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Background  Accelerated‐FEV 1 ‐decline, defined as rate of decline in FEV 1  > 64 ml/year, is a risk factor for asthma and chronic obstructive pulmonary disease in World Trade Center (WTC)‐exposed firefighters. Accelerated‐FEV 1 ‐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 FEV 1  decline rate in those with accelerated‐FEV 1 ‐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 FEV 1  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 FEV 1  decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders.    Results  In WTC‐exposed firefighters with accelerated‐FEV 1 ‐decline, IL‐4, IL‐13, and IL‐5 measured 1–6 months post‐9/11/2001 were associated with greater FEV 1  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 FEV 1  decline rate (−4.0 ± 1.6 ml/year per IL‐4 doubling).    Conclusions  In WTC‐exposed firefighters with accelerated‐FEV 1 ‐decline, elevated serum IL‐4 measured both 1–6 months and 12–13 years after 9/11 is associated with greater FEV 1  decline/year. Drugs targeting the IL‐4 pathway may improve lung function in this high‐risk subgroup.

Serum Th‐2 cytokines and FEV 1 decline in WTC‐exposed firefighters: A 19‐year longitudinal study