Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure: A Longitudinal Study

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.

Keywords: COPD; airway obstruction; asthma; biomarkers; eosinophils.

Figure 1

Firefighters who participated in the asthma/COPD overlap study. Shown is the source population of male firefighters who were employed by the FDNY on 9/11/2001, present at the WTC site between 9/11/2001 and 9/24/2001, and had at least three routine monitoring PFTs taken between 9/11/2001 and 9/10/2017 for FEV₁ slope measurement. The final study population included those who had received a post-9/11/2001 clinically indicated PFT with BD measurement. The serum biomarker population was a subgroup who had biomarkers measured on serum drawn between 10/2001 and 2/2002. BD = bronchodilator; FDNY = Fire Department of the City of New York; PFT = pulmonary function test; WTC = World Trade Center.

Figure 2

Asthma/COPD overlap in WTC-exposed firefighters who had a BD-PFT. The Venn diagram demonstrates abnormalities on BD-PFTs obtained via the WTC treatment program. Isolated-asthma was diagnosed in 202 individuals who had FEV₁ BD response of > 12% and 200 mL. Isolated-COPD was diagnosed in 215 individuals who had a post-BD FEV₁/FVC ratio < 0.70. Asthma/COPD overlap was diagnosed in 99 who had both an FEV₁ BD response > 12% and 200 mL, and an FEV₁/FVC ratio < 0.70. The remainder of the study population (n = 1,621) did not have a BD response or airflow limitation. See Figure 1 legend for expansion of abbreviations.

Figure 3

A-B, Lung function over time. A, Mean ± SEM (SEM not shown if it is smaller than the size of the symbol) FEV₁ % predicted in each year between 9/11/2000 and 9/10/2017 in the asthma/COPD overlap (orange), isolated-COPD (gray), isolated-asthma (blue), and asthma-free and COPD-free (red) groups. The vertical line at 0 represents 9/11/2001. The number of spirometries per year is shown below the x-axis. B, Mean FEV₁/FVC ratio in the aforementioned groups in each year, adjusted for race, height, and age, using the same number of spirometries per year as shown in panel A.

Figure 4

A-C, Cumulative incidence of asthma/COPD overlap in WTC-exposed firefighters who had a BD PFT. A, Cumulative incidence of asthma/COPD overlap in participants with blood EOS concentration ≥ 300 cells/μL (red) and < 300 cells/μL on first post-9/11 medical monitoring examination (blue). The level of significance shown in each panel was determined by using the log-rank test. B, Cumulative incidence in those who reported ever smoking (red) and never smoking (blue). C, Cumulative incidence in participants who had an accelerated rate of post-9/11 FEV₁ decline > 64 mL/y (red) and those with expected FEV₁ decline ≤ 64 mL/y (blue). EOS = eosinophil. See Figure 1 legend for expansion of other abbreviations.