Ankura Singh1, Charles Liu2, Barbara Putman3, Rachel Zeig-Owens4, Charles B Hall5, Theresa Schwartz1, Mayris P Webber6, Hillel W Cohen7, Kenneth I Berger2, Anna Nolan3, David J Prezant1, Michael D Weiden8. 1. Bureau of Health Services and the FDNY World Trade Center Health Program, Fire Department of the City of New York, Brooklyn, NY; Pulmonary Medicine Division, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY. 2. Pulmonary, Critical Care and Sleep Medicine Division, Department of Medicine and Department of Environmental Medicine, New York University School of Medicine, New York, NY. 3. Bureau of Health Services and the FDNY World Trade Center Health Program, Fire Department of the City of New York, Brooklyn, NY; Pulmonary, Critical Care and Sleep Medicine Division, Department of Medicine and Department of Environmental Medicine, New York University School of Medicine, New York, NY. 4. Bureau of Health Services and the FDNY World Trade Center Health Program, Fire Department of the City of New York, Brooklyn, NY; Pulmonary Medicine Division, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY; Division of Epidemiology, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. 5. Division of Biostatistics, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. 6. Bureau of Health Services and the FDNY World Trade Center Health Program, Fire Department of the City of New York, Brooklyn, NY; Division of Epidemiology, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. 7. Division of Epidemiology, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. 8. Bureau of Health Services and the FDNY World Trade Center Health Program, Fire Department of the City of New York, Brooklyn, NY; Pulmonary, Critical Care and Sleep Medicine Division, Department of Medicine and Department of Environmental Medicine, New York University School of Medicine, New York, NY. Electronic address: michael.weiden@nyumc.org.
Abstract
BACKGROUND: Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined. METHODS: This study included 2,137 WTC-exposed firefighters who underwent a clinically indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001 and 9/10/2017. A post-BD FEV1 increase of > 12% and 200 mL from baseline defined asthma, and a post-BD FEV1/FVC ratio < 0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (n = 215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC exposure, first post-9/11 FEV1/FVC ratio, and BMI included as covariates. RESULTS: BD-PFT diagnosed asthma/COPD overlap in 99 subjects (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration ≥ 300 cells/μL was associated with increased risk of asthma/COPD overlap (hazard ratio [HR], 1.85; 95% CI, 1.16-2.95) but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR, 1.51 per doubling of cytokine concentration; 95% CI, 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HRs of 1.73 [95% CI, 1.27-2.35] and 2.06 [95% CI, 1.31-3.23], respectively). CONCLUSIONS: In WTC-exposed firefighters, elevated blood eosinophil and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific T-helper cell type 2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.
BACKGROUND: Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined. METHODS: This study included 2,137 WTC-exposed firefighters who underwent a clinically indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001 and 9/10/2017. A post-BD FEV1 increase of > 12% and 200 mL from baseline defined asthma, and a post-BD FEV1/FVC ratio < 0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (n = 215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC exposure, first post-9/11 FEV1/FVC ratio, and BMI included as covariates. RESULTS: BD-PFT diagnosed asthma/COPD overlap in 99 subjects (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration ≥ 300 cells/μL was associated with increased risk of asthma/COPD overlap (hazard ratio [HR], 1.85; 95% CI, 1.16-2.95) but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR, 1.51 per doubling of cytokine concentration; 95% CI, 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HRs of 1.73 [95% CI, 1.27-2.35] and 2.06 [95% CI, 1.31-3.23], respectively). CONCLUSIONS: In WTC-exposed firefighters, elevated blood eosinophil and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific T-helper cell type 2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.
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