to 6th generations with similar correlation coefficients (WA% for FEV1 %predicted, r = −0.410 to −0.556).Conclusions: In older patients with stable asthma, airway wall thickening and narrowing might occur in a parallel manner through 3rd to 6th generation airways. Airway dimensions at these areas of airways may thus have significant and similar correlations with indices of airflow limitation. more >>
Summary: Background: The exact prevalence and etiology of exertional dyspnea in the clinical course of acute pulmonary embolism (PE) have not yet been established.Methods: A large cohort of consecutive patients diagnosed with acute PE was subjected to a dyspnea questionnaire and invited for cardiopulmonary work-up including the 6-min walk test, spirometry and echocardiography. The prevalence, severity, determinants and underlying diseases of exertional dyspnea were evaluated.Results: Of the registered 877 patients, 259 (30%) had died and 11 (1.3%) were excluded for geographical reasons. From the remaining 607 patients, 217 reported exertional dyspnea (36%; 95% CI 32–40%) 3.6 ± 1.7 years after the PE. In 76% this dyspnea had developed or worsened after the acute PE. 421 patients completed the cardiopulmonary work-up. Cardiopulmonary comorbidity (OR 12; 95% CI 6.5–20), advanced age (OR 1.02 per year; 95% CI 1.01–1.03), higher BMI (OR 1.06 per kg/m2; 95% CI 1.01–1.1) and a smoking history (OR 1.6; 95% CI 1.02–2.6) were identified as independent predictors of exertional dyspnea. A pre-defined dyspnea explaining diagnosis could be established in all patients with exertional dyspnea. In only 4 patients, this diagnosis was directly correlated to the acute PE. Increased severity of dyspnea was associated with decreased exercise performance (p < 0.001) and a higher number of dyspnea-related diagnoses (p < 0.001).Conclusion: Exertional dyspnea is a frequent symptom in the long term clinical course of acute PE. More severe dyspnea results in decreased exercise capacity and increased burden of cardiopulmonary comorbidity. This dyspnea is likely to be unrelated to the past thromboembolic event in the vast majority of patients. more >>
Summary: Background: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. ATS/IDSA guidelines state that all patients with HCAP should receive empirical therapy directed at multidrug-resistant pathogens. However, recent data from other countries have reported a different picture of HCAP.Methods: We conducted a retrospective observational study of patients with HCAP and CAP who were hospitalized through the emergency department in January–December 2008 at Samsung Medical Center, Seoul, Korea, and compared clinical characteristics, severity, distribution of pathogen, and outcomes.Results: In total, 345 patients hospitalized with pneumonia were eligible, 182 (52.8%) with HCAP and 163 (47.2%) with CAP. Patients with HCAP had greater comorbidity and higher Pneumonia Severity Index (PSI) score (P < 0.001). Although Streptococcus pneumoniae was the most frequently isolated pathogen in HCAP and CAP patients, the occurrence of potentially drug-resistant pathogens (29.3% vs. 13.0%; P = 0.044) and inappropriate initial antimicrobial treatment (24.6% vs. 8.7%; P = 0.032) were significantly higher in HCAP patients. Patients with HCAP had a longer duration of hospital stay (13 [8–18] vs. 8 [6–12] days; P < 0.001), and higher in-hospital mortality (19.2% vs. 7.4%; P = 0.001). In a multiple logistic regression analysis, however, in-hospital mortality was independently associated with higher PSI class (OR 2.82, 95% CI 1.19–6.70) and ICU admission (OR 15.37, 95% CI 3.58–66.05).Conclusions: Severity of illness, rather than type of pneumonia, was the main predicting factor for in-hospital mortality among patients with pneumonia hospitalized through the emergency department. more >>
Summary: Objective: This population-based longitudinal study aimed to investigate trends in use of inhaled corticosteroids (ICS) and determinants of ICS use in young Danish adults with asthma.Methods: 106 757 users, aged 18–44 years, of anti-asthmatic drugs were identified in the Danish Register of Medical Product Statistics during 1997–2006. One year prevalences of ICS use were calculated in categories of gender, age, and annual consumption of inhaled beta-2-agonists (IBA) in defined daily doses (DDD) per year. Determinants of ICS use were estimated by logistic regression models.Results: The one year prevalence of ICS use was constant, approximately 64%, during 1997–2000. An annual increase was observed from 67% in 2001 to 77% in 2006. This trend also existed when stratifying on gender, age and IBA use. Using 1997 as baseline, the adjusted odds ratios (ORs) of ICS use in 2000 was 0.98 (95% CI 0.96–1.01) compared to 1.12 (95% CI 1.09–1.15) in 2001, and 1.81 (95% CI 1.75–1.87) in 2006. Other determinants of high ICS use were female gender, young age, and high annual IBA consumption. Among those using at least 400 DDD of IBA per year (corresponding to 4.4 powder inhalations daily), nearly 20% had no ICS prescriptions in 2006.Conclusion: Treatment with ICS among young Danish adult asthmatics has increased since 2001. This apparent improvement was associated with the introduction of fixed dose combination inhalers with ICS and inhaled long-acting beta-2-agonists. However, there is still room for improvement. more >>
Summary: Background: Cryptogenic organizing pneumonia (COP) is a rare disease, and its diagnosis requires histological confirmation. The objective of our study was to describe the findings of the thoracic high-resolution computed tomography (HR-CT) and bronchoalveolar lavage (BAL) in patients with confirmed COP and evaluate the complementary diagnostic use of BAL and thoracic HR-CT.Methods: Patients recorded in the registry of interstitial pulmonary diseases between 1991 and 2008 were located and the COP patients selected.Results: We identified 21 patients with histological confirmation of COP. The median age was 58.0 ± 15.9 years, and 61.9% of patients were female. The most frequent thoracic HR-CT profile was patchy infiltrate (71.4%), followed by parenchymatous consolidation (42.9%). The most frequent BAL profile was mixed alveolitis (62%) with lymphocyte predominance, a CD4/CD8 index of 0.4 and foamy macrophages. The effectiveness of transbronchial biopsy was 66.6%. The diagnostic utility of Poletti’s BAL criteria gives us a specificity of 88.8%, although the sensitivity obtained was low. The specificity of certain HR-CT profiles is 99%. In addition, we observed a complementary use of the HR-CT and the BAL.Conclusions: The imaging findings and BAL could be useful for patients with appropriate clinical presentation and for those whose transbronchial biopsy is negative or for whom a confirmatory biopsy cannot be performed. more >>
Summary: Background: abitual snoring and elevated high-sensitive C-reactive protein (HsCRP) have both been associated with increased risk of cardiovascular disease. However, snoring and HsCRP are elevated in obese states which may thus be the primary determinant of both. We therefore investigated whether snoring may mediate the increased vascular risk directly through increased inflammation as indicated by HsCRP levels or if other determinants predominated in a large older Chinese population.Methods: A total of 2508 males and 5709 females aged 50–85 years received a medical check-up including measurement of blood pressure, obesity indices, fasting total, LDL-, HDL-cholesterol, triglycerides, glucose and HsCRP. Information on self-reported snoring status was collected by standardized interview.Results: The age-adjusted geometric mean HsCRP concentrations increased significantly with higher snoring frequency in both genders (linear trend, p=0.02 for men and p<0.001 for women), but the association was no longer significant after controlling for waist and BMI. Furthermore, HsCRP levels were not significantly associated with snoring frequency groups stratified by BMI/waist quintiles in both genders, except for the 4th waist quintile in men. No interaction was observed between snoring and BMI/waist on HsCRP levels. The multivariate analysis showed that, in both genders, obesity, but not HsCRP, was associated with snoring.Conclusions: Our results showed that snoring frequency did not have an independent effect on inflammation after adjusting for adiposity, and may thus contribute to vascular disease through alternative mechanisms. more >>
Summary: Background: The influence of gender in the clinical expression of COPD has received important attention. Limited information exists regarding gender differences in the skeletal muscle characteristics in COPD subjects. The present study was aimed to determine the differences in the skeletal muscle characteristics in men and women with and without COPD.Methods: For comparison we studied 24 female (61 ± 9 years) and 30 male (65 ± 8 years) COPD patients with similar disease severity. In addition healthy subjects, 17 women (58 ± 8 years), and 9 men (57 ± 8 years) were studied. Pulmonary function, health status, six minute walk distance test (6MWD) and vastus lateralis muscle biopsy were assessed. Fiber type proportion, fiber type cross sectional area (CSA), capillary counts, and activity of citrate synthase (CS), 3-hydroxyacyl-CoA-dehydrogenase (HAD) and lactate-dehydrogenase (LDH) were determined.Results: Pulmonary function, health status and 6MWD were similar in male and female COPD patients. Fiber type distribution was similar between women (I = 42 ± 9%, IIA = 39 ± 13%, IIX = 19 ± 7%) and men (I = 39 ± 13%, IIA = 38 ± 9%, IIX = 29 ± 10%) with COPD, as well as CSA, capillarity and enzymes (CS 8.59 ± 1.6 vs.9.74 ± 2.6, HAD 9.03 ± 1.9 vs. 9.84 ± 2.5, LDH 124 ± 48 vs. 151 ± 68 μmol min−1 g−1). In normal subjects a decrease in type IIX fibers CSA was found in women compared with men (3703 ± 1478 vs. 5426 ± 1386 μm2, respectively).Conclusions: Female and male with COPD have similar skeletal muscle characteristics; it is possible that the disease blurs the gender differences. On the other hand, there seems to be fewer differences in muscle characteristics between older men and women, perhaps due to lower male testosterone levels and physical inactivity. more >>
Summary: Rationale: Patient-reported outcomes provide new insights into the dynamics of asthma management. Further to asthma control and quality of life, self-reported side effects of treatment can be assessed with the validated Inhaled Corticosteroid Questionnaire (ICQ).Objectives: To compare patient-reported side effects between the inhaled corticosteroids ciclesonide and fluticasone propionate.Methods: Patients with moderate or moderate-to-severe asthma, pre-treated with a constant dose and type of medication, were randomized in three separate studies: 1) once daily ciclesonide 320 μg (n = 234) or twice daily fluticasone propionate 200 μg (n = 240); 2) twice daily ciclesonide 320 μg (n = 255) or twice daily fluticasone propionate 375 μg (n = 273); and 3) twice daily ciclesonide 320 μg (n = 259) or twice daily fluticasone propionate 500 μg (n = 244). Patients rated the side effect questions of the 15 domain ICQ on a 7-point Likert scale (0 = not at all, 6 = a very great deal) during scheduled visits.Results: The majority of side effect scores remained similar with ciclesonide but worsened statistically significantly with fluticasone propionate from baseline to the end of the study in within-treatment analyses. In between-treatment analyses of studies 1 and 3 ciclesonide significantly improved total side effect scores (p < 0.025) and 14 out of 30 individual local and systemic domain scores (p < 0.025) compared with fluticasone propionate. In Study 2, although ciclesonide improved the majority of scores compared with fluticasone propionate only ‘oropharyngeal itching’ reached statistical significance (p < 0.025, one-sided).Conclusion: Patient-perceived side effects differ depending on the type of inhaled corticosteroids used. Patients with moderate-to-severe asthma report less intense side effects assessed with ICQ with ciclesonide than with fluticasone propionate.Clinical trial registration: The reported trials were completed before July 1 2005 and, therefore, are not registered. more >>
Summary: Asthmatics with overproduction of mucus that is viscous and sticky have impaired mucociliary clearance (MCC) leading to mucus plugs, and airway obstruction. Inhaled mannitol improves mucus clearance in other hypersecretory diseases. This study investigated the effect of mannitol and cough in asthmatics with mucociliary dysfunction.Seven stable asthmatics, age 52 ± 20 yr, lifelong non-smokers, without the diagnosis of bronchiectasis, with chronic cough and sputum production, treated with inhaled corticosteroids participated in the study. MCC and cough clearance (CC) was measured on 4 visits: at baseline (no cough or mannitol), with mannitol (240 and 480 mg) and cough control (no mannitol) over total 90 min using a radioaerosol technique and imaging with a gamma camera. Cough clearance was assessed after MCC by asking subjects to cough 100 times over 30 min. Premedication with eformoterol (12 μg) on all visits protected all subjects from bronchoconstriction (fall in FEV1 > 15%) in response to mannitol.Mean (±SD) clearance over 60 min increased from 5.5 ± 5.6% at baseline and 7.3 ± 6.6% with cough control to 19.5 ± 14.6% and 26.4 ± 11.5% with 240 mg (p 0.05). Mannitol improved clearance in all lung regions (p < 0.005).In conclusion, mannitol improved both mucociliary and cough clearance in asthmatics with mucociliary dysfunction and ineffective cough clearance.Clinical Trial registered with www.anzctr.org.au; Number ACTRN 12609001066279.aspx. more >>
Summary: Background: Muscle respiratory strength studies during pregnancy are very scarce. The aim of this paper is to describe maximum inspiratory (PImax) and expiratory (PEmax) mean pressure values in women during their first pregnancy and to determine the relationship between the anthropometric, morphologic and physiologic variables of these pressures.Methods: One hundred and twenty women (120) primigravidas were studied from the 5th to 40th gestational week, ages ranging from 20 to 29 years old, euthrophic and with low risk pregnancies.Results: PImax and PEmax mean values were 88.5 ± 16.52 cmH2O and 99.76 ± 18.19 cmH2O respectively. There was no association between gestational age and PImax (r = −0.06; p = 0.49) or PEmax (r = −0.11; p = 0.22). There was also no difference between PImax and PEmax during pregnancy trimesters and no correlation between pregnancy age and the pressures in each trimester. Height was the only anthropometric variable indicating a significant PImax (r = 0.20; p = 0.02) association. Fundal uterus height and inter-recti abdominis distance were not associated to respiratory pressure values. PEmax is not associated with the group of predictor variables (p = 0.127) and PImax demonstrated an independent association with height and dyspnea during physical exertion reflected by the following equation: PImax = 0.6 + 57.9 height – 1.68 dyspnea under effort. The present study suggests that inspiratory and expiratory maximum pressure values are not altered during different stages of pregnancy, however longitudinal studies are needed to assess changes over time. more >>
Summary: Background: The Pneumonia Severity Index (PSI) and CRB-65 are scores used to predict mortality in patients with community-acquired pneumonia (CAP). It is unknown how well either score predicts time to clinical stability in hospitalized patients with CAP. Thus, it is also not known which score predicts time to clinical stability better.Methods: A secondary analysis of 3087 patients from the Community-Acquired Pneumonia Organization (CAPO) database was performed. Time-dependent receiver-operator characteristic (ROC) curves for time to clinical stability were calculated for the PSI and CRB-65 scores at day seven of hospitalization. Secondary outcomes were to assess the relationship of the PSI and CRB-65 to in-hospital mortality and length of stay (LOS). ROC curves for LOS and mortality were calculated.Results: The area under the ROC curve (AUC) for time to clinical stability by day seven was 0.638 (95% CI 0.613, 0.660) when using the PSI, and 0.647 (95% CI 0.619, 0.670) while using the CRB-65. The difference in AUC values was not statistically significant (95% CI for difference of −0.03 to 0.01). However, the difference in the AUC values for discharge within 14 days (0.651 for PSI vs 0.63 for CRB-65, 95% CI for difference 0.001–0.049), and 28-day in-hospital mortality (0.738 for PSI vs 0.69 for CRB-65, 95% CI for difference 0.02–0.082) were both statistically significant.Conclusions: This study demonstrates a moderate ability of both the PSI and CRB-65 scores to predict time to clinical stability, and found that the predictive accuracy of the PSI was equivalent to that of the CRB-65 for this outcome. more >>
Summary: Background: Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted.Methods: Hospital discharge diagnoses data on COPD were analysed in 22,422 Danish twin pairs, 20–71 years of age. The analyses were replicated in a population of 27,668 Swedish twin pairs, 45–108 years of age. A Cox-regression model was applied to the discordant time from the age at first hospital admission for COPD in the co-twin of an affected twin. Latent factor models were used to estimate genetic and environmental effects.Results: The probandwise concordance rate for COPD was higher in monozygotic (MZ) than in dizygotic (DZ) twins, 0.19 vs. 0.07 (p = 0.08) in the Danish population, and 0.20 vs. 0.08 (p = 0.006) in the Swedish population.After adjusting for sex, smoking and age at first hospital admission the risk of developing COPD in the co-twin of an affected twin was higher in MZ than in DZ twins, with hazards ratio 4.3 (95% confidence interval 1.2–15.8, p = 0.03) in Danish twins and 3.4 (1.5–7.7, p = 0.004) in Swedish twins. According to the most parsimonious model, additive genetic factors explained 63% (46–77%) of the individual COPD-susceptibility in the Danish population and 61% (48–72%) in the Swedish population.Conclusion: The susceptibility to develop severe COPD, as defined by hospitalizations, is strongly influenced by genetic factors. Approximately 60% of the individual susceptibility can be explained by genetic factors. more >>
Summary: Introduction: The functional significance of pulmonary hypertension (PH) in COPD is unclear. The purpose of the study was to define the prevalence, severity and associated functional impact of PH in patients with severe COPD listed for lung transplant.Methods: A retrospective review of the Organ Procurement and Tissue Network (OPTN) database between 1997 and 2006 for patients with the primary diagnosis of COPD. Baseline demographics, hemodynamics, pulmonary function tests, six minute walk distance test (6MWD) and pre-transplant survival data was analyzed.Results: 4930 patients with COPD had evaluable right heart catheterization data (RHC). PH was present in 30.4%, with pulmonary venous hypertension (PVH) accounting for an additional 17.2% of patients. Patients with pulmonary hypertension walked an average of 28 m less than those with normal hemodynamics. Normal hemodynamics group: 261 ± 104 m, PH; 238 ± 106 m (p < 0.01), PVH: 228 ± 104 m (p < 0.05). In a multivariable analysis, the mean pulmonary artery pressure (β = −1.33; p = 0.01) was an independent predictor of a reduced 6MWD, as were forced vital capacity (β = 1.48; p < 0.001) and patient age (β = −1.91; p < 0.001). Both PH (HR 1.23 95%CI [1.01–1.50]) and PVH (HR 1.35 95%CI [1.11–1.65]) were shown to be independent risk factors for mortality on the waiting list, even after adjustment for age sex, race, BMI, lung function, severity of illness and diabetes (PH: HR 1.27; 95%CI [1.04–1.55], PVH: HR 1.40; 95%CI [1.13–1.73]).Conclusion: PH is common in advanced COPD and is associated with functional impairment and an increased mortality risk. Stratification by RHC determined pulmonary hemodynamics appears important in distinguishing distinct clinical phenotypes. more >>
Summary: Background: COPD patients have varying degrees of airways disease and emphysema. CT scanning can differentiate these pathological subtypes. We evaluated airway dimensions and emphysema severity with low dose CT scanning in COPD patients to determine relationships with clinical features of the disease.Methods: Fifty six patients with COPD had a low dose thoracic CT scan. Airways were analysed using novel software as either proximal (1st and 2nd generation) or distal (3rd to 6th generation); the extent of emphysema was assessed as the percentage of pixels less than −950 Hounsfield units. CT measures were related to clinical features of COPD.Results: Thicker walls in the proximal airways were associated with clinical features that may represent a bronchitic phenotype (MRC Bronchitis Score; β = 0.20, p = 0.003, Frequent Exacerbations; β = 0.14, p = 0.017, Total St George’s Score; β = 0.50, p = 0.001 and body mass index [BMI]; β = 0.26, p = 0.049); these associations were independent of emphysema. BMI was negatively correlated with the degree of emphysema (β = −0.41, p = 0.001). Airway wall thickness was negatively correlated with CT measured emphysema for both proximal and more distal airways (r = −0.30, p = 0.025 and r = −0.32, p = 0.015).Conclusions: CT measured airway dimensions are associated with several clinical measures of COPD; these are related to a bronchitic phenotype and the effect is independent of emphysema. more >>
Summary: Background: Questionnaires are often used in assessing health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). It is important that these questionnaires have good reliability, validity, and responsiveness. The aim of this study was to investigate and compare these properties in the disease specific Clinical COPD Questionnaire (CCQ) and the Chronic Respiratory Questionnaire self-reported (CRQ-SR).Methods: Two hundred ninety six participants with spirometry confirmed mild to moderate COPD were included in a smoking cessation trial. It was assumed that health-related quality of life would improve in participants who stopped smoking. The questionnaires were administered at baseline and at weeks 5, 26, and 52 after the target quit date.Results: At baseline, 292 (97%) participants returned the CCQ and 296 (100%) the CRQ-SR questionnaire. For both instruments, the internal consistency was good (Cronbach’s alpha >70%) as was the convergent validity with each other but not with spirometry. The CCQ was responsive to improvements in respiratory symptoms at both week 26 (−1.02, SD = 0.81) and 52 (−1.04, SD = 0.91) and in the total score at week 26 (−0.54, SD = 0.50) and 52 (−0.43, SD = 0.44). The mastery domain and the total score of the CRQ-SR were responsive at week 26 (1.14, SD = 0.82; 0.67, SD = 0.97 respectively) but not at week 52 (0.04, SD = 0.93; 0.38, SD = 0.57 respectively).Conclusion: Both the CCQ and CRQ-SR are equally reliable and valid. The long-term responsiveness of the CCQ is better. Both questionnaires can be used in future studies involving patients with mild to moderate COPD. However, when the follow-up exceeds 26 weeks, the CCQ is the recommended alternative.Netherlands Trial Register: ISRCTN 64481813. more >>
Summary: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients.Methods: A multicentre study was carried out in 121 COPD patients (92% males, 63 ± 11 yr, FEV1, 49 ± 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PImax), and expiratory (PEmax) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses.Results: Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV1 (PEmax, OR = 6.8, p < 0.01; PImax, OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV1, was associated with current acute exacerbations.Conclusions: Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction more >>
Summary: Backgrounds: Epithelial cell apoptosis plays an important role in the pathogenesis of idiopathic interstitial pneumonia (IIP).Methods: Serum levels of caspase-cleaved cytokeratin-18 (M30) were measured in 55 patients with IIP and 34 healthy controls using enzyme-linked immunosorbent assays. The IIP cases included usual interstitial pneumonia (UIP; n = 30), nonspecific interstitial pneumonia (NSIP; n = 15), and cryptogenic organizing pneumonia (COP; n = 10). The radiological scoring was performed based on high-resolution computed tomography (HRCT) findings.Results: Patients with IIP had higher serum M30 levels than did the control group (178.6 ± 91.5 vs. 113.7 ± 46.8 U/L, p < 0.05). Among IIP patients, COP patients had higher serum M30 levels than did UIP or NSIP patients (264.9 ± 132.7, 139.2 ± 49.7, and 201.2 ± 81.1 U/L, respectively; COP vs. UIP, p < 0.01). Serum M30 levels were negatively correlated with forced vital capacity (FVC; rs = −0.31), percent-predicted FVC (FVC%; rs = −0.38), and percent-predicted forced expiratory volume in 1 s (FEV1%; rs = −0.36). Serum M30 levels were correlated with radiological ground-glass opacity scores (rs = 0.61).Conclusion: The epithelial apoptosis marker serum level was correlated with IIP clinical status and is a potential marker to assess IIP. more >>
Summary: Objectives: The identification of early phase interstitial changes may influence the understanding of idiopathic interstitial pneumonitis. This study aimed to clarify its radiological patterns and the association with smoking.Methods: The subjects underwent low-dose computed tomography to screen lung cancer. The selected subjects with interstitial changes were monitored for the precise morphology of interstitial changes using a high-resolution computed tomography (HRCT) scan. The subjects were classified into normal and abnormal HRCT subjects. The radiological findings on the HRCT scan, serum Klebs von der Lungen-6 (KL-6), surfactant protein (SP)-A, SP-D, pulmonary function, and computed tomography (CT) scores were analyzed. Abnormal HRCT subjects were classified based on the radiological patterns, and were followed-up over a 4-year period.Results: HRCT abnormalities suggesting interstitial changes were identified in 80 of 3079 subjects. Seven subjects with honeycombing and 14 with combined pulmonary fibrosis and emphysema (CPFE) were identified. The frequencies of sex (male) and smoking in the subjects with honeycombing was higher than that of other patterns. The smoking history and the levels of serum KL-6, SP-A, and SP-D in abnormal HRCT subjects were significantly higher than those in normal HRCT subjects. Thirty-two of 73 abnormal HRCT subjects showed a progression of the CT scores in a chest HRCT over a 4-year period. Eighteen abnormal HRCT current smokers were included in the progression of CT scores.Conclusions: HRCT patterns, excluding interlobular septal thickening, show the progression of CT scores. Smokers with CT abnormalities may have a tendency to demonstrate worsening interstitial changes. more >>
Bedside ultrasound examination could be used to assess the jugular venous pressure (JVP), and thus central venous pressure (CVP), more reliably than clinical examination.
Methods:
The study was a prospective, blinded evaluation comparing physical examination of External jugular venous pressure (JVPEXT), Internal jugular venous pressure (JVPINT) and Ultrasound collapse pressure (UCP) with CVP measured using an indwelling catheter. We compared the examination of the external and internal jugular venous pressure with each other and with the UCP and CVP. JVPEXT, JVPINT, UCP, and CVP were compared graphically using Bland-Altman plots and correlation coefficients were calculated.
Results:
The correlation coefficients comparing CVP to UCP, JVPEXT, and JVPINT were 0.62, 0.57, and 0.50, respectively. When UCP was compared to JVPEXT and JVPINT, correlation coefficients were 0.91 and 0.81, respectively. Lastly, the correlation coefficient comparing JVPEXT and JVPINT was 0.98. The Bland-Altman graphical comparison of methods technique revealed that CVP was often underestimated by UCP, and clinical examination of JVPEXT and JVPINT. In contrast, there was no systematic bias between UCP and either JVPEXT or JVPINT, nor between JVPEXT and JVPINT
Conclusion:
Ultrasound examination is capable of measuring accurately the JVP as judged from the internal or external jugular vein. However, like the JVP, ultrasound typically underestimates CVP. A systematic bias between UCP and CVP suggests the presence of a variable degree of venous tone, possibly signaling contraction of jugular venous smooth muscle.
We designed a simple and integrated diagnostic algorithm for acute pulmonary embolism (PE). Diagnosis was based on clinical probability assessment, plasma D-Dimer testing, then sequential testing to include lower limb venous compression ultrasonography, ventilation perfusion lung scan and chest multi-detector computed tomography (MDCT).
Methods
We included 321 consecutive patients presenting at the University Hospital of Brest, Brest, France with clinically suspected PE and positive D-dimer or high clinical probability. Patients in whom venous thromboembolism was deemed absent were not given anticoagulants and were followed up for 3 months.
Results
Detection of deep vein thrombosis by ultrasonography established the diagnosis of PE in 43 (13%). Lung scan associated with clinical probability was diagnostic in 243 (76%) of the remaining patients. MDCT scan was required in only 35 (11%) of the patients. The 3- month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 0.53% (95% CI 0.09–2.94).
Conclusions
A diagnostic strategy combining clinical assessment, D-dimer, ultrasonography, and lung scan gave a non-invasive diagnosis in the vast majority of outpatients with suspected pulmonary embolism, and appeared to be safe.
Ultrasound-guidance is commonly used for the placement of central venous catheters (CVC). The Agency for Healthcare Research and Quality (AHRQ) recommends the use of ultrasound for CVC placement as 1 of their 11 practices to improve patient care. Despite increased access to portable ultrasound machines and comfort with ultrasound-guided CVC access, fewer clinicians are familiar with ultrasound-guided techniques of arterial catheterization. The goal of this systematic review and meta-analysis was to determine the utility of real-time two-dimensional (2-D) ultrasound-guidance for radial artery catheterization.
Methods:
A comprehensive literature search of Medline, Embase, and the Cochrane Central Register of Controlled Trials by two independent reviewers identified prospective, randomized controlled trials (RCT) comparing ultrasound-guidance with traditional palpation techniques of radial artery catheterization. Data were extracted on study design, study size, operator and patient characteristics, and the rate of first-attempt success. A meta-analysis was constructed to analyze the data.
Results:
Four trials with a total of 311 subjects were included in the review, with 152 subjects included in the palpation group and 159 subjects in the ultrasound-guided group. Compared with the palpation method, ultrasound-guidance for arterial catheterization was associated with a 71% improvement in the likelihood of first-attempt success (relative risk 1.71, 95% confidence interval 1.25-2.32).
Conclusion:
The use of real-time 2-D ultrasound-guidance for radial artery catheterization improved first pass success rate.
The high prevalence of airway hyper-responsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained.
Methods:
To determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multi-center, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness since 30% of participants did not achieve PC20. Multiple linear regression analysis was performed to identify independent predictors of DRS.
Results:
Methacholine challenge was performed in 99 children with SCA ages 5.6 to 19.9 years of age (median 12.8 years). Fifty-four (55%) children had a PC20 less than 4 mg/ml. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age (P < .001), IgE (P = .009) and LDH (P = .005). There was no association between methacholine responsiveness and a parent report of a doctor-diagnosis of asthma (P = .986). Other characteristics of asthma were not associated with methacholine responsiveness including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airflow obstruction.
Conclusions:
In children with SCA, airway hyper-responsiveness to methacholine is prevalent. Younger age, serum IgE and LDH, a marker of hemolysis, are associated with AHR. With the exception of serum IgE, no signs or symptoms of an allergic diathesis are associated with AHR. Although the relationship between methacholine responsiveness and LDH suggests that factors related to SCA may contribute to AHR, these results will need to be validated in future studies.
The purpose of this study was to investigate poor prognostic factors in patients with stage IB NSCLC according to the seventh edition TNM classification.
Methods:
Between July 1992 and December 2004, 1204 consecutive stage I patients with diagnoses based on the sixth edition TNM classification underwent complete resection with systematic node dissection. Of the 1204 patients, 434 patients were reclassified as stage IB according to the seventh edition classification. Univariate analyses were performed using the log-rank test to select prognostic factors. The Cox proportional hazards regression model was used for multivariate analyses to identify independent factors indicating an unfavorable prognosis.
Results:
On multivariate analyses, 2 variables were shown to be independent significant factors indicating an unfavorable prognosis: presence of intratumoral vascular invasion (IVI) and presence of visceral pleural invasion (VPI). According to subgroup analyses combining these 2 risk factors, 5-year disease-specific survival probabilities were 93%, 83%, and 73% for patients with 0, 1, or 2 risk factors, respectively. The 5-year disease-specific survival of patients without risk factors was not statistically different from that of stage IA patients. In addition, the 5-year disease-specific survival curve of patients with 2 risk factors lay beneath that of T2b or T3N0M0, stage II patients, and there were no statistically significant differences between them.
Conclusions:
We identified 2 independent poor prognostic factors in patients with stage IB NSCLC: presence of IVI, and presence of VPI. When these 2 factors are combined, higher- and lower-risk subgroups can be identified, which will help personalize adjuvant chemotherapy.
Database studies have reported associations between idiopathic pulmonary arterial hypertension (IPAH) and: older age, black race, diabetes, and increases in IPAH mortality.
Methods:
We investigated reported deaths and hospital discharges coded as IPAH compared to other forms of pulmonary hypertension (PH). Three databases were used: the US National Center for Health Statistics Database (NCHS, 1979-2006); queried for mortality data, the Nationwide Inpatient Sample Database (NIS, 1993-2007); queried for hospital discharge data, and our University Hospital discharge database (1999, 2002).
Results:
Marked increases in mortality attributable to IPAH and to PH generally (all codes combined) were reported from 1979 until 2002 in the NCHS. In 2003, reported IPAH mortality fell sharply while total PH deaths increased. The NIS database showed a similar pattern of changes beginning approximately two years earlier. In both cases, the timing of these observations corresponded to changes made to the International Classification of Disease (ICD) coding system in use for PH in that particular database. Review of pulmonary hypertension discharges from our own University Hospital identified similar changes in diagnosis code use.
Conclusions:
Sudden shifts in reported IPAH mortality and hospital discharges were seen in all databases, likely related to coding changes. These findings raise questions about the accuracy of PH diagnosis codes. Studies based on ICD-9 or ICD-10 codes may have inadvertently included patients with other forms of PH, and should be re-evaluated in this context. Validation studies of the IPAH diagnosis code are needed and changes in the ICD coding system should be considered.
Ventilator-associated tracheobronchitis (VAT) is considered an intermediate condition between bacterial airway colonization and ventilator-associated pneumonia (VAP). The purpose of this prospective cohort study was to further characterize VAT in terms of incidence, etiology, and impact on patient outcomes.
Methods:
Patients intubated for more than 48 hours in the surgical and medical ICUs of Barnes-Jewish Hospital were screened daily for the development of VAT and VAP over one year. Patients were followed until hospital discharge or death and patient demographics, causative pathogens, and clinical outcomes were recorded.
Results:
A total of 28 patients with VAT and 83 with VAP were identified corresponding to frequencies of 1.4% and 4.0% respectively. VAP was more common in surgical than medical ICU patients (5.3% versus 2.3%; p < 0.001) but the occurrence of VAT was similar between surgical and medical patients (1.3% versus 1.5%; p = 0.845). VAT progressed to VAP in 9 cases (32.1%) despite antibiotic therapy. There was no significant difference in hospital mortality between patients with VAP and VAT (19.3% versus 21.4%; p = 0.789). VAT was caused by a multidrug resistant (MDR) pathogen in 9 cases (32.1%).
Conclusion:
VAT occurs less commonly than VAP but at a similar incidence in medical and surgical ICU patients. VAT frequently progressed to VAP and patients diagnosed with VAT had similar outcomes to those diagnosed with VAP suggesting that antimicrobial therapy is appropriate for VAT. VAT is also frequently caused by MDR organisms and this should be taken into account when choosing antimicrobial therapy.
The study aimed to evaluate the effect of upper extremity resistance training for patients with COPD on dyspnea during activity of daily living (ADL), arm function, arm exercise capacity, muscle strength and health related quality of life (HRQL)
Methods:
Patients were randomly assigned to an intervention or control group. The intervention group underwent arm resistance training. The control group performed a sham. Both groups exercised 3 times a week for 6 weeks. Dyspnea during ADL and HRQL were measured using the chronic respiratory disease questionnaire (CRDQ). Arm function and exercise capacity were measured using the 6-minute pegboard and ring test (6PBRT) and the unsupported upper limb exercise test (UULEX), respectively. Muscle strength for the biceps, triceps, anterior and middle deltoids was obtained using an isometric dynamometer.
Results:
Thirty-six patients with COPD (66 ± 9 yrs) participated in the study. Compared with the control group, the magnitude of change in the intervention group was greater for the 6PBRT (p = 0.03), UULEX (p = 0.01) and elbow flexion force (p = 0.01); elbow extension force (p = 0.02), shoulder flexion force (p = 0.029) and shoulder abduction force (p = 0.01). There was no between-group difference in dyspnea during ADL, HRQL or symptoms during the 6PBRT or UULEX (all p values greater than 0.08).
Conclusions:
Resistance based arm training improved arm function, arm exercise capacity and muscle strength in patients with COPD. No improvement in dyspnea during ADL, HRQL or symptoms was demonstrated.
The non-specific (NS) pulmonary function (PF) pattern refers to a PF test with a normal Total Lung Capacity (TLC), normal FEV1/FVC ratio AND a low FEV1, a low FVC or both. Currently, no information is available regarding the long term stability of the NS pattern or variables that predict changes in subjects with an initial NS PF pattern.
Methods:
From 1990-2005, we identified 1284 subjects with a NS pattern on initial PF testing with one or more follow up PF tests 6 months or more after the initial NS test. Lung volumes, diffusing capacity and spirometry data were analyzed. A multivariate, multinomial logistic regression model was used to study the association between different variables and the final PF pattern.
Results:
Overall, 3674 PF tests were performed in 1284 subjects over a median follow up period of 3 years. At last follow up, 818/1284 (64%) subjects continued to show the NS pattern; whereas 208/1284 (16%) showed a restrictive pattern; 191/1284 (15%) an obstructive pattern; 42/1284 (3%) a normal pattern and 25/1284 (2%) showed a mixed pattern. The multinomial logistic regression analysis showed that increasing values for specific airway resistance (Sraw) and TLC-Va were predictors of a change to an obstructive pattern on follow up.
Conclusion:
The NS pattern is a distinct and stable PF test pattern with roughly 2/3rd of patients continuing to show this pattern on follow up testing. Current interpretation guidelines erroneously label the NS pattern as representing obstruction and need to be changed to reflect these data.
The obstructive abnormality of bronchiolitis obliterans syndrome (BOS) following allogeneic hematopoietic stem cell transplantation (HSCT) is deemed to be virtually insensitive to inhaled bronchodilators. We studied whether non-conventional assessment of bronchodilation may help detect physiologically meaningful airway responses missed by traditional criteria.
Methods:
Standard spirometry, partial and maximal expiratory flow-volume curves, and lung volumes were measured before and 90 min after inhalation of albuterol plus tiotropium in 17 patients who developed mild-to-very-severe BOS following HSCT.
Results:
After bronchodilators, the standard criteria of reversibility based on forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were met in 7 out of 17 patients. In 8 patients, residual volume (RV) decreased beyond its within-session spontaneous variability and in 4 of them also functional residual capacity (FRC). Partial forced expiratory flow ($$\stackrel{\cdot }{\mathrm{V}}\hbox{ part }$$) increased beyond its within-session spontaneous variability in 9 patients. Out of 10 patients in whom neither FEV1 nor FVC met the standard criteria of reversibility, 6 had a positive increase in $$\stackrel{\cdot }{\mathrm{V}}\hbox{ part }$$ or a decrease of lung hyperinflation, i.e., FRC, or RV. In 6 patients, who were expiratory flow-limited during tidal breathing, the post-bronchodilator increase in $$\stackrel{\cdot }{\mathrm{V}}\hbox{ part }$$ was correlated with a decrease in FRC (R2=0.83, P=0.011).
Conclusions:
This study suggests that (a) airway smooth muscle tone plays a significant role in BOS following HSCT, and (b) the common knowledge of BOS as an irreversible obstructive disease may stem from the limitation of simple spirometry to detect changes in small airways.
Organizing pneumonia (OP) is a distinct clinical and pathological entity. This condition can be cryptogenic (COP) or secondary to other known etiologies (secondary OP). In the present study, we reviewed the features associated with COP and secondary OP in patients from two teaching hospitals.
Methods:
The medical records of 61 patients with biopsy proven OP were retrospectively reviewed. 40 patients were diagnosed with COP and 21 patients with secondary OP. The clinical presentation, radiolographic studies, pulmonary function tests (PFT), laboratory data, bronchoalveolar lavage (BAL) findings, treatment and outcome were analyzed.
Results:
The mean age at presentation was 60,46 ± 13,57 years. Malaise, cough, fever, dyspnea, bilateral alveolar infiltrates and a restrictive pattern were the most common symptoms and findings. BAL lymphocytosis was observed in 43,8% of patients with OP. The relapse rate and mortality rate after one year of follow-up were 37,8% and 9,4% respectively. The in-hospital mortality was 5,7 %. The clinical presentation and radiographic findings did not differ significantly between patients with COP and secondary OP. A mixed PFT pattern (obstructive and restrictive physiology) and lower blood levels of Na, K, platelets, albumin, protein and pH were observed among patients with secondary OP. Higher blood levels of creatinine, bilirubin, PaCO2 and BAL lymphocytes were also more common among patients with secondary OP. There were no differences in the relapse rate or mortality between patients with COP and secondary OP. The one-year mortality correlated with an elevated ESR, low albumin and low haemoglobin levels.
Conclusions:
The clinical and radiographic findings in patients with COP and secondary OP are similar and nonspecific. While certain laboratory abnormalities are more common in secondary OP and can be associated with worse prognosis, they are likely due to the underlying disease. COP and secondary OP have similar treatment response, relapse rates and mortality.
Identification of persons with Parkinson’s disease (PD) who are "at-risk" for aspiration is important, especially because of the high incidence of aspiration pneumonia.
Methods:
Fifty eight consecutive patients (HY stage II-III; average age 72.3) were enrolled in the study. Measures of airflow during a voluntary cough production and the degree of penetration/ aspiration on a 3oz oropharyngeal swallow task, derived from videofluorographic images, were examined.
Results:
To detect "at-risk" persons (penetration and/or aspiration on the 3 oz swallow task) four objective measures of voluntary cough [compression phase duration (CPD), expiratory phase rise time (EPRT), expiratory phase peak flow (EPPF), and cough volume acceleration (CVA)] were collected. CPD, EPRT, EPPF, and CVA produced significant area under the curve (AUC) analyses and likelihood ratios equal to 0.83 (2.72), 0.71 (2.68), 0.69 (1.75), 0.78 (18.42) respectively. CPD, EPRT, EPPF, and CVA demonstrated sensitivities of 95.83%, 70.83%, 87.50%, 84.53%, and specificities of 64.71%, 73.53%, 50.01%, 97.06%. For detection of aspiration, EPPF was significantly associated with AUC equal to 0.88, and with an EPPF <5.24 had a sensitivity of 57.15% and a specificity of 100%.
Discussion:
The data from this pilot study suggests that, in PD, objective airflow measures from voluntary cough production may identify "at-risk" penetrator/aspirators. To our knowledge this is the first study to evaluate the discriminative ability of voluntary cough airflow characteristics to model airway compromise persons with PD.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used as antipyretics and analgesics and may affect the host response to acute infection. We investigated the potential influence of NSAIDs on the presentation and short-term outcomes of non-immuno-compromised inpatients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU).
Methods:
All consecutive patients with CAP admitted to the ICU or step-down unit of a university hospital during a 4-year period were prospectively included, except when receiving long-term NSAIDs and/or steroids. Drug exposures, presentation and hospital course were recorded.
Measurements and Main Results:
Of the 90 patients included, 32 (36%) had taken NSAIDs prior to hospital referral. As compared with non-exposed patients, they were younger, had less comorbidities but similar severity of disease at presentation, despite a longer duration of symptoms before referral. However, they developed more often pleuro-pulmonary complications such as pleural empyema and lung cavitation (37.5% vs. 7%; P=0.0009) and had a trend to more invasive disease, with a higher frequency of pleural empyema (25% vs. 5%, P=0.014) and bacteremia, especially in those not having received concomitant antibiotics (69% vs. 27%, P=0.009). Nevertheless, the NSAIDs patients had no more severe systemic inflammation or remote organ dysfunction. In multivariable analyses, NSAIDs exposure was independently associated with the occurrence of pleuro-pulmonary complications (OR 8.1; CI 2.3-28).
Conclusions:
Our findings suggest that NSAIDs exposure at the early stage of CAP is associated with a more complicated course but a blunted systemic response, which may be associated with a delayed diagnosis and a protracted course.
Catheter-related bloodstream infection (CRBSI) is a preventable cause of a potentially lethal intensive care unit (ICU) infection. The optimal method to teach healthcare providers correct sterile techniques during central vein catheterization (CVC) remains unclear.
Methods:
We randomly assigned second and third-year internal medicine residents trained by traditional apprenticeship model to simulation-based plus video-training or video-training alone from December 2007 to January 2008 with a follow-up period to examine CRBSI ending in July 2009. During the follow-up period, a simulation-based training program in sterile techniques during CVC was implemented in the MICU. Surgical ICU where no residents received study interventions was used for comparison. The primary outcome measures were median residents’ scores in sterile techniques and rates of CRBSI per 1000 catheter-days.
Results:
Of the 47 enrolled residents, 24 were randomly assigned to simulation-based plus video-training group and 23 to video-training group. Median baseline scores in both groups were equally poor: 12.5-13 (52-54 %) out of maximum score of 24 (p = 0.95; Median difference 95% CI: 0, 0.2-2.0). After training, median score was significantly higher for simulation-based plus video-training group 22 (92%) vs. 18 (75%) for video-training group (p <0.001; Median difference 95% CI: 4, 3-6). During the follow-up period, there was a significantly lower rate of CRBSI in the MICU (1.0 per 1000 catheter-days) compared to the SICU (3.4 per 1000 catheter-days) (p= 0.03). The incidence rate ratio derived from the Poisson regression (0.30; 95% CI, 0.10-0.91) indicated there was a 70% reduction in the incidence of CRBSI in the post-intervention MICU compared with the pre-intervention MICU and the post-intervention SICU.
Conclusions:
Simulation-based training in sterile techniques during CVC is superior to traditional-training or video-training alone and is associated with decreased rate of CRBSI. Simulation-based training in CVC should be routinely utilized to reduce iatrogenic risk.
Obstructive sleep apnea (OSA) is associated with disorders of glucose metabolism. Previous studies revealed high prevalence of OSA among type 2 diabetes mellitus (DM) subjects. The aims of this study were to find out the prevalence of OSA and associated clinical factors in Chinese patients with DM.
All records of the DM clinic at a teaching hospital in Hong Kong were screened between January 2007 and June 2008. Inclusion criteria were Chinese, age 18–75 years and type 2 DM. Patients with unstable medical illnesses, gestational diabetes or on renal replacement therapy were excluded.
Of 3489 records screened, 1859 subjects were eligible. A random sample of 663 (mean age 58.2±10.8, mean BMI 26.0±4.6), except six with known OSA, were invited for polysomnography(PSG). Of 165 subjects with PSG performed, OSA was diagnosed (Apnea-hypopnea index[AHI] ≥ 5.0/hr) in 89 subjects(53.9%, median Epworth Sleepiness Scale: 6 [3,10]). Fifty-four(32.7%) had moderate-severe OSA(AHIgreater double equals15/hr). The estimated OSA prevalence in this diabetic cohort was 17.5%(24.7% in men, 10.3% in women). Regression analysis identified that AHI was associated independently with higher BMI, advanced age, male gender and higher diastolic blood pressure(R2=29.6%). The adjusted odds ratio of requiring ≥ three antihypertensive drugs in moderate/severe OSA was 2.48 (95% CI 1.05 - 5.87). No association with glycemic control(HbA1c) and sleep was identified. In conclusion, OSA is more prevalent in Chinese adults with DM than in the general population. A high index of suspicion for OSA in DM patients is warranted since they may not have overt daytime sleepiness.
Ambrisentan is a selective endothelin receptor antagonist (ERA) that is FDA-approved to treat pulmonary artery hypertension. We describe hemodynamic responses and clinical outcomes of patients with portopulmonary hypertension (POPH) treated with ambrisentan.
Methods:
In this observational study, we prospectively identified and followed consecutive adult POPH patients from January 2007 until December 2009 that received monotherapy with ambrisentan up to 10 mg daily. Liver enzymes were assessed monthly. Pulmonary hemodynamics were assessed by echocardiograms and right heart catheterizations.
Results:
We identified 13 patients (7 males) with POPH and began monotherapy with ambrisentan. The median age (IQR) was 57(52-60). Patients were followed for a median (IQR) of 613 days (385-1011). The median MELD score was 10(8.5-15); eight patients had Child’s A classification. Median time on ambrisentan therapy was 390 days (363-611). Two patients died, one of advanced hepatocellular carcinoma, and one of septic shock following pneumonia. The mean pulmonary artery pressure decreased from a baseline median (IQR) of 58 mmHg (37-63) to 41 mmHg (27-48) (p=0.004). Pulmonary vascular resistance median (IQR) was reduced from 445 (329-834) to 174 dyne·sec/cm5 (121-361) (p=0.008). There was no difference in the longitudinal analysis of liver function tests (AST, ALT, Total bilirubin and INR) after 12 months of therapy. One patient underwent successful liver transplantation and normalized pulmonary hemodynamics after transplantation.
Conclusion:
In this small cohort of patients with moderate to severe pulmonary hypertension in the setting of POPH, we have shown that ambrisentan monotherapy can significantly improve pulmonary hemodynamics without adverse effect on hepatic function.
There is a paucity of normal age stratified data for exhaled nitric oxide (FeNO) (Olin AC et al. Chest 2007; 131:1852-1856). Our goal was to obtain normal data for large airway NO flux (J`awno) and small airway/alveolar NO concentration (Cano) in non-smoking healthy adult subjects of varying age.
Methods:
In 106 normal volunteers (60F), age 55±20yr (mean ± SD), FeNO(ppb) was measured at 50,100,150, and 200 mL/s and J`awno(nL/s) and Cano(ppb) were calculated using a two-compartment model (Tsoukias NM, George S. C. JAP 1998;85:653-666) with correction for axial NO back-diffusion (Condorelli P et al. JAP 2007;102:417-425). Fourteen older normals were also treated for 14 days with ICS (540 µg budesonide bid).
Results:
We studied 34 Younger normals (17F), age 18-39yr; 26 Middle-age normals (22F), age 40-59yr, and 46 Older normals (21F), age 60-86yr. FeNO at 50mL/s in Younger group was 21(14-28)ppb (median, 1-3 interquartile); Middle-age was 22(18-30)ppb and Older was 27(21-33)ppb, (ANOVA) p=0.02. Younger vs Older (Mann-Whitney) p=0.03; and combined Younger and Middle-age was 21(15-29)ppb vs Older 27(21-33)ppb, p=0.006. Corrected J`awno in Younger was 1.5(1.0-2.1)nL/s; Middle-age was 1.4(1.0-2.0)nL/s and Older was 1.8(1.2-2.4)nL/s,(ANOVA) p=0.3. Corrected Cano in Younger was 1.9(0.8-3.0)ppb; Middle-age was 2.8(0.8-5.1)ppb and Older was 3.9(1.4-6.6)ppb,(ANOVA) p=0.02. Younger vs Older p=0.003, and combined Younger and Middle-age was 2.0(0.8-3.8) vs Older: 3.9(1.4-6.6), p=0.01. No change in NO gas exchange with ICS.
Conclusion:
In non-smoking, healthy subjects with normal spirometry, FeNO at 50mL/s and Cano increased significantly with age ≥60 yr whereas J`awno did not. We suspect the increase in Cano was due to decrease in capillary blood volume with reduced NO diffusion, and is also reflected in increased FeNO. Inhaled budesonide had no anti-NO mediated inflammatory effect. Age-matched controls will be needed in NO comparative studies.
Phenotypic characterisation of patients with Chronic Obstructive Pulmonary Disease (COPD) may have potential prognostic and therapeutic implications. Available information on the relationship between emphysema and the clinical presentation in COPD patients is limited to advanced stages of the disease.
Objective:
To describe emphysema presence, severity, and distribution and its impact on clinical presentation of patients with mild to moderate COPD.
Methods:
One hundred and fifteen COPD patients underwent clinical and chest computed tomography (CT) evaluation for the presence, severity and distribution of emphysema. Patients with and without emphysema and with different forms of emphysema distribution (upper/lower/core/peel) were compared. The impact of emphysema severity and distribution on clinical presentation was determined.
Results:
Fifty percent of the patients had mild homogeneously distributed emphysema (1.84; 0.76-4.77%). Upper and core zones had the more severe degree of emphysema. Patients with emphysema were older, more frequently males, and had lower FEV1%, higher TLC% and lower DLCO. No differences were found between the clinical or physiological parameters of the different emphysema distributions.
Conclusions:
In patients with mild to moderate COPD, although the presence of emphysema has an impact on physiological presentation, its severity and distribution seem to have little impact on clinical presentation.
Lysosomal disruption and consequent apoptosis have been implicated in lung diseases characterized by iron-overload. Free reactive iron in lysosomes sensitizes cells to oxidative stress. Apoptosis is prevented by H-ferritin, which can incorporate lysosomal iron into ferritin molecules. TNF- stimulates the synthesis of H-ferritin. Idiopathic pulmonary hemosiderosis presents with the accumulation of iron and the up-regulation of ferritin synthesis. We therefore analyzed the lysosomal response to oxidants and the role of H-ferritin synthesis in lung macrophages harvested from the first Swedish case of Lane-Hamilton syndrome.
Methods:
Iron-exposed murine macrophages were used as a reference. Both cell types were stimulated with TNF- (or not), then iron was assessed cytochemically and by atomic absorption spectrophotometry. H-ferritin expression was analyzed by Western-blot and reduced glutathione by spectrofluorometry. Following H2O2-exposure, lysosomal membrane integrity and DNA-degradation were analyzed by flow cytometry, while morphologic signs of apoptosis/necrosis were assessed by light microscopy.
Results:
Reduced glutathione levels were approximately equal in lung macrophages and murine macrophages. Although lung macrophages contained much more iron than murine macrophages, lysosomal iron was bound in a harmless un-reactive state by ample amounts of ferritin and hemosiderin, its lysosomal degradation product. Therefore, lysosomes of lung macrophages were more oxidant-resistant, and these cells were more adept at surviving oxidative stress. In both cell types, TNF- prevented oxidant-induced lysosomal damage and cell death by up-regulating synthesis of H-ferritin and reduced glutathione.
Conclusions:
Iron-overloaded lung macrophages are equipped with an efficient armor of anti-oxidative mechanisms of which H-ferritin and hemosiderin seem to be particularly important.
The aldo-keto reductase (AKRs) represent a gene superfamily that code for monomeric, soluble NAD(P)H-dependent oxidoreductases that mediate elimination reactions. AKR1B10, an AKR that functions to eliminate retinals, has been observed to be upregulated in squamous metaplasia and non small cell lung cancer, and has been suggested as a diagnostic marker specific to tobacco-related carcinogenesis.
Methods:
We hypothesized that up-regulation of AKR1B10 expression may be initiated in healthy smokers, prior to the development of evidence of lung cancer. For this purpose, expression of AKR1B10 was assessed at the mRNA level using microarrays with TaqMan confirmation in the large airway epithelium (21 healthy nonsmokers, 31 health smokers) and small airway epithelium (51 healthy nonsmokers, 58 healthy smokers) obtained by fiberoptic bronchoscopy and brushing.
Results:
Compared to healthy nonsmokers, ARK1B10 mRNA levels were significantly up-regulated in both the large and small airway epithelium of healthy smokers. Consistent with the mRNA data, AKR1B10 protein was significantly upregulated in the airway epithelium of healthy smokers as assessed by Western analysis and immunohistochemistry, with AKR1B10 expressed in both differentiated and basal cells. Finally, cigarette smoke extract mediated up-regulation of AKR1B10 in airway epithelial cells in vitro and transfection of AKR1B10 into airway epithelial cells enhances the conversion of retinal to retinol.
Conclusions:
Thus, smoking per se mediates up-regulation of AKR1B10 expression in the airway epithelium of healthy smokers with no evidence of lung cancer. In the context of these observations and the link of AKR1B10 to the metabolism of retinals and to lung cancer, the smoking-induced up-regulation of AKR1B10 may be an early process in the multiple events leading to lung cancer.
NF-B activation and oxidative stress are physiological responses of skeletal muscle to exercise but may be impaired in COPD patients. Therefore, we investigated NF-B activity and expression of NF-B regulated genes in muscle of COPD patients and controls before and after exercise.
Methods:
Quadriceps specimens were obtained before, immediately and 2h after a submaximal cycle ergometry test from 7 COPD patients (50.6 ± 5.7 SEM) and 7 age-matched controls. NF-B DNA binding activity in muscle and peripheral blood mononuclear cells (PBMCs) was determined using electrophoretic mobility shift assay and ELISA respectively. mRNA expression and protein carbonylation were measured by RT-PCR and Western blot, respectively.
Results:
In controls, IL-6, IB, TNF-, IL-1β, superoxide dismutase, thioredoxin, heme oxygenase 1 and heat shock protein70 were upregulated in muscle after exercise, whereas in COPD only IL-6 mRNA was increased. Exercise-induced anti-apoptotic Bcl2 mRNA levels were attenuated in COPD compared to controls. Basal muscle protein oxidation was higher in COPD than in controls, but attenuated in response to exercise. No exercise-induced changes in NF-B DNA binding activity in muscle and PBMCs of both groups were detected.
Conclusions:
Skeletal muscle of COPD patients is characterized by an impaired response to exercise of NF-B regulated genes encoding inflammatory cytokines, antioxidants, stress proteins and survival factors.
Severe pneumonia requiring intensive care unit admission has not been well characterized with respect to long-term outcomes or predictors thereof. We aimed to examine the association between premorbid functional status and mortality in patients with severe pneumonia.
METHODS
From 2000-2002, a population-based cohort of critically ill adults with pneumonia was enrolled and prospectively followed. Short- (30-day) and long-term (1-year) mortality were examined using multivariable Cox regression models.
RESULTS
The final cohort included 271 patients; mean age 61 years, 59% male, 16% from nursing homes. Mean Pneumonia Severity Index was 113 (71% Class IV or V) and mean APACHE II score was 17. Overall, 121 (45%) patients were functionally independent, 115 (42%) had limited mobility and 35 (13%) were completely dependent. Mortality was 11% at 30-days and 27% at 1-year; by functional status it was 6% at 30-days and 17% at 1-year for independent patients, 10% and 31% for limited mobility patients, 39% and 48% for dependent patients. Mortality was greater for completely dependent patients when compared with independent (adjusted hazard ratio [aHR] 5.3, 95%CI 2.0-14.1, p<0.001 at 30-days; aHR 3.0, 95%CI 1.5-6.1, p=0.002 at 1-year) or limited mobility patients (aHR 4.8, 95%CI 2.0-11.2, p<0.001 at 30-days; aHR 2.3, 95%CI 1.3-4,4, p=0.007 at 1-year). There were no mortality differences between limited mobility and independent patients.
CONCLUSIONS
One-quarter of critically ill patients with pneumonia are dead within 1-year. Severely limited premorbid functional status was associated with mortality – this should be considered at presentation for prognosis and discharge for targeted follow-up.
Pleural effusions frequently occur in patients requiring mechanical ventilatory support. Treatment of the precipitating cause and resolution of the pleural effusion may take considerable time. We retrospectively studied the effect of chest tube drainage of transudative pleural effusions on the liberation of patients from mechanical ventilatory support.
Methods:
Patients in the medical intensive care unit (MICU) between January 1, 2009 and October 31, 2009 requiring mechanical ventilatory support with a transudative pleural effusion were retrospectively studied. They were divided into two groups: standard care or standard care plus chest tube drainage. Chest tubes were placed under ultrasound guidance by trained intensivists. Duration of mechanical ventilatory support was the primary end point. Secondary end points included measures of oxygenation, amount of fluid drained and complications associated with the chest tube.
Results:
A total of 168 patients were studied; 88 were treated with standard care and 80 underwent chest tube drainage. Total duration of mechanical ventilatory support was significantly shorter for patients who had chest tube drainage 3.8 days (± 0.5) versus 6.5 days (± 1.1) for the standard group (P=0.03). No differences in oxygenation were noted between the two groups. The average amount of fluid drained was 1220 mL. No significant complications were caused by chest tube drainage.
Conclusions:
Chest tube drainage of transudative pleural effusions resulted in more rapid liberation from mechanical ventilatory support. It is a very safe procedure when performed under ultrasound guidance by experienced personnel.
Mannose-binding lectin (MBL) deficiency is associated with susceptibility to respiratory infections. We investigated the impact of MBL2 gene polymorphisms and MBL deficiency on the recurrence of infective exacerbation in patients with chronic obstructive pulmonary disease (COPD).
Methods:
A prospective study was conducted among 215 COPD individuals and 137 healthy subjects. MBL deficiency was determined by the MBL2 gene polymorphisms and serum levels of MBL.
Results:
The average frequency of infective exacerbations over three years in the 215 COPD patients was 2.5 ± 1.3 episodes. The COPD group with ≥ 3 episodes of infective exacerbation (recurrent exacerbators) included 96 patients. The other 119 COPD patients had ≤ 2 episodes of exacerbation (less frequent exacerbators). Among the 96 recurrent exacerbators, 12 (12.50%) had the MBL deficiency genotype, compared with 5 (4.20%) among the less frequent exacerbators (OR 3.25, 95% CI 1.01 to 11.07, p = 0.0253). In recurrent exacerbators, the frequency of infective exacerbation was significantly higher in patients with MBL-deficient genotypes than in those with non-MBL-deficient genotypes (4.75 ± 1.22 vs. 3.52 ± 0.78, p < 0.0001). In addition, the mortality was significantly increased in recurrent exacerbators with MBL-deficient genotypes compared with those with non-MBL-deficient genotypes (66.7% vs. 31.0%, p = 0.0153).
Conclusions:
MBL deficiency due to MBL2 polymorphisms increases the risk of recurrent infective exacerbation and worsens its outcome in COPD patients.
The frequencies of aetiological bacterial agents of intrapleural infections which have been reported until now have been widely varied, largely depending upon the implemented detective methods. The aims of this study is to evaluate bacterial aetiologies of bacterial pleurisy using a cultivation-independent method.
Materials and Methods:
Pleural fluids were collected from 42 febrile patients with hemipleural effusion. The bacterial clone library was analyzed by a clone library method using amplified fragment of the 16S ribosomal RNA gene (rDNA) with universal primers in addition to conventional cultivation methods.
Results:
Forty two specimens were obtained from 26 patients with bacterial pleurisy, 7 with mycobacterial pleurisy and 9 with other pleural effusions. In 26 bacterial cases, 16 (61.5%) cases showed positive results for 16S rDNA sequencing analysis, of which 11 (42.3%) cases were also positive for cultivation method. In 7(42.3%) out of the 16 PCR positive cases, anaerobic phylotypes were predominantly detected. Anaerobic phylotypes (six out of the above 7 cases) were not detected by cultivation method. In 9 of 26 bacterial pleural cases (34.6%), the results from the clone library methods were not accordant with those of the cultivation method. In 7 of the above 9 cases, the discrepancies between the two detection methods were due to the existence of anaerobes.
Conclusion:
The clone library analysis using the 16S rRNA gene of pleural fluid showed a higher incidence of anaerobic bacteria in infectious pleurisy than that was previously expected, and provided additional bacterial information for cultivation methods.
Little is understood about the characteristics of dyspnea in patients with interstitial lung disease, and its severity is likely influenced by multiple factors. Depression and functional status are known to influence dyspnea in patients with chronic obstructive pulmonary disease. The aim of this study was to determine the relationship of dyspnea with clinical parameters including depression and functional status in patients with interstitial lung disease.
Methods:
Dyspnea was measured with the Baseline Dyspnea Index and the University of California San Diego Shortness of Breath Questionnaire. Clinical parameters were recorded. Regression analysis was performed to determine independent correlates of dyspnea.
Results:
Fifty-two subjects were enrolled. The two dyspnea scales were strongly correlated (r = -0.79, p < 0.00005). The mean levels of dyspnea were 6.5 and 41.0, representing a moderate degree of dyspnea. Clinically meaningful depressive symptoms were found in 23% of subjects. Independent correlates of dyspnea severity for each dyspnea scale were depression score (p = 0.002 and < 0.0005), 4-meter walk time (p = 0.001 and 0.06), forced vital capacity (p = 0.07 and 0.004), and diffusing capacity of carbon monoxide (p = 0.007). Body mass index had borderline significant association with the Baseline Dyspnea Index (p = 0.10).
Conclusions:
In patients with interstitial lung disease, dyspnea is associated with depression score, functional status, and pulmonary function. These results suggest that attention to depression and functional status is important in these patients and that treatment directed at these comorbidities may improve dyspnea and quality of life.
Acute lung injury (ALI) is a potentially fatal lung disease with few treatment options. Platelet activation is a key component of ALI pathophysiology and may provide an opportunity for prevention strategies. We examined the association of pre-hospitalization anti-platelet therapy with development of ALI in critically ill patients.
Methods:
All Olmsted County, MN residents with a medical ICU admission in the year 2006 were evaluated. Patients with at least one major risk factor for ALI who did not meet criteria for ALI at the time of hospital admission were included in the analysis. Baseline characteristics, major risk factors for ALI, the presence of anti-platelet therapy at the time of hospitalization, and the propensity to receive this therapy were determined. The primary outcome was ALI or ARDS during the hospitalization. Secondary outcomes included ICU and hospital free days, and ICU and hospital mortality.
Results:
A total of 161 patients were evaluated. Seventy-nine (49%) were receiving anti-platelet therapy at hospital admission. Thirty-three (21%) developed ALI/ARDS. Anti-platelet therapy was associated with a reduced incidence of ALI/ARDS (12.7% vs. 28.0%; OR: 0.37, 95% CI: 0.16 to 0.84; p = 0.02). This association remained significant after adjusting for confounding variables.
Conclusions:
Pre-hospitalization anti-platelet therapy was associated with a reduced incidence of ALI/ARDS. If confirmed in a more diverse patient population, these results would support the use of anti-platelet agents in an ALI prevention trial.
An increased VE/VCO2 relationship (ventilatory inefficiency, VI) is associated with increased morbidity and mortality in patients with left ventricular systolic dysfunction (LVSD). A direct link between VI and a specific cardiac abnormality has not been established.
Methods:
We analyzed cardiopulmonary exercise test (CPET) data from patients (n=83) with severe LVSD (ischemic and nonischemic; LVEF 19±7%) and at least moderate exercise intolerance. Subjects were stratified into two groups based on the VE/VCO2 ratio at anaerobic threshold (Group 1 VE/VCO2@AT ≤ 34; Group 2 VE/VCO2@AT >34). Clinical, CPET, echocardiographic and hemodynamic data were compared between groups.
Results:
Group 2 subjects had lower exercise capacity (peak VO2 45.7±11.8% vs. 50.4±8.9% predicted; P<0.05), with a significantly lower O2 pulse (71.6±24.5% vs. 85.4±18.5% predicted) and systolic BPmax (122±19 vs. 138±22 mmHg; P<0.001 for both), suggesting a more blunted stroke volume to exercise vs. Group 1. There were no differences in LV size, LVEF, or mitral regurgitation between the two groups. In sharp contrast, Group 2 had larger RV dimensions (4.5±1.1 vs. 3.9±0.8 cm) and more severe RV systolic dysfunction (RV fractional area change 26±11 vs. 33±12%; tricuspid annular plane systolic excursion (TAPSE) 1.6±0.5 vs. 2.0±0.5cm; all P<0.001) vs. Group 1. Multivariable analysis revealed that only TAPSE and Doppler-estimated pulmonary artery systolic pressure were independently associated with VE/VCO2@AT and the VE/VCO2 slope. The VE/VCO2@AT, VE/VCO2 slope, and TAPSE had nearly identical predictive value for death or transplant.
Conclusion:
The present study suggests that VI is a functional, noninvasive marker of more advanced right heart dysfunction in patients with severe LVSD.
Vitamin D is a steroid hormone with pleiotropic effects including immune system modulation, lung tissue remodeling, and bone health. Vitamin D deficiency has been implicated in the development of autoimmune diseases. We sought to evaluate the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease (ILD) and hypothesized that vitamin D deficiency would be associated with an underlying connective tissue disease (CTD), and reduced lung function.
Methods:
Patients in the University of Cincinnati ILD Center database were evaluated for serum 25-hydroxyvitamin D levels as part of a standardized protocol. Regression analysis evaluated associations between 25-hydroxyvitamin D levels and other variables.
Results:
118 subjects were included (67 with CTD-ILD, 51 with other forms of ILD). The overall prevalence of vitamin D deficiency and insufficiency in the study population was 38% and 59%, respectively. Those with CTD-ILD were more likely to have vitamin D deficiency (52% vs 20%, p<0.0001) and insufficiency (79% vs 31%, p<0.0001) than other forms of ILD. Diminished forced vital capacity (FVC) was associated with lower 25-hydroxyvitamin D levels (p=0.01). The association between vitamin D insufficiency and CTD-ILD persisted (OR 11.8, p<0.0001) after adjustment for potential confounders. Among subjects with CTD-ILD, reduced 25-hydroxyvitamin D levels were strongly associated with reduced lung function (FVC p=0.015, DLCO p=0.004).
Conclusions:
There is a high prevalence of vitamin D deficiency in patients with ILD, particularly those with CTD-ILD, and it is associated with reduced lung function. Vitamin D may have a role in the pathogenesis of CTD-ILD.
A large proportion of patients infected with new influenza A (H1N1) are obese. Obesity has been proposed as a risk factor influencing outcome in these patients. However, its role remains unclear. We evaluate the outcome of obese patients infected by new influenza A (H1N1)v in the ICU determining whether obesity is a risk factor for mortality.
Design:
Prospective, observational and multicenter study performed in 144 ICU. Data were obtained from the GTEI/SEMICYUC registry.
Patients:
Adult patients with influenza A (H1N1) confirmed by rt-PCR were included in the analysis. Obese (BMI>30) were compared with non-obese patients. Cox regression analysis was used to determine adjusted mortality. Differences of p <0.05 were considered significant.
Measurements and results:
In January 2010, the GTEI/SEMICYUC registry had complete records for 416 patients. One hundred and fifty patients (36.1%) were obese, of whom 67 (44.7%) were morbidly obese (BMI >40). MV was more frequently applied in obese patients (64 % vs 52.4% p<0.01) Patients with obesity remained longer on MV than non-obese patients (6.5±10.3 vs 9.3±9.7 days, p=0.02), had longer ICU LOS (10.8±12.1 vs 13.7±11.7 days; p=0.03), and longer hospitalization (18.2±14.6 vs 22.2±16.5 days; p=0.02). Mortality adjusted by severity and potential confounders identified that obesity was not significantly associated with ICU mortality [HR 1.1 (95% CI 0.69-1.75), p = 0.68].
Conclusion:
In our cohort, obese infected with the novel influenza A (H1N1)v did not have increased mortality. However, there was an association between obesity and higher ICU resource consumption.
Omalizumab is a humanized monoclonal anti-IgE for the treatment of severe allergic asthma. Because omalizumab targets an immune system molecule there has been particular interest in the drug's safety.
Methods:
To establish the efficacy and safety of subcutaneous omalizumab as add on therapy to corticosteroids, a systematic review of placebo-controlled studies was performed.
Primary outcomes were reduction of steroid use and asthma exacerbations. Secondary outcomes measures included lung function, rescue medication use, asthma symptoms, health-related quality of life, and adverse effects.
Results:
Eight trials (3429 participants) fulfilled the selection criteria. At the end of steroid reduction phase, patients taking omalizumab were more likely to be able to withdraw corticosteroids completely compared with placebo (Relative Risk [RR] = 1.80; 95% CI, 1.42, 2.28, p = 0.00001). Omalizumab patients showed a decreased risk for asthma exacerbations at the end of stable (RR = 0.57, 95% CI: 0.48-0.66, p = 0.0001) and adjustable-steroid phases (RR = 0.55, 95% CI, 0.47, 0.64, p = 0.0001; post-hoc analysis suggests this effect was independent of duration of treatment, age, severity of asthma, and risk of bias. The frequency of serious adverse effects was similar between omalizumab (3.8%) and placebo (5.3%). However, injection site reactions were more frequent in the omalizumab patients (19.9% vs. 13.2%). There were no indications of increased risk of hypersensitivity reactions, cardiovascular effects, and malignant neoplasms.
Conclusions:
Data indicate that the efficacy of add on omalizumab in patients with moderate to severe allergic asthma is accompanied by an acceptable safety profile.
While common in many Middle Eastern Countries, waterpipe smoking is increasingly popular in Western cultures. The primary objective of this study was to systematically review the effects of waterpipe tobacco smoking on lung function. The secondary objective was to compare the effects of waterpipe tobacco smoking and cigarette smoking on lung function.
Methods:
We conducted a systematic review using the approach of the Cochrane Collaboration to searching for, selecting and abstracting studies. We conducted two separate meta-analyses comparing respectively: (1) waterpipe smokers and non-smokers, and (2) waterpipe smokers and cigarette smokers for each of 3 spirometric measurements (Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC), and FEV1/FVC). We used the standardized mean difference (SMD) to pool the results.
Results:
Six cross-sectional studies were eligible for this review. Compared with no smoking, waterpipe smoking was associated with a statistically significant reduction in FEV1 (SMD = -0.43; 95% confidence interval (CI) -0.58, -0.29; equivalent to a 4.04% lower FEV1%), and a trend toward lower FVC (SMD = -0.15; 95% CI -0.34, 0.04; equivalent to a 1.38% reduction in FVC%), and FEV1/FVC (SMD = -0.46; 95% CI -0.93, 0.01; equivalent to a 3.08% lower FEV1/FVC). Comparing waterpipe smoking with cigarette smoking, there was no statistically significant difference in FEV1, FVC, and FEV1/FVC. The six studies suffered from methodological limitations.
Conclusion:
Waterpipe tobacco smoking negatively affects lung function and may be as harmful as cigarette smoking. Waterpipe smoking, therefore, is likely to be a cause of COPD.
Sputum cell-subtype profiles in cough variant asthma (CVA) are unknown.
Methods:
Ninety eight inhaled corticosteroid (ICS)-naïve CVA patients were classified according to sputum eosinophil/neutrophil counts, as reported in asthmatics, as: eosinophilic (E: eos≥1.0%, neu<61%; n=28), neutrophilic (N: eos<1.0%, neu≥61%; n=31), mixed granulocytic (M: eos≥1.0%, neu≥61%; n=12), and paucigranulocytic (P: eos<1.0%, neu<61%; n=27) subtypes. Patient characteristics, sputum levels of eosinophil cationic protein (ECP), interleukin (IL)-8 and neutrophil elastase, and daily ICS doses required to maintain control during follow-up (6, 12, 18, and 24 months) were retrospectively compared.
Results:
Subtype N patients, predominantly females, were marginally older than the other subtypes, while FEV1, airway responsiveness, and total and specific IgE results did not differ. ECP levels were higher in M and E than in N and P subtypes, being similar between M and E or N and P subtypes. Levels of IL-8 and neutrophil elastase were higher in M than in other subtypes, being similar among the latter. ICS doses were initially similar in all subtypes (800 µg equivalent of beclomethasone) but were higher in M than in N and P throughout follow-up, with E being intermediate between M and N or P. ICS doses decreased (halved or quartered) in E, N and P patients followed for 24 months (p<0.0001 for all) but remained unchanged in M. IL-8 and neutrophil elastase levels correlated positively with ECP levels.
Conclusions:
In addition to eosinophils, neutrophils which are possibly activated in the presence of eosinophils may participate in the pathophysiology of CVA.
Pulmonary endarterectomy (PEA) provides a potential cure for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, successfully operated patients may continue to suffer from a limitation of exercise capacity, despite normalization of pulmonary vascular resistance (PVR). The purpose of the present study was to explore the cardiopulmonary exercise test (CPET) profile and the pulmonary hemodynamic response to exercise in these patients.
Methods:
13 successfully operated CTEPH patients with persistent dyspnea and controls underwent a CPET and a right heart catheterization at rest and during exercise.
Results:
The CPET profile of patients was characterized by mild hyperventilation and decreased peak oxygen uptake (peak Vo2). While there were no differences in resting hemodynamics between patients and controls, PVR was higher in patients after 10 minutes of exercise (111±46 dynes.s.cm-5 versus 71±42 dynes.s.cm-5, p=0.04), and pulmonary arterial compliance (Ca) was lower (5.5±2.3ml/mmHg versus 8.1±3.5ml/mmHg, p=0.048). Ca under exercise correlated with peak Vo2 in patients (R2=0.825, p=0.022).
Conclusions:
Patients after successful PEA with persistent exertional dyspnea display an abnormal pulmonary hemodynamic response to exercise, characterized by increased PVR and decreased Ca. Decreased Ca under exercise is a strong predictor of limited exercise capacity in these patients.
ARDS patients present with intrapulmonary and systemic coagulation abnormalities. We previously demonstrated that circulating KL-6/MUC1 could predict complications of disseminated intravascular coagulation (DIC) in ARDS. Recent studies indicate that circulating mucin can induce intravascular coagulation via interactions with selectin. We therefore investigated whether circulating mucins carrying selectin ligands are associated with DIC in ARDS.
Methods:
We evaluated newly diagnosed patients with ARDS (n=46) or bacterial pneumonia (n=17), and healthy controls (n=60). Using serum collected at diagnosis, circulating levels of KL-6/MUC1, KL-6/MUC1 carrying sialyl Lewisa (SLAK), KL-6/MUC1 carrying sialyl Lewisx (SLXK), and P-selectin glycoprotein ligand-1 (PSGL-1) were measured.
Results:
Serum mucins with selectin ligands were significantly elevated in ARDS patients compared with healthy controls. Significantly elevated levels of SLAK and SLXK were found in ARDS patients subsequently complicated with DIC as compared to those without DIC. In contrast, serum PSGL-1 levels were significantly decreased in ARDS patients with DIC. Furthermore, SLAK was discovered to be an independent predictor for DIC complication in ARDS. Using cutoff levels obtained by receiver operating characteristic curves, we found that these mucins can be used to distinguish between ARDS patients with and without subsequently occurring DIC. Among the analyzed mucins, SLAK has the highest sensitivity and specificity for predicting future DIC development.
Conclusions:
These results suggest that mucins with selectin ligands are novel markers for ARDS with future complications of DIC, and KL-6/MUC1 carrying selectin ligands may be involved in the pathogenesis of DIC in ARDS patients.
Cardiovascular (CV) risk assessment is important in clinical practice. An autonomic state indicator (ASI) algorithm based on pulse oximetry was developed and validated for CV risk assessment.
Methods:
148 sleep clinic patients (98 male, mean age 50±13 years) underwent an overnight study using a novel photoplethymographic sensor. CV risk was classified according to the ESH/ESC risk factor matrix. Five signal components reflecting cardiac and vascular activity (pulse wave attenuation, pulse rate acceleration, pulse propagation time, respiration related pulse oscillation and oxygen desaturation) extracted from 99 randomly selected subjects were used to train the classification algorithm. The capacity of the algorithm for CV risk prediction was validated in 49 additional patients.
Results:
Each signal component contributed independently to CV risk prediction. The sensitivity and specificity of the algorithm to distinguish high/low CV risk in the validation group was 80% and 77%, respectively. The area under the ROC for high CV risk classification was 0.84. β-blocker treatment was identified as an important factor for classification that was not in line with the ESH/ESC reference matrix.
Conclusions:
Signals derived from overnight oximetry recording provide a novel potential tool for CV risk classification. Prospective studies are warranted to establish the value of the ASI algorithm for prediction of outcome in CV disease.
Pulmonary hypertension is defined as resting mean pulmonary artery pressure (MPAP) equal to or higher than 25 mm Hg. MPAP pressure estimation by right heart catheterization (RHC) is considered the gold standard; however, its invasiveness limits repeated and frequent use. The purpose of this study was to compare the accuracy and precision of 3 echocardiographic methods for estimating MPAP.
Methods:
We prospectively studied 117 patients with simultaneous RHC and echocardiography. MPAP was calculated by 3 echocardiographic methods: 1) mean gradient method (adding the right ventricular–right atrial mean systolic gradient to the right atrial pressure); 2) Chemla formula (0.61xsystolic pulmonary artery pressure+2 mm Hg); and 3) Syyed formula (0.65xsystolic pulmonary artery pressure+0.55 mm Hg). MPAP calculated by these 3 methods was compared with that obtained invasively by RHC.
Results:
The mean±standard deviation of the differences between invasive MPAP and the 3 echocardiographic methods were –1.6±7.7 mm Hg for the mean gradient method, –3.7±7.4 mm Hg for the Chemla formula, and –3.2±7.6 mm Hg for the Syyed formula. Median absolute differences were 5.5 mm Hg (mean gradient), 5.7 mm Hg (Chemla; P=.45 vs mean gradient), and 6.0 mm Hg (Syyed; P=.23 vs mean gradient). Accuracy (calculated MPAP within 10 mm Hg of RHC-measured MPAP) was 81% (mean gradient), 77% (Chemla), and 76% (Syyed).
Conclusions:
Echocardiographic estimation of MPAP by the mean gradient method had similar accuracy and precision compared with the Chemla and Syyed methods. The acceptable accuracy of these methods suggests that they are equally suitable for clinical use.
Obstructive sleep apnea (OSA) is a risk factor for a number of cardiovascular conditions. Although homocysteine (Hcy) and cysteine (Cys) are regarded as cardiovascular risk factors, few studies have analyzed Hcy and Cys plasma concentrations in OSA patients. The aim of this study was to evaluate the role of Hcy and Cys in OSA in comparison to non-OSA subjects and to determine the possible influence of obesity on these variables.
Methods:
Patients submitted to polysomnography were recruited to engage in an 8-hour fasting period for blood sample withdrawal, physical examination, ECG, and echocardiogram. A subgroup of lean OSA patients (BMI < 25 kg/m2) were analyzed to rule out the influence of obesity. Fifteen patients were randomly assigned to participate in a continuous positive airway pressure (CPAP) protocol to assess the influence of OSA treatment on the obtained measurements.
Results:
A total of 75 patients and 75 controls matched for age and gender were analyzed. The Cys plasma levels were higher in OSA patients compared to controls (490.16 ± 67.00 vs. 439.81 ± 76.12, respectively, p < 0.01); however, the Hcy plasma levels did not differ between groups. Cys plasma levels were also higher in the OSA lean subgroup when compared to lean controls (484.21 ± 71.99 vs. 412.01 ± 70.73, respectively, p = 0.009). There was a significant decrease of Cys plasma levels after 6 months of CPAP effective therapy.
Conclusion:
Cys is a potential biomarker of OSA in obese and non-obese patients and is reduced after effective OSA treatment.
The use of single-dose etomidate to facilitate intubation in critically ill patients has recently been debated given its suppression of steroidogenesis with possible resultant adverse outcomes. Our objective was to assess the effects of single-dose etomidate used during rapid sequence intubation on various measures of outcome such as mortality, vasopressor use, corticosteroid use, ICU-length of stay and number of ventilator-days.
Methods:
A retrospective 18-month cohort study was performed in a multidisciplinary ICU of an academic tertiary care institution. Consecutive patients with severe sepsis or septic shock who were intubated and mechanically ventilated were identified and grouped as having received single-dose etomidate during intubation or not. Hospital mortality, ICU length of stay, number of ventilator-days, corticosteroid use, vasopressor use, as well as demographic and clinical variables were recorded.
Results:
A total of 224 patients were identified; 113 had received etomidate. The mean APACHE II scores in the etomidate and non-etomidate groups were 21.3 +8.1 and 21.9 +8.3 respectively (p=0.62). The relative risks for mortality and vasopressor use were 0.92 (C.I. 0.74-1.14, p=0.51) and 1.16 (C.I. 0.9-1.51, p= 0.31) respectively, in the etomidate group. There were no significant differences in ICU-LOS (Mean 14 versus 12 days, p=0.31) or number of ventilator-days (Mean 11 versus 8 days, p=0.13) between the etomidate and non-etomidate groups, respectively. The relative risk for corticosteroid use in the etomidate group was 1.34 (C.I. 1.11-1.61, p=0.003). Multivariate analysis using logistic regression demonstrated no significant association of etomidate with mortality (OR 0.9, C.I. 0.45-1.83, p=0.78).
Conclusion:
Single-dose etomidate used during rapid-sequence intubation in critically ill patients with severe sepsis and septic shock was not associated with increased mortality, vasopressor use, ICU-LOS or number of ventilator-days. Patients intubated with etomidate had an increased incidence of subsequent corticosteroid use, with no difference in outcomes.
Tracheobronchomalacia (TBM) is increasingly recognized as a condition associated with significant pulmonary morbidity. However, treatment is invasive and complex, and since there is no appropriate animal model, novel diagnostic and treatment strategies are difficult to evaluate. We endeavored to develop a reliable airway model to simulate hyperdynamic airway collapse in humans.
Methods:
Seven 20kg male sheep were enrolled in this study. Tracheomalacia was created by submucosal resection of more than 50% of the circumference of ten consecutive cervical tracheal cartilage rings through a midline cervical incision. A silicone stent was placed in the trachea to prevent airway collapse during recovery. Tracheal collapsibility was assessed at protocol specific time points by bronchoscopy and multi –detector computed tomography (MDCT) imaging while temporarily removing the stent. Esophageal pressure and flow data were collected to assess flow limitation during spontaneous breathing.
Results:
All animals tolerated the surgical procedure well and were stented without complications. One sheep died at 2 weeks due to respiratory failure related to stent migration. In all sheep, near total forced inspiratory airway collapse was observed up to 3 months post-procedure. Esophageal manometry demonstrated flow limitation associated with large negative pleural pressure swings during rapid spontaneous inhalation.
Conclusions:
Hyperdynamic airway collapse can reliably be induced with this technique. It may serve as a model for evaluation of novel diagnostic and therapeutic strategies for TBM.
Myocardial dysfunction in sepsis may be associated with changes in left ventricular size.
Objectives:
Evaluate the impact of myocardial dysfunction and changes in left ventricular diameter on hemodynamics and survival in a murine model of sepsis.
Methods:
C57Bl/6 mice (n =30); Septic mice (n= 24) had cecal ligation and puncture (CLP) followed by fluid and antibiotic resuscitation, and Control mice (n =6) received sham ligation. Echocardiography with a 30mHz probe was performed at baseline and at frequent predefined time points after CLP. Stroke volume (SV), cardiac output (CO), left ventricular internal diameter in diastole (LVIDd), and fractional shortening (FS) were measured. LV dilation was prospectively defined as an increase in LVIDd ≥ 5% from baseline values. Septic animals were classified as Dilators or Non-Dilators.
Measurements and Main Results:
Among septic animals, 37 % were Dilators, and 63% were Non-Dilators. After CLP, SV and CO decreased early in both groups. With resuscitation SV and CO improved to a greater extent in Dilators than Non-Dilators; (for SV 46.0±8.2 vs. 36.1±12.7µL at 24 hours, p = 0.05, for CO 20.4±4.8 vs. 14.8±6.7 mL/ml, p = 0.04). Survival at 72 hours was significantly improved in Dilators compared to Non-Dilators (88% vs. 40%, p = 0.01).
Conclusions:
In a clinically relevant murine model of sepsis, animals with LV dilation had better cardiovascular performance and increased survival. Our results suggest that left ventricular dilation is associated with improved SV and CO, a pattern resulting in greatly improved survival. These studies highlight the importance of diastolic function in septic shock.
On 9/11/2001 the World Trade Center (WTC) collapse caused massive air pollution, producing variable amounts of lung function reduction in the New York City Fire Department (FDNY) rescue workforce. Alpha-1 antitrypsin (AAT) deficiency is a risk factor for obstructive airway disease.
Methods:
This prospective, longitudinal cohort study investigated influence of AAT deficiency on adjusted longitudinal spirometric change (forced expiratory volume during the first second [FEV1]) in 90 WTC-exposed FDNY rescue workers over the first 4 years post-9/11/2001. Workers with protease inhibitor (Pi) Z heterozygosity were considered moderately AAT-deficient; PiS homozygosity or PiS heterozygosity without concomitant PiZ heterozygosity was mildly deficient, and PiM homozygosity was normal. Alternately, workers had low AAT levels if serum AAT was ≤ 20 µmol/l.
Results:
In addition to normal aging-related decline (37 ml/year), significant FEV1 decline accelerations developed with increasing AAT deficiency severity (110 ml/year and 32 ml/year for moderate and mild deficiency) or with low AAT serum levels (49 ml/year). Spirometric rates pre-9/11/2001 did not show accelerations with AAT deficiency. Among workers with low AAT levels, cough persisted in a significant number of individuals to 4 years post-9/11/2001.
Conclusions:
AAT-deficient FDNY rescue workers had significant spirometric decline accelerations and persistent airway symptoms during the first 4 years after the WTC exposure. This represents a novel gene-by-environment interaction. Clinically meaningful decline acceleration occurred even with the mild serum AAT level reductions associated with PiS heterozygosity (without concomitant PiZ heterozygosity).
Admission of lung cancer patients to the intensive care unit (ICU) has been criticized. We evaluated whether ICU admission improved 3-month survival in patients with nonresectable lung cancer. Factors associated with survival were identified.
Methods:
Retrospective study in consecutive non-surgical lung cancer patients admitted to three ICUs in France (2000-2007, 2005-2007, and 2005-2006, respectively).
Results:
We included 103 patients with a median [Q1-Q3] SAPS II of 33 [25-46] and a median LOD of 3 [1-4] points. Invasive mechanical ventilation was required in 41 (40%) patients. Sixty-three (61%) patients had metastasis and 26 (25%) an ECOG performance status (PS) >2. The reason for ICU admission was acute respiratory failure in 58 (56%) patients. Three-month survival rate was 37% (95% confidence interval [95% CI], 28-46). By multivariate analysis, variables associated with mortality were ECOG-PS >2 (hazard ratio [HR], 2.65; 95% CI, 1.43-4.88), metastasis at admission (HR, 1.90; 95% CI, 1.08-3.33), and worse LOD score (HR, 1.19; 95% CI, 1.08-1.32). LOD score decrease over the first 72 hours was associated with survival.
Conclusions:
Survival in patients with non-surgical lung cancer requiring ICU admission was 37% after 90 days. Our results provide additional evidence that ICU management may be appropriate in patients with nonresectable lung cancer and organ failures.
The diagnosis of Primary Ciliary Dyskinesia (PCD) can prove difficult due to secondary damage of ciliated tissue.
Methods:
Here we audit culturing cells, obtained by nasal brushing, to a ciliated phenotype using an air-liquid interface method to determine if the effects of secondary damage on cilia were reduced following culture.
Results:
Of 231 patients consecutively referred for diagnostic testing, culture was attempted in 187 with 101 (54%) becoming ciliated. Of the 90 brush biopsies with a low dyskinesia score (<40%) 71 grew cilia after culture (79% Success). Significant secondary damage (>40% dyskinesia) was present in 69 (43%) of the initial brush biopsies, and of these, 18 (26%) became ciliated after culture. In these samples, ciliary dyskinesia was significantly (p<0.001) reduced (64±6.8% before culture, 31±4.5% after culture). Ciliary beat frequency (CBF) after cell culture was similar to CBF before culture. Cell culture helped to exclude PCD in 8 patients where ciliary dyskinesia was present in over 70% of the initial brush biopsy, a level at which a re-biopsy would normally be requested. In 6 patients where no cilia were found in the initial brush biopsy, ciliated cell culture was successful and excluded the diagnosis. PCD was diagnosed in 28 patients and ciliated cell culture was successful in 12 (43%) showing identical ciliary beat pattern and electron microscopy findings.
Conclusions:
Ciliary dyskinesia was reduced following cell culture to a ciliated phenotype compared to the initial brush biopsy. The specific PCD phenotype was maintained after culture.
Many obstructive sleep apnea (OSA) patients use nasal continuous positive airway pressure (nCPAP) as a first-line therapy. Previous studies have reported mid-facial hypoplasia in children using nCPAP. The aim of this study is to assess the craniofacial changes in OSA adults subjects after nCPAP use.
Methods:
Some 46 Japanese subjects who used nCPAP for minimum of 2 years had both a baseline and a follow-up cephalometric radiograph taken. These two radiographs were analyzed and changes in craniofacial structures were assessed. The cephalometric measurements evaluated were related to face height, interarch relationship and tooth position.
Results:
Most of the OSA patients were male (89.1%) and the mean baseline values for age, Body Mass Index (BMI) and Apnea-Hypopnea Index (AHI) were 56.3±13.4 years, 26.8±5.6 kg/m2 and 42.0±18.6/hour. The average duration of nCPAP use was 35.0±6.7 months. After nCPAP use, cephalometric variables demonstrated a significant retrusion of the anterior maxilla, a decrease in maxillary-mandibular discrepancy, a setback of the supramentale and chin positions, a retroclination of maxillary incisors and a decrease of convexity However, significant correlations between the craniofacial changes, demographic variables or the duration of nCPAP use could not be identified. None of the patients self-reported any permanent change of occlusion or facial profile.
Conclusion:
The use of a nCPAP machine for more than 2 years may change craniofacial form by reducing maxillary and mandibular prominence and/or by altering the relationship between the dental arches.
To determine the validity and reliability of the Dyspnoea-12 (D-12) for the assessment of breathlessness in patients with interstitial lung disease (ILD).
Methods:
101 patients with ILD completed the D-12 (scaling range 0-36, high score indicates worse dyspnea), MRC dyspnea scale, St George’s Respiratory Questionnaire (SGRQ), and Hospital anxiety and depression scale (HADS) at baseline, and 84 patients completed the D-12 and a global health transition score at follow-up 2-weeks later. D-12 psychometric properties, including floor and ceiling effects, internal consistency, test-retest reliability and construct validity of the D-12 were examined.
Results:
The D-12 showed good internal consistency (Cronbach’s =0.93) and repeatability (Intra-class correlation coefficient = 0.94). Its scores were significantly associated with MRC grade (r = 0.56, p<0.001), SGRQ (symptoms r = 0.57; activities r = 0.78; impacts r = 0.75; total r = 0.79, p<0.001). Confirmatory factor analysis confirmed the previously determined structure of the D-12 in this patient group.
Conclusion:
In patients with ILD, the patient reported D-12 - a patient reported measure of dyspnoea severity that requires no reference to activity, is a reliable and valid instrument. It is short, simple to complete, and easy to score.
The seventh edition of TNM classification for non-small cell lung cancer (NSCLC) is applied recently. Vascular invasion has been reported being a strong risk factor, therefore we reviewed the impact of vascular invasion on new TNM classification.
Methods:
We reviewed patients with completely resected NSCLC without lymph node metastasis treated at our institute between January 1993 and December 2003. Vascular invasion was examined using Victoria blue-van Gieson (VVG) stains performed in maximum cut sections of tumor. Correlation between vascular invasion and other clinicopathologic factors such as age, gender, histology, serum CEA levels, smoking habitation, and T descriptors were assessed. In addition, we evaluated the impact of vascular invasion on survival.
Results:
A total of 826 patients were analyzed. Median age was 65 years (32 - 86). Thirty-two percent of patients were over 70 years, 44 % female, 78 % adenocarcinoma, 41 % never smoker, 39 % smoked more than 30 pack-year, and 31 % had elevated serum CEA. Vascular invasion was detected in 279 patients (33.8%), and more observed in patients with male, non-adenocarcinoma, smoker, and elevated CEA levels. Positive vascular invasion was significantly correlated with worse prognosis compared with negative (5-year survival, 90.5% vs. 71.0%, p<0.001). This trend was observed in each subgroup of T1a (92.9% vs. 72.5% p<0.001), T1b (89.7% vs. 77.2%, p = 0.015), and T2a (86.3% vs. 65.6%, p<0.001).
Conclusion:
Vascular invasion was a strong prognostic factor in the revised TNM classification. Further investigation is warranted to generalize these findings.
Severe alpha-1 antitrypsin deficiency is a known genetic risk factor for chronic obstructive pulmonary disease (COPD). Heterozygous (PI MZ) individuals have moderately reduced serum levels of alpha-1 antitrypsin, but whether they have an increased risk of COPD is uncertain.
Methods:
We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n=1669) and a multicenter family-based study from Europe and North America (n=2707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT measurements of emphysema and airway disease.
Results:
PI MZ was associated with 3.5% lower FEV1/FVC ratio in the case-control study (p=0.035), and 3.9% lower FEV1/VC ratio in the family study (p=0.009). In the case-control study, PI MZ was also associated with 3.7% more emphysema on quantitative analysis of chest CT scans (p=0.003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among individuals with low smoking exposure (<20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies.
Conclusions:
Compared to PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to development of airflow obstruction than PI MM individuals.
Pulmonary artery occlusion pressure (PAOP) is used to differentiate patients with pulmonary hypertension (PH) associated with left heart disease from other etiologies. Technical errors in the measurement of PAOP are common and lead to incorrect classification of the etiology of PH. We investigated the agreement among PAOP measurements obtained from both pulmonary arteries with balloon full (1.5 ml) and half (0.75 ml) inflation, in patients undergoing right heart catheterization for suspected PH.
Methods:
Thirty-seven patients suspected or known to have PH who underwent right heart catheterization were included. Seventy-six percent had PH (mPAP > 25 mm Hg). The validity of the measurements was assessed by using five pre-established criteria, based on hemodynamic, fluoroscopic and gasometric data. For each patient, the measurement that most likely represented the left atrial pressure was labeled "best PAOP".
Results:
Seventy percent of all the PAOP measurements met four or more of the pre-established criteria for validity. In patients with PH (n=28) the mean (standard error, SE) PAOP was 23.1 (2) mm Hg, 19.1 (2) mm Hg, 23.54 (2) mm Hg and 19.07 (2) mm Hg for right PA with full and half balloon inflation and left PA with full and half balloon inflation, respectively (p=0.05). Bland-Altman analysis revealed lower bias and narrower limits of agreement with half balloon inflation. Wedge angiography showed that some balloon inflations failed to occlude upstream flow while others had a collateral vessels draining after the occlusion.
Conclusions:
Pulmonary artery occlusion pressure can be falsely elevated in patients with PH according to the balloon inflation volume. Balloon half inflation was safe and correlated with higher precision and lower bias in the PAOP measurements.
Sarcoidosis is a systemic granulomatous disorder of unknown etiology that occurs among men and women of all races. In the United States, black women are most frequently and most severely affected. There have been few epidemiologic studies of sarcoidosis focusing on black women.
Methods:
In this paper we present data on incidence, prevalence, and clinical characteristics of sarcoidosis among participants in the Black Women’s Health Study, a cohort study of 59,000 black women from across the United States. Data on incident disease and potential risk factors are obtained through biennial questionnaires. Follow-up has been over 80% through six completed cycles.
Results:
There were 685 prevalent cases of sarcoidosis at baseline in 1995, and 435 incident cases reported during 611,585 person-years of follow-up through 2007, for an average annual incidence rate of 71/100,000 and a current prevalence of 2.0%. The sarcoid diagnosis was confirmed in 96% of self-reported cases for whom medical records or physician checklists were obtained. The most frequently affected site was the lung. Most patients also had extra-pulmonary involvement with the most common sites being lymph nodes, skin, and eyes. Prednisone had the highest prevalence of use, followed by inhaled corticosteroids.
Conclusion:
This study confirms previous reports of high incidence and prevalence of sarcoidosis among black women, as well as the extent of extra-pulmonary disease, frequent need for steroid therapy, and co-morbid conditions in this population. The prospective identification of sarcoidosis cases from a defined population will enable a valid assessment of risk factors for incident disease as follow-up continues.
Sarcoidosis, an inflammatory granulomatous disease, is associated with various cardiac disorders, including threatening ventricular arrhythmias and sudden cardiac death. Heart rate recovery after exercise is a function of vagal reactivation, and its impairment is an independent prognostic indicator for cardiovascular and all-cause mortality. The aim of our study was to evaluate heart rate recovery in patients with sarcoidosis.
Methods:
The study population included 56 patients with sarcoidosis (23 men, mean age = 47.3 ± 13.0 years, and mean disease duration = 38.4 ± 9.7 months) and 54 healthy control subjects (20 men, mean age = 46.5 ± 12.9 years). Basal electrocardiography, echocardiography, and treadmill exercise testing were performed on all patients and control participants. The heart rate recovery index was defined as the reduction in the heart rate at peak exercise to the 1st-minute rate (HRR1), 2nd-minute (HRR2), 3rd-minute (HRR3) and 5th-minute (HRR5) after the cessation of exercise stress testing.
Results:
There are significant differences in HRR1 and HRR2 indices between patients with sarcoidosis and the control group (25 ± 6 vs 34 ± 11; p<0.001 and 45 ± 10 vs 53 ± 12; p<0.001, respectively). Similarly, HRR3 and HRR5 indices of the recovery period were lower in patients with sarcoidosis, when compared with indices in the control group (53 ± 12 vs 61 ± 13; p<0.001 and 60 ± 13 vs 68 ± 13; p<0.001, respectively). Exercise capacity was notably lower (9.2 ± 2.1 vs 11.6 ± 2.8 METs; p=0.001, respectively) and systolic pulmonary arterial pressure at rest was significantly higher in patients with sarcoidosis compared with the control group (29.7 ± 5.5 mm Hg vs. 25.6 ± 5.7 mm Hg, p = 0.001, respectively). Furthermore, HRR indices were found to be different among radiographic stage groups.
Conclusions:
The heart rate recovery index was impaired in patients with sarcoidosis as compared with control subjects. When the prognostic significance of the heart rate recovery index is considered, these results may partially explain the increased occurrence of arrhythmias and sudden cardiac death in patients with sarcoidosis. Our findings suggest that the heart rate recovery index may be clinically helpful in identifying high risk patients with sarcoidosis.
On February 24, 2010, the Food and Drug Administration approved a 13 valent pneumococcal protein conjugate vaccine (PCV13) for use in children. Currently, the only pneumococcal vaccine approved for use in adults in the United States is the 23 valent pneumococcal polysaccharide vaccine (PPV23). While PPV23 provides partial protection against invasive pneumococcal disease, it does not appear to impact the risk of pneumonia in elderly patients or younger adults with co-morbidities. Experience with PCV7 in children and studies of the immunogenicity of PCV7 in high risk adults suggest that PCV13 may be effective in adults. However, prior receipt of PPV23 may blunt the antibody response to protein conjugate vaccination; thus, receipt of PPV23 could potentially diminish the benefit of later pneumococcal conjugate vaccination. The approval of PCV13 for children has created a unique dilemma for physicians seeking to provide optimum protection for their high risk adult patients. Potential options could include use of the PCV13 "off-label" perhaps followed by PPV23, withholding pneumococcal vaccination of adults while awaiting approval of PCV13, or continuing to use the PPV23. Although there are limited data on PCVs in adults, the availability of PCV13 for children will likely cause uncertainty for some physicians until there is updated official guidance regarding the optimum strategies for prevention of pneumococcal infection in adults.
Formal family meetings have been recommended as a useful approach to assist in goal setting, facilitate decision making, and reduce use of ineffective resources in the ICU. We examined patient outcomes before and after implementation of an "intensive communication system" to test the effect of regular, structured formal family meetings on patient outcomes among long-stay ICU patients.
Methods:
135 patients receiving usual care and communication were enrolled as the control group, followed by enrollment of intervention patients (n=346), from 5 ICUs. The intensive communication system included: (1) family meeting within 5 days of ICU admission and weekly thereafter; (2) each meeting addressed medical update, values and preferences, goals of care; treatment plan, and milestones for judging effectiveness of treatment.
Results:
in multivariate analysis, there were no significant differences between control and intervention patients in length of stay, the primary end point. Similarly, there were no significant differences in indicators of aggressiveness of care or treatment limitation decisions (ICU mortality, LOS, duration of ventilation, treatment limitation orders, or use of tracheostomy or percutaneous gastrostomy). Exploratory analysis suggested that in the medical ICUs the intervention was associated with a lower incidence of tracheostomy among patients who died or had DNAR orders in place.
Conclusions:
the negative findings of the main analysis, in combination with preliminary evidence of differences among types of unit, suggest that further examination of the influence of patient, family and unit characteristics on the effects of a system of regular family meetings may be warranted. Despite the lack of influence on patient outcomes, structured family meetings may be an effective approach to meeting information and support needs.
Anti-endothelial cell antibodies (AECA) are circulating antibodies that bind to endothelial antigens and induce endothelial cell damage. These antibodies have been detected in patients with collagen vascular diseases and systemic vasculitis. Recently, autoimmune mechanisms and vascular involvement have attracted attention in chronic obstructive pulmonary disease (COPD). This study aimed to investigate the expression of AECA in patients with COPD.
Methods:
A total of 116 COPD patients, whose diagnosis was established based on the Global Initiative for Chronic Obstructive Lung Disease criteria, were evaluated. Serum samples were examined for AECA by a cellular enzyme-linked immunosorbent assay using human umbilical vein endothelial cells. In addition, 157 subjects without any clinical or radiological evidence of COPD or pulmonary diseases served as a reference population.
Results:
The COPD patients exhibited significantly higher serum AECA concentrations than those in the reference population. The expression of AECA was significantly elevated in the COPD patients, even when compared with that in smokers among the reference population who had similar smoking habits to the COPD patients but normal spirometry.
Conclusion:
These findings suggest that an autoimmune component associated with endothelial cell damage is possibly involved in COPD.
In observational studies using acute lung injury (ALI) as an outcome, varying spectrum of lung injury and difficult-to-interpret chest radiographs (CXR) may hamper efforts to uncover risk factor associations. We assessed the impact of excluding patients with a "difficult to classify" or equivocal ALI diagnosis on clinical and genetic risk factor associations for ALI after trauma.
Methods:
Prospective cohort study of 280 critically ill trauma patients. The primary outcome was development of ALI. Patients were classified into 1 of 3 groups: 1) "Definite ALI" patients who fulfilled the American European Consensus Conference (AECC) criteria for ALI; 2) "Equivocal ALI" patients who had difficult to interpret CXRs; and 3) "Definite non-ALI" patients. We compared clinical and genetic ALI risk factor associations between two classification schemes: AECC classification ("Definite ALI" patients vs. rest) and an Alternative classification ("Definite ALI" patients vs. "Definite non-ALI" patients, excluding "equivocal ALI" patients).
Results:
93 patients (35%) were classified as "definite ALI", 67 (25%) as "equivocal" and 104 (39%) as "definite non-ALI". Estimates of clinical and genetic ALI risk factors associations were further from the null using the Alternative classification. In a multivariable risk factor model, the C-statistic of the Alternative classification was significantly higher than that derived from the AECC classification (0.82 vs. 0.74, p <0.01).
Conclusions:
The ability to detect ALI risk factors may be improved by excluding patients with an "equivocal" or "difficult to classify" ALI diagnosis. Such analyses may provide improved ability to detect clinical and genetic risk factor associations in future epidemiological studies of ALI.
Rational prescription of antibiotics in acute exacerbations of COPD (AECOPD) requires predictive markers. We aimed to analyze whether markers of systemic inflammation can predict response to antibiotics in AECOPD.
Methods:
We used data from 243 exacerbations out of 205 patients from a placebo-controlled trial on doxycycline in addition to systemic corticosteroids for AECOPD. Clinical and microbiological response, serum C-reactive protein (CRP, cut-offs 5 and 50 mg/L) and serum procalcitonin (PCT, cut-offs 0.1 and 0.25 µg) were assessed.
Results:
Potential bacterial pathogens were identified in the majority of exacerbations (58%). We found a modest positive correlation between PCT and CRP (r= 0.46, p<0.001). The majority of patients (75%) had low PCT levels, with mostly elevated CRP levels. While CRP levels were higher in the presence of bacteria (median, 33.0 mg/L [IQR, 9.75-88.25] vs. 17 mg/L [IQR, 5.0-61.0] [p= 0.004]), PCT levels were similar. PCT and CRP performed similarly as markers of clinical success and we found a clinical success rate of 90% in patients with CRP ≤5 mg/L. A significant effect of doxycycline was observed in patients with a PCT <0.1 µg/L (treatment effect, 18.4%; P=0.003). A gradually increasing treatment effect of antibiotics (6%, 10% and 18%), although not significant, was found for patients with CRP values of ≤5, 6-50 and >50 mg/L.
Conclusions:
Contrary to the current literature, this study suggests that patients with low PCT values do benefit from antibiotics. CRP might be a more valuable marker in these patients. (ClinicalTrials.gov number, NCT00170222).
Pneumonia is an important complication of chronic obstructive pulmonary disease (COPD) and is reported more often in patients receiving inhaled corticosteroids (ICS). Little is known about the clinical course and factors pre-disposing to pneumonia in COPD. We investigated patient characteristics and symptoms occurring before pneumonia reports in the INSPIRE study.
Methods:
A 2-year, double-blind, double-dummy parallel study of 1,323 patients randomized to salmeterol/fluticasone propionate 50/500 µg BID (SFC) or tiotropium (Tio) 18 µg once daily. Baseline demographics including serum C-reactive protein (CRP) were measured and Daily Record Cards (DRCs) were completed.
Results:
We identified 87 pneumonia reports from adverse event records (SFC = 62; Tio = 25) in 74 patients (SFC = 50; Tio = 24), compared with 2,255 exacerbations (SFC = 1,185; Tio = 1,070). Pneumonia was commoner in patients with severe dyspnea and in those with a baseline CRP > 10 mg/L. Numbers of de novo pneumonias (events that were not preceded by symptoms of an exacerbation) were similar between treatment groups, but pneumonia was more likely after either a treated or untreated unresolved exacerbation in patients receiving ICS (SFC = 32; Tio = 7). Similar results were seen when analysis was confined to radiologically confirmed events.
Conclusions:
Pneumonia is much less frequent than exacerbation in COPD. The excess of events with ICS treatment appears to be associated with protracted symptomatic exacerbations. Earlier identification and treatment of these events to prevent pneumonia merits further investigation.
It is unknown whether efficiency of neural drive as expressed by a ratio of ventilation to the diaphragm electromyogram (EMGdi) in patients with COPD differs from that of healthy subjects during exercise and whether maximal neural drive is exhibited at the point of exercise termination.
Methods:
We studied 12 male patients with COPD (mean±SD age 62.8±10.3 years, FEV1 28.1±10.2% predicted) and 12 age- and gender-matched healthy subjects (age 61.1±7.2 years, FEV1 101.5±11.9% predicted). EMGdi was recorded from a multipair esophageal electrode during a constant work (80% of maximal oxygen consumption derived from a previous incremental exercise test) treadmill exercise. Minute ventilation (Ve) and oxygen consumption (VO2) were also measured.
Results:
Root mean square (RMS) of the EMGdi increased initially and reached a plateau at submaximal drive during constant load exercise in both COPD patients and healthy subjects. The ratio of ventilation to EMGdi remained stable during exercise in healthy subjects from beginning to the end (100%±70% at the beginning and 100%±39% at the end, p>0.05), whereas the ratio decreased gradually during exercise in patients with COPD (from 85%±66% to 42%±13%, p<0.05).
Conclusions:
Efficiency of neural drive decreases in patients with COPD during treadmill exercise. Neural respiratory drive reached a submaximal plateau during constant load exercise in both healthy subjects and patients with COPD, indicating that it may not be the only factor determining exercise capacity.
Although lobectomy is the standard treatment for Stage I non small cell lung cancer (NSCLC), recent studies have suggested that limited resection may be a viable alternative for small sized tumors. The objective of the study was to compare survival after lobectomy versus limited resection among patients with Stage IA tumors ≤1cm by utilizing a large, nationally representative cancer registry.
Methods:
Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 2,090 cases of Stage I NSCLC ≤1 cm in size that underwent lobectomy or limited resection (segmentectomy or wedge resection). We used propensity score analysis to adjust for potential differences in baseline characteristics of patients in the two treatment groups. Overall and lung cancer-specific survival of patients undergoing lobectomy vs limited resection were compared in stratified and adjusted analyses, controlling for propensity scores.
Results:
Overall, 688 (33%) patients underwent limited resection. For the entire cohort, we were not able to identify a difference in outcomes among patients treated with lobectomy vs limited resection, as demonstrated by an adjusted hazard ratio (HR) for overall survival (1.12; 95% confidence interval [CI]: 0.93-1.35) and lung cancer-specific survival (HR: 1.24; 95% CI: 0.95-1.61). Similarly, when the cohort was divided into propensity score quintiles, we did not find a difference in survival between the two groups.
Conclusions:
Limited resection and lobectomy may lead to equivalent survival among patients with Stage I NSCLC tumors ≤1cm in size. If confirmed in prospective studies, limited resection may be preferable for the treatment of small tumors as it may be associated with fewer complications and better postoperative lung function.
N terminal pro B type natriuretic peptide (NTproBNP), a marker of ventricular strain, and C reactive protein (CRP), a marker of inflammation, are reportedly elevated in school-age children with obstructive sleep apnea (OSA).
We hypothesized that cardiovascular morbidity affects circulating markers and their echocardiographic and polysomnographic (PSG) correlates, in young children with OSA.
Methods and results:
We assessed young children undergoing adenotonsillectomy (TA) for OSA by polysomnography, echocardiography and serum CRP and NTproBNP. A total of 90 children with OSA (mean age 19±7 months, 71.2% male, BMI z= 0.62±1.04) and 45 age and gender matched controls were included. Three months following TA, 72 children were re-assessed for NTproBNP and CRP. NTproBNP (pg/ml) was higher in OSA (189.1±112.7) vs controls (104.8±49.5; p=0.006). Both NTproBNP (187.8±114 vs 86±32.6; p=0.002) and CRP (mg %) (0.49±0.41 vs 0.1±0.17; p<0.05) decreased following TA. Doppler pulse wave measuring tricuspid regurgitation (TR), a reflection of pulmonary hypertension, correlated with CRP (r=0.61, p<0.01) but not NTproBNP (r= –0.14, p=0.53). Left ventricle end diastolic diameter (LVEDD) was at the maximal normal range (0.91±0.11), but did not correlate with CRP or NTproBNP. Both CRP and TR correlated with PSG variables reflecting nocturnal hypoxemia, while NTproBNP and LVEDD did not. Echocardiography in forty children (out of 90) showed a decline in TR that was abnormal before TA and correlated with the decrease in CRP following TA.
Conclusions:
NTproBNP levels are increased in children with OSA and decrease following TA. Echocardiographic parameters suggesting increased pulmonary pressure in young children with OSA are related to nocturnal hypoxemia and systemic inflammation, which also decrease following therapy
The endemic region of blastomycosis has historically included the State of Indiana. However, few published reports of blastomycosis exist to substantiate this distinction. A surge of blastomycosis patients in central Indiana (Indianapolis and surrounding counties) beginning in 2005 prompted us to review our local experience. We proposed this surge was related to major highway construction around Indianapolis, Indiana.
Methods:
We reviewed all microbiologically confirmed cases from four hospitals serving central Indiana. Chart review was completed for adult patients and data were collected on clinical presentations, methods of diagnosis, comorbidities, radiologic findings, treatment, and outcomes. We plotted patient residence addresses with sites of highway construction.
Results:
Fifty-nine patients were identified from laboratory results and physician referral. Interestingly, a surge of 34 patients between 2005 and 2008 occurred, during which time major highway projects were underway around the Indianapolis metropolitan area. The majority of these patients presented acutely and with pulmonary involvement. Fungal culture and antigen testing were the most sensitive means of diagnosis. Antifungal therapy was highly effective.
Conclusions:
This "urban" outbreak of blastomycosis in Indianapolis should prompt clinicians to consider blastomycosis in this highly endemic area of histoplasmosis.
Recently it has been shown that emphysematous destruction of the lung is associated with a decrease in the total number of terminal bronchioles. It is unknown whether a similar decrease is visible in the more proximal airways. We aimed to assess the relationships between proximal airway count, CT measures of emphysema, and clinical prognostic factors in smokers; and to determine whether airway count predicts BODE Index.
Methods:
In fifty smokers emphysema was measured on CT scans and airway branches from the 3rd to 8th generations of the right upper lobe apical bronchus were manually counted. The sum of airway branches from the 6th to 8th generations represented the total airway count (TAC). For each subject, the BODE Index was determined. We used logistic regression to assess the ability of TAC to predict a high BODE (≥7 points).
Results:
TAC was inversely associated with CT emphysema (r=-0.54, P<0.0001). TAC correlated with the modified Medical Research Council Dyspnea Score (r=-0.42, P=0.004), FEV1% predicted (r=0.52, P=0.0003), six-minute walk distance (r=0.36, P=0.012), and BODE (r=-0.55, P<0.0001). The C statistic, which corresponds to the area under the ROC curve, for the ability of TAC alone and TAC, CT emphysema and age to predict a high BODE, was 0.84 and 0.92, respectively.
Conclusion:
Total airway count is lower in subjects with greater emphysematous destruction and is a predictor of a high BODE Index. These results suggest that CT-based total airway count may be a unique COPD-related phenotype in smokers.
Concerns about the achievement of children with asthma and respiratory conditions are especially important in New Zealand, which has one of the world’s highest rates of childhood asthma. The present study evaluated whether entering school with asthma was associated with low achievement after the first year.
Methods:
A child cohort was recruited to a prospective study at time of first enrolment into randomly selected schools in Christchurch. Parent interviews covered demographics and respiratory status. Physician reports were sought for children with asthma and all respiratory information was clinically reviewed. Children’s achievement in reading and math was individually assessed at school entry and re-assessed after 12 months. Schools reported absences. Intelligence sub-tests were administered.
Results:
298 children were recruited including 55 (18.5%) with Current Asthma. At one-year follow-up, retention was 93.7%. Children who entered school with asthma were more likely to be 6 or more months behind other participants in reading words (p=0.023) and books (p=0.026), but not math (p=0.167) at the end of the first year of school. Achievement was not related to asthma severity. Entering school with asthma reliably predicted low reading achievement independent of other known covariates of low achievement (high absenteeism, minority status, male gender, single-parent family, poor academic skills at school entry and low socio-economic status).
Conclusions:
Entering school with asthma was a significant predictor of low achievement in reading at 12 month follow-up, independent of asthma severity, high absenteeism or other covariates of low achievement.
The Registry to EValuate Early And Long-term pulmonary arterial hypertension (PAH) Disease Management (REVEAL) provides current demographics of patients diagnosed with Group I PAH in the United States.
Methods:
2967 patients diagnosed with PAH by right heart catheterization were enrolled in REVEAL between 3/2006 and 9/2007. Demographics from the REVEAL Registry patient cohort and REVEAL subpopulations (matched by inclusion criteria to other registries) were compared with historic US registry data and other contemporary US and non-US national PAH registries by inclusion criteria. These included the National Institutes of Health (NIH) PAH registry and the French PAH registry.
Results:
REVEAL patients matched to NIH registry patients were older at diagnosis (44.9±0.6 years vs 36.4±1.1 years; difference, 8.5±1.4; P<0.001) and more likely female (78.7±1.2% vs 63.1±3.5%; P<0.001). REVEAL patients matched to French registry patients had similar age and severity at diagnosis, but REVEAL patients were more likely female (79.8+0.8% vs 65.3+1.8%; P<0.001) and obese (body mass index ≥30 kg/m2, 32.5+1.0% vs 14.8+1.4%; P<0.001), whereas French patients were more likely to have HIV-associated PAH (6.2% vs 2.3%). The female preponderance is similar to that in other US-based contemporary registries.
Conclusions:
At diagnosis, REVEAL patients were older than NIH registry patients and similar in age to patients enrolled in contemporary registries. Compared with NIH and contemporary European and UK registries, there was a striking preponderance of women and REVEAL patients were more likely to be obese. These observations and the difference in HIV-associated PAH between REVEAL and other non-US contemporary registries warrant further investigation.
Infections caused by multidrug-resistant gram-negative bacteria have caused the resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients and no attempts have been made to evaluate its concentration in bronchoalveolar lavage (BAL).
Methods:
In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulphonate (CMS) intravenously, 2 million IU (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 hours. Colistin was measured by a selective, sensitive HPLC-based method. Pharmacokinetic parameters were determined by non-compartmental analysis.
Results:
Patients received 2.19±0.38 mg/Kg (range 1.58-3.16) of CMS per dose. At steady-state, mean(±SD) plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21±1.08 and 1.03±0.69 mcg/ml, respectively. Mean(±SD) AUC(0-8h), t1/2 and apparent volume of distribution (Vd/fm) were 11.5±6.2 mcg·h/ml, 5.9±2.6 h, and 1.5±1.1 L/Kg, respectively. Cmax/MIC ratio and AUC0-24/MIC ratio (MIC = 2mcg/ml) were 1.1±0.5 and 17.3±9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed.
Conclusions:
Although the pharmacodynamic parameters which better predict the efficacy of colistin are not known in humans, in adult critically ill patients the intravenous administration of CSM 2 million IU (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin which is undetectable in BAL. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality with MRSA pneumonia has not been determined.
Methods:
Adult intensive care unit (ICU) patients with a diagnosis of MRSA HAP, VAP, HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables.
Results:
The study sample consisted of 158 patients. All-cause mortality at 28 days was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥1.5 µg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 µg/mL (P≤0.001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality.
Conclusion:
Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 µg/mL should be undertaken with caution and alternative therapies should be considered.
Laryngo-hypopharyngeal sensitivity (LPS) as measured by thresholds to mechano and chemostimulation is important in preventing pulmonary aspiration. The presence of gastroesophageal reflux disease (GERD) increases thresholds to mechanostimulation. However, the effect of GERD on thresholds to chemostimulation remains unknown.
Objectives:
The aim of this study was to compare laryngo-hypopharyngeal thresholds to chemostimulation in subjects with GERD to healthy subjects, and determine the relationship between thresholds to mechano and chemostimulation
Methods:
48 patients with GERD and 18 healthy control subjects without GERD underwent LPS testing using the Fibreoptic Endoscopic Evaluation of Swallowing with Sensory Testing (FEESST) technique. All patients and 10 controls also underwent threshold testing to chemostimulation via hypopharyngeal infusions of normal saline and 0.1N HCl performed on separate days in a randomised, blinded manner.
Measurement:
Thresholds to mechanical stimulation, as measured by the lowest air pressure required to elicit the laryngeal adductor reflex (LAR), were determined before and after laryngo-hypopharyngeal infusions. Thresholds to chemical stimulation were measured by determining the infusion volume of acid or saline required to trigger an airway protection response.
Results:
The mean LAR threshold of the patient group was significantly higher compared to controls (9.5mmHg vs 3.9mmHg, p< 0.01). Compared to controls, significantly less acid (0.13ml vs 0.21ml, p< 0.01) was required to be infused in GERD subjects to trigger airway protective responses. There is a strong negative correlation between volume of acid required to be infused and LAR thresholds in controls (r = – 0.69, p< 0.05).
Conclusions:
Compared to controls, subjects with GERD have significantly increased thresholds to mechanical stimulation, suggesting reduced mechanosensitivity, but significantly reduced thresholds to chemical stimulation suggesting heightened chemosensitivity. There is an inverse relationship between mechanosensitivity and chemosensitivity. This relationship may be integral in maintaining airway protection. Web site: http://www.anzctr.org.au/
Although mediastinoscopy is still the gold standard for diagnosis of mediastinal lymphadenopathy, minimally invasive procedures have been developed: transbronchial needle aspiration using a flexible bronchoscope (conventional TBNA) or linear echo-endoscope (endobronchial ultrasound, EBUS) allowing real-time guided lymph node aspiration. The observation of contamination of samples by foreign particles led us to determine the frequency and the nature of this material and to identify its origin.
Methods:
From June 2007 to November 2008, 141 consecutive patients underwent conventional TBNA (n = 84) or EBUS-guided TBNA (n = 57). All cytological samples were reviewed in blind and contamination was assessed semiquantitatively. Mineral analysis using a transmission electron microscope equipped with an energy dispersive X-ray spectrometer was performed on the solution obtained after rinsing unused needles and on 4 samples of calf thymuses punctured with EBUS needles.
Results:
Foreign material, different from anthracosis, was identified in samples obtained with five different batches of needles, only from EBUS-TBNA (p<0.0001). The contamination score was correlated to the number of passes (p=0.035). Mineral analyses of the rinsing solutions from conventional TBNA needles were negative while metal alloys of iron, titanium, nickel and chromium were released with EBUS needles. The same contamination was identified in 3 of the 4 punctured calf thymuses.
Conclusion:
Dedicated EBUS-TBNA needles Vizishot are able to release metal particles, probably by friction between the stylet and the needle with a potential risk to inject particles into nodes. The long-term consequences are unknown, but the need for safety measures should be evaluated.
Asthma and chronic obstructive pulmonary disease (COPD) are characterised by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognised in asthma, particularly in severe disease. The Th17 cytokines IL-17A and F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain.
Methods:
We assessed IL-17A and F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild-moderate COPD, and 27 non-smoking and 14 smoking controls. Sputum IL-17 concentration was measured in 165 subjects with asthma, 27 with COPD.
Results:
The median (IQR) IL-17A cells/mm2 submucosa was increased in mild-moderate asthma (2.1 [2.4]) compared to healthy controls (0.4[2.8]), but not severe asthma (p=0.04). In COPD IL-17A+ cells/mm2 submucosa were increased (0.5 [3.7]) compared to non-smoking controls (0[0]), but not smoking controls, (p=0.046). IL-17F+ cells/mm2 submucosa were increased in severe asthma (2.7 [3.6]) and mild-moderate asthma (1.6 [1.0]) compared to healthy controls (0.7 [1.4]) (p=0.001), but was not increased in COPD. IL-17A and F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs=0.5, p=0.005). The sputum IL-17 concentration in COPD was increased compared to asthma (2 (0-7) pg/ml versus 0 (0-2) pg/ml (p<0.0001) and was correlated with post-bronchodilator FEV1 % predicted (r=-0.5, p=0.008) and FEV1/FVC (r=-0.4, p=0.04).
Conclusions:
Our findings support a potential role for the Th17-cytokines IL-17A and F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation.
The goals of asthma care are reduction of risk and impairment, but achieving these goals requires collaborative work between patients and their clinicians. The purpose of this study was to improve inhaled corticosteroid (ICS) adherence and asthma control by cueing therapeutic communication between patients with asthma and their primary care clinicians.
Methods:
We conducted a prospective, cluster randomized, controlled, effectiveness trial to assess the effect of providing visually standardized, interpreted peak flow graphs (CUE intervention) to patients and their clinicians on ICS adherence and asthma control. Asthma control outcomes were analyzed by season, to account for seasonal variations in exacerbation frequency.
Results:
Although mean log-transformed ICS adherence was not significantly different between the two groups, there was a trend towards preserved adherence in the intervention group over time (p=0.16). Intervention patients required fewer courses of oral steroids during Winter (9% vs. 23%, p<0.001) and Spring (3% and 17%, p<0.001) compared with controls. Intervention patients also had fewer periods of worsening symptoms (65% vs. 89%, p<0.001) and fewer urgent care visits (10% vs. 23%, p<0.001) during Winter compared to controls. Post-hoc analysis showed significant improvement in the intervention group with respect to ICS adherence during Winter months (p<0.05), the likely explanation for the reduction in prednisone use and symptoms. Day-to-day peak flow variability in the intervention group fell consistently throughout the study from an average of 32% at baseline to 23% at final measurement (p<0.001) indicating less airway reactivity over time.
Conclusions:
Our findings provide evidence of the value of peak flow monitoring for patients with asthma during seasons of greatest vulnerability, cold/flu season. The peak flow information apparently led to improvements in ICS adherence resulting in less need for prednisone rescue and fewer episodes of worsening symptoms.
Differences in COPD classification have been shown in population datasets when using 5th percentiles as the lower limit of normal (LLN) versus the current GOLD guidelines of FEV1/FVC <0.70 for detecting airway obstruction and FEV1 as 80% predicted (PP) for detecting and classifying the severity of COPD (GOLD/PP). Many lung function laboratories use 80% predicted to determine if results are abnormal. Misclassification of the full range of lung diseases in large patient groups when using GOLD/PP criteria instead of the LLN has not been previously explored.
Methods:
We have determined the discrepancy rates in PFT interpretation between these two methods on pre-bronchodilator lung function results from a large number of adult patients from the UK, New Zealand and USA.
Results:
In 11,413 patients the GOLD/PP method misclassified 24% of all patients; 10% of patients who were normal were falsely classified with a disease category and 7% of patients were falsely attributed with emphysema. The GOLD/PP method gave false positive diagnoses for airflow obstruction and restrictive defects to significantly more male (p<0.01) and older patients (p<0.0001) and missed airflow obstruction and restrictive defects in younger subjects (p<0.0001).
Conclusions:
Using lung function tests on their own with 80% predicted and fixed cut points to determine if a test is abnormal could misdiagnose over 20% of patients referred to PFT labs. This methodology introduces clinically important biases in assessing disease status that could affect allocation to treatment groups. This misclassification is avoided by using the LLN based on the 5th percentile values.
Clinical trialists involved in projects aimed at assessing the impact of a device or therapy on exercise capacity must select an end point that can detect a therapy-derived change and do so in a manner that is both sensitive to the change and valid. Using baseline data from the PEERLESS-HF (Prospective Evaluation of Elastic Restraint to LESSen the effects of Heart Failure) trial, we describe the coefficient of variation (CV) for peak oxygen uptake (VO2) and other parameters measured during a cardiopulmonary exercise (CPX) test.
Methods:
Prior to conducting CPX testing, a CPX core laboratory conducted training with testing staff at each site and a standardized quality assurance protocol was completed. During screening, subjects performed two symptom-limited CPX tests (CPX-0 and CPX-1) within 14 days.
Results:
The CV for peak VO2, ventilatory efficiency, and ventilatory-derived anaerobic threshold were 5.9%, 4.8%, and 6.8%, respectively. During CPX-0, the percent of subjects with a respiratory exchange ratio (RER) <1.05 that increased their peak VO2 by ≥ 6% during CPX-1 was 47%, compared to 12% of subjects also with an RER <1.05 that experienced a decrease in peak VO2 ≥ 6%.
Conclusions:
In a multi-site clinical trial setting we showed that the achieved test-retest reproducibility for peak VO2 can be acceptable, as evidenced by a CV at 5.9%. Until more data is available to identify patients who may demonstrate greater test-retest variance and to avoid repeat testing in all subjects at baseline, clinical trialists might consider repeating tests when RER <1.05.
Lung transplantation is associated with a high incidence of gastroesophageal Reflux (GERD). The presence of GERD is considered a risk factor for the subsequent development of obliterative bronchiolitis (OB), and surgical correction of GERD by gastrofundoplication (GF) may be associated with increased freedom from OB. The mechanisms underlying a protective effect from OB remain elusive.
Objectives:
To analyze the flow cytometric properties of bronchoalveolar lavage (BAL) cells in patients who have undergone GF early after transplant.
Methods:
In a single center lung transplant center 8 patients with GERD who were in the first transplant year underwent GF. Prior to and immediately following GF, BAL cells were analyzed by polychromatic flow cytometry. Spirometry was performed before and after GF.
Results:
GF was associated with a significant reduction in frequency of BAL CD8 lymphocytes expressing the intra cellular effector marker granzymeB compared to the pre-GF levels. 26% of CD8 cells were granzymeBhi pre-GF compared to 12% of CD8 cells post GF, range 8-50% pre GF, 2-24% post GF, p=0.01. In contrast, GF was associated with a significant interval increase in the frequency of CD8 cells with an exhausted phenotype (granzymeBlo, CD127lo, PD1hi) from 12% of CD8 cells pre-GF to 24% post GF (range 1.7-24% pre and 11-47% post, p=0.05). No significant changes in spirometry were observed during the study interval.
Conclusions:
Surgical correction of GF is associated with a decreased frequency of potentially injurious effector CD8 cells in the BAL of lung transplant recipients.
REVEAL is the largest U.S. cohort of patients with pulmonary arterial hypertension confirmed by right heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH) patients.
Methods:
All newly and previously diagnosed patients with WHO Group I PAH meeting RHC criteria at 54 U.S. centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA).
Results:
Compared to idiopathic patients (n=1,251), CTD-APAH patients (n=641) had better hemodynamics and favorable right ventricular echocardiographic findings, but a higher prevalence of pericardial effusions, lower 6 minute walk distance (300.5±118.0 vs. 329.4±134.7 m, p=0.01), higher B-type natriuretic peptide (BNP) levels (432.8±789.1 vs. 245.6±427.2 pg/mL, p<0.0001) and lower diffusing capacity of carbon monoxide (DLCO) (44.9±18.0% vs. 63.6±22.1% predicted, p<0.0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs. 93%, p<0.0001; 67% vs. 73%, p=0.03). Compared with SSc-APAH patients (n=399), those with other CTDs (SLE n=110; MCTD n=52; RA n=28) had similar hemodynamics; however, SSc-APAH patients had the highest BNP levels (552.2±977.8 pg/mL), lowest DLCO (41.2±16.3% predicted), and poorest one-year survival (82% vs. 94% in SLE-APAH, 88% in MCTD-APAH, 96% in RA-APAH).
Conclusions:
Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest DLCO, and poorest survival of all CTD-APAH subgroups.
Several severity scores have been advanced to predict patient’s outcome from community acquired pneumonia (CAP). The purpose of this study is to compare the accuracy of CURB, CURB-65, CRB-65, and SOAR scoring systems in predicting 30-day mortality and ICU admission in patients with nursing home acquired pneumonia (NHAP).
Methods:
A retrospective analysis of a prospectively collected database of 457 nursing home residents hospitalized with pneumonia at two university-affiliated tertiary care facilities. Clinical and laboratory features were used to compute severity scores using the British Thoracic Society severity rules and the SOAR criteria. The sensitivity, specificity, positive and negative predictive values were compared for need of ICU admission and 30-day mortality.
Results:
The overall 30-day mortality and ICU admission rates were 23% and 25%, respectively. CURB, CURB-65, and CRB-65 performed similarly in predicting mortality with areas under the receiver operating characteristic curves (AUC) of 0.605 (95% CI 0.559-0.650), 0.593 (95% CI 0.546-0.638), and 0.592 (95% CI 0.546-0.638), respectively while SOAR showed superior accuracy with an AUC of 0.765 (95% CI 0.724-0.803) (p<0.001). The need for ICU care was also better identified with SOAR model compared to the other scoring rules.
Conclusions:
All three British Thoracic Society rules had lower performance accuracy in predicting 30-day mortality of hospitalized NHAP than SOAR. SOAR is also a superior alternative for better identification of severe NHAP. An improved rule for severity assessment of hospitalized NHAP is needed.
Limited understanding of the presentation and course of influenza A/H5N1 infection in humans hinders evidence-based management.
Methods:
Review of case records of patients with real time, PCR confirmed H5N1 influenza admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia.
Results:
22 previously well patients, age 3 to 47 years (median 24.5), were identified. All attended a clinic or hospital after a median of 2 days of illness (range 0-7). Times to first dose of oseltamivir (3 died before receiving oseltamivir) were 2 to 12 days (median 7), administered mostly (n=15) at RSP. 19 patients required mechanical ventilation. Deaths numbered 18 (case fatality=82%) occurring within hours to 6 days of RSP admission, corresponding to 6 to 16 days of illness.
Admission hyperglycemia (≥ 140 mg/dL), unrelated to steroids or known underlying diabetes mellitus, and raised d-dimers (0.81 – 5.2 mg/L, ULN < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively. Fibrinogen concentrations were mostly low/normal 129.9-517.9 mg/dL (median 241.1, normal 200-400 mg/dL) whilst CRP (9/11) and ferritin (6/8) were raised. Risk factors for death (univariate analysis) included: (i) raised d-dimers, (ii) hyperglycemia, (iii) raised urea, (iv) more extensive chest X ray shadowing, and (v) lower admission oxygen saturation.
Conclusions:
Early diagnosis and effective treatment of human H5N1 infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Raised d-dimers, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.
Acute respiratory distress syndrome (ARDS) may occur after either septic or nonseptic injuries. Sepsis is the major cause of ARDS. However, little is known about the differences between sepsis-related and non-sepsis-related ARDS.
Methods:
Consecutive 2786 patients with ARDS predisposing conditions were enrolled into the prospective cohort, of which 736 patients developed ARDS. We defined sepsis-related ARDS as ARDS developing in patients with sepsis, and non-sepsis-related ARDS as ARDS developing after nonseptic injuries such as trauma, aspiration, and multiple transfusions. Patients with both septic and nonseptic risks were excluded from analysis.
Results:
Compared to non-sepsis-related ARDS patients (n=62), sepsis-related ARDS patients (n=524) were more likely to be female, diabetics, less likely to have preceding surgery, and had longer pre-ICU hospital stays and higher APACHE III scores (median, 78 vs. 65, p<0.0001). There were no differences in lung injury score, blood pH, PaO2/FiO2 ratio, and PaCO2 on ARDS diagnosis. However, sepsis-related ARDS patients had significantly lower PaO2/FiO2 ratios than non-sepsis-related ARDS patients on ARDS day 3 (p=0.018), day 7 (p=0.004), and day 14 (p=0.004) (repeat measures analysis, p=0.011). Compared with non-sepsis-related ARDS patients, sepsis-related ARDS patients had a higher 60-day mortality (38.2% vs. 22.6%, p=0.016), a lower successful extubation rate (53.6% vs. 72.6%, p=0.005), and fewer ICU-free days (p=0.0001) and ventilator-free days (p=0.003). In multivariate analysis, age, APACHE III score, liver cirrhosis, metastatic cancer, admission serum bilirubin and glucose levels, and treatment with activated protein C were independently associated with 60-day ARDS mortality. After adjustment, sepsis-related ARDS was no longer associated with higher 60-day mortality, (HR, 1.26, 95% CI, 0.71-2.22).
Conclusion:
Sepsis-related ARDS has a higher overall disease severity, poorer recovery from lung injury, lower successful extubation rate, and higher mortality than non-sepsis-related ARDS. Worse clinical outcomes in sepsis-related ARDS appear to be driven by disease severity and comorbidities.
Survival outcomes of never smokers with non-small cell lung cancer (NSCLC) who undergo surgery are poorly characterized. This investigation compared surgical outcomes of never and current smokers with NSCLC.
METHODS:
This is a single institution retrospective study of never and current smokers with NSCLC from 1975-2004. From an analytic cohort of 4,546 NSCLC patients, we identified 724 never smokers and 3,822 current cigarette smokers. Overall, 1,142 patients underwent surgery with curative intent. For survival analysis by smoking status, hazard ratios were estimated using Cox Proportional Hazard Modeling, and then further adjusted by other covariates.
RESULTS:
Never smokers were significantly more likely than current smokers to be female (p<0.01), older (p<0.01), have adenocarcinoma (p<0.01) as well as bronchioloalveolar carcinoma (p<0.01). No statistically significant differences existed in stage distribution at presentation for the analytic cohort (p=0.35) or for the subgroup undergoing surgery (p=0.24). The strongest risk factors of mortality among NSCLC patients who underwent surgery were advanced stage (aHR=3.43; 95% CI 2.32-5,07, p<0.01) and elevated ASA classification (aHR=2.18; 95% CI 1.40-3.40, p<0.01). The minor trend towards an elevated risk of death on univariate analysis for current versus never smokers in the surgically treated group (HR=1.20, 95% CI 0.98-1.46, p=0.07), was completely eliminated when the model was adjusted for covariates (p=0.97).
CONCLUSIONS:
Our findings suggest smoking status at time of lung cancer diagnosis has little impact on the long-term survival of patients with NSCLC especially after curative surgery. Despite different etiologies between lung cancer in never and current smokers, the prognosis is equally dismal.
Influenza vaccination is recommended for all persons with cystic fibrosis (CF). Despite this recommendation, no study has been performed to determine factors associated with receipt of influenza vaccination among persons with CF.
Methods:
We conducted a two-year cohort study from 2006 through 2007 using the CF Foundation (CFF) Patient Registry to assess predictors of influenza vaccination using logistical regression modeling.
Results:
In 2006, the cohort consisted of 16,435 persons with vaccination data seen at CFF care centers. Vaccination rates were high for children <5 years (90.5%), children 5 to <18 years (91.1%), and adults (87.9%). In 2006, decreased odds of vaccination were seen among adults with other/unknown insurance (0.37, 95%CI 0.15, 0.87). Among children 5 to <18 years and adults, decreased odds of vaccination were seen among Hispanics (0.74, 95%CI 0.55, 0.98; and 0.67, 95%CI 0.46, 0.98) and with use of oxygen therapy (0.55 95%CI 0.38, 0.78; and 0.68, 95%CI 0.55, 0.86), while ≥4 clinic visits annually was associated with increased odds of vaccination (2.33, 95%CI 1.92, 2.84; and 2.05, 95%CI 1.71, 2.47). Findings associated with decreased vaccine receipt remained significant in sensitivity analyses that assumed missing vaccination data were vaccine positive.
Conclusion:
Overall influenza vaccination rates are very high in the United States CF population. Knowledge of influenza vaccination predictors among persons with CF may aid clinicians to target patients at greater risk for influenza infection. This data may have important implications for the evolving pandemic influenza A (H1N1).
Altered levels of circulating adhesion molecules found in several carcinomas, including lung cancer, reflect local loss of diffusion barriers and tumor volume and can be potentially used as biomarkers. In the present study we investigated the role of soluble E-cadherin (sE-cad), soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-sel) as biomarkers in lung cancer.
Methods:
Sixty-two patients with recently diagnosed lung cancer, 42 with small cell lung cancer (SCLC) and 20 with non-small cell lung cancer (NSCLC), as well as 29 healthy volunteers were enrolled. Blood samples were collected at the time of diagnosis and measurement of soluble adhesion molecules in the serum samples was performed by ELISA using monoclonal antibodies against E-cadherin, E-selectin and ICAM-1.
Results:
Serum levels of sE-cad, sE-sel and sICAM-1 in both SCLC and NSCLC were significantly elevated compared to controls (p< 0.001). In addition, both SCLC and NSCLC patients with distant metastasis had marked increase of sE-Cad (p< 0.001) but no such correlation with sE-sel and sICAM-1 was found.
Conclusions:
Our findings suggest that sE-cad, sE-sel and sICAM-1 have an adjunctive diagnostic role in lung cancer. Furthermore, sE-cad may also have a prognostic role and could be used as a useful biomarker in the prediction of lung cancer outcome.
Pulmonary Artery Dilatation is one of the consequences of Pulmonary Arterial Hypertension (PAH) and is used for non-invasive detection. However, it is unclear how the size of the pulmonary artery behaves over time and if it's related to pressure changes. The aim of this study is to evaluate the pulmonary artery size during follow-up in treated PAH-patients and whether it reflects pulmonary vascular hemodynamics.
Methods:
Fifty-one patients with PAH, who underwent at least two Right Heart Catheterizations (RHC) both together with cardiac Magnetic Resonance Imaging, were included in this study. Another eighteen subjects who had normal pressure at RHC were included for comparison at baseline. From RHC we derived pulmonary artery pressures and cardiac output. From the MRI images we derived PA diameter and the diameter ratio of the PA and Ascending Aorta (rPAD/AAD).
Results:
The PA diameter was significantly larger in PAH patient compared with non-PAH patients. (p<0.001). A ratio PAD/AAD>1 had a positive predictive value of 92% for PAH. Mean follow up time was 942 days. There was a significant dilatation during this follow-up (p<0.001). The change of the PA diameter did not correlate with the changes in pressure or cardiac output. A moderate correlation with follow-up time was found (r=0.56, p< 0.001).
Conclusions:
A dilatated pulmonary artery is useful for identifying PAH patients. However, during follow-up of PAH patients, progressive dilatation of the pulmonary artery is independent of the change in pulmonary artery pressure and cardiac output and might become independent from hemodynamics.
Low-density gas mixtures and oxygen (O2) supplementation are known to improve physical performance and ventilatory adaptation during incremental maximal exercise in COPD. We investigated whether their combined use during intense physical training is also effective in ameliorating exercise tolerance in patients affected by moderate-to severe COPD.
Methods:
To this aim, 30 patients (FEV1 <60% of predicted) underwent a 2-month rehabilitation program. Leg-cycle training was conducted thrice weekly at 80% of the initial peak work rate for at least 20 min with breathing room air, or a 60%-helium and 40%-O2 mixture, or supplemental O2 40% inhaled from a Douglas bag. The study was conducted at random and with a double-blind design. Before and at the end of the training period the subjects were tested for spirometry, arterial gas tension, diffusing lung capacity for CO, and incremental and constant work rate exercise test on a cycle ergometer.
Results:
Physical training resulted in a significant improvement in peak oxygen consumption and power output (p<0.01 for both) and in exercise endurance time (p<0.05) independently of the kind of inhaled gas during the rehabilitation program (p≥0.42). No changes were observed with respect to lung function tests or gas exchange.
Conclusions:
It is concluded that the use of low-density gas mixtures or O2 supplementation do not contribute to improve exercise performance in moderate-to-severe COPD patients without a significantly decreased diffusion lung capacity for CO who are able to tolerate intense physical training.
Studies evaluating the quality of life (QoL) in patients with a history of acute pulmonary embolism (PE) are not available, even though QoL is a key component of outcome of medical care and a predictor of disease specific prognosis.
Methods:
As part of a large follow-up study the Short Form-36 (SF-36) was presented to consecutive patients who had survived one or more episodes of acute PE. The results of all 9 subscales of the SF-36 were compared to sex and age adjusted Dutch population norms. Single and multivariate analyses were performed to identify independent determinants of the quality of life in our study population.
Results:
The SF-36 was completed by 392 patients. Except for the subscale health change, patients had substantially lower QoL than population norms on all 8 remaining subscales. After multivariate analysis, the time interval between the last thromboembolic episode and study inclusion was inversely related to QoL, and significant determinants of poor QoL were prior PE, age, obesity, active malignancy and cardiopulmonary comorbid conditions. Regression models including all identified significant determinants proved to be quite modest predictors for QoL in the individual patient. Illness cognitions, coping mechanisms and self management behaviour might be additional important indicators of QoL in our study population but remain to be studied.
Conclusion:
We identified several PE- and non-PE related determinants of QoL in patients with a history of acute PE, which is impaired compared to sex and age adjusted population norms. QoL after acute PE should be studied more extensively and added as standard measure to outcome studies.
Unrecognized obstructive sleep apnea (OSA) may lead to poor asthma control despite optimal therapy. Our objective was to evaluate the relationship between OSA risk and asthma control in adults.
Methods:
Asthma patients at routine tertiary care clinic visits completed the validated Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) and Asthma Control Questionnaire (ACQ). ACQ ≥1.5 defined not well controlled asthma, and SA-SDQ ≥36 for men and ≥32 for women defined high OSA risk. Logistic regression was used to model associations of high OSA risk with not well controlled asthma (ACQ full and short versions).
Results:
Among 472 subjects with asthma, the mean ACQ (full version) score was 0.87±0.90 and 80 subjects (17%) were not well controlled. Mean SA-SDQ score was 27±7, and 109 subjects (23%) met the definition of high OSA risk. High OSA risk was associated on average with 2.87 times higher odds for not well controlled asthma (ACQ full version) (95% confidence interval [1.54-5.32], p=0.0009), after adjusting for obesity and other factors known to worsen asthma control. Similar independent associations were seen when using the short ACQ versions.
Conclusions:
High OSA risk is significantly associated with not well controlled asthma, independent of known asthma aggravators and regardless of the ACQ version used. Patients who have difficulty achieving adequate asthma control should be screened for OSA.
Neutrophil gelatinase associated lipocalin (NGAL) is an antimicrobial peptide that could be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The current study aimed to measure the plasma levels of NGAL in a large cohort of COPD patients and controls, and examine the levels of NGAL by COPD disease characteristics.
Methods:
402 COPD patients and 229 controls, age 40-76, from the Bergen COPD Cohort Study were included. All COPD patients had an FEV1/FVC ratio of <0.7, and an FEV1 of <80% predicted, and a smoking history of at least 10 packyears. Plasma levels of NGAL were determined by enzyme immunoassay. Linear regression models were fitted with NGAL as the outcome variable. Confounders examined were sex, age, smoking, Charlson comorbidity score, use of inhaled steroids, neutrophil cell count, plasma creatinine and ferritin, and C-reactive protein (CRP).
Results:
Mean (SD) plasma concentration of NGAL was 75.1 (31.8) ng/mL in COPD patients and 56.5 (22.0) ng/mL in controls (p<0.01). NGAL levels were bivariately associated with age, smoking, body composition, Charlson score, neutrophil blood count, creatinine and CRP. However, NGAL was significantly elevated in COPD patients compared to controls even after adjustment for confounders.
Frequent exacerbations and hypoxemia was associated with higher levels of NGAL, whereas increasing Global Initiative for chronic obstructive Lung Disease (GOLD) stage was associated with lower levels of NGAL among the COPD patients.
Conclusion:
Plasma levels of NGAL were significantly higher in COPD patients compared with controls. NGAL was related to important COPD disease characteristics.
Lung cancer is the leading cause of cancer-related deaths in the United States and the second most common type of cancer in both men and women. Optical coherence tomography (OCT) can generate high resolution cross-sectional images of complex, living tissues in real time. The objectives of this study were to determine the feasibility of using OCT during flexible bronchoscopy, and to preliminarily assess the ability of OCT to distinguish an endobronchial malignancy from normal endobronchial mucosa.
Methods:
A NirisTM OCT probe was introduced into the airways of patients with an endobronchial mass during flexible bronchoscopy. An investigational device exemption was approved by the FDA for the use of the OCT system in this study. Conventional OCT scans of an endobronchial mass and a control area of normal bronchial mucosa were done to generate real time images in each patient. Following OCT imaging, the same sites were biopsied for pathologic correlation.
Results:
We report on the first 5 patients enrolled. A total of 60 OCT images with corresponding endobronchial biopsies were obtained. The average procedure time was 29 minutes. The histopathologic diagnoses of the endobronchial masses included 2 small cell carcinomas, 1 squamous cell carcinoma, 1 adenocarcinoma, and 1 endobronchial schwannoma. Microstructures of normal bronchial mucosa, including epithelium and lamina propria, were identified with OCT. OCT features of malignancy included loss of normal, identifiable microstructures and subepithelial "optical fracture" of tissues. All patients tolerated the endobronchial imaging well without complications.
Conclusions:
Preliminary results suggest that OCT is a technically feasible adjunct to flexible bronchoscopy in the diagnosis of lung cancer. This is the first reported use of OCT to generate images of endobronchial neoplasms during flexible bronchoscopy in the United States. This technology may in the future provide a non-invasive "optical biopsy", which could potentially guide the bronchoscopist to areas for biopsy or even obviate the need for conventional lung biopsies.
The transepithelial nasal potential difference (NPD) is used to assess cystic fibrosis transmembrane conductance regulator (CFTR) activity. Unreliability, excessive artifacts, and lack of standardization of current testing systems can compromise its use as a diagnostic test and outcome measure for clinical trials.
Methods:
To determine whether a non-perfusing (agar gel) nasal catheter for NPD measurement is more reliable and less susceptible to artifacts than a continuously perfusing nasal catheter, we performed a multicenter, randomized, crossover trial comparing a standardized NPD protocol using an agar nasal catheter with the same protocol using a continuously perfusing catheter. The data capture technique was identical in both protocols. A total of 26 normal adult subjects underwent NPD testing at 6 different centers.
Results:
Artifact frequency was reduced 75% (p<0.001), and duration was less pronounced using the agar catheter. The measurement of sodium conductance was similar between the two catheter methods, but the agar catheter demonstrated significantly greater CFTR-dependent hyperpolarization, as zero Cl- + isoproterenol measurements were significantly more hyperpolarized with the agar catheter (-24.2 ± 12.9 mV with agar- vs. -18.2 ± 9.1 mV with perfusion; p<0.05).
Conclusions:
The agar nasal catheter approach demonstrates superior reliability compared to the perfusion nasal catheter method for measurement of NPD. This non-perfusion catheter method should be considered for adoption as a standardized protocol to monitor CFTR activity in clinical trials.
Chronic illness is a significant risk factor for the development of internalizing psychopathology, however, evidence for the prevalence of these symptoms in patients with Cystic Fibrosis (CF) is limited. We investigated the prevalence of anxious and depressive symptoms in German-speaking patients with CF and the association of these symptoms to physical health status.
Methods:
A representative sample of German patients with CF (N=670, age range 12-64 years, 52.7% male) completed the Hospital Anxiety and Depression Scale. Their medical data were taken from the German CF registry. Data on the study sample were compared to a control group from the German general population.
Results:
Elevated anxiety scores were found in 20.6% of the patients with CF, whereas 9.6% reported high levels of depressive symptoms. Adult patients with CF reported more elevated symptoms of anxiety than healthy controls, whereas no age group of patients was more or less depressed than the general population. Younger patients reported less anxious and depressive symptoms than older patients and females reported more anxious symptoms than males. Recent hemoptysis/pneumothorax and recent diagnosis of diabetes were associated with anxiety, whereas impaired lung function and transplant listing were associated with depression.
Conclusions:
Anxiety in particular is an important issue for a large proportion of patients with CF. The risk of depression increased with greater impairment in pulmonary function. Annual screening of symptoms of anxiety and depression, as well as appropriate referrals for those in the clinically elevated range, are recommended.
Tissue hypercarbia is related to hypoperfusion and microcirculatory disturbances in septic shock. Transcutaneous CO2 devices using a heated sensor to arterialize the tissue have been used as an alternative method for estimation of arterial PCO2. This study investigates whether the cutaneous sensor, attached to an ear lobe and regulated to 37°C, could be used to measure cutaneous tissue CO2(PcCO2) and evaluate microperfusion in septic patients.
Methods:
Fifteen ICU stable patients were studied as a control. Forty-six ventilated septic shock patients were enrolled. The differences between PcCO2 and PaCO2(Pc-aCO2), and between cutaneous PcCO2 and end tidal PCO2(Pc-etCO2) were evaluated for 36 hours. Variations of the Pc-aCO2 and Pc-etCO2 during fluid challenge were compared to microcirculatory skin blood flow (mBFskin) assessed by Laser Doppler flowmetry.
Results:
At baseline levels, Pc-aCO2 and Pc-etCO2 were significantly higher in septic shock than in the control group (14.8(12.6) versus 6(2.7) and 25(16.3) versus 9(3.8) mmHg, p<0.0001 respectively). During the following 36 hours, surviving septic patients decreased significantly the Pc-aCO2 and Pc-etCO2 compared to the non survivors (p<0.01). The evolution of macro-hemodynamic parameters showed no differences between survivors and non-survivors. At H24, a Pc-aCO2 >16 mmHg and a Pc-etCO2 > 26 mmHg was related to poor outcome. Pc-aCO2 and Pc-etCO2 variations during fluid challenge were inversely correlated with changes in mBFskin (r2= 0.7).
Conclusion:
Ear lobe cutaneous PCO2 at 37°C represents a non invasive technique to assess tissue PCO2 measurement. Pc-aCO2 and Pc-etCO2 were related to outcome and provide continuous information on microperfusion in septic patients.
The role of Candida albicans in the cystic fibrosis (CF) airway is underexplored. Considered a colonizer, few question its pathogenic potential despite high isolation frequencies from sputum culture. We evaluated the frequency and identified the strongest predictors of C. albicans colonization in CF. Independent associations of colonization with clinical outcomes were determined and the longitudinal effects of C. albicans acquisition on body mass index (BMI) and forced expiratory volume in the first second (FEV1) evaluated.
Methods:
A prospective observational study of 89 CF patients was performed (3,916 sputum samples over 11 years). Frequency of C. albicans growth in sputum allowed classification of the cohort into colonizers and non-colonizers. BMI, FEV1, hospital-treated exacerbations and other clinical parameters were followed throughout the study to determine association with colonization status. Multivariate regression determined the strongest predictors of colonization and for clinical effects after adjustment for confounders. Repeated measure ANOVA assessed the longitudinal effect of colonization on BMI and FEV1.
Results:
Colonization with C. albicans was frequent (49.4%) and best predicted by pancreatic insufficiency (p=0.014), osteopenia (p=0.03) and co-colonization with Pseudomonas spp. (p=0.002). C. albicans colonization significantly predicted hospital-treated exacerbations (p=0.004) after adjustment for confounders. Exacerbation rate significantly increased in the chronically or intermittently colonized following first acquisition of C. albicans. Colonization accelerated rates of decline for BMI (p<0.0001) and FEV1 (p<0.001).
Conclusion:
Airway colonization with C. albicans presaged a greater rate of FEV1 decline and hospital-treated exacerbations in CF.
Great variability exists in the occurrence of multi-antibiotic resistant bacteria in ICUs around the world. The contribution of specific ICU care variables to these geographic variations is unknown.
Methods:
ICU patients from two ICUs (in Jerusalem and Toronto) who were admitted for >48 hours and who grew a resistant bacteria in any culture during ICU admission were compared to those without resistant organisms across a wide range of demographic and ICU care interventions. Significant variables were investigated with logistic regression to identify factors predictive of infection/colonization with a resistant organism.
Results:
Resistant organisms were acquired by 82/423 (19%) patients. Patients acquiring a resistant organism had a higher incidence of diabetes mellitus (21/82, 26% vs 52/341, 15%, p=0.026), were more frequently admitted from another ICU (17/82, 21% vs 33/341, 10%, p=0.005), received more antibiotics in ICU (19±17 vs 14±14 days, p=0.005), and had more ventilator (10±10 vs 7±8, p=0.031) and central line days (10±8 vs 7±8, p<0.001). These patients had a lower incidence of limitation of therapy orders (9/82, 11% vs 78/341, 23 %, p=0.015). Only absence of a limitation of therapy order (OR 2.62, 95%CI 1.21 - 5.68, p=0.014) was independently associated with acquisition of resistant organisms.
Further, amongst ICU fatalities, 5/45 (11%) patients dying after withdrawal acquired resistant bacteria vs 17/44 (39%) non-withdrawal fatalities (p=0.003). Non-withdrawal fatalities received significantly more third line antibiotics (7±14 vs 2±4, p=0.031) despite similar ICU lengths of stay (15±21 days for non withdrawal fatalities vs 10±11 for withdraw fatalities, p=0.210)
Conclusion:
End-of-life treatment is independently associated with acquisition of resistant bacteria. Patients dying without withdraw orders receive more antibiotics, and develop more resistant organisms. These patients may represent a reservoir of resistant bacteria in the ICU.
Asthma is a major public health problem affecting millions of children worldwide, and exacerbations account for most of its morbidity and costs. Primary care providers lack efficient tools to identify children at high risk for exacerbations. We aimed to construct a clinical score to help providers in identifying such children.
Methods:
Our main outcome was severe asthma exacerbations, defined as any hospitalization, urgent visit, or systemic steroid course for asthma in the previous year. A clinical score (including asthma symptoms, use of medications and healthcare, and past history) was built and validated in a cross-sectional study of Costa Rican asthmatic children. It was then evaluated using data from the Childhood Asthma Management Program (CAMP), a longitudinal cohort of North American children.
Results:
The clinical score is a checklist-type questionnaire with 17 yes/no questions. Compared to children at average risk in the Costa Rican validation set, the odds of an exacerbation among children in the low- (OR=0.2, 95% confidence interval=0.1-0.4) and high-risk (OR=5.4, 95% CI=1.5-19.2) score categories were significantly reduced and increased, respectively. In CAMP, the hazard ratios for an exacerbation after 1 year of follow-up in the low- and high-risk groups were 0.6 (95% CI=0.5-0.7) and 1.9 (95% CI=1.4-2.4), respectively, with similar results at 2 years.
Conclusions:
The proposed Asthma Exacerbation Clinical Score is simple to use and effective at identifying children at high and low risk for asthma exacerbations, and can easily be used in primary care settings.
Smoking is a well known risk factor for cardiovascular, lung and many other diseases. Smoking can induce pulmonary arterial hypertension (PAH) in animal models and PAH is common in smokers with chronic obstructive pulmonary disease (COPD) and thereby not correlated to the degree of airway obstruction. The impact of tobacco smoke exposure on the development of PAH in human is not known.
Methods:
In a case control study we assessed smoking and secondhand smoke exposure in all patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH) seen at our PH clinic from 2002 until July 2008. Data from PAH-patients were compared with CTEPH and healthy controls from the Swiss health survey 2007 (SHS).
Results:
91 PAH-patients were compared with 64 CTEPH-patients and 18747 controls (women 58, 36, 10331 respectively). Tobacco smoking was significantly more common in PAH compared to CTEPH and controls. This difference could be attributed to men. PAH-patients also smoked longer and heavier compared to CTEPH. In addition, secondhand smoke exposure was significantly longer in PAH-non-smokers compared to controls.
Conclusion:
Our data indicate that tobacco smoke exposure may be a risk factor for men with PAH. Considering smoking as a risk factor for PAH will have implication in counseling patients and especially their hitherto unaffected relatives. Further research on the pathogenetic role of smoking in PAH is warranted.
Pneumonia is an infection of the lung and a common presentation problem in emergency departments (EDs). The objective of this study was to describe the epidemiology of pneumonia presentations to EDs in the province of Alberta, Canada.
Methods:
Provincial administrative databases were used to obtain all ED encounters for pneumonia during six fiscal years (April 1999 to March 2005). Information extracted included demographics, ED visit timing, and subsequent visits to non-ED settings. Data analysis included descriptive summaries and directly standardized visit rates.
Results:
190,896 ED visits for pneumonia were made by 140,913 distinct individuals (average of 1.4 visits per individual). Most (80.6%) had only one pneumonia-related ED visit. Males presented in slightly higher numbers than females. Standardized visit rates decreased overall from 12.5/1000 population in 1999/2000 to 9.1/1000 in 2004/2005. Admission occurred in 28.2% of the cases. In a discharged subset, 4.8% had a repeat ED visit within 7 days. Overall, 67.0% of individuals had yet to have a non-ED follow-up visit by one week; the estimated median time to the first follow-up visit was 21 days (95% CI 20 to 22).
Conclusions:
Pneumonia is a common presenting problem in Alberta EDs and further study is required to understand the factors associated with the variation in presentations. Findings include the decrease in presentations after the first fiscal year, disparities based on age, sex, and socio-economic/cultural status, and the low rate of early follow-up.
The effects of physical activity on asthma have been explored extensively. Exercise can trigger later bronchoconstriction in many patients and deconditioning due to a sedentary life style may be the consequence. However, the immediate effect of physical activity in asthma and health is a bronchodilation. To date little is known about the association between physical activity and lung function in daily life of asthma patients.
Method:
We studied 20 asthmatic individuals and 20 controls using an electronic diary of activities and spirometry (peak expiratory flow, PEF; forced expiratory volume in the first second, FEV1). Participants rated their shortness of breath and their intensity of physical and social activity for the preceding 30min. Assessments were made over the course of three weeks three times daily (morning, afternoon, evening/night).
Results:
Stronger physical activity was concurrently associated with significantly higher lung function. In contrast, it also showed a positive concurrent association with shortness of breath. In prospective cross-lag analyses, lower PEF and FEV1 earlier in the day predicted lower physical and social activity levels later in the day, but shortness of breath did not.
Conclusion:
The findings show that detrimental effects observed in exercise-induced bronchoconstriction cannot be generalized to physical activity in daily lives of individuals with asthma. Nevertheless, asthmatics still feel more shortness of breath when being more physically active. They adjust their activity levels throughout the day according to their earlier lung function, but this does not fully explain the concurrent positive association of physical activity and lung function.
A serum galactomannan (GM) assay has been approved for diagnosing invasive aspergillosis (IA). However, the role of bronchoalveolar lavage (BAL)-GM assay has not been well established, we conducted a meta-analysis to determine the overall accuracy of GM-BAL in the diagnosis of IA.
Methods:
After a systematic review of English-language studies, sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR, respectively) of BAL-GM for the diagnosis of IA were pooled using a bivariate meta-analysis. Hierarchical summary receiver operating characteristic curves were used to summarize overall test performance. Potential between-study heterogeneity was explored by subgroup analyses. We calculated post-test probability to evaluate the clinical utility.
Results:
Twelve reports including 13 studies met our inclusion criteria. The summary estimates of BAL-GM assay for proven or probable IA were as follows: SEN, 0.90 (95% confidence interval [CI], 0.79 - 0.96); SPE, 0.94 (95% CI, 0.90 - 0.96); PLR, 14.87 (95% CI, 8.89 - 24.90); NLR, 0.10 (95% CI, 0.04 - 0.24). These four summary estimates of BAL-GM assay for proven IA were 0.94 (95% CI 0.86 -0.98), 0.79 (95% CI 0.68 - 0.86), 4.41 (95% CI 2.87 - 6.77), 0.07 (95% CI 0.03 - 0.09), respectively. Significant heterogeneity was present.
Conclusions:
BAL-GM determination is a sensitive and specific test for the diagnosis of proven and probable IA. The measurement of BAL-GM is thus likely to be a useful tool for diagnosing IA. Further studies focused on the impact of treatment agents are needed.
Acutely ill hospitalized medical patients are at risk of venous thromboembolism (VTE). Despite guidelines for VTE prevention, prophylaxis use in these patients is still poor, possibly due to fear of bleeding risk. We used data from the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) to assess the in-hospital bleeding incidence, and identify risk factors at admission associated with in-hospital bleeding risk in acutely ill medical patients.
Methods:
IMPROVE is a multinational, observational study which enrolled 15,156 medical patients. The in-hospital bleeding incidence was estimated by Kaplan-Meier analysis. A multiple regression model analysis was performed to identify risk factors at admission associated with bleeding.
Results:
The cumulative incidence of major and nonmajor in-hospital bleeding within 14 days of admission was 3.2%. Active gastroduodenal ulcer (odds ratio [OR], 4.15; 95% confidence interval [CI], 2.21 to 7.77), prior bleeding (OR, 3.64; 95% CI, 2.21 to 5.99), and low platelet count (OR, 3.37; 95% CI, 1.84 to 6.18) were the strongest independent risk factors at admission for bleeding. Other bleeding risk factors were increased age, hepatic or renal failure, intensive care unit stay, central venous catheter, rheumatic disease, cancer, and male sex. Using these bleeding risk factors, a risk score was developed to estimate the bleeding risk.
Conclusions:
We assessed the incidence of major and clinically relevant bleeding in a large population of hospitalized medical patients and identified risk factors at admission associated with in-hospital bleeding. This information may assist physicians in deciding whether to use mechanical or pharmacological VTE prophylaxis.
Tregulatory cells (Tregs) may play a role in suppression of effector lymphocyte activity in asthma. We hypothesized that Treg numbers would be increased in patients with more severe asthma. We also investigated the regulatory function of CD4 cells by expression of CTLA4, and the number of these cells that are intra-epithelial lymphocytes expressing CD103.
Objectives:
The primary aim was to investigate Treg numbers in the BAL of patients with moderate to severe asthma compared to mild asthma and healthy controls. The secondary aim was to investigate BAL CD4+CTLA4 and CD4+CD103 expression in these groups.
Methods:
Airway lymphocytes obtained by bronchoscopy from healthy controls (6), patients with mild (15) and moderate to severe asthma (13) were characterised by multi-parameter flow cytometric analysis using 3 methods to determine the numbers of CD4+ Treg cells: CD4+CD25bright, CD4+CD25+CD127-, CD4+FoxP3+.
Results:
%CD4+FoxP3+ Tregs were increased in BAL of patients with moderate to severe asthma (median 4.8%) compared to both mild asthma patients (median 2.5%, p=0.03) and healthy subjects (median 0.95, p=0.003). Similar findings were observed for CD4+CD25+CD127- Treg numbers, but not CD4CD25bright. CD4+ CTLA4 and CD103 expression were raised in moderate to severe asthma patients compared to mild asthma and healthy controls.
Conclusions:
The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, are increased in moderate to severe asthma. CD4+CD103+ intra-epithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.
Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function, and hence EAdi. We aimed to evaluate how PEEP affects breathing pattern and neuro-ventilatory efficiency during NAVA.
Methods:
In 20 adult patients, adequate assist (NAVAAL) was first identified based on Paw and tidal volume (Vt) responses to systematic increases in NAVA level while using preset PEEP (PEEPbl). Thereafter, using NAVAAL, PEEP was increased to 20cmH2O (PEEPhigh) and then lowered stepwise to 1cmH2O (PEEP1). EAdi, Paw, and Vt were recorded.
Results:
Median NAVAAL was 2.7 (interquartile range 2.3-3.5)cmH2O/µV, and was similar to NAVAAL identified post hoc by 17 independent physicians (2.5 [2.0-3.4]cmH2O/µV; p=n.s.). Reducing PEEPhigh to PEEP1 increased inspiratory EAdi by 34% (2-67; p=0.046) associated with an increase in mean Paw above PEEP from 8.5 (6.7-11.4)cmH2O to 12.2 (8.8-16.7)cmH2O (p=0.008), whereas Vt and respiratory rate remained unchanged. The response pattern in Vt/EAdi, indicating changes in neuro-ventilatory efficiency, differed among patients. Tidal breathing occurred at the lowest EAdi cost in 7 patients with PEEP1 or half PEEPbl, in 6 patients with PEEPbl, and in 7 patients with PEEPhigh.
Conclusions:
During NAVAAL increasing PEEP reduces respiratory drive. Patients adapt their neuro-ventilatory efficiency such that the individual ventilatory pattern is preserved over a wide range of PEEP levels. Monitoring Vt/EAdi during PEEP changes allows identification of a PEEP level at which tidal breathing occurs at minimal EAdi cost.
Current data on bronchiectasis prevalence, trends, and risk factors are lacking; such data are needed to estimate the burden of disease and for improved medical care and public health resource allocation. The objective of the present study was to estimate the trends and burden of bronchiectasis-associated hospitalizations in the United States.
Methods:
We extracted hospital discharge records containing ICD-9-CM codes for bronchiectasis (494, 494.0, and 494.1) as any discharge diagnosis from the State Inpatient Databases from the Agency for Healthcare Research and Quality. Discharge records were extracted for 12 states with complete and continuous reporting from 1993 to 2006.
Results:
The average annual age-adjusted hospitalization rate from 1993 to 2006 was 16.5 hospitalizations per 100,000 population. From 1993 to 2006 the age-adjusted rate increased significantly with an average annual percent increase of 2.4% among men and 3.0% among women. Women and persons aged >60 years had the highest rate of bronchiectasis-associated hospitalizations. Median cost for inpatient care was 7,827 USD (range: 13-543914).
Conclusions:
The average annual age-adjusted rate of bronchiectasis-associated hospitalizations increased from 1993 to 2006. This study furthers the understanding of the impact of bronchiectasis and demonstrates the need for further research to identify risk-factors and reasons for the increasing burden.
Obesity is associated with poor outcomes in many diseases, though recent data suggest that acute lung injury (ALI) is an exception. This is particularly interesting as obesity is marked by increased levels of proinflammatory mediators associated with increased morbidity and mortality in ALI. We hypothesized that cytokine response might be attenuated in obese critically ill patients or that obesity might modify the relationship between plasma cytokines and clinical outcomes in ALI.
Methods:
We analyzed plasma biomarker levels (interleukin [IL]-6, IL-8, tumor necrosis factor- receptor 1 [TNFR1], surfactant protein D [SP-D], soluble intracellular adhesion molecule, vonWillebrand Factor, Protein C, and plasminogen activator inhibitor-1) collected at baseline and day 3 in 1409 participants in prior NHLBI Acute Respiratory Distress Syndrome Network trials. Body mass index (BMI) was calculated for each patient, and associations with cytokine levels and ventilator-free days (VFD), organ failure-free days (OFD), and mortality were investigated in regression models adjusting for confounders.
Results:
Even though the ARDSnet studies excluded patients with a body weight more than 1 kg/cm height, 74 of the 1409 patients in our cohort were severely obese with BMI>40kg/m2. In adjusted analyses, plasma IL-6 (p=0.052), IL-8 (p=0.001), and SP-D (p<0.001) were inversely related to BMI while vWF (p=0.001) and white blood cell count (p=0.042) increased proportionally with BMI. BMI was not associated with increased morbidity or mortality and did not modify the association between baseline biomarker levels and mortality, VFD, or OFD.
Conclusions:
Obese ALI patients have lower levels of several proinflammatory cytokines, suggesting that the inflammatory response may be altered in ALI patients with a high BMI. Lower SP-D but higher vWF suggests decreased epithelial and increased endothelial injury in the lung of obese patients. Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms.
While angiogenesis, the formation of new blood vessels from pre-existing vessels, may be beneficial in restoring the failing myocardium, apoptosis may contribute to progression of heart failure (HF). We investigated the role of pigment epithelium-derived factor (PEDF), a new antiangiogenic factor with additional proapoptotic effects, in patients with advanced HF.
Methods and Results:
We assayed PEDF levels in 351 patients with advanced HF at baseline. During the median follow-up time of 16 months 50% of patients experienced the composite endpoint rehospitalization and/or death. The risk of a clinical event increased with concentrations of the antiangiogenic marker PEDF with a 1.94-fold higher risk in the third tertile compared to the first tertile (95% confidence interval: 1.33-2.84). This association remained significant after adjustment for B-type natriuretic peptide (BNP) and other risk factors in a Cox regression model (P=0.015). Experimental data revealed that PEDF may contribute to progression of HF by inducing apoptosis in human cardiac myocytes and fibroblasts via activation of caspase 3.
Conclusion:
We suggest a role of PEDF in the progression of HF by inducing apoptosis of human cardiac myocytes and fibroblasts. Our clinical data suggest that PEDF concentrations may have the potential to become a valuable marker of the prognosis of HF in addition to BNP.
Existing pneumonia severity scores focus on admission blood urea to assess acute kidney injury (AKI). A consensus definition of AKI, the RIFLE criteria, is based on creatinine values and has been shown to predict mortality in general hospital and ICU populations. We aimed to assess its value on admission in patients admitted with Community Acquired Pneumonia (CAP).
Methods:
A prospective observational study of consecutive patients (January 2005 to January 2008) admitted with CAP was carried out. We classified each patient according to their maximum RIFLE class using admission creatinine (Risk≥1.5 x baseline creatinine, Injury≥2 x baseline or Failure≥3 x baseline or no-AKI<1.5 x baseline). Outcome variables of interest were predictors for 30-day mortality, requirement for mechanical ventilation/inotropic support and requirement for renal replacement therapy.
Results:
1241 patients were included (no-AKI: 1018, Risk: 130, Injury: 63 and Failure: 30). Patients were evenly matched with regards to age and sex. On multivariate analysis, factors predicting development of AKI include severity of pneumonia (using the Pneumonia Severity Index (PSI)), [Adjusted Odds Ratio (AOR) 1.74 (1.46-2.08), p<0.0001], elevated C-reactive protein [AOR 1.04 (1.03-1.06), p<0.0001] and prior use of angiotensin converting enzyme inhibitors/angiotensin-II-receptor blockers [AOR 1.77 (1.19-2.58), p=0.005].
On multivariate analysis adjusting for severity of pneumonia using PSI, RIFLE criteria independently predicted requirement for renal replacement therapy [AOR 3.20 (2.01-5.11), p<0.0001], for mechanical ventilation/inotropic support [AOR 2.22, (1.74-2.83), p<0.0001] and 30-day mortality [AOR 1.48, (1.15-1.91), p=0.002]. Prior use of angiotensin converting enzyme inhibitors/angiotensin-II-receptor blockers was not independently associated with adverse outcome either in the entire cohort or on those without AKI.
Conclusions:
The RIFLE classification is a simple tool to assess and classify AKI on admission and independently predicts need for 30-day mortality, mechanical ventilation and/or inotropic support and renal replacement therapy in patients with CAP.
Electromagnetic navigation bronchoscopy (ENB) has been developed as a novel ancillary tool for the bronchoscopic diagnosis of pulmonary nodules. Despite successful navigation in 90% of patients, ENB diagnostic yield does not generally exceed 70%.
Objective:
We sought to determine whether the presence of a bronchus sign on CT conditions diagnostic yield of ENB, and might account for the discrepancy between successful navigation and diagnostic yield.
Patients and Methods:
We conducted a prospective single center study of ENB in 51 consecutive patients with pulmonary nodules. ENB was chosen as the least invasive diagnostic technique in patients with a high surgical risk, suspected metastatic disease, advanced stage disease, or those who demanded a pre-operative diagnosis prior to undergoing curative resection. We studied patient and technical variables which might condition diagnostic yield including ; size, etiology, location, distance to the pleural surface, and FDG uptake of a given nodule, the presence of a bronchus sign on CT, registration point divergence, and the minimum distance from the tip of the locatable guide to the nodule measured during the procedure.
Results:
The diagnostic yield of ENB was 67% (34/51). The sensitivity and specificity of ENB for malignancy in this study were 71 and 100% respectively. ENB was diagnostic in 30/38 (79%) patients with a bronchus sign on CT, but only in 4/13 (31%) with no discernible bronchus sign. Univariate analysis identified the bronchus sign (p=0.005) and nodule size (p=0.04) as statistically significant variables conditioning yield, but on multivariate analysis only the bronchus sign remained significant (OR: 7.6; 95% CI: 1.8-31.7). No procedure related complications were observed.
Conclusions:
ENB diagnostic yield is highly dependent on the presence of a bronchus sign on CT.
Respiratory viruses are frequently recovered in the upper respiratory tract during COPD acute exacerbations (AECOPD), but their role as contributing pathogens remains unclear. The usefulness of procalcitonin and C-reactive protein as indicators of presence or absence of viral infection, in this setting also needs to be evaluated.
Methods:
Prospective cohort study of COPD patients admitted to the emergency ward for AECOPD. Reverse transcriptase polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition.
Results:
86 patients (mean age, 72 y, male, 64%) were included. During AECOPD, upper respiratory viral infections were detected in 44 (51%): picornavirus (n=22); metapneumovirus (n=7); coronavirus (n=8); influenza A/B (n=2); parainfluenza (n=2); and respiratory syncytial virus (n=3). A dual infection was present in three patients. After recovery, viruses were detected in only 8 of 71 (11%) patients (p<0.001 compared to AECOPD phase). In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up. During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection.
Conclusions:
Prevalence of upper respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD are frequently triggered by viral infections initiated in the upper respiratory tract. In our study, serum procalcitonin and CRP did not discriminate virus-associated exacerbations from others.
Patients who are receiving vitamin K antagonist (VKA) therapy pose challenges when they require surgery or invasive procedures as the risk for bleeding during the procedure needs to be balanced against the risk of an atherothrombotic event if the VKA is interrupted. However, it may be possible to safely perform some procedures such as coronary angiography, with or without percutaneous coronary intervention (PCI), without VKA interruption.
Methods:
We undertook a systematic review and meta-analysis to assess the safety of a periprocedural management strategy of uninterrupted VKA versus interrupted VKA with or without ‘bridging’ with low-molecular-weight heparin in patients undergoing elective coronary angiography with or without PCI.
Results:
Eight studies were included in the review. Most were of moderate to very low quality. A strategy of uninterrupted VKA appears to confer approximately half the risk (odds ratio, 0.43; 95% confidence interval [CI]: 0.26-0.73) of experiencing an access site bleeding complication within one week of the procedure as compared to a strategy of interrupted VKA. The uninterrupted VKA strategy was associated with a pooled access site bleeding complication rate of 4.0% (95% CI: 3.0-7.0), and while high heterogeneity precluded pooling of such a rate in the interrupted VKA group, these rates ranged from 2-14%.
Conclusions:
While it appears that coronary angiography with or without PCI can be safely performed without interrupting VKA, the low methodological quality of existing studies precludes any definitive conclusions. Randomized trials assessing different anticoagulation strategies are needed to establish evidence-based practice guidelines in this setting.
Lowest receptor occupancy for a drug occurs at trough, prior to the next dose. Previous studies have focussed on the effects of ‘triple therapy’ at peak dose intervals using forced expiratory manoeuvres. Impulse oscillometry (IOS) and body plethysmography (PLETH) are more sensitive than spirometry to assess inhaled therapies in COPD.
Methods:
19 COPD patients (FEV1/FVC<0.7, FEV1<60%) completed a double-blind randomised crossover trial of tiotropium(TIO) 18µg/day or placebo for 2wks each, with a 1wk washout. Prior to this there was a non-randomised 4wk run-in of budesonide/formoterol 200/6 2puffs bid which continued throughout. Spirometry, IOS and PLETH were performed pre and post budesonide/formoterol run-in, and at trough following the first and last dose of TIO; i.e. 24h post TIO and 12h post budesonide/formoterol.
Results:
Mean(SEM) age and FEV1 were 65(2)yrs and 42%(2) respectively. Following initial budesonide/formoterol there were no significant changes in spirometry, however all measures of IOS and PLETH deteriorated (p<0.01 for all outcomes). Compared to placebo, TIO was additive to budesonide/formoterol after single and chronic dosing measured by FEV1 (p<0.001, p=0.014 respectively) and FEF25-75 (p=0.001, p=0.026); while specific airway resistance (sRaw), reactance (X5), resonant frequency (RF) and area under the reactance curve (AX) showed additive benefits at single dose only.
Conclusions:
Budesonide/formoterol caused an unexpected worsening of IOS and PLETH outcomes compared to a washed-out baseline in the non-placebo controlled run-in. This was not observed with spirometry. Subsequent addition of TIO improved lung function with all techniques after single dose and for spirometry after chronic dosing. These paradoxical findings may reflect β2ADR down-regulation and M3 receptor crosstalk. Placebo controlled studies are required to explore this.
The Global Initiative for Obstructive Lung Disease (GOLD) guideline removed stage-0 (chronic cough and sputum without airflow obstruction, GOLD-0) due to poor prognostic value. Preventative intervention may be relevant for those with chronic symptoms, therefore, we assessed the stability of, morbidity and FEV1 decline associated with GOLD stage-0 in a representative adult population cohort.
Methods:
Baseline (n=4060) and follow-up (n=3206, mean 3.5 years) clinic assessment of the North West Adelaide Health Study included post-bronchodilator spirometry, anthropometry, and measures of doctor-diagnosed asthma, respiratory symptoms, smoking status, quality of life, and depression.
Results:
Baseline GOLD-0 prevalence was 17.0% (n=584). At follow-up (n=420), 39.8% remained stable, 1.4% progressed to GOLD stage 1-2 and 58.8% resolved to no symptoms. Persistent GOLD-0 at follow-up was associated with persistent smoking (males: OR=11.9, 95%CI: 6.4-22.1, females: OR=4.0, 2.1-7.4), depressive symptoms (males: OR=3.8, 1.9-7.6; females: OR=3.2, 1.7-5.9) and with highest quartile of FEV1 decline/year (OR=2.1 1.2-3.7), the metabolic syndrome (OR=1.7, 1.01-3.0) in males, and in females, with older age. These associations generally held in smokers and never-smokers. Resolving GOLD-0 was associated with smoking cessation (OR=13.7, 4.6-40.1), FEV1 decline/year below the median (OR=2.0, 1.1-3.5), normal BMI, and younger age groups. Sensitivity analyses based upon the presence of sputum did not change the observed associations.
Conclusion:
Persistent GOLD-0 identified people with physical and psychological morbidity in both smokers and non-smokers. Identification of those with persistent respiratory symptoms is therefore important. Excess FEV1 decline in men suggests GOLD-0 may identify a group at risk to progress to COPD over time.
Chronic pulmonary diseases such as asthma and COPD are associated with particularly high rates of cost-related medication nonadherence (CRN), but the degree to which inhaler costs contribute to this is not known. Here, we examine the relationship between inhaler-specific out of pocket costs and CRN in chronic pulmonary disease.
Methods:
Using data obtained in 2006 in a national stratified random sample (N=16,072) of community-dwelling Medicare beneficiaries age 65 and older, we used logistic regression to examine the relationship between inhaled medications, various types of out of pocket costs, and CRN in persons with chronic pulmonary disease.
Results:
The prevalence of CRN in Medicare recipients with chronic pulmonary disease using inhalers was 31%. In multivariate models, the odds that respondents with chronic pulmonary disease on inhalers would report CRN was 1.43 (95% CI 1.21-1.69) compared to respondents without chronic pulmonary disease who were not on inhalers. Adjustment for out of pocket inhaler costs – but not adjustment for total medication costs, or non-inhaler costs – eliminated this excess risk of CRN (OR 0.95, CI 0.71-1.28). Patients paying over $20 per month for inhalers were at significantly higher risk for CRN compared to those who had no out-of-pocket inhaler costs.
Conclusions:
Individuals with chronic pulmonary disease and high out-of-pocket inhaler costs are at increased risk for CRN relative to individuals on other medications. Physicians should be aware that inhalers can pose a particularly high-risk of medication nonadherence for some patients.
The majority of women with Lymphangioleiomyomatosis (LAM) present with cystic lung disease and most require lung biopsy for definitive diagnosis.
Objectives:
To determine the prospective diagnostic utility of a serologic test for VEGF-D, a lymphangiogenic growth factor.
Methods:
We prospectively measured serum VEGF-D levels by enzyme linked immunoassay in 48 women presenting with cystic lung disease. Diagnostic test performance was determined from a cohort of 195 females, including Tuberous Sclerosis Complex (TSC), TSC-LAM, Sporadic LAM (S-LAM), and other cystic lung diseases in the differential diagnosis, including biopsy or genetically proven pulmonary Langerhans' cell histiocytosis, emphysema, Sjögrens syndrome, or Birt-Hogg-Dubé syndrome.
Results:
Serum VEGF-D levels were significantly greater in S-LAM (median 1175(IQR:780-2013)pg/mL; n=56) than in other cystic lung diseases (median 281(IQR 203-351)pg/mL; n=44), p<0.001). In the cohort evaluated prospectively, 12 of the 15 individuals ultimately diagnosed with LAM by biopsy had VEGF-D levels of greater than 800pg/mL, while levels were less than 600pg/mL in all 18 subjects later diagnosed with other causes of cystic lung disease. Receiver operating characteristic curves demonstrated that VEGF-D effectively identified LAM, with an area under the curve of 0.961(95%CI 0.923-0.992). A VEGF-D level of greater than 600pg/mL was highly associated with a diagnosis of LAM (specificity 97.6%, likelihood ratio 35.2) and values greater than 800pg/mL were diagnostically specific. Serum VEGF-D levels were significantly elevated in women with TSC-LAM (median 3465(IQR 1970-7195)pg/mL) compared to women with TSC only (median 370(IQR 291-520)pg/mL), p<0.001).
Conclusions:
A serum VEGF-D level of greater than 800pg/ml in a woman with typical cystic changes on HRCT is diagnostically specific for S-LAM and identifies LAM in women with TSC. A negative VEGF-D result does not exclude the diagnosis of LAM. The utility of serum VEGF-D testing in males or in women who do not have cystic lung disease on HRCT is unknown.
Exhaled breath condensate (EBC) is composed of droplets of airway surface liquid (ASL) diluted by water vapor. The goal of this study was to determine if the composition of EBC is affected by changes in airway caliber, minute ventilation or forceful exhalation, factors that may differ among asthmatics in cross sectional studies.
Methods:
In a group of asthmatics, we measured the effects of 1) a series of three deep inspiration and forceful exhalation maneuvers, 2) a doubling of minute ventilation, and 3) acute bronchoconstriction induced by methacholine on EBC volume, dilution of ASL, and concentration of cysteinyl leukotrienes (CysLTs).
Results:
With the exception of an increase in EBC volume with increased minute ventilation, there were no significant changes in the volume, dilution or levels of CysLTs in EBC introduced by each of these factors. The confidence intervals surrounding the differences introduced by each factors showed that the maximum systematic errors due to these factors were modest.
Conclusions:
These results indicate that changes in airway caliber, minute ventilation or breathing pattern among subjects with asthma do not significantly alter the measurements of mediator concentrations in EBC.
Chronic obstructive pulmonary disease (COPD) is common in patients undergoing percutaneous coronary intervention (PCI), but its association with outcomes following PCI has received only limited study. The effects of severity of COPD on outcomes after PCI are not known.
Methods:
We conducted a retrospective cross-sectional analysis of prospectively acquired data in 14346 consecutive patients enrolled in the Mayo PCI registry. Those with the diagnosis of COPD were identified by ICD 9 coding and pulmonary function test [PFT] results. Outcomes of COPD versus non-COPD cohorts were compared.
Results:
The COPD group included 2001 patients (70 ± 10 yrs, 72% male), and the non-COPD group 12345 patients (66 ± 12 yrs, 70% male). In the follow up period after PCI (median = 4.1 years, interquartile range 1.9 to 7.0 years) the COPD patients experienced a significantly higher incidence of all-cause mortality (p<0.0001), cardiac mortality (p<0.0001), and myocardial infarction (p<0.0001). Additionally, severity of COPD was associated with increased mortality after PCI (p<0.0001). In a multivariate analysis COPD presence and severity remained a significant risk factor for mortality, cardiac mortality, and occurrence of myocardial infarction after PCI (p<0.0001, p<0.0001, and 0<0.0001, respectively).
Conclusion:
COPD is associated with significantly increased overall long-term mortality, cardiac mortality, and occurrence of MI in patients undergoing PCI. Increasing severity of COPD as measured by PFT is associated with decreased survival after PCI. Screening for COPD in patients undergoing PCI could contribute importantly to risk stratification, identify those subjects needing closer follow-up, and optimize targeted therapeutic interventions.
Purinergic signaling is involved in asthma pathogenesis. Not only adenosine, but adenosine triphosphate (ATP) might also play a role, but human evidence is scarce. ATP can be measured in exhaled breath condensate (EBC), a non-invasive airway sample suggested being suitable for patient monitoring. We determined EBC ATP concentration in asthma and investigated its relation to disease parameters and calculated airway ATP level.
Methods:
EBC was collected from 45 patients with persistent asthma (age 34.7 ± 13.2 yrs; FEV1 (% pred) 87.0 ± 15.5; mean ± SD) and 32 healthy controls (age 36.9 ± 12.6 yrs; FEV1 98.9 ± 9.9 % pred). Exhaled nitric oxide concentration (FENO) and lung function were measured and Asthma Control Test (ACT) score was obtained. EBC ATP was measured in luciferin-luciferase assay. Airway ATP concentration was calculated using dilution estimated from conductivity of vacuum-treated EBC samples. Parametric tests were applied in the analyses, ATP concentrations and nitric oxide levels were logarithmically transformed.
Results:
EBC ATP and calculated airway ATP concentrations were not elevated in asthma and none of them was related to FENO or ACT score. EBC ATP concentration was influenced by airway droplet dilution (r=-0.32, p<0.05) and there was a relation between calculated airway ATP level and FEV1 (r=-0.35, p<0.05).
Conclusions:
EBC ATP concentration does not seem to be useful for asthma monitoring. The relation between EBC mediator concentration and EBC conductivity highlights the importance of further standardization of EBC methodology and the need for more studies to understand airway droplet formation.
Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure with a high yield for lymph node staging of lung cancer. The aim of this study was to assess the utility of sonographic features of lymph nodes during EBUS-TBNA for the prediction of metastasis in patients with lung cancer and to establish a standard EBUS image classification system.
Methods:
Digital images of lymph nodes obtained during EBUS-TBNA in patients with lung cancer were categorized according to the following characteristics; 1) size (short axis); less or more than 1 cm, 2) shape; oval or round, 3) margin; indistinct or distinct, 4) echogenecity; homogeneous or heterogeneous, 5) presence or absence of central hilar structure and 6) presence or absence of coagulation necrosis sign. The sonographic findings were compared to the final pathological results.
Results:
A total of 1061 Lymph nodes were retrospectively evaluated in 487 patients. The accuracy of predicting metastatic property for each category was high as 63.8 % to 86.0%. A multivariate analysis revealed that round shape, distinct margin, heterogenous echogenecity and presence of coagulation necrosis sign were independent predictive factors for metastasis. 285/664 lymph nodes (42.9%) having at least one metastatic features of the four categories were pathologically proven metastatic, and 96.0% of lymph nodes (381/397) were proven not metastatic when all the four categories were determined as benign.
Conclusions:
Sonographic features of lymph nodes based on the new EBUS imaging classification may be helpful in prediction of metastatic lymph nodes during EBUS-TBNA.
Emphysematous change as assessed by computed tomography (CT) has previously been reported to correlate with chronic obstructive pulmonary disease (COPD) prognostic factors such as forced expiratory volume in one second (FEV1) and the diffusion capacity of carbon monoxide (DLCO). However, few studies have assessed the relationship between CT assessment and COPD mortality from mild to severe stage of the diseases. Here, we analyzed this relationship in patients with various stages of COPD.
Methods:
Two hundred and fifty-one outpatients with stable COPD were included in the study. CT and pulmonary function tests were performed at study entry in a single institute. The percentage of low attenuation area was measured to quantitatively evaluate emphysematous change with our custom-made software. Prognosis data were also collected and the median follow-up time was eight years.
Results:
Of the 251 patients, 79 had died. Forty of these were classified as respiratory deaths not involving lung cancer. Univariate Cox analysis revealed that emphysematous change as assessed by CT, lung function, age, or body mass index (BMI) were significantly correlated with mortality. Multivariate analysis revealed that emphysematous change as assessed by CT had the best association with mortality.
Conclusions:
Emphysematous change as assessed by CT predicts respiratory mortality in outpatients with various stages of COPD.
Pleural ultrasonography (PU) is more sensitive than chest X-ray (CXR) for diagnosing pneumothorax and could be useful for detecting resolution of pneumothorax after drainage. The aim of this prospective double-blind observational study was to assess PU accuracy during pneumothorax follow-up after drainage.
Methods:
All patients hospitalized with pneumothorax requiring drainage were eligible. After drainage, residual pneumothorax was assessed by CXR and PU: 1) 24 hours after bubbling in the aspiration device had stopped; 2) 6 hours after clamping the pleural catheter; 3) 6 hours after removing the pleural catheter. Pneumothorax indicated by PU but not CXR was confirmed by computed tomography or by aspiration of more than 10cc of air.
Results:
Forty-four unilateral pneumothoraces were studied (primary spontaneous: 70.5%), and 162 pairs of examinations (CXR and PU) were performed. Twenty residual pneumothoraces were detected by both CXR and PU. Furthermore, PU suspected 14 pneumothoraces that were not identified by CXR; 13 were confirmed. All of these pneumothoraces resulted in therapeutic intervention. Thus, 39% (13/33) of the confirmed residual pneumothoraces were missed by CXR. In patients with primary spontaneous pneumothorax, the positive predictive value of PU for residual pneumothorax diagnosis was 100%; for other pneumothoraces, this value ranged from 90% in the absence of a lung point to 100% when a lung point was observed. PU results were obtained faster than results from CXR (35 ± 34 min vs. 71 ± 56 min, p<0.0001).
Conclusions:
The accuracy of PU is excellent for detecting residual pneumothorax during pneumothorax follow-up after drainage.
Spontaneous pneumothorax (SPTX) is an uncommon phenomenon in the general population, and is most commonly associated with prior bulous emphysema, cystic parenchymal lung disease, and tuberculous lung disease. A rare cause of SPTX is malignant disease, either in the form of primary lung or pleural cancers, or in metastatic disease to the lungs. The purpose of this investigation was to compile patient characteristics, treatments received, and outcomes of patients with SPTX complicating sarcomatous cancer.
Methods:
Case reports and series published in the medical literature were identified through a MEDLINE search and compiled to determine similarities of patient characteristics, treatments received, and outcomes.
Results:
153 cases representing 20 different sarcoma cell types were included. 126 (82.3%) had received some form of treatment prior to the development of pneumothorax, and 70 (45.7%) experienced recurrence of pneumothorax at an average of 61 (±112) days. Patients had poor survival with only 7 of 81 subjects remaining alive at 2 years after initial diagnosis of SPTX.
Conclusion:
SPTX complicating sarcoma is associated with most cell types and is associated with increased mortality compared to patients without this complication.
Use of intensive care units (ICU) is rising rapidly at the end of life (EOL). The purpose of this population-based study was to determine the prevalence of ICU care in the last month of life of cancer patients and the associations between ICU care and patient demographics, disease characteristics, physician specialty, hospital characteristics, and availability of healthcare resources at the hospital and regional levels in Taiwan.
Methods:
Retrospective cohort study using administrative data among 204,850 cancer decedents in 2001-2006.
Results:
Rates of ICU care in the last month of life did not change significantly from 2001 to 2006 (11.27%-12.71%). ICU utilization in the last month of life was more likely for patients who were male, <65 years old, single, with hematological malignancies or esophageal cancer, and had more comorbidities or a non-oncologist as primary care physician. Cancer patients were one-third less likely to use ICU care in their last month if they received care in a private hospital than if they were cared for in a public hospital. Patients’ propensity to receive ICU care in the last month of life was positively associated with increasing quartile of total hospital beds in their primary hospital's region.
Conclusions:
Slightly more than one-tenth of Taiwanese cancer patients received ICU care in their last month of life. ICU utilization was strongly influenced by receiving care in hospitals and regions with abundant healthcare resources. Resources should be devoted to ensure ICU care at EOL that best meets patients’ individual needs and interests.
Endotracheal tube (ETT) intubation impairs mucus clearance and this can lead to respiratory compromise. ETTs have been developed with intrinsic capacity to aspirate secretions pooling above the cuff. We evaluated the ability of three ETTs with suction (Hi-Lo Evac, Mallinckrodt; ISIS, Teleflex; and Blue Line SACETT, Portex) to aspirate saliva and mucus simulants at continuous or intermittent vacuum pressures. We also evaluated the potential for a flexible tracheal membrane to obstruct the ETT suction port with applied vacuum. We measured the dimensions of the suction tubing at critical points to calculate differences in flow.
Results:
In a rigid tracheal model the ISIS was able to aspirate saliva simulant more quickly with continuous low pressure suction (p = 0.0006 ISIS vs. Evac and p < 0.0001 ISIS vs SACETT) and intermittent high pressure suction (p<0.0001 ISIS vs. others). For mucus simulant, the ISIS aspirates secretions better than the other tubes at high intermittent suction (p<0.0001) and the Evac was more effective than the SACETT (p = 0.0019). For low and continuous suction, suction ports in all ETTs occluded with mucus except for ISIS at the highest continuous suction tested. In a trachea model with a flexible posterior membrane, this membrane either partially or completely occluded the suction port of all tubes at high continuous or intermittent suction. The ISIS was more prone to obstruction by the flexible membrane than the Evac. We found large differences in suction tubing cross sectional area between the ISIS and the other tubes, and flow calculations using the Hagen-Poiseuille equation can explain the observed differences in volumes aspirated and the tendency toward lumen obstruction.
Conclusion:
The ISIS transmits suction pressure to the tube orifice more powerfully than the Evac or SACETT. This makes the ISIS less prone to obstruction by mucus but more likely to obstruct by tissue suction.
Use of nucleic acid amplification techniques has increased the identification of respiratory viruses (RV) in adult patients with community-acquired pneumonia (CAP) . The objectives of the present study were to identify RV in CAP patients using three different sampling methods and to compare CAP virus proportions and types with two comparison groups.
Methods:
The study population included 183 adult CAP patients, 450 control subjects and 201 patients with non-pneumonic lower respiratory tract infection (NPLRTI). Each participant was sampled by oropharyngeal swab, nasopharyngeal swab, and nasopharyngeal washing and the samples were tested for detection of 12 RV by multiplex TaqMan probe-based real time PCR (mqRT-PCR).
Results:
At least one RV was identified in 58 CAP patients (31.7%) compared to 32 (7.1%) in control subjects and 104 (51.7%) in NPLRTI patients (P<0.01 and P<0.01, respectively). Coronaviruses were identified in 24 CAP patients (13.1%), compared to 17 (3.8%) in control subjects, and 21 patients (10.4%) in NPLRTI. RSV was identified in 13 (7.1%), 4 (0.9%), and 7 (3.5%), rhinovirus in 9 (4.9%), 9 (2.0%), and 15 (7.5%), and influenza viruses in 8 (4.4%), 2 (0.4%), and 63 (31.3%), respectively.
Conclusions:
The proportion of RV involvement in CAP is higher that previously reported. The proportion of RV identified in healthy subjects is significantly lower than in CAP, but is not zero and should be weighed when interpreting corresponding proportions among patients.
Several studies have identified airflow obstruction as a risk factor for lung cancer independently of smoking history, but the risk associated with the presence of radiographic emphysema has not been extensively studied. We proposed to assess this risk using a quantitative volumetric computed tomography analysis.
Methods:
Sixty-four cases of lung cancer were identified from a prospective cohort of 1520 participants enrolled in a spiral CT lung cancer screening trial. Each case was matched to 6 controls for age, gender and smoking history. Quantitative computed tomography analysis of emphysema was performed. Spirometric measures were also conducted. Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched controls.
Results:
Both decreased FEV1 and FEV1/FVC were significantly associated with a diagnosis of lung cancer with odds-ratios of 1.15 (1.00 to 1.32, p=0.046) and 1.29 (1.02 to 1.62, p=0.031) respectively. The quantity of radiographic emphysema was not found to be a significant risk for lung cancer with an odds-ratio of 1.042 (0.816 to 1.329, p=0.743). Additionally, there was no significant association between severe emphysema and lung cancer with an odds-ratio of 1.57 (0.73 to 3.37).
Conclusions:
We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer. The absence of a clear relationship between radiographic emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies, radiographic emphysema quantitation methodology or absence of any relationship between emphysema and lung cancer risk.
We performed this study to evaluate the role of transesophageal fine needle aspiration using an ultrasound bronchoscope (EUS-B-FNA) following endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in the mediastinal staging of lung cancer.
Methods:
In this prospective study, we applied transbronchial and transesophageal ultrasonography using an ultrasound bronchoscope on patients with confirmed or strongly suspected potentially operable non-small cell lung cancer. Following EBUS-TBNA, EUS-B-FNA was used for mediastinal nodes inaccessible or difficult to access by EBUS-TBNA. The accessibility by EBUS-TBNA and EUS-B-FNA to mediastinal nodal stations having at least one node ≥5mm was also checked.
Results:
In 150 patients, we performed EBUS-TBNA and EUS-B-FNA on 299 and 64 mediastinal nodal stations, respectively. Among 143 evaluable patients, EBUS-TBNA diagnosed 38 cases of mediastinal metastasis. EUS-B-FNA diagnosed an additional 3 cases. Surgery diagnosed 4 more cases. The sensitivity, negative predictive value and diagnostic accuracy of EBUS-TBNA in the detection of mediastinal metastasis were 84.4%, 93.3% and 95.1%, respectively. These values for the combined approach of EBUS-TBNA and EUS-B-FNA increased to 91.1%, 96.1% and 97.2%, respectively, although the differences were not statistically significant (p=0.332, p=0.379 and p=0.360, respectively). Among 473 mediastinal nodal stations having at least one node ≥5 mm that were evaluated, the proportion of accessible mediastinal nodal stations by EBUS-TBNA was 78.6% and the proportion increased to 84.8% by combining EUS-B-FNA with EBUS-TBNA (p=0.015).
Conclusion:
Following EBUS-TBNA in the mediastinal staging of potentially operable lung cancer, the accessibility to mediastinal nodal stations increased by adding EUS-B-FNA and an additional diagnostic gain might be obtained by EUS-B-FNA.
Pulmonary hypertension has been associated with increased mortality in advanced pulmonary sarcoidosis patients. Sarcoidosis associated pulmonary hypertension may be the result of left ventricular dysfunction or isolated pulmonary vasculature abnormality.
Objectives:
To determine if the etiology of pulmonary hypertension affects survival in sarcoidosis patients with persistent dyspnea.
Methods:
Sarcoidosis patients with persistent dyspnea despite immunosuppressive therapy underwent right heart catheterization. Patients with a PAO of 15 mm Hg or greater were defined as having left ventricular dysfunction (LVD). Patients were classified based on hemodynamics as No PH (PA mean<25 mm Hg), PH without LVD (PAmean≥25 mm Hg and PAO<15 mm Hg) and PH with LVD (PH/LVD) (PAmean≥25 mm Hg and PAO≥15 mm Hg).
Results:
One hundred and thirty patients were studied at one institution: 50 (38.5%) patients had PH without LVD while 20 (15.4%) had PH/LVD. All patients had their diagnostic procedure at least 18 months prior to analysis. The hazard ratio for dying for PH without LVD versus No PH was 10.39 (2.99-13.78, 95% C.I., p<0.0001). The hazard ratio for dying for PH without LVD versus PH/LVD was 3.14 (1.01-5.62, 95% C.I., p<0.05). The presence of stage four chest roentgenograms and need for supplemental oxygen were different between the groups. In a Cox proportional-hazards model, independent predictors for survival were stage four chest roentgenogram (p<0.005) and hemodynamic group (p<0.02).
Conclusion:
Pulmonary hypertension without LVD was associated with increased mortality. Proper characterization of patients required hemodynamic evaluation, since 29% of sarcoidosis associated pulmonary hypertension was due to LVD.
The new Local Coverage Determination (LCD) adherence criterion for continued reimbursement of CPAP after 90 days has heretofore not been validated, including effects of the policy on care for patients with obstructive sleep apnea.
Methods:
Examined a retrospective database of 150 patients who received neuropsychological testing prior to treatment and 3 and 6 months post-treatment. We categorized participants using the new LCD criteria. Comparisons were made between adherent and non-adherent groups on neuropsychological variables.
Results:
55 participants (37%) failed to meet the new criterion although this number may not reflect the actual rates of adherence in clinical settings as some efforts beyond standard care were made to ensure adherence to treatment among many of the participants. Of the 63 patients who did not receive any special adherence intervention, only 29 (46%) met the criterion. Poor adherers demonstrated neuropsychological improvements similar to their adherent counterparts on most measures. Non-adherers realized additional improvements in working memory between 3 and 6 months post-treatment.
Conclusions:
This study highlights the potential effects of the new criteria for adherence on patients with obstructive sleep apnea and their clinical care. These data was taken from a study which was not designed to examine these criteria, so controlled trials are needed to better understand the effect of the guidelines on adherence and treatment outcomes.
Despite extensive use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and the increased bleeding risk associated with such OAC use, no handy quantification tool of assessing this risk exists. We aimed to develop a practical risk score to estimate the one-year risk for major bleeding (intracranial, hospitalization, hemoglobin drop >2g/L and/or transfusion) in a cohort of ‘real world’ AF patients.
Methods:
Based on 3978 patients in the EuroHeart Survey on AF with complete follow-up, all univariate bleeding risk factors in this cohort were used in a multivariate analyses along with ‘historic’ bleeding risk factors. A new bleeding risk score (acronym HAS-BLED: Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly (>65), Drugs/alcohol concomitantly) was calculated, incorporating risk factors from the derivation cohort.
Results:
Fifty-three (1.5%) major bleeds occurred during 1-year follow-up. The annual bleeding rate rose with increasing risk factors. The predictive accuracy in the overall population using significant risk factors in the derivation cohort (c-statistic 0.72) was consistent when applied in several subgroups. Application of the new bleeding risk score (HAS-BLED) gave similar c-statistics except where patients were receiving antiplatelet agents alone or no antithrombotic therapy, with c-statistics of 0.91 and 0.85, respectively.
Conclusions:
This simple, novel bleeding risk score (acronym HAS-BLED) provides a practical tool to assess the individual bleeding risk of ‘real world’ AF patients, potentially supporting clinical decision-making regarding antithrombotic therapy in AF patients.
There were limited studies concerning ambient air pollution exposure on development of bronchitic symptoms among children. They also provided suggestive but inconclusive results.
Objectives:
To assess the association between air pollutants and the prevalence of bronchitic symptoms in Taiwan Children Health Study.
Methods:
We conducted a nationwide cross-sectional study of 5,049 Taiwanese children in 2007. Routine air-pollution monitoring data was used for sulfur dioxide (SO2), nitrogen dioxides (NO2), ozone (O3), carbon monoxide (CO), and particles with an aerodynamic diameter of 2.5 µm or less (PM2.5). The exposure parameters were calculated using the between-community 3-year average concentration. The effect estimates were presented as odds ratios (ORs) per interquartile changes for SO2, NO2, and O3, CO, and PM2.5.
Results:
In the two-stage hierarchical model adjusting for confounding, the prevalence of bronchitic symptoms with asthma was positively associated with the between community 3-year average concentrations of NO2 (adjusted odds ratio (OR) 1.81 per 8.79 ppb; 95% confidence interval (CI) 1.14, 2.86), and CO (OR 1.31 per 105 ppb; 95% CI 1.04, 1.64). The prevalence of phlegm with no asthma was related to O3 (OR 1.32 per 8.77 ppb; 95% CI 1.06, 1.63).
Conclusions:
The results suggest that long-term exposure to outdoor air pollutants such as NO2, CO, and O3 may increase the prevalence of bronchitic symptoms among children.
Patient self-administration of medications for analgesia and procedural sedation is common. However, it is not known whether mechanically ventilated ICU patients can self-administer their own sedation to manage symptoms.
Methods:
This descriptive pilot study examined the safety, adequacy and satisfaction of patient-controlled sedation (PCS) with a convenience sample of critically ill mechanically ventilated patients (n = 17) in the ICUs at University of Minnesota Medical Center, Fairview, Minneapolis, MN. Dexmedetomidine was administered via a patient-demand and infusion pump system for a maximum of 24 hours. Pumps were programmed with a basal infusion + patient-triggered boluses; nurses adjusted the basal infusion based on a dosing algorithm. Data were collected on sedation adequacy, additional dosing of analgesics and sedatives, hemodynamic parameters, safety of PCS, patient satisfaction with PCS, and nurse satisfaction with PCS.
Results:
While a majority of the hemodynamic values were within the established safety parameters for the study, 25% of patients experienced mild adverse physiologic effects. Further, despite patients’ perception of sedation adequacy with PCS, 70% received supplemental opiates or benzodiazepine medications while on the study. Patients rated dexmedetomidine PCS favorably for self-management of anxiety, level of relaxation obtained, and comfort in self-administering sedation. Nurses also were generally satisfied with PCS as a method of sedation, dexmedetomidine as the sedative and patient response to the sedation.
Conclusions:
PCS warrants further investigation as a means to promote comfort in mechanically ventilated critically ill patients.
Improved communication between patients and clinicians may lead to better health but little is known about which type of outcomes are affected for patients with COPD.
Methods:
Using a cross-sectional study of 342 Veterans enrolled in a randomized controlled trial, we evaluated the association of communication, measured with the Quality of Communication (QOC) instrument, with subject-reported quality of clinician care, breathing problem confidence, and general self-rated health. We measured these associations utilizing general estimating equations and adjusted odds ratios (OR) of patient-reported outcomes associated with one point changes in QOC scores.
Results:
Nearly half of the subjects reported receiving the best imaginable care (47%) while fewer reported being confident with their breathing problems all the time (29%) or in very good or excellent health (15%). General communication was associated with best imagined quality care (OR 4.29, 95% CI, 2.84 – 6.48, P < 0.001) and confidence dealing with breathing problems all of the time (OR 1.74, 95% CI, 1.34 – 2.25, P < 0.001) but not general self-rated health (OR 1.19, 95% CI, 0.92 - 1.55, P = 0.19). Specific clinician behaviors with larger associations with higher quality care included listening, caring, and attentiveness. The associations between general communication and quality care increased over time (P for interaction 0.03).
Conclusions:
Communication between patients and clinicians is associated with quality of care and confidence in dealing with breathing problems and this association may change over time. Attention to specific communication strategies may lead to improvements in the care of patients with COPD.
Protocol-driven early goal-directed therapy (EGDT) has been shown to reduce mortality in patients with severe sepsis and septic shock in the Emergency Department (ED). EGDT appears to be underutilized, even in centers with formalized protocols. The aim of our study was to identify factors associated with not initiating EGDT in the ED.
Methods:
Cohort study of 340 EGDT-eligible patients presenting to a single center ED from 2005-2007. EGDT eligibility was defined as a serum lactate ≥4 mmol/L or systolic blood pressure <90 mm Hg after volume resuscitation. EGDT initiation was defined as the measurement of central venous oxygen saturation via central venous catheter. Multivariable logistic regression was employed to adjust for potential confounding.
Results:
EGDT was not initiated in 142 eligible patients (42%). EGDT was not completed in 43% of patients in whom EGDT was initiated. Compliance with the protocol varied significantly at the physician level, ranging from 0-100%. Four risk factors were found to be associated independently with decreased odds of initiating EGDT: female gender of the patient (p=0.001), female gender of the clinician (p=0.041), serum lactate, rather than hemodynamic, criterion for EGDT (p=0.018), and non-consultation to the Severe Sepsis Service (p<0.001).
Conclusions:
Despite a formalized protocol, we found that EGDT was underutilized. We identified potential barriers to the effective implementation of EGDT at the patient, clinician and organizational level. The use of a consultation service to facilitate the implementation of EGDT may be an effective strategy to improve protocol adherence.
There are no data on the association between acute inflammation during critical illness and long-term mortality in intensive care unit (ICU) patients.
Methods:
Non-surgical patients with an ICU length of stay >24 hours surviving until ICU discharge were included into this prospective, observational, follow-up study. Demographics, chronic diseases, admission diagnosis, the Simplified Acute Physiology Score II, length of ICU stay, maximum CRP levels during the ICU stay (CRPmax) and CRP levels at ICU discharge (CRPdis) were documented. After a follow-up time of 1.88±1.16 (range, 0.5-4) years, the survival status was determined.
Results:
Seven-hundred-five patients were enrolled into the study protocol. Hundred-fifty-eight patients (20.7%) died within 0.62±0.88 years after ICU discharge. Cumulative survival rates differed between patients grouped into CRPmax and CRPdis quartiles. Patients in the first and second CRPmax quartile had better cumulative survival rates than those in higher CRPmax quartiles (all p<0.001). Patients in the first CRPdis quartile had better cumulative survival rates than those in higher CRPdis quartiles (all p<0.001). Using adjusted Cox proportional hazards models, both CRPmax and CRPdis were independently associated with post-ICU mortality (both p<0.001). Furthermore, the number of chronic diseases (p<0.001), age (p<0.001) and the Simplified Acute Physiology Score II (p=0.03) were associated with post-ICU mortality in both Cox models.
Conclusions:
CRP levels during critical illness seem independently associated with post-ICU survival in non-surgical ICU patients. Future research focusing on the association between acute systemic inflammation and post-ICU outcome is warranted in order to improve long-term survival of critically ill patients.
Our study aimed to determine the prevalence of habitual snoring (HS) in primary school children, and to evaluate the diurnal symptoms and conditions that may be associated with it.
Methods:
A validated questionnaire completed by parents was used to assess the sleep and daytime behaviors of Chinese children aged 5-14 years. Thirteen primary schools in two representative districts were randomly selected.
Results:
A total of 6,349 out of 9,172 questionnaires (response rate 69.2%) with complete answers were returned. The prevalence rate of HS was 7.2%. Male gender [OR(95%CI): 2.5(1.7-3.6)]; BMI z score [OR(95%CI): 1.4(1.1-1.6)]; maternal HS [OR(95%CI): 3.4(2.0-5.7)]; paternal HS [OR(95%CI): 3.8(2.7-5.5)]; allergic rhinitis [OR(95%CI): 2.9(2.0-4.2)]; asthma [OR(95%CI): 2.4(1.2-5.2)]; nasosinusitis [OR(95%CI): 4.0(1.5-10.6)] and tonsillitis [OR(95%CI): 3.1(1.9-5.1)] in the past 12 months were identified to be independent risk factors associated with HS. HS was also associated with daytime, nocturnal, parasomnaic and sleep-related breathing symptoms. HS was demonstrated to be an independent risk factor for parent-reported poor temper [OR(95%CI): 1.9(1.4-2.5)]; hyperactivity [OR(95%CI): 1.7(1.2-2.5)] and poor school performance [OR(95%CI): 1.7(1.2-2.5)].
Conclusions:
HS was a significant and prevalent problem in primary school children. Male gender, obesity, parental HS, atopic symptoms and history of upper respiratory infections were significant risk factors. HS was also associated with sleep-disordered breathing symptoms and adverse neurobehavioral outcomes.
transthoracic contrast echocardiography (TTCE) can detect pulmonary right-to-left shunting (RLS) and is used to screen for pulmonary arteriovenous malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia (HHT). We studied the prevalence and size of pulmonary RLS in HHT type 1, HHT type 2, and HHT negative controls, and its positive (PPV) and negative (NPV) predictive value for PAVMs that can be treated by embolotherapy.
Methods:
In 343 consecutive persons, referred for possible HHT as first degree family members of index patients, a TTCE and chest CT were performed. All persons were offered genetic analysis.
Results:
An HHT causing mutation was confirmed in 92 (mean age 41±15 yr; 59% female) HHT1, and in 95 (mean age 47±14 yr; 52% female) HHT2 relatives. TTCE showed a pulmonary RLS in 78 (85%) HHT1, and in 34 (35%) HHT2 related mutation carriers, respectively (p<0.0001). In HHT1 relatives 29 of 53 (55%) PAVMs, and in HHT2 relatives 3 of 17 (18%) PAVMS were treated, resulting in a PPV of TTCE for treatable PAVMs of 36.3% and 8.3%, respectively. The accompanying NPV was 100%. A minimal, moderate and large shunt was present in 12 (13%), 24 (26%) and 42 (46%) HHT1, and in 20 (21%), 6 (6%) and 8 (8%) HHT2 related mutation carriers, respectively (p for trend < 0,0001). A large shunt predicted treatable PAVMs in 55.8% of HHT1, and 37.5% of HHT2 relatives. TTCE was positive in 4 (6%) of 63 persons without HHT.
Conclusion:
A pulmonary shunt on TTCE is more prevalent and larger inHHT1, as compared with HHT2 related mutation carriers. Shunt grading is helpful to predict treatable PAVMs, particularly in the HHT2 group. TTCE is also positive in a small fraction of persons without HHT.
Cigarette smoking is causally related to several cancers, in particular lung cancer, yet for some cancers there are inconsistent associations. This study investigates the association of smoking with other cancers by correlating them with the regional incidence rates for lung cancer, which was used as a proxy for cigarette smoking. This ecologic approach relating cigarette smoking to cancer utilizing a large database avoids the limitations and bias present in case-control and cohort studies.
Methods:
Based on the assumption that regions with a high rate of lung cancer also have a high rate of cigarette smoking, our original hypothesis is that these high intensity regions will also have high rates of other cancers if they are associated with cigarette smoking. Linear regression and correlation analysis of regional incidence rates for lung cancer, obtained from the SEER Program, were plotted with incidence rates of other cancers to determine the association between lung cancer and the other cancers.
Results:
Cancers that have shown a strong correlation with cigarette smoking in the literature also demonstrate a strong correlation with lung cancer. These cancers included urinary bladder, laryngeal, esophageal, colorectal, and kidney cancer. A number of cancers showed a weak association with cigarette smoking, such as pancreatic and liver cancer. Other cancers showed no correlation, such as ovarian and prostate cancer.
Conclusions:
Cancers that respectively showed a strong or absent correlation with lung cancer in the SEER Program were similarly strongly or weakly correlated with cigarette smoking in the literature. Cancers with borderline correlations show ambiguous results or confounding variables in the literature.
Mediastinal lymph nodes must often be biopsied to accurately stage lung cancer. Endobronchial ultrasound-guided, transbronchial needle aspiration (EBUS-TBNA) allows real-time guidance in sampling paratracheal, subcarinal, and hilar lymph nodes, and esophageal, ultrasound-guided-guided fine-needle aspiration (EUS-FNA) can sample mediastinal lymph nodes located adjacent to the esophagus.
Nodes can be sampled and staged more completely by combining these procedures, but to date, use of two different endoscopes has been required. We examined whether both procedures could be performed with a single EBUS bronchoscope.
Patients and Methods:
Consecutive patients with a presumptive diagnosis of non-small cell lung cancer (NSCLC) underwent endoscopic staging by EBUS-TBNA and EUS-FNA through a single linear ultrasound- bronchoscope. Surgical confirmation and clinical follow-up was used as the reference standard.
Results:
Among 150 evaluated patients, 139 (91%; 83 male; 56 female; mean age 57.6 y) were diagnosed with NSCLC. In these 139 patients, 619 nodes were endoscopically biopsied: 229 by EUS-FNA and 390 by EBUS-TBNA. Sensitivity was 89% for EUS-FNA and 92% for EBUS-TBNA. The combined approach had a sensitivity of 96% and negative predictive value of 95%, values higher than either approach alone. No complications occurred.
Conclusions:
The two procedures can easily be performed with a dedicated linear EBUS bronchoscope in one setting and by one operator. They are complementary and provide better diagnostic accuracy than either one alone. The combination may be able to replace more invasive methods as a primary staging method for lung cancer patients.
Theoretical considerations and limited scientific evidence suggest that whole body plethysmography overestimates lung volume in patients with severe airflow obstruction. We sought to compare plethysmographic-, helium dilution- and CT-derived lung volume measurements in a sample containing many patients with severe airflow obstruction.
Methods:
We measured total lung capacity (TLC) in 132 patients at 3 hospitals, with monitored application of recommended techniques for plethysmographic and helium dilution (He) measurements of lung volume and by thoracic CT scans obtained during breath hold at full inspiration.
Results:
Average TLC among 132 subjects was 6.18L (± 1.69L) by plethysmography, 5.55L (± 1.39L) by helium dilution, and 5.31L (±1.47) by CT. Plethysmographic TLC was significantly greater than either He- or CT-TLC (p≤0.001) while there was no significant difference between He and CT values. When examined separately, there were significant within subject differences in TLC by measurement technique among subjects with airflow obstruction, but not among those without airflow obstruction. Plethysmographic overestimation of TLC was greatest among subjects with FEV1 less than 30% of predicted.
Conclusions:
In the setting of airflow obstruction, plethysmography systematically overestimates lung volume relative to helium dilution or thoracic imaging despite adherence to current recommendations for proper measurement technique.
The majority of new cases of cystic fibrosis (CF) are diagnosed before age two. Diagnoses in older individuals have increased because of improved genetic testing and increased awareness of the disease. A comprehensive description of clinical, genetic and microbiologic characteristics of adult-age presentation of CF does not exist. We compare newly diagnosed CF in adults with newly diagnosed CF in children and adolescents in the United States.
Methods:
This is a cross-sectional study of new CF diagnoses from the Cystic Fibrosis Foundation Patient Registry between 1995 and 2005. Diagnostic, microbiologic and clinical features during year of diagnoses were analyzed for subjects by age group. Descriptive statistics were calculated for variables on characteristics by age group.
Results:
9766 new diagnoses of CF were reported to the Registry between 1995 and 2005. Proportion of adult diagnoses increased significantly in the years 2001-2005 as compared to 1995-2000 (9.0% vs. 7.7%, p=0.012). FEV1% predicted decreased with increasing age at diagnosis (p<0.001). Infection with Pseudomonas aeruginosa was most common in adults (p<0.001). Both the number of positive sweat chloride tests and prevalence of F508 mutation, the most common mutation in the U.S., decreased significantly with older age at diagnosis (p<0.001).
Conclusions:
Between 1995 and 2005, the proportion of new diagnoses of CF in adults in the U.S. increased significantly. Adults present with commonly described CF respiratory disease (Pseudomonas aeruginosa infection and reduced lung function), but have lower sweat chloride values and lower frequency of F508 mutation. Knowledge of clinical characteristics and diagnostic limitations of adult patients presenting with CF will hopefully lead to earlier recognition and intervention.
Lower respiratory tract infection (LRTI) is common in the community, and may result in hospitalization or death. This observational study aimed to investigate the role of antibiotics in the management of LRTI in UK primary care.
Methods
Patients receiving a first diagnosis of LRTI during 2004 and satisfying inclusion and data quality criteria were identified in the General Practice Research Database. Factors associated with respiratory infection-related admissions and death in the 3 months following initial diagnosis were identified using Cox proportional hazards regression.
Results
Antibiotic prescribing on the day of diagnosis was associated with a decreased rate of respiratory infection-related admission (hazard ratio: 0.73; 95% confidence interval: 0.58–0.92), while antibiotic prescribing in the previous 7 days (1.92; 1.24–2.96) and prior referral or hospitalization (1.48; 1.20–1.83) were associated with an increased risk of admission. Female sex (0.73; 0.64–0.84), allergic rhinitis (0.48; 0.27–0.83), influenza vaccination (0.75; 0.65–0.87), prior inhaled corticosteroid use (0.63; 0.52–0.76) and antibiotic prescription on the day of diagnosis (0.31; 0.26–0.37) were associated with decreased respiratory infection-related mortality, while a Charlson comorbidity index of > 2 (2.24; 1.72–2.92), antibiotic prescription in the previous 7 days (1.56; 1.20–2.03) and frequent consultation (1.62; 1.09–2.40) were associated with increased mortality.
Conclusions
Antibiotic prescribing on the day of LRTI diagnosis was associated with reductions in admissions and mortality related to respiratory infection. Antibiotics may help to prevent adverse outcomes for some patients with LRTI.
Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemo-reflexes resulting in sleep hypoventilation. We report a Chinese family with PHOX2B mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness on its various manifestations.
Methods
After identifying central hypoventilation in an adult male (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offsprings. Pulmonary function tests, overnight polysomnography, arterial blood gases, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter, and echocardiography were done on members with clinically diagnosed central hypoventilation.
Results
The index patient and four offsprings manifested with clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit of 70%. The first and fourth children had frequent cyanotic spells and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir SpO2 of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received BiPAP treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemo-sensitivity.
Conclusions
Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.
Maternal smoking during pregnancy has detrimental effects on the respiratory health of infants and children. Polymorphisms of antioxidant genes including glutathione-S-transferases (GSTs) have been proposed as candidates for asthma and reduced lung function in children.
Methods
Women enrolled in the Avon Longitudinal Study of Parents and Children reported smoking habits during pregnancy. Asthma status in their children was established at age 7.5 years from parental reports and lung function was measured by spirometry at age 8.5 years. Maternal and child DNA were genotyped for deletions of GSTM1 and GSTT1 and functional polymorphisms of GSTP1 and Nrf2 genes. Associations of prenatal tobacco smoke exposure with asthma and lung function in children were stratified by maternal genotype.
Results
In 6606 children, maternal smoking during pregnancy was negatively associated with maximal mid expiratory flow (FEF25-75) (–0.05 SD units, 95% CI –0.07 to –0.03, p<0.001). There was little evidence for interactions between maternal smoking and any maternal genotype considered on children's asthma or lung function. Maternal smoking was associated with reduced childhood FEF25-75 only in mother-child pairs (n=1227) with both copies of GSTM1 deleted (–0.08 SD units, 95% CI –0.14 to –0.02, p=0.01) or (n=2313) at least one copy of GSTT1 present (–0.05 SD units, 95% CI –0.09 to 0, p=0.03).
Conclusion
This study confirms a detrimental effect of intrauterine tobacco smoke exposure on childhood lung function but no strong evidence of modification by maternal genotype for important antioxidant genes. Adverse effects of fetal exposure to tobacco smoke on the respiratory health of children may be mediated by pathways other than oxidative stress.
Non-invasive ventilation (NIV) has been remarkably effective in the management of chronic respiratory failure, despite initially rudimentary equipment and limited understanding of what was actually happening, minute by minute when ventilation was applied. Modern ventilators, controlled by complex algorithms, and with integrated monitoring allow for sophisticated customisation of ventilatory support to an individual. However, if problems with ventilation are not recognised, and their significance understood, they cannot be fixed. Experience of monitoring during sleep from patients predominantly with sleep apnoea can be transferred and extended to patients receiving NIV. This article, the first in a series, explores the rationale for NIV and how its application to an individual patient can be monitored using simple tools and, when problems are identified, the causes can be identified using sophisticated interpretation of more detailed monitoring. This requires a detailed understanding of how different modes of ventilation work and some knowledge of the algorithms that control each machine. These themes are explored in this article and developed in subsequent articles in the series.
Several scoring systems have been used to predict mortality in patients with community-acquired pneumonia. The properties of commonly used risk stratification scales were systematically reviewed.
Methods
MEDLINE and EMBASE (January 1999–October 2009) were searched for prospective studies that reported mortality at 4–8 weeks in patients with radiographically-confirmed community-acquired pneumonia. The search focused on the Pneumonia Severity Index (PSI) and the three main iterations of the CURB (confusion, urea nitrogen, respiratory rate, blood pressure) scale (CURB-65, CURB, CRB-65), and test performance was evaluated based on ‘higher risk’ categories as follows: PSI class IV/V, CURB-65 (score ≥3), CURB (score ≥2) and CRB-65 (score ≥2). Random effects meta-analysis was used to generate summary statistics of test performance and receiver operating characteristic curves were used for predicting mortality.
Results
402 articles were screened and 23 studies involving 22 753 participants (average mortality 7.4%) were retrieved. The respective diagnostic odds ratios for mortality were 10.77 (PSI), 6.40 (CURB-65), 5.97 (CRB-65) and 5.75 (CURB). Overall, PSI had the highest sensitivity and lowest specificity for mortality, CRB-65 was the most specific (but least sensitive) test and CURB-65/CURB were between the two. Negative predictive values for mortality were similar among the tests, ranging from 0.94 (CRB-65) to 0.98 (PSI), whereas positive predictive values ranged from 0.14 (PSI) to 0.28 (CRB-65).
Conclusions
The current risk stratification scales (PSI, CURB-65, CRB-65 and CURB) have different strengths and weaknesses. All four scales had good negative predictive values for mortality in populations with a low prevalence of death but were less useful with regard to positive predictive values.
International guidelines recommend a severity-based approach to management in community-acquired pneumonia. CURB65, CRB65 and the Pneumonia Severity Index (PSI) are the most widely recommended severity scores. The aim of this study was to compare the performance characteristics of these scores for predicting mortality in community-acquired pneumonia.
Methods
A systematic review and meta-analysis was conducted according to MOOSE (meta-analysis of observational studies in epidemiology) guidelines. PUBMED and EMBASE were searched (1980–2009). 40 studies reporting prognostic information for the PSI, CURB65 and CRB65 severity scores were identified. Performance characteristics were pooled using a random effects model. Relationships between sensitivity and specificity were plotted using summary receiver operator characteristic (sROC) curves.
Results
All three scores predicted 30 day mortality. The PSI had the highest area under the sROC curve, 0.81 (SE 0.008), compared with CURB65, 0.80 (SE 0.008), p=0.1, and CRB65, 0.79 (0.01), p=0.09. These differences were not statistically significant. Performance characteristics were similar across comparable cut-offs for low, intermediate and high risk for each score. In identifying low risk patients, PSI (groups I and II) had the best negative likelihood ratio 0.08 (0.06–0.12) compared with CURB65 (score 0–1) 0.21 (0.15–0.30) and CRB65 (score 0), 0.15 (0.10–0.22).
Conclusion
There were no significant differences in overall test performance between PSI, CURB65 and CRB65 for predicting mortality from community-acquired pneumonia.
It is difficult to determine the impact of community-acquired pneumonia (CAP) in Europe, because precise data are scarce. Mortality attributable to CAP varies widely between European countries and with the site of patient management. This review analysed the clinical and economic burden, aetiology and resistance patterns of CAP in European adults. All primary articles reporting studies in Europe published from January 1990 to December 2007 addressing the clinical and economic burden of CAP in adults were included. A total of 2606 records were used to identify primary studies. CAP incidence varied by country, age and gender, and was higher in individuals aged ≥65 years and in men. Streptococcus pneumoniae was the most common agent isolated. Mortality varied from <1% to 48% and was associated with advanced age, co-morbid conditions and CAP severity. Antibiotic resistance was seen in all pathogens associated with CAP. There was an increase in antibiotic-resistant strains, but resistance was not related to mortality. CAP was associated with high rates of hospitalisation and length of hospital stay. The review showed that the clinical and economic burden of CAP in Europe is high. CAP has considerable long-term effects on quality of life, and long-term prognosis is worse in patients with pneumococcal pneumonia.
Initial pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is currently treated with intensive antibiotic therapy. At this stage, inflammation and tissue injury might have already occurred. Moreover, bacterial eradication is not always achieved. Prophylactic treatment against P aeruginosa seemed to have a preventive effect in retrospective studies. A study was undertaken to establish prospectively the effect of cycled prophylactic treatment on prevention of initial P aeruginosa infection in children with CF.
Methods
This 3-year triple-blind randomised controlled trial included 65 children with CF without P aeruginosa infection. Intervention existed of 3-monthly 3-week treatments with oral ciprofloxacin and inhaled colistin or both placebo controls. The primary outcome was P aeruginosa infection. Secondary outcomes were serum anti-Pseudomonas antibodies, pulmonary function, exacerbations, chest x-ray scores, inflammation parameters, respiratory pathogens and antimicrobial resistance.
Results
There was no difference in acquisition of P aeruginosa infection between the control and treatment groups (annual incidence 14% vs 11%; HR 0.738, 95% CI 0.299 to 1.822). Anti-Pseudomonas antibodies emerged earlier in the control group, but this difference had disappeared after 3 years. Chronic infection was observed in 19% of controls and 12% of treated patients. Decline in pulmonary function and other clinical outcomes did not differ between the two groups. In the treatment group, significantly fewer Gram-positive bacteria and Enterobacteriaceae were observed but there were more non-P aeruginosa non-fermentative Gram-negative bacteria.
Conclusions
Three-monthly cycled anti-P aeruginosa prophylaxis does not reduce the risk of initial and chronic infection in P aeruginosa-negative children with CF of all ages. Shifts in bacterial colonisation demand caution.
The passage of infiltrated tissue granulocytes across airway epithelium into airway lumen is generally considered to be a pathogenic process in asthma and chronic obstructive pulmonary disease (COPD). An alternative hypothesis is proposed here—namely that the transepithelial egression of infiltrated leucocytes acts to rid diseased airway tissues of proinflammatory cells efficiently and non-injuriously. Several clinical observations previously discussed as ‘unexpected’ and ‘puzzling’ support this hypothesis. In acutely resolving allergen challenge-induced inflammation, in patients with mild asthma, airway wall eosinophils disappear without evidence of apoptosis but with evidence of a developing airway lumen eosinophilia. In the same postchallenge resolution phase, lymphocytes, neutrophils and mast cells exhibit peak numbers in airway lumen of individuals with asthma. In severe asthma requiring intubation, clinical improvement is similarly parallelled by a marked increase over several days in airway lumen neutrophils. Increased numbers of sputum neutrophils and lymphocytes also occur as symptoms improve in COPD over several months after smoking cessation. Conversely, when the transepithelial exit of leucocytes has been inhibited in inflamed animal airways the inflammation in the airway wall has been much aggravated. Finally, transepithelial egression of numerous granulocytes and lymphocytes clearly can occur without any harm to airway epithelial barriers. The present hypothesis of ‘resolution through egression’ provides a novel interpretation of common airway lumen data, cautions against administration of agents that impede leucocyte egression in inflammatory airway diseases and infers new approaches in disease resolution research.
Guidelines on contraindications for lung function tests have been based on expert opinion from >30 years ago. High-risk contraindications to lung function testing are associated with cardiovascular complications such as myocardial infarct, pulmonary embolism or ascending aortic aneurysm. Slightly less risky but still serious contraindications are predominantly centred on recovery from major thoracic, abdominal or head surgery. Less serious surgical procedures will present a possible risk, but the RR depends upon whether the lung function is essential or can wait until the patient's condition improves. In recent decades there have been moves towards less invasive surgical techniques, keyhole surgery and new technology such as laser surgery which minimise the amount of collateral damage to surrounding tissues. In thoracic surgery there is a shift in emphasis to quicker postsurgical mobility. Furthermore there has been little analysis of the scientific facts behind the current recommendations and contraindications. The principle absolute and relative contraindications are in need of revision, and recommended times of abstaining from lung function tests needs to be reviewed. This review aims to outline the key issues and suggests newer recommendations for contraindications for performing lung function using a risk matrix, as well as offering alternative approaches to testing patients who may be at risk of complication from testing. In general, the previous recommendation of waiting for 6 weeks after surgical procedures or medical complications before performing lung function can often now be reduced to <3 weeks with modern less invasive surgical techniques.
Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited responsiveness to available treatments. It is characterised by epithelial cell injury, fibroblast activation and proliferation and extracellular matrix deposition. Serotonin (5-hydroxytryptamine; 5-HT) induces fibroblast proliferation via the 5-HTR2A and 5-HTR2B receptors, but its pathophysiological role in IPF remains unclear. A study was undertaken to determine the expression of 5-HT receptors in IPF and experimental lung fibrosis and to investigate the effects of therapeutic inhibition of 5-HTR2A/B signalling on lung fibrosis in vivo and in vitro.
Methods and results
Quantitative RT-PCR showed that the expression of 5-HTR1A/B and 5-HTR2B was significantly increased in the lungs of patients with IPF (n=12) and in those with non-specific interstitial pneumonia (NSIP, n=6) compared with transplant donors (n=12). The expression of 5-HTR2A was increased specifically in IPF lungs but not in NSIP lungs. While 5-HTR2A protein largely localised to fibroblasts, 5-HTR2B localised to the epithelium. To assess the effects of 5HTR2A/B inhibition on fibrogenesis in vivo, mice were subjected to bleomycin-induced lung fibrosis and treated with the 5-HTR2A/B antagonist terguride (or vehicle) in a therapeutic approach (days 14–28 after bleomycin). Terguride-treated mice had significantly improved lung function and histology and decreased collagen content compared with vehicle-treated mice. Functional in vitro studies showed that terguride is a potent inhibitor of transforming growth factor β1- or WNT3a-induced collagen production.
Conclusion
The studies revealed an increased expression of 5-HTR2A specifically in IPF. Blockade of 5-HTR2A/B signalling by terguride reversed lung fibrosis and is thus a promising therapeutic approach for IPF.
It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that identifies a sputum eosinophil count ≥3% in an unselected population of patients with asthma has been poorly studied.
Methods
This retrospective study was conducted in 295 patients with asthma aged 15–84 years recruited from the asthma clinic of University Hospital of Liege. Receiver-operating characteristic (ROC) curve and logistic regression analysis were used to assess the relationship between sputum eosinophil count and FeNO, taking into account covariates such as inhaled corticosteroids (ICS), smoking, atopy, age and sex.
Results
Derived from the ROC curve, FeNO ≥41 ppb gave 65% sensitivity and 79% specificity (AUC=0.777, p=0.0001) for identifying a sputum eosinophil count ≥3%. Using logistic regression analysis, a threshold of 42 ppb was found to discriminate between eosinophilic and non-eosinophilic asthma (p<0.0001). Patients receiving high doses of ICS (≥1000 µg beclometasone) had a significantly lower FeNO threshold (27 ppb) than the rest of the group (48 ppb, p<0.05). Atopy also significantly altered the threshold (49 ppb for atopic vs 30 ppb for non-atopic patients, p<0.05) and there was a trend for a lower threshold in smokers (27 ppb) compared with non-smokers (46 ppb, p=0.066). Age and sex did not affect the relationship between FeNO and sputum eosinophilia. When combining all variables into the logistic model, FeNO (p<0.0001), high-dose ICS (p<0.05) and smoking (p<0.05) were independent predictors of sputum eosinophilia, while there was a trend for atopy (p=0.086).
Conclusion
FeNO is able to identify a sputum eosinophil count ≥3% with reasonable accuracy and thresholds which vary according to dose of ICS, smoking and atopy.
Chronic obstructive pulmonary disease (COPD) is characterised by an inflammatory response by the lungs to inhaled substances such as cigarette smoking and air pollutants. In addition to the pulmonary features of COPD, several systemic effects have been recognised even after controlling for common aetiological factors such as smoking or steroid use. These include skeletal muscle dysfunction, cardiovascular disease, osteoporosis and diabetes. Individuals with COPD have significantly raised levels of several circulating inflammatory markers indicating the presence of systemic inflammation. This raises the issue of cause and effect. The role of tumour necrosis factor in COPD is thought to be central to both lung and systemic inflammation and has been implicated in skeletal muscle dysfunction, osteoporosis and type 2 diabetes. It has been hypothesised that inflammation in the lung results in ‘overspill’ into the circulation causing systemic inflammation. There is supportive evidence that protein movement can occur from the lung surface to the systemic circulation. Evidence from inhaled substances such as air pollutants and cigarette smoke has demonstrated a temporal link between the inflammatory process in the lung and systemic inflammation. Also, studies have shown alterations in circulating inflammatory cells in patients with COPD compared with controls which may reflect the effects of inflammatory mediators (derived from the lung) on circulating cells or the bone marrow. This paper considers the concept of ‘overspill’ in depth, reviews the current evidence and highlights problems in generating direct evidence to support or refute this concept.
An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma.
Methods
Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge.
Results
Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO.
Conclusions
Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.
Tuberculous pleuritis remains the commonest cause of exudative effusions in areas with a high prevalence of tuberculosis and histological and/or microbiological confirmation on pleural tissue is the gold standard for its diagnosis. Uncertainty remains regarding the choice of closed pleural biopsy needles.
Objectives
This prospective study compared ultrasound-assisted Abrams and Tru-Cut needle biopsies with regard to their diagnostic yield for pleural tuberculosis.
Methods
89 patients (54 men) of mean±SD age 38.7±16.7 years with pleural effusions and a clinical suspicion of tuberculosis were enrolled in the study. Transthoracic ultrasound was performed on all patients, who were then randomly assigned to undergo ≥4 Abrams needle biopsies followed by ≥4 Tru-Cut needle biopsies or vice versa. Medical thoracoscopy was performed on cases with non-diagnostic closed biopsies. Histological and/or microbiological proof of tuberculosis on any pleural specimen was considered the gold standard for pleural tuberculosis.
Results
Pleural tuberculosis was diagnosed in 66 patients, alternative diagnoses were established in 20 patients and 3 remained undiagnosed. Pleural biopsy specimens obtained with Abrams needles contained pleural tissue in 81 patients (91.0%) and were diagnostic for tuberculosis in 54 patients (sensitivity 81.8%), whereas Tru-Cut needle biopsy specimens only contained pleural tissue in 70 patients (78.7%, p=0.015) and were diagnostic in 43 patients (sensitivity 65.2%, p=0.022).
Conclusions
Ultrasound-assisted pleural biopsies performed with an Abrams needle are more likely to contain pleura and have a significantly higher diagnostic sensitivity for pleural tuberculosis.
Background: Current guidelines recommend the use of
a combination of inhaled beta2-agonists and
anticholinergics, particularly for patients with acute
severe or life threatening asthma in the emergency
setting. However, this statement is based on a relatively
small number of randomised controlled trials and related
systematic reviews. This review was undertaken to
incorporate the more recent evidence available about the
effectiveness of treatment with beta2-agonists and
anticholinergics compared with beta2-agonists in acute
asthma treatment.
Methods: A search was conducted of all randomised
controlled trials published prior to April 2005.
Results: Data from 32 randomised controlled trials
(n = 3611 subjects) showed significant reductions in
hospital admissions in both children (RR = 0.73; 95% CI:
0.63 to 0.85, p = 0.0001) and adults (RR = 0.68; 95% CI:
0.53 to 0.86, p = 0.002) that received inhaled
anticholinergics. Combined treatment also produced a
significant increase on spirometric tests at 60-120 min
after the last treatment in children (SMD = -0.54; 95% CI:
-0.28 to -0.81, p = 0.0001) and adults (SMD = -0.36; 95%
CI: -0.23 to -0.49, p = 0.00001).
Conclusions: This review strongly suggests that the
addition of multiple doses of inhaled ipratropium bromide
to beta2-agonists seems indicated as the standard
treatment in children, adolescent and adult patients with
moderate to severe exacerbations of asthma in the
emergency setting.
