Blood leukocyte concentrations, FEV ₁ decline, and airflow limitation A 15-year longitudinal study of world trade center-exposed firefighters

Rationale: Rescue/recovery work at the World Trade Center disaster site (WTC) caused a proximate decline in lung function in Fire Department of the City of New York firefighters. A subset of this cohort experienced an accelerated rate of lung function decline over 15 years of post-September 11, 2001 (9/11) follow-up. Objectives: To determine if early postexposure blood leukocyte concentrations are biomarkers for subsequent FEV ₁ decline and incident airflow limitation. Methods: Individual rates of forced expiratory volume in 1 second (FEV1) change were calculated for 9,434 firefighters using 88,709 spirometric measurements taken between September 11, 2001, and September 10, 2016. We categorized FEV ₁ change rates into three trajectories: accelerated FEV ₁ decline (FEV ₁ loss >64 ml/yr), expected FEV ₁ decline (FEV ₁ loss between 0 and 64 ml/yr), and improved FEV ₁ (positive rate of change >0 ml/yr). Occurrence of FEV ₁ /FVC less than 0.70 after 9/11 defined incident airflow limitation. Using regression models, we assessed associations of post-9/11 blood eosinophil and neutrophil concentrations with subsequent FEV ₁ decline and airflow limitation, adjusted for age, race, smoking, height, WTC exposure level, weight change, and baseline lung function. Results: Accelerated FEV1 decline occurred in 12.7% of participants (1,199 of 9,434), whereas post-9/11 FEV1 improvement occurred in 8.3% (780 of 9,434). Higher blood eosinophil and neutrophil concentrations were each associated with accelerated FEV ₁ decline after adjustment for covariates (odds ratio [OR], 1.10 per 100 eosinophils/μl; 95% confidence interval [CI], 1.05-1.15; and OR, 1.10 per 1,000 neutrophils/μl; 95% CI, 1.05-1.15, respectively). Multivariable-adjusted linear regression models showed that a higher blood neutrophil concentration was associated with a faster rate of FEV1 decline (1.14 ml/yr decline per 1,000 neutrophils/μl; 95% CI, 0.69-1.60 ml/yr; P < 0.001). Higher blood eosinophil concentrations were associated with a faster rate of FEV1 decline in ever-smokers (1.46 ml/yr decline per 100 eosinophils/μl; 95% CI, 0.65-2.26 ml/yr; P < 0.001) but not in never-smokers (P for interaction = 0.004). Higher eosinophil concentrations were also associated with incident airflow limitation (adjusted hazard ratio, 1.10 per 100 eosinophils/μl; 95% CI, 1.04-1.15). Compared with the expected FEV ₁ decline group, individuals experiencing accelerated FEV ₁ decline were more likely to have incident airflow limitation (adjusted OR, 4.12; 95% CI, 3.30-5.14). Conclusions: Higher post-9/11 blood neutrophil and eosinophil concentrations were associated with subsequent accelerated FEV ₁ decline in WTC-exposed firefighters. Both higher blood eosinophil concentrations and accelerated FEV ₁ decline were associated with incident airflow limitation in WTC-exposed firefighters.