Pulmonary Function after Exposure to the World Trade Center Collapse in the New York City Fire Department; G.I. Banauch, C. Hall, M. Weiden, H.W. Cohen, T.K. Aldrich, V. Christodoulou, N. Arcentales, K.J. Kelly, D.J. Prezant (Am J Respir Crit Care Med 2006 Aug 1; 174(3):312–319). Epub 2006 Apr 27.
Rationale: On September 11, 2001, the World Trade Center collapse created an enormous urban disaster site with high levels of airborne pollutants. First responders, rescue and recovery workers, and residents have since reported respiratory symptoms and developed pulmonary function abnormalities. Objectives: To quantify respiratory health effects of World Trade Center exposure in the New York City Fire Department. Measurements: Longitudinal study of pulmonary function in 12,079 New York City Fire Department rescue workers employed on or before 09/11/2001. Between 01/01/1997 and 09/11/2002, 31,994 spirometries were obtained and the FEV1 and FVC were analyzed for differences according to estimated World Trade Center exposure intensity. Adjusted average FEV1 during the first year after 09/11/2001 was compared with the 5 years before 09/11/2001. Median time between 09/11/2001 and a worker's first spirometry afterwards was 3 mo; 90% were assessed within 5 mo. Main Results: World Trade Center-exposed workers experienced a substantial reduction in adjusted average FEV1 during the year after 09/11/2001 (372 ml; 95% confidence interval, 364–381 ml; p < 0.001). This exposure-related FEV1 decrement equaled 12 year of aging-related FEV(1) decline. Moreover, exposure intensity assessed by initial arrival time at the World Trade Center site correlated linearly with FEV1 reduction in an exposure intensity-response gradient (p = 0.048). Respiratory symptoms also predicted a further FEV1 decrease (p < 0.001). Similar findings were observed for adjusted average FVC. Conclusions: World Trade Center exposure produced a substantial reduction in pulmonary function in New York City Fire Department rescue workers during the first year after 09/11/2001.
Comments: The long-term health consequences for rescue workers who were involved the day and several days thereafter in recovery operations following the World Trade Center Tragedy remain to be determined however this report shows significant decrements in spirometry within the first year (most within the first 3 months) following exposure. This report and others that document the decrease in lung function, airway hyper-responsiveness and cough indicate that such massive irritant exposures may cause chronic and persistent airflow limitation. The constituents of the exposure following the collapse of the twin towers is complex and a mixture of dust and smoke and it may not be possible to fully delineate the relative contributions from the various components, nonetheless, following this cohort over the next several years will provide invaluable information with regard to the effects (both pulmonary and non-pulmonary) of massive irritant exposure (both single and multiple). Specifically it will be interesting to see if the airflow limitation persists or if there is significant recovery and whether complications such as chronic obstructive lung disease versus bronchiolitis obliterans or interstitial manifestations such as seen in classic pneumoconiotic lung diseases develop.
Feasibility of Retinoids for the Treatment of Emphysema Study; M.D. Roth, J.E. Connett, J.M. D'Armiento, R.F. Foronjy, P.J. Friedman, J.G. Goldin, T.A. Louis, J.T. Mao, J.R. Muindi, G.T. O'connor, J.W. Ramsdell, A.L. Ries, S.M. Scharf, N.W. Schluger, F.C. Sciurba, M.A. Skeans, R.E. Walter, C.H. Wendt, R.A. Wise (Chest 2006 Nov; 130(5):1334–1345).
Background: Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema. Methods: One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema, defined by diffusing capacity of the lung for carbon monoxide (Dlco) [37.1 ± 12.0% of predicted] and CT density mask (38.5 ± 12.8% of voxels <-910 Hounsfield units) [mean ± SD] were enrolled into a randomized, double-blind, feasibility study at five university hospitals. Participants received all-trans retinoic acid (ATRA) at either a low dose (LD) [1 mg/kg/d] or high dose (HD) [2 mg/kg/d], 13-cis retinoic acid (13-cRA) [1 mg/kg/d], or placebo for 6 months followed by a 3-month crossover period. Results: No treatment was associated with an overall improvement in pulmonary function, CT density mask score, or health-related quality of life (QOL) at the end of 6 months. However, time-dependent changes in Dlco (initial decrease with delayed recovery) and St. George Respiratory Questionnaire (delayed improvement) were observed in the HD-ATRA cohort and correlated with plasma drug levels. In addition, 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels. Retinoid-related side effects were common but generally mild. Conclusions: No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study. However, time-and dose-dependent changes in Dlco, CT density mask score, and health-related QOL were observed in subjects treated with ATRA, suggesting the possibility of exposure-related biological activity that warrants further investigation.
Comments: The notion that emphysema may be even partially reversible could have profound impact on how many view COPD. Patients had to be over 45 years old with at least 10% emphysema on CT evaluation, FEV-1 between 25 to 80% predicted and a PaO2 greater than 90%. They could not have smoked for 6 months or been on oral corticosteroids within 2 months. The small numbers of individuals in this trial and the relatively short time of the study are possible reasons no significant findings were noted, however, the fact there were even any indications of a response provides room for cautious optimism. While this is only a feasibility trial it suggests that further investigation of larger numbers, longer duration and perhaps higher doses are required to assess the efficacy and safety of retinoids.
Developing COPD: A 25-Year Follow-Up Study of the General Population; A. Lokke, P. Lange, H. Scharling, P. Fabricius, J. Vestbo (Thorax 2006 Nov; 61(11):935–939).
Background: Smokers are more prone to develop chronic obstructive pulmonary disease (COPD) than non-smokers, but this finding comes from studies spanning 10 years or less. The aim of this study was to determine the 25-year absolute risk of developing COPD in men and women from the general population. Methods: As part of the Copenhagen City Heart Study, 8045 men and women aged 30–60 years with normal lung function at baseline were followed for 25 years. Lung function measurements were collected and mortality from COPD during the 25-year observation period was analysed. Results: The percentage of men with normal lung function ranged from 96% of never smokers to 59% of continuous smokers; for women the proportions were 91% and 69%, respectively. The 25-year incidence of moderate and severe COPD was 20.7% and 3.6%, respectively, with no apparent difference between men and women. Smoking cessation, especially early in the follow-up period, decreased the risk of developing COPD substantially compared with continuous smoking. During the follow-up period there were 2912 deaths, 109 of which were from COPD. 92% of the COPD deaths occurred in subjects who were current smokers at the beginning of the follow up period. Conclusions: The absolute risk of developing COPD among continuous smokers is at least 25%, which is larger than was previously estimated.
Comments: The data utilized for this study were from four periodic examinations starting in 1976 (and subsequently in 1981–1983, 1991–1994, and 2001–2003) of a sub-cohort of smokers identified between the ages of 30–60 years with smoking and spirometric data. All members of the cohort had normal lung function at the start of the study. Almost half of the cohort had spirometry only in the first and fourth examinations. The remaining cohort had spirometry during each of the follow up exams and allowed an assessment of risk of developing COPD related to changes in smoking habits. This study did not have data regarding individual pack year histories. They also had quite substantial drop off by the fourth examination with only 2912 of 5133 surviving initial participants partaking in the final follow-up. This suggests that the true incidence of COPD may have been underestimated in that the most infirm or ill may have missed follow-up. It is interesting that there was no evidence of differences between men and women as reported in other studies from the United States, Canada, and the UK. This may reflect differences in current and past smoking habits of this Danish cohort compared to these other groups. This study points out a higher incidence rate of COPD than previously reported and as outlined above may still underestimate the incidence of COPD in smokers.
Role of Gastroesophageal Reflux Symptoms in Exacerbations of COPD; I.E. Rascon-Aguilar, M. Pamer, P. Wludyka, J. Cury, D. Coultas, L.R. Lambiase, N.S. Nahman, K.J. Vega (Chest 2006 Oct; 130(4):1096–1101).
Background and Aims: The impact of gastroesophageal reflux disease (GERD) on exacerbations of COPD has never been evaluated. The aims of this investigation were to determine the prevalence of gastroesophageal reflux (GER) symptoms in COPD patients and the effect of GER on the rate of exacerbations of COPD per year. Methods: A questionnaire-based, cross-sectional survey was performed. Subjects were recruited from the outpatient pulmonary clinics at the University of Florida Health Science Center/Jacksonville. Included patients had an established diagnosis of COPD. Exclusion criteria were respiratory disorders other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger–Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse. Those meeting criteria and agreeing to participate were asked to complete the Mayo Clinic GERD questionnaire by either personal/telephone interview. Clinically significant reflux was defined as heartburn and/or acid regurgitation weekly. Other outcome measures noted were frequency and type of COPD exacerbations. Statistical analysis was performed using the Fisher exact test for categorical data and the independent t-test for interval data. Results: Eighty-six patients were enrolled and interviewed (mean age, 67.5 years). Male patients accounted for 55% of the study group. Overall, 37% of patients reported GER symptoms. The mean FEV1 percentage of predicted was similar in those with or without GER. The rate of exacerbations of COPD was twice as high in patients with GER symptoms compared to those without GER symptoms (3.2/yr vs 1.6/yr, p = 0.02). Conclusions: The presence of GER symptoms appears to be associated with increased exacerbations of COPD.
Comments: The relationship between GERD and asthma has been studied extensively in the past but less is known about the frequency and complications of GERD in COPD patients. The patients selected for this study had an FEV-1/FVC less than 70%. The mean FEV1 was 45.9 ± 16.0 L in the GERD-positive group and 40.7 ± 17.6 L in the GERD negative group. The GERD-positive group also had statistically significant higher rates of exacerbations requiring hospitalization (p = 0.007), ER visits (p = 0.005), unscheduled clinic visits (p = 0.01) and antibiotic use (p = 0.01). Several studies have demonstrated that COPD exacerbations have an infectious etiology less than 50% of the time. Interestingly this study did not demonstrate any particular reduction in exacerbations regardless of whether patients were on antireflux medication. This may point to the presence of complications such as laryngopharyngeal reflux and possibly intercurrent aspiration as further manifestations of GERD for which standard antireflux therapy is often inadequate. This study highlights that recurrent GERD and possible periodic aspiration may be a significant cause of COPD exacerbations and should be considered, investigated and treated as in asthma patients.