Search

Background: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity., Methods: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis., Results: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO 2 /FiO 2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein., Conclusions: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients., (© 2024. The Author(s).)

A 44-year-old man presented to the accident and emergency department with chest pain and shortness of breath. Admission ECG revealed ischaemic changes. He had markedly elevated troponin T and a severely impaired left ventricular ejection fraction with regional motion wall abnormalities. He was initially treated in intensive care for acute myocardial infarction. When his renal function improved, an angiogram was performed, which showed unobstructed coronary arteries. He was later found to have a phaeochromocytoma. This case illustrates a rare diagnosis presenting with common symptoms that could easily have been missed. On admission to hospital, patients can easily be labelled with a diagnosis and put on a treatment pathway, such as acute coronary syndrome. It is important for clinicians to keep an open mind and be prepared to review the diagnosis if the history does not fit., (2015 BMJ Publishing Group Ltd.)

Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear., Objectives: To determine the impact of occupational exposures on COPD morbidity., Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years., Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03)., Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

The effect of environmental tobacco smoke (ETS) exposure on adults with asthma has not been well characterized. In a prospective cohort study of 451 nonsmoking adults with asthma, we evaluated the impact of ETS exposure on asthma severity, health status, and health care utilization over 18 mo. There were 129 subjects (29%; 95% CI, 25-33%) who reported regular ETS exposure, falling into three categories: exposure at baseline but none at follow-up (n = 43, 10%), no baseline exposure and new exposure at follow-up (n = 56, 12%), and exposure at both baseline and follow-up (n = 30, 7%). In cross-sectional analyses, subjects with baseline ETS exposure had greater severity-of-asthma scores (score difference, 1.7; 95% CI, 0. 2-3.1), worse asthma-specific quality of life scores (score difference, 3.5; 95% CI, 0.03-7.0), and worse scores on the Medical Outcomes Study SF-36 physical component summary (score difference, 3. 0; 95% CI, 0-6.0) than unexposed subjects. They also had greater odds of emergency department visits (odds ratio [OR] = 2.1; 95% CI, 1.2-3.5), urgent physician visits (OR = 1.9; 95% CI, 1.1-3.3), and hospitalizations (OR = 1.9; 95% CI, 1.02-3.6). In longitudinal follow-up, subjects reporting ETS cessation showed improvement in severity-of-asthma scores (score reduction, -3.2; 95% CI, -4.4 to -2. 0) and physical component summary scores (score increase, 5.3; 95% CI, 2.6-8.1). Environmental tobacco smoke cessation decreased the odds of emergency department visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations (OR = 0.2; 95% CI, 0.04-0.97) after adjustment for covariates. Environmental tobacco smoke initiation was associated with greater asthma severity only in subjects with high-level (>= 3 h/wk) exposure (score increase, 1.4; 95% CI, 0.03-2.7). In conclusion, self-reported ETS exposure is associated with greater asthma severity, worse health status, and increased health care utilization in adults with asthma.

Omalizumab, a recombinant humanized monoclonal antibody, is the first approved anti-immunoglobulin E (IgE) agent for the treatment of subjects with moderate to severe persistent allergic asthma that are inadequately controlled by the standard of care. The objective of this study was to quantitatively characterize relationships between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) as well as serum free IgE and airway inflammation (as measured by fractional exhaled nitric oxide [FeNO]) using population-based efficacy models. Data were collected from patients in the EXTRA trial who received omalizumab or placebo 150 to 375 mg subcutaneously every 2 or 4 weeks from week 0 to 48 with constant standard of care as background therapy. None of the covariates evaluated, including demographics, disease status, and baseline pharmacodynamic biomarkers, were significant in explaining the variability in the FEV1 or FeNO response to omalizumab. Results from the efficacy models further confirmed the current omalizumab dosing rationale based on the mean target free IgE level of 25 ng/ml and quantified the variability for the target. In addition, the resulting population models could be used to predict population FEV1 or FeNO response for omalizumab and/or other anti-IgE therapeutics for which PK-IgE models are constructed.

Background: Omalizumab is a recombinant humanized monoclonal anti-IgE antibody approved in adults and adolescents with moderate-to-severe persistent allergic asthma inadequately controlled with inhaled corticosteroids (ICS). EXCELS is an ongoing prospective observational cohort study of approximately 5000 omalizumab-treated and >2800 non-omalizumab-treated patients aged ≥12 years., Objective: We evaluated concomitant medication use changes (total ICS dose [including monotherapy and combination therapy, fluticasone equivalent], short-acting beta-agonists [SABA], and leukotriene modifier [LTM]) over 2 years among subsets of patients enrolled in EXCELS., Methods: Patient subsets included "new starts" (omalizumab initiated at baseline [n = 549], "established users" (omalizumab initiated >7 days before baseline [n = 4421]), and "non-omalizumab" patients (not treated with omalizumab [n = 2867])., Results: At baseline, mean ± SD total daily ICS doses were 680 ± 414 μg/d in new starts, 642 ± 431 μg/d in established users, and 548 ± 382 μg/d in non-omalizumab patients. From baseline through year 2, total ICS dose decreased in 65% of new starts (mean ± SD change, -393 ± 504 μg/d), 57% of established users (-287 ± 492 μg/d), and 54% of non-omalizumab patients (-232 ± 431 μg/d). At baseline, SABA use for new starts, established users, and non-omalizumab patients was 1.9, 1.3, and 1.4 puffs/d, respectively. At year 2, SABA use decreased in 65% of new starts, 55% of established users, and 54% of non-omalizumab patients. At year 2, LTM dose decreased in 52% of new starts, 44% of established users, and 40% of non-omalizumab patients., Conclusion: Omalizumab therapy initiation was associated with decreased doses of ICS, SABA, and LTM over 2 years of follow-up for the majority of patients in a "real-world" cohort study of moderate-to-severe allergic asthma patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.

Rationale: Cigarette smoking has been demonstrated in laboratory studies to have effects on lung epithelial and endothelial function similar to those observed in acute lung injury (ALI). However, the association between active and passive cigarette smoke exposure and susceptibility to ALI has not been prospectively studied., Objectives: We hypothesized that both active and passive cigarette smoke exposure would be associated with increased susceptibility to ALI after severe blunt trauma., Methods: We measured levels of cotinine, a metabolite of nicotine and validated biomarker of tobacco use, in plasma samples obtained immediately on arrival at the emergency department from 144 adult subjects after severe blunt trauma. Patients were then followed for the development of ALI., Measurements and Main Results: Increasing quartiles of plasma cotinine were associated with the development of ALI (odds ratio [OR] for developing ALI in highest cotinine quartile, 3.25; 95% confidence interval [CI], 1.22-8.68; P = 0.017 for trend across quartiles). Moderate to heavy passive smoke exposure was associated with nearly the same odds of developing ALI as active smoking (OR for moderate to heavy passive smoking compared with no exposure or low level exposure, 3.03; 95% CI, 1.15-8.04; OR for active smoking, 2.77; 95% CI, 1.28-5.99). This association persisted after adjusting for other predictors of ALI, including Injury Severity Score and alcohol abuse., Conclusions: Both moderate to heavy passive smoking and active smoking are independently associated with the development of ALI after severe blunt trauma. This finding has important implications both for public health and for understanding the pathogenesis of ALI.

Background: Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes., Methods: We utilized data from the placebo arm (n=126) of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models., Results: At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p=0.03), FVC (p<0.001), carbon monoxide transfer factor (p=0.03), resting oxygen saturation (p=0.02), and ISWT distance walked (p=0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p=0.04) and oxygen saturation (p<0.001). MMP-9 also predicted worsening lung density (p=0.003), increasing TLC (p=0.02), and more frequent COPD exacerbations over follow-up (p=0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes., Conclusions: Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema., (© 2011 Omachi et al; licensee BioMed Central Ltd.)

Background: Although chronic obstructive pulmonary disease (COPD) is a common cause of death and disability, little is known about the effects of socioeconomic status (SES) and race-ethnicity on health outcomes., Methods: The aim of this study is to determine the independent impacts of SES and race-ethnicity on COPD severity status, functional limitations and acute exacerbations of COPD among patients with access to healthcare. Data were used from the Function, Living, Outcomes and Work cohort study of 1202 Kaiser Permanente Northern California Medical Care Plan members with COPD., Results: Lower educational attainment and household income were consistently related to greater disease severity, poorer lung function and greater physical functional limitations in cross-sectional analysis. Black race was associated with greater COPD severity, but these differences were no longer apparent after controlling for SES variables and other covariates (comorbidities, smoking, body mass index and occupational exposures). Lower education and lower income were independently related to a greater prospective risk of acute COPD exacerbation (HR 1.5; 95% CI 1.01 to 2.1; and HR 2.1; 95% CI 1.4 to 3.4, respectively)., Conclusion: Low SES is a risk factor for a broad array of adverse COPD health outcomes. Clinicians and disease management programs should consider SES as a key patient-level marker of risk for poor outcomes.

Objectives: Cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are widely used biomarkers for tobacco-derived nicotine and the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. The discrepancy between cotinine levels in relation to disease risk comparing active versus passive smoking suggests a nonlinear tobacco smoke dose-response and/or that cotinine is not providing an accurate measure of exposure to the toxic constituents of secondhand tobacco smoke., Methods: Cotinine and NNAL were measured in the urine of 373 active smokers and 228 passive smokers., Results: Average cotinine levels were 1,155 (interquartile range, 703-2,715) for active smokers and 1.82 (0.45-7.33) ng/mg creatinine for passive smokers. Average NNAL levels were 183 (103-393) and 5.19 (2.04-11.6) pg/mg creatinine, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 × 10(3) versus 0.16 × 10(3), P < 0.0001)., Conclusions: Passive smoking is associated with a much higher ratio of NNAL/cotinine in the urine compared with active smoking., Impact: Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from secondhand smoke when compared with active smoking., (©2010 AACR.)

Background: several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group. This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD. In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy., Methods: we used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD. Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points. Disease severity was using Forced Expiratory Volume in one second (FEV(1)); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index. Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking., Results: COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043-6.64). Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases). Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014-29.2; P = 0.048). Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07-0.27; P < 0.0001)., Conclusion: COPD is a major risk factor for cognitive impairment. Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective. Health care providers should consider screening their COPD patients for cognitive impairment.

Aims: Individuals with asthma may be at increased risk of depression, but few studies have identified precursors to the onset of depression. The study goal was to identify risk factors for depression onset among a community-based sample of adults with asthma., Methods: Data were obtained from three telephone interviews conducted at 2-yearly intervals on a longitudinal cohort of adults with asthma (n=439). The Center for Epidemiologic Studies Depression scale (CESD) was used to measure depressive symptoms. Multiple regression analyses tested associations of sociodemographic and health-related variables with depression prevalence (cross-sectional analyses) and incident depression (longitudinal analyses)., Results: 15% of subjects were classified as "depressed" (CESD> or =23) at each interview. Individuals depressed at baseline were more likely to drop out (OR=1.76 [95% CI 1.05, 2.96]). Low perceived control of asthma (measured with the Perceived Control of Asthma Questionnaire [PCAQ]) exhibited the most consistent association with depression. Lower PCAQ was cross-sectionally associated with depression (OR=0.51 per 0.5 SD difference in PCAQ [0.35, 0.75]). Onset of depression was noted in 38 individuals. Decrease in perceived control at follow-up was associated with depression onset (OR=7.47 [2.15, 26.01])., Conclusions: Low perceived control of asthma predicted depression onset among adults with asthma. This risk factor may respond to self-management education.

Rationale: Although cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), a substantial proportion of COPD cases cannot be explained by smoking alone., Objectives: To evaluate the risk factors for COPD besides personal cigarette smoking., Methods: We constituted an ad hoc subcommittee of the American Thoracic Society Environmental and Occupational Health Assembly. An international group of members was invited, based on their scientific expertise in a specific risk factor for COPD. For each risk factor area, the committee reviewed the literature, summarized the evidence, and developed conclusions about the likelihood of it causing COPD. All conclusions were based on unanimous consensus., Measurements and Main Results: The population-attributable fraction for smoking as a cause of COPD ranged from 9.7 to 97.9%, but was less than 80% in most studies, indicating a substantial burden of disease attributable to nonsmoking risk factors. On the basis of our review, we concluded that specific genetic syndromes and occupational exposures were causally related to the development of COPD. Traffic and other outdoor pollution, secondhand smoke, biomass smoke, and dietary factors are associated with COPD, but sufficient criteria for causation were not met. Chronic asthma and tuberculosis are associated with irreversible loss of lung function, but there remains uncertainty about whether there are important phenotypic differences compared with COPD as it is typically encountered in clinical settings., Conclusions: In public health terms, a substantive burden of COPD is attributable to risk factors other than smoking. To prevent COPD-related disability and mortality, efforts must focus on prevention and cessation of exposure to smoking and these other, less well-recognized risk factors.

Background: Diverse environmental exposures, studied separately, have been linked to health outcomes in adult asthma, but integrated multi-factorial effects have not been modeled. We sought to evaluate the contribution of combined social and physical environmental exposures to adult asthma lung function and disease severity., Methods: Data on 176 subjects with asthma and/or rhinitis were collected via telephone interviews for sociodemographic factors and asthma severity (scored on a 0-28 point range). Dust, indoor air quality, antigen-specific IgE antibodies, and lung function (percent predicted FEV1) were assessed through home visits. Neighborhood socioeconomic status, proximity to traffic, land use, and ambient air quality data were linked to the individual-level data via residential geocoding. Multiple linear regression separately tested the explanatory power of five groups of environmental factors for the outcomes, percent predicted FEV1 and asthma severity. Final models retained all variables statistically associated (p < 0.20) with each of the two outcomes., Results: Mean FEV1 was 85.0 +/- 18.6%; mean asthma severity score was 6.9 +/- 5.6. Of 29 variables screened, 13 were retained in the final model of FEV1 (R2 = 0.30; p < 0.001) and 15 for severity (R2 = 0.16; p < 0.001), including factors from each of the five groups. Adding FEV1 as an independent variable to the severity model further increased its explanatory power (R2 = 0.25)., Conclusions: Multivariate models covering a range of individual and environmental factors explained nearly a third of FEV1 variability and, taking into account lung function, one quarter of variability in asthma severity. These data support an integrated approach to modeling adult asthma outcomes, including both the physical and the social environment.

Cigarette smoking represents the single most preventable cause of premature morbidity and mortality in the United States and the burden of tobacco use is apparent world-wide. Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease, the third leading cause of death in the United States in 2004. The American Thoracic Society (ATS) and its members have contributed significantly to an understanding of the biological and pathophysiologic mechanisms responsible for the development and management of tobacco-attributable disease and disability. The society's active involvement in tobacco control advocacy and policy-related initiatives are central to its mission. Within the ATS, there is also increased interest in accelerating the society's efforts to understand the mechanisms responsible for the uptake, persistence, and cessation of tobacco use. Scientific, clinical, and educational activities that include an examination of these underlying mechanisms are warranted. This paper describes findings from an ATS initiative that developed a preliminary strategy for enhancing scientific, clinical, educational, and policy-related tobacco control efforts that are consistent with the vision of the ATS. The specific aims of this project included the identification of existing mechanisms, as well as the current governance in place within the ATS infrastructure, to address tobacco control issues related to scientific inquiry, policy initiatives, and advocacy for tobacco control. This assessment generated recommendations to inform the ATS leadership with regard to the future development of relevant tobacco control initiatives.

Objectives: Self-reported exposure to vapours, gas, dust or fumes (VGDF) has been widely used as an occupational exposure metric in epidemiological studies of chronic lung diseases. Our objective was to characterise the performance of VGDF for repeatability, systematic misclassification, and sensitivity and specificity against exposure likelihood by a job-exposure matrix (JEM)., Methods: We analysed data from two interviews, 24 months apart, of adults with asthma and chronic rhinitis. Using distinct job as the unit of analysis, we tested a single response item (exposure to VGDF) against assignment using a JEM. We further analysed VGDF and the JEM among a subset of 199 subjects who reported the same job at both interviews, using logistic regression analysis to test factors associated with VGDF inconsistency and discordance with the JEM., Results: VGDF was reported for 193 (44%) of 436 distinct jobs held by the 348 subjects studied; moderate to high exposure likelihood by JEM was assigned to 120 jobs (28%). The sensitivity and specificity of VGDF against JEM were 71% and 66%, respectively. Among 199 subjects with the same job at both interviews, 32% had a discordant VGDF status (kappa = 0.35). Those with chronic rhinitis without concomitant asthma compared to asthma alone were more likely to have a VGDF report discordant with the JEM (OR 3.6, 95% CI 1.4 to 9.0; p = 0.01). Rhinitis was also associated with reported VGDF in a job classified by the JEM as low exposure (OR 3.9, 95% CI 1.6 to 9.4; p = 0.003)., Conclusion: The VGDF item is moderately sensitive measured against JEM as a benchmark. The measure is a useful assessment method for epidemiological studies of occupational exposure risk.

The occupational contribution to chronic obstructive pulmonary disease (COPD) has yet to be put in a global perspective. In the present study, an ecological approach to this question was used, analysing group-level data from 90 sex-specific strata from 45 sites of the Burden of Obstructive Lung Disease study, the Latin American Project for the Investigation of Obstructive Lung Disease and the European Community Respiratory Health Survey follow-up. These data were used to study the association between occupational exposures and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or above. Regression analysis of the sex-specific group-level prevalence rates of COPD at each site against the prevalence of occupational exposure and ever-smoking was performed, taking into account mean smoking pack-yrs and mean age by site, sex, study cohort and sample size. For the entire data set, the prevalence of exposures predicted COPD prevalence (0.8% increase in COPD prevalence per 10% increase in exposure prevalence). By comparison, for every 10% increase in the proportion of the ever-smoking population, the prevalence of COPD GOLD stage II or above increased by 1.3%. Given the observed median population COPD prevalence of 3.4%, the model predicted that a 20% relative reduction in the disease burden (i.e. to a COPD prevalence of 2.7%) could be achieved by a 5.4% reduction in overall smoking rates or an 8.8% reduction in the prevalence of occupational exposures. When the data set was analysed by sex-specific site data, among males, the occupational effect was a 0.8% COPD prevalence increase per 10% change in exposure prevalence; among females, a 1.0% increase in COPD per 10% change in exposure prevalence was observed. Within the limitations of an ecological analysis, these findings support a worldwide association between dusty trades and chronic obstructive pulmonary disease for both females and males, placing this within the context of the dominant role of cigarette smoking in chronic obstructive pulmonary disease causation.

Secondhand smoke (SHS) is a major contributor to indoor air pollution. Because it contains respiratory irritants, it may adversely influence the clinical course of persons with chronic obstructive pulmonary disease (COPD). We used data from nonsmoking members of the FLOW cohort of COPD (n = 809) to elucidate the impact of SHS exposure on health status and exacerbations (requiring emergency department visits or hospitalization). SHS exposure was measured by a validated survey instrument (hours of exposure during the past week). Physical health status was measured by the SF-12 Physical Component Summary Score and disease-specific health-related quality of life (HRQL) by the Airways Questionnaire 20-R. Health care utilization for COPD was determined from Kaiser Permanente Northern California computerized databases. Compared to no SHS exposure, higher level SHS exposure was associated with poorer physical health status (mean score decrement -1.78 points; 95% confidence interval [CI] -3.48 to -0.074 points) after controlling for potential confounders. Higher level SHS exposure was also related to poorer disease-specific HRQL (mean score increment 0.63; 95% CI 0.016 to 1.25) and less distance walked during the Six-Minute Walk test (mean decrement -50 feet; 95% CI -102 to 1.9). Both lower level and higher level SHS exposure was related to increased risk of emergency department (ED) visits (hazard ratio [HR] 1.40; 95% CI 0.96 to 2.05 and HR 1.41; 95% CI 0.94 to 2.13). Lower level and higher level SHS exposure were associated with a greater risk of hospital-based care for COPD, which was a composite endpoint of either ED visits or hospitalizations for COPD (HR 1.52; 95% CI 1.06 to 2.18 and HR 1.40; 95% CI 0.94 to 2.10, respectively). In conclusion, SHS was associated with poorer health status and a greater risk of COPD exacerbation. COPD patients may comprise a vulnerable population for the health effects of SHS.

Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days., Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI., Methods: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 microg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days., Measurements and Main Results: APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups., Conclusions: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity.

The authors' objective was to analyze the impact of respiratory impairment on the risk of physical functional limitations among adults with chronic obstructive pulmonary disease (COPD). They hypothesized that greater pulmonary function decrement would result in a broad array of physical functional limitations involving organ systems remote from the lung, a key step in the pathway leading to overall disability. The authors used baseline data from the Function, Living, Outcomes, and Work (FLOW) study, a prospective cohort study of adults with COPD recruited from northern California in 2005-2007. They studied the impact of pulmonary function impairment on the risk of functional limitations using validated measures: lower extremity function (Short Physical Performance Battery), submaximal exercise performance (6-Minute Walk Test), standing balance (Functional Reach Test), skeletal muscle strength (manual muscle testing with dynamometry), and self-reported functional limitation (standardized item battery). Multiple variable analysis was used to control for confounding by age, sex, race, height, educational attainment, and cigarette smoking. Greater pulmonary function impairment, as evidenced by lower forced expiratory volume in 1 second (FEV(1)), was associated with poorer Short Physical Performance Battery scores and less distance walked during the 6-Minute Walk Test. Lower forced expiratory volume in 1 second was also associated with weaker muscle strength and with a greater risk of self-reported functional limitation (p < 0.05). In conclusion, pulmonary function impairment is associated with multiple manifestations of physical functional limitation among COPD patients. Longitudinal follow-up can delineate the impact of these functional limitations on the prospective risk of disability, guiding preventive strategies that could attenuate the disablement process.

Background: A convincing body of literature links obesity with a higher risk for developing adult-onset asthma. The impact of obesity on asthma severity among adults with pre-existing asthma, however, is less clear., Methods and Procedures: In a prospective cohort study of 843 adults with severe asthma, we studied the impact of BMI on asthma health status., Results: The prevalence of obesity and overweight were 44% (95% confidence interval (CI) 41-47%) and 28% (95% CI 25-32%). The obese BMI group was associated with a higher risk for daily or near daily asthma symptoms than was the normal BMI group (odds ratio (OR) 1.81; 95% CI 1.10-2.96). Compared to the normal BMI group, generic physical health status was worse in the overweight (mean score decrement -2.42 points; 95% CI -4.39 to -0.45) and the obese groups (-6.31 points; 95% CI -8.14 to -4.49). Asthma-specific quality of life was worse in the underweight (mean score increment 8.66 points; 95% CI 2.53-14.8) and obese groups (4.51 points; 95% CI 2.21-6.81), compared to those with normal BMI. Obese persons also had a higher number of restricted activity days that past month (5.05 days; 95% CI 2.90-7.19 days)., Discussion: It appears that obesity has a substantive negative effect on health status among adults with asthma. Further work is needed to clarify the precise mechanisms. Clinicians should counsel dietary modification and weight loss for their overweight and obese patients with asthma.

Background: Inequalities in the use of new medications may contribute to health disparities. We analyzed socioeconomic gradients in the use of tiotropium for chronic obstructive pulmonary disease (COPD)., Methods: In a cohort of adults with COPD aged > or = 55 years identified through population-based sampling, we elicited questionnaire responses on demographics, socioeconomic status (SES; lower SES defined as high school education or less or annual household income < US $20,000), and medication use and other clinical variables. In a subset we obtained pulmonary function testing. We used multiple logistic regression analysis to estimate the associations between SES and tiotropium use in COPD, adjusting for disease severity measured by a COPD Severity Score., Results: Of 427 subjects, 44 (10.3%) reported using tiotropium in 2006. Adjusting for COPD severity, lower SES was associated with reduced odds of tiotropium use (OR 0.3; 95% CI 0.1-0.7; p = 0.005). Among the subset with lung function data (n = 95), after including COPD Global Obstructive Lung Disease (GOLD) Stage > or = 2 in the model, lower SES remained associated with reduced odds oftiotropium use (OR 0.03; 95% CI < 0.001-0.7; p = 0.03). Including forced expiratory volume in one second in the model as a continuous variable instead of GOLD Stage > or = 2 yielded similar results for lower SES (OR 0.1; 95% CI < 0.001-0.5; p = 0.02)., Conclusion: There was a strong SES gradient in tiotropium use such that there was less use with lower SES. To the extent that this is an efficacious medication for COPD, this gradient represents a potential source of health disparities.

Rationale: Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI)., Objectives: We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be associated with worse clinical outcomes, and (2) ventilation with lower VT would reduce urine NO as a result of less stretch injury., Methods: Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr)., Results: Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure-free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p = 0.04)., Conclusions: Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI.

Background: The relationship between stress and quality of life in adults with asthma has not been well studied. Stress, quantified by negative life events, may be linked to quality of life in asthma through multiple pathways, including increase in disease severity and adverse effects on socioeconomic status (SES)., Methods: The responses to a self-completed questionnaire assessing negative life events (NLEs) in the previous 12 months (from a 24-item checklist) among 189 adults with asthma from a well-characterised cohort were analysed. The relationship between the number of NLEs reported and asthma-specific quality of life (AQOL) was measured with the Marks instrument. General linear modelling was used to test the conjoint effects of NLEs, SES and disease severity based on the Severity of Asthma Score, a validated acute and chronic disease measure., Results: Those with annual family incomes < 60,000 dollars reported significantly more NLEs than those with higher incomes (p = 0.03). The number of NLEs did not differ significantly between those with forced expiratory volume in 1 s <80% predicted and those with >80% predicted, nor among those with lower compared with higher Severity of Asthma Score. The frequency of NLEs was associated with poorer (higher numerical score) AQOL (p = 0.002). When studied together in the same model, combinations of income level and asthma severity (greater or lesser Severity of Asthma Score; p < 0.001) and number of NLEs (p = 0.03) were both significantly associated with AQOL., Conclusion: NLEs are associated with quality of life among adults with asthma, especially among those of lower SES. Clinicians should be aware of this relationship, especially in vulnerable patient subsets.

Background: Low body mass index has been associated with increased mortality in severe COPD. The impact of body composition earlier in the disease remains unclear. We studied the impact of body composition on the risk of functional limitation in COPD., Methods: We used bioelectrical impedance to estimate body composition in a cohort of 355 younger adults with COPD who had a broad spectrum of severity., Results: Among women, a higher lean-to-fat ratio was associated with a lower risk of self-reported functional limitation after controlling for age, height, pulmonary function impairment, race, education, and smoking history (OR 0.45 per 0.50 increment in lean-to-fat ratio; 95% CI 0.28 to 0.74). Among men, a higher lean-to-fat ratio was associated with a greater distance walked in 6 minutes (mean difference 40 meters per 0.50 ratio increment; 95% CI 9 to 71 meters). In women, the lean-to-fat ratio was associated with an even greater distance walked (mean difference 162 meters per 0.50 increment; 95% CI 97 to 228 meters). In women, higher lean-to-fat ratio was also associated with better Short Physical Performance Battery Scores. In further analysis, the accumulation of greater fat mass, and not the loss of lean mass, was most strongly associated with functional limitation among both sexes., Conclusion: Body composition is an important non-pulmonary impairment that modulates the risk of functional limitation in COPD, even after taking pulmonary function into account. Body composition abnormalities may represent an important area for screening and preventive intervention in COPD.

Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P=0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P=0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury.

Background: Although personal cigarette smoking is the most important cause and modulator of chronic obstructive pulmonary disease (COPD), secondhand smoke (SHS) exposure could influence the course of the disease. Despite the importance of this question, the impact of SHS exposure on COPD health outcomes remains unknown., Methods: We used data from two waves of a population-based multiwave U.S. cohort study of adults with COPD. 77 non-smoking respondents with a diagnosis of COPD completed direct SHS monitoring based on urine cotinine and a personal badge that measures nicotine. We evaluated the longitudinal impact of SHS exposure on validated measures of COPD severity, physical health status, quality of life (QOL), and dyspnea measured at one year follow-up., Results: The highest level of SHS exposure, as measured by urine cotinine, was cross-sectionally associated with poorer COPD severity (mean score increment 4.7 pts; 95% CI 0.6 to 8.9) and dyspnea (1.0 pts; 95% CI 0.4 to 1.7) after controlling for covariates. In longitudinal analysis, the highest level of baseline cotinine was associated with worse COPD severity (4.7 points; 95% CI -0.1 to 9.4; p = 0.054), disease-specific QOL (2.9 pts; -0.16 to 5.9; p = 0.063), and dyspnea (0.9 pts; 95% CI 0.2 to 1.6 pts; p < 0.05), although the confidence intervals did not always exclude the no effect level., Conclusion: Directly measured SHS exposure appears to adversely influence health outcomes in COPD, independent of personal smoking. Because SHS is a modifiable risk factor, clinicians should assess SHS exposure in their patients and counsel its avoidance. In public health terms, the effects of SHS exposure on this vulnerable subpopulation provide a further rationale for laws prohibiting public smoking.

Objectives: We investigated associations between perceived neighborhood problems and quality of life (QOL), physical functioning, and depressive symptoms among adults with asthma., Methods: Using cross-sectional data from adults with asthma in northern California (n=435), we examined associations between 5 types of perceived neighborhood problems (traffic, noise, trash, smells, and fires) and asthma-specific QOL (Marks instrument), physical functioning (Short Form-12 physical component summary), and depressive symptoms (Center for Epidemiological Studies-Depression). We used multivariate regression analysis., Results: When asthma severity and sociodemographics were taken into account, people reporting a score of 8 or higher on a scale of 0 to 25 for serious problems (the top quartile of seriousness) in their neighborhoods had significantly poorer QOL scores (mean difference=5.91; standard error [SE]=1.63), poorer physical functioning (mean difference=-3.04; SE=1.27), and almost a fivefold increase in depressive symptoms (odds ratio=4.79; 95% confidence interval=2.41, 9.52)., Conclusions: A high level of perceived neighborhood problems was associated with poorer QOL, poorer physical functioning, and increased depressive symptoms among people with asthma when disease severity and sociodemographic factors were taken into account.

Socio-economic status (SES) may affect health status in airway disease at the individual and area level. In a cohort of adults with asthma, rhinitis or both conditions, questionnaire-derived individual-level SES and principal components analysis (PCA) of census data for area-level SES factors were used. Regression analysis was utilised to study the associations among individual- and area-level SES for the following four health status measures: severity of asthma scores and the Short Form-12 Physical Component Scale (SF-12 PCS) (n = 404); asthma-specific quality of life (QoL) scores (n = 340); and forced expiratory volume in one second (FEV1) per cent predicted (n = 218). PCA yielded a two-factor solution for area-level SES. Factor 1 (lower area-level SES) was significantly associated with poorer SF-12 PCS and worse asthma QoL. These associations remained significant after adding individual-level SES. Factor 1 was also significantly associated with severity of asthma scores, but not after addition of the individual-level SES. Factor 2 (suburban area-level SES) was associated with lower FEV1 per cent predicted in combined area-level and individual SES models. In conclusion, area-level socio-economic status is linked to some, but not all, of the studied health status measures after taking into account individual-level socio-economic status.

Background: We examined the link between functioning and psychological status among persons with chronic obstructive pulmonary disease (COPD), using measures of both general functional status and performance of life activities., Methods: 334 persons with COPD were interviewed by telephone. Functioning was assessed with two measures of difficulty with specific types of activities (self-care, recreational activities/hobbies) and a general measure of functional status (SF-12 Physical Component Score (PCS))., Results: About 16.2% of the sample had SF-12 Mental Component Score (MCS) scores indicative of psychological distress (MCS < 35). In separate regression models, difficulty with self-care and recreational activities was associated with an increased likelihood of distress (self-care: OR=2.9, 95%CI 1.3, 6.6; recreation: OR=7.5 [2.4, 23.7]), while PCS scores were not. In a model including all three predictors, difficulty with recreation was strongly associated with distress (OR=7.7 [2.1, 29.2]), difficulty with self-care was less strongly associated with distress (OR=2.1 [0.8, 5.5]), and PCS did not contribute significantly to the predictive ability of the model. However, low functioning as measured by the PCS was a significant risk factor for difficulty performing activities., Conclusions: Measures of activity difficulty were independent predictors of psychological distress, while general physical function was not. Poor general physical function was a risk factor for activity difficulties, suggesting an indirect relationship between low PCS and psychological distress, with activity difficulties as the intermediate variable.

Objective: To evaluate the longitudinal impact of asthma specialist care on the risk of emergency department (ED) visits and hospitalization for asthma., Data Sources/study Setting: A prospective cohort study using both telephone survey and computerized utilization data., Study Design: We recruited a prospective cohort of 4,742 adult members of a closed panel managed care organization who were hospitalized for asthma (the "baseline hospitalization")., Data Collection/extraction Methods: Visits to asthma specialists were ascertained from computerized utilization databases. Specialist visits after baseline hospitalization were defined as time-dependent covariates. An alternative analysis defined specialist visits during the year preceding baseline hospitalization. A subcohort of 596 subjects completed telephone interviews., Principal Findings: Compared with subjects who received no specialist visits after baseline hospitalization, treatment by allergists (hazard ratio (HR) 1.04; 95 percent confidence interval (CI) 0.87-1.26) or pulmonologists (HR 0.92; 95 percent CI 0.71-1.19) was not associated with a reduction in the risk of future ED visits for asthma in the entire cohort, controlling for age, sex, race, recent asthma medication dispensing, and pharmacy benefits status. There was also no association between allergist visits and the risk of subsequent hospitalizations for asthma (HR 0.93; 95 percent CI 0.75-1.14). In contrast, visits to pulmonologists (HR 0.74; 95 percent CI 0.55-0.99) were related to a reduced risk of rehospitalization., Conclusions: Pulmonary specialist visits appeared to reduce the risk of hospitalization for asthma, whereas asthma specialist visits did not reduce the risk of ED visits. In the context of comprehensive prepaid health care, the benefit of specialist care was modest.

Background: Because they have chronic airway inflammation, adults with asthma could have symptomatic exacerbation after exposure to second hand smoke (SHS). Surprisingly, data on the effects of SHS exposure in adults with asthma are quite limited. Most previous epidemiological studies used self-reported SHS exposure which could be biased by inaccurate reporting. In a prospective cohort study of adult non-smokers recently admitted to hospital for asthma, the impact of SHS exposure on asthma health outcomes was examined., Methods: Recent SHS exposure during the previous 7 days was directly measured using a personal nicotine badge (n = 189) and exposure during the previous 3 months was estimated using hair nicotine and cotinine levels (n = 138). Asthma severity and health status were ascertained during telephone interviews, and subsequent admission to hospital for asthma was determined from computerised utilisation databases., Results: Most of the adults with asthma were exposed to SHS, with estimates ranging from 60% to 83% depending on the time frame and methodology. The highest level of recent SHS exposure, as measured by the personal nicotine badge, was related to greater asthma severity (mean score increment for highest tertile of nicotine level 1.56 points; 95% CI 0.18 to 2.95), controlling for sociodemographic covariates and previous smoking history. Moreover, the second and third tertiles of hair nicotine exposure during the previous month were associated with a greater baseline prospective risk of hospital admission for asthma (HR 3.73; 95% CI 1.04 to 13.30 and HR 3.61; 95% CI 1.0 to 12.9, respectively)., Conclusions: Directly measured SHS exposure appears to be associated with poorer asthma outcomes. In public health terms, these results support efforts to prohibit smoking in public places.

Background: Exposure to environmental tobacco smoke (ETS), which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction. Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies., Methods: Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD. Participants were recruited from all 48 contiguous U.S. states by random digit dialing. Lifetime ETS exposure was ascertained by structured telephone interview. We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD., Results: Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD. The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21). The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84). The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure., Conclusion: ETS exposure may be an important cause of COPD. Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure.

Ventilator-induced lung injury (VILI) is an inflammatory process that can be attenuated by lung protective ventilation strategies. Our objectives to further investigate the pathogenesis of ALI and VILI and the mechanism of lung protection in these syndromes were: 1) to determine if plasma measurements of soluble TNF receptor I (sTNFRI) and II (sTNFRII) would predict the development of ALI and mortality in a small single center trial; 2) to test the predictive value of these markers and of TNF-alpha in a larger, broader group of patients with ALI; 3) to test the hypothesis that low tidal volume ventilation (LTVV) would be associated with a decrease in plasma levels of TNF-alpha, sTNFRI, and sTNFRII. In the single center study, sTNFRI and II levels were higher in patients at risk for and with ALI, but they did not predict the development of the syndrome. In the multicenter trial sTNFRI and II were strongly associated with mortality (OR 5.76/1 log10 increment in receptor level; 95% CI 2.63-12.6 and OR 2.58; 95% CI 1.05-6.31, respectively) and morbidity measured as fewer nonpulmonary organ failure-free and ventilator-free days. The LTVV strategy was associated with an attenuation of plasma sTNFRI levels. In vitro, stimulated A549 cells release sTNFRI but not sTNRFII. In conclusion, plasma levels of sTNFRI and II can serve as biomarkers for morbidity and mortality in patients with ALI. Furthermore, LTVV is associated with a specific decrease in sTNFRI levels. This suggests that one beneficial effect of LTVV may be to attenuate alveolar epithelial injury.

Systemic endothelial activation and injury are important causes of multiorgan system failure. We hypothesized that plasma levels of von Willebrand factor (VWF), a marker of endothelial activation and injury, would be associated with clinical outcomes in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In 559 patients with ALI/ARDS enrolled in the National Heart, Lung, and Blood Institute ARDS Network trial of two VT strategies, plasma VWF levels were measured at randomization (mean 350 +/- 265% of normal control plasma) and Day 3 (344 +/- 207%). Baseline VWF levels were similar in patients with and without sepsis, and were significantly higher in nonsurvivors (435 +/- 333%) versus survivors (306 +/- 209%) even when controlling for severity of illness, sepsis, and ventilator strategy (increased odds ratio of death of 1.6 per SD size increase in VWF; 95% confidence interval, 1.4-2.1). Higher VWF levels were also significantly associated with fewer organ failure-free days. Ventilator strategy had no effect on VWF levels. In conclusion, the degree of endothelial activation and injury is strongly associated with outcomes in ALI/ARDS, regardless of the presence or absence of sepsis, and is not modulated by a protective ventilatory strategy. To improve outcomes further, new treatment strategies targeted at the endothelium should be investigated.

Background: Inflammation plays a role in the pathogenesis of athero-thrombosis. Because of the chronic, inflammatory nature of asthma, we hypothesized a possible link asthma and prospective risk of coronary heart disease (CHD)., Methods: We performed a cohort study among 70 047 men and 81 573 women, 18-85 years old, enrolled in a large managed care organization in Northern California. Asthma was ascertained by self-report at baseline in 1964-1973 and/or interim hospitalization for asthma during follow-up. The primary endpoint was combined non-fatal or fatal CHD., Results: After a median follow-up time of 27 years, and adjusting for age, race/ethnicity, education level, smoking status, alcohol consumption, body mass index, serum total cholesterol, white blood cell count, hypertension, diabetes, and history of occupational exposures, asthma was associated with a 1.22-fold (95% CI: 1.14, 1.31) increased hazard of CHD among women. This association was seen both in never and in ever smoking women, and in younger and older women. By contrast, asthma was not associated with CHD among men (multivariate-adjusted hazard ratio = 0.99; 95% CI: 0.93, 1.05)., Conclusions: Asthma was independently associated with a modest but statistically significant increased hazard of CHD among women. Further studies are warranted to confirm or refute these preliminary epidemiological findings.

Background and Aims: Despite recognition that occupational exposures may make a substantive contribution to the aetiology of COPD, little is known about the potential role of work related factors in COPD related health outcomes., Methods: Prospective cohort study using structured telephone interviews among a random sample of adults aged 55-75 reporting a COPD condition (emphysema, chronic bronchitis, or COPD). Using multivariate models adjusting for smoking and demographic factors, the separate and combined associations were estimated between occupational exposure to vapours, gas, dust, or fumes (VGDF) and leaving work due to lung disease (respiratory related work disability) with health outcomes and utilisation ascertained at one year follow up., Results: Of 234 subjects, 128 (55%) reported exposure to VGDF on their longest held jobs, 58 (25%) reported respiratory related work disability, and 38 (16%) subjects reported both. Combined exposure to VGDF and respiratory related work disability (rather than either factor alone) was associated with the greatest risk at follow up of frequent (everyday) restricted activity days attributed to a breathing or lung condition (OR 3.8; 95% CI 1.4 to 10.1), emergency department (ED) visit (OR 3.9; 95% CI 1.4 to 10.5), and hospitalisation (OR 7.6; 95% CI 1.8 to 32)., Conclusions: Among persons with COPD, past occupational exposures and work disability attributed to lung disease, particularly in combination, appear to be risk factors for adverse health related outcomes.

Background: Because injury to the alveolar epithelial barrier is a characteristic feature of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), plasma surfactant protein levels may have prognostic value. To test this hypothesis plasma surfactant proteins A and D (SP-A and SP-D) levels were measured in patients with ALI or ARDS enrolled in the NHLBI sponsored multicentre ARDS Network randomised controlled trial of a 6 ml/kg v 12 ml/kg tidal volume strategy., Methods: Data from 565 participants in the clinical trial were used. Plasma levels of SP-A and SP-D were measured at baseline and on day 3 after the start of the mechanical ventilation protocol. The longitudinal impact of baseline plasma surfactant protein levels on clinical outcomes was examined by multivariate analysis, controlling for mechanical ventilation group, APACHE III score, and other clinical covariates. The effect of 6 ml/kg tidal volume ventilation on plasma SP-A and SP-D levels was evaluated using analysis of covariance., Results: Baseline plasma SP-A levels were not related to any clinical outcome. In contrast, higher baseline plasma SP-D levels were associated with a greater risk of death (OR 1.21 per 100 ng/ml increment; 95% CI 1.08 to 1.35), fewer ventilator-free days (mean decrease -0.88 days; p=0.001), and fewer organ failure-free days (mean decrease -1.06 days; p<0.0001). The 6 ml/kg tidal volume strategy had no effect on the rise in plasma SP-A levels (p=0.91) but attenuated the rise in plasma SP-D levels (p=0.0006)., Conclusions: Early in the course of ALI/ARDS an increased level of plasma SP-D is associated with a worse clinical outcome. The 6 ml/kg tidal volume strategy attenuated the rise of SP-D early in the clinical course. Taken together, these observations indicate that plasma SP-D, a product of alveolar type II cells, is a valuable biomarker in ALI/ARDS.

Background: Gas stoves release respiratory irritants, such as nitrogen dioxide and other combustion by-products. Adults with asthma may be susceptible to the effects of gas stove exposure because of their underlying airway hyperresponsiveness, but this association has been difficult to establish., Aims: To examine the association between gas stove use and respiratory health., Methods: The analysis used data from the US Third National Health and Nutrition Examination Survey among 445 adults with asthma (representing 4.8 million persons with the condition)., Results: Nearly half of the adults with asthma had a gas stove in their home (47.1%). There was no association between gas stove use and FEV1 (mean change 146 ml; 95% CI -50 to 342 ml), FVC (0 ml; 95% CI -151 to 152 ml), or FEF25%-75% (357 ml; 95% CI -7 to 722 ml). There was also no relation between gas stove use and the risk of self reported cough (OR 0.8; 95% CI 0.4 to 1.7), wheeze (OR 1.5; 95% CI 0.7 to 3.2), or other respiratory symptoms. Controlling for sociodemographic, smoking, housing, and geographic factors did not appreciably affect these results., Conclusions: Among adults with asthma, there was no apparent impact of gas stove use on pulmonary function or respiratory symptoms. These results should be reassuring to adults with asthma and their health care providers.

Although chronic obstructive pulmonary disease (COPD) is attributed predominantly to tobacco smoke, occupational exposures are also suspected risk factors for COPD. Estimating the proportion of COPD attributable to occupation is thus an important public health need. A randomly selected sample of 2,061 US residents aged 55-75 yrs completed telephone interviews covering respiratory health, general health status and occupational history. Occupational exposure during the longest-held job was determined by self-reported exposure to vapours, gas, dust or fumes and through a job exposure matrix. COPD was defined by self-reported physician's diagnosis. After adjusting for smoking status and demography, the odds ratio for COPD related to self-reported occupational exposure was 2.0 (95% confidence interval (CI) 1.6-2.5), resulting in an adjusted population attributable risk (PAR) of 20% (95% CI 13-27%). The adjusted odds ratio based on the job exposure matrix was 1.6 (95% CI 1.1-2.5) for high and 1.4 (95% CI 1.1-1.9) for intermediate probability of occupational dust exposure; the associated PAR was 9% (95% CI 3-15%). A narrower definition of COPD, excluding chronic bronchitis, was associated with a PAR based on reported occupational exposure of 31% (95% CI 19-41%). Past occupational exposures significantly increased the likelihood of chronic obstructive pulmonary disease, independent of the effects of smoking. Given that one in five cases of chronic obstructive pulmonary disease may be attributable to occupational exposures, clinicians and health policy-makers should address this potential avenue of chronic obstructive pulmonary disease causation and its prevention.

Background: Because they have chronic airway inflammation, adults with asthma may be particularly susceptible to indoor air pollution. Despite widespread exposure to environmental tobacco smoke (ETS), gas stoves, and woodsmoke, the impact of these exposures on adult asthma has not been well characterised., Methods: Data were used from a prospective cohort study of 349 adults with asthma who underwent structured telephone interviews at baseline and 18 month follow up. The prospective impact of ETS, gas stove, and woodsmoke exposure on health outcomes was examined., Results: ETS exposure at baseline interview was associated with impaired health status at longitudinal follow up. Compared with respondents with no baseline self-reported exposure to ETS, higher level exposure (>/=7 hours/week) was associated with worse severity of asthma scores at follow up, controlling for baseline asthma severity, age, sex, race, income, and educational attainment (mean score increment 1.5 points; 95% CI 0.4 to 2.6). Higher level baseline exposure to ETS was also related to poorer physical health status (mean decrement -4.9 points; 95% CI -8.4 to -1.3) and asthma specific quality of life (mean increase 4.4 points; 95% CI -0.2 to 9.0) at longitudinal follow up. Higher level baseline ETS exposure was associated with a greater risk of emergency department visits (OR 3.4; 95% CI 1.1 to 10.3) and hospital admissions for asthma at prospective follow up (OR 12.2; 95% CI 1.5 to 102). There was no clear relationship between gas stove use or woodstove exposure and asthma health outcomes., Conclusion: Although gas stove and woodstove exposure do not appear negatively to affect adults with asthma, ETS is associated with a clear impairment in health status.

Objectives: This study examined the impact of asthma and chronic obstructive pulmonary disease (COPD) on health status and work disability., Methods: We used data from a population-based sample of 3805 California adults., Results: Compared with adults with no chronic health conditions, adults with COPD or asthma had a greater risk of self-reported diminished general health (odds ratio [OR] = 10.95; 95% confidence interval [CI] = 6.31, 19.0 and OR = 3.92; 95% CI = 2.31, 6.65, respectively). Respondents with COPD or asthma also had worse mental health status, as indicated by a greater risk of depressive symptoms (OR = 10.05; 95% CI = 5.29, 19.08 and OR = 2.59; 95% CI = 1.33, 5.04). COPD was associated with reduced current employment (OR = 0.41; 95% CI = 0.24, 0.71)., Conclusions: Asthma and COPD are associated with poor health status and greater work disability.