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

Ankura Singh, Charles Liu, Barbara Putman, Rachel Zeig-Owens, Charles B. Hall, Theresa Schwartz, Mayris P. Webber, Hillel W. Cohen, Kenneth I. Berger, Anna Nolan, David J. Prezant, Michael D. Weiden

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
JournalChest
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Firefighters
Dust
Chronic Obstructive Pulmonary Disease
Longitudinal Studies
Asthma
Eosinophils
Bronchodilator Agents
Respiratory Function Tests
Irritants
Interleukin-4
Biomarkers
Serum
Cytokines
Th2 Cells
Hematologic Tests
Proportional Hazards Models
Immunoglobulin E

Keywords

  • airway obstruction
  • asthma
  • biomarkers
  • COPD
  • eosinophils

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure : A Longitudinal Study. / Singh, Ankura; Liu, Charles; Putman, Barbara; Zeig-Owens, Rachel; Hall, Charles B.; Schwartz, Theresa; Webber, Mayris P.; Cohen, Hillel W.; Berger, Kenneth I.; Nolan, Anna; Prezant, David J.; Weiden, Michael D.

In: Chest, 01.01.2018.

Research output: Contribution to journalArticle

Singh, Ankura ; Liu, Charles ; Putman, Barbara ; Zeig-Owens, Rachel ; Hall, Charles B. ; Schwartz, Theresa ; Webber, Mayris P. ; Cohen, Hillel W. ; Berger, Kenneth I. ; Nolan, Anna ; Prezant, David J. ; Weiden, Michael D. / Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure : A Longitudinal Study. In: Chest. 2018.
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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 = "airway obstruction, asthma, biomarkers, COPD, eosinophils",
author = "Ankura Singh and Charles Liu and Barbara Putman and Rachel Zeig-Owens and Hall, {Charles B.} and Theresa Schwartz and Webber, {Mayris P.} and Cohen, {Hillel W.} and Berger, {Kenneth I.} and Anna Nolan and Prezant, {David J.} and Weiden, {Michael D.}",
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T2 - A Longitudinal Study

AU - Singh, Ankura

AU - Liu, Charles

AU - Putman, Barbara

AU - Zeig-Owens, Rachel

AU - Hall, Charles B.

AU - Schwartz, Theresa

AU - Webber, Mayris P.

AU - Cohen, Hillel W.

AU - Berger, Kenneth I.

AU - Nolan, Anna

AU - Prezant, David J.

AU - Weiden, Michael D.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - airway obstruction

KW - asthma

KW - biomarkers

KW - COPD

KW - eosinophils

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