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

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.

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.

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).

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.