Serum Th-2 cytokines and FEV1 decline in WTC-exposed firefighters: A 19-year longitudinal study

Michael D Weiden; Ankura Singh; David G Goldfarb; Barbara Putman; Rachel Zeig-Owens; Theresa Schwartz; Hillel W Cohen; David J Prezant

doi:10.1002/ajim.23276

Serum Th-2 cytokines and FEV₁ decline in WTC-exposed firefighters: A 19-year longitudinal study

Am J Ind Med. 2021 Oct;64(10):845-852. doi: 10.1002/ajim.23276. Epub 2021 Jul 20.

Authors

Michael D Weiden^{1

2

3

4}, Ankura Singh^{1

2

5}, David G Goldfarb^{1

2

5}, Barbara Putman^{3

4

6}, Rachel Zeig-Owens^{1

2

5

7}, Theresa Schwartz^{1

2

5}, Hillel W Cohen⁷, David J Prezant^{1

2

5}

Affiliations

¹ The Bureau of Health Services and the FDNY World Trade Center Health Program, Brooklyn, New York, USA.
² Fire Department of the City of New York, Brooklyn, New York, USA.
³ Department of Medicine, New York University School of Medicine, New York, New York, USA.
⁴ Department of Environmental Medicine, Pulmonary, Critical Care and Sleep Medicine Division, New York University School of Medicine, New York, New York, USA.
⁵ Department of Medicine, Pulmonary Medicine Division, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, USA.
⁶ Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
⁷ Department of Epidemiology and Population Health, Division of Epidemiology, Albert Einstein College of Medicine, Bronx, New York, USA.

Abstract

Background: Accelerated-FEV₁ -decline, defined as rate of decline in FEV₁ > 64 ml/year, is a risk factor for asthma and chronic obstructive pulmonary disease in World Trade Center (WTC)-exposed firefighters. Accelerated-FEV₁ -decline in this cohort is associated with elevated blood eosinophil concentrations, a mediator of Th-2 response. We hypothesized that an association exists between Th-2 biomarkers and FEV₁ decline rate in those with accelerated-FEV₁ -decline.

Methods: Serum was drawn from Fire Department of the City of New York (FDNY) firefighters 1-6 months (early) (N = 816) and 12-13 years (late) (N = 983) after 9/11/2001. Th-2 biomarkers IL-4, IL-13, and IL-5 were assayed by multiplex Luminex. Individual FEV₁ decline rates were calculated using spirometric measurements taken: (1) between 9/11/2001 and 9/10/2020 for the early biomarker group and (2) between late measurement date and 9/10/2020 for the late biomarker group. Associations of early and late Th-2 biomarkers with subsequent FEV₁ decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders.

Results: In WTC-exposed firefighters with accelerated-FEV₁ -decline, IL-4, IL-13, and IL-5 measured 1-6 months post-9/11/2001 were associated with greater FEV₁ decline ml/year between 9/11/2001 and 9/10/2020 (-2.9 ± 1.4 ml/year per IL-4 doubling; -8.4 ± 1.2 ml/year per IL-13 doubling; -7.9 ± 1.3 ml/year per IL-5 doubling). Among late measured Th-2 biomarkers, only IL-4 was associated with subsequent FEV₁ decline rate (-4.0 ± 1.6 ml/year per IL-4 doubling).

Conclusions: In WTC-exposed firefighters with accelerated-FEV₁ -decline, elevated serum IL-4 measured both 1-6 months and 12-13 years after 9/11 is associated with greater FEV₁ decline/year. Drugs targeting the IL-4 pathway may improve lung function in this high-risk subgroup.

Keywords: FEV1 slope; Th-2 biomarkers; World Trade Center; cohort studies; firefighting.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Cytokines
Firefighters*
Humans
Longitudinal Studies
Occupational Exposure* / adverse effects
September 11 Terrorist Attacks*

Substances

Cytokines

Grants and funding

U01 OH011682/OH/NIOSH CDC HHS/United States