Association of Lung Function Decline with All-Cause and Cancer-Cause Mortality after World Trade Center Dust Exposure

Rationale: In numerous cohorts, lung function decline is associated with all-cause and cardiovascular-cause mortality, but the association between the decrease in forced expiratory volume in 1 second (FEV₁) and cancer-cause mortality, particularly after occupational/environmental exposure(s), is unclear. Exposure to dust/smoke from the World Trade Center (WTC) disaster caused inflammation and lung injury in Fire Department of the City of New York rescue/recovery workers. In addition, prior research found that .10% of the cohort experienced greater than twice the age-related decrease in FEV₁ (>64 ml/yr). Objectives: To evaluate the association of longitudinal lung function with all-cause and cancer-cause mortality after exposure to the WTC disaster. Methods: We conducted a prospective cohort study using longitudinal prebronchodilator FEV₁ data for 12,264 WTC-exposed firefighters and emergency medical service providers. All-cause and cancer-cause mortality were ascertained using National Death Index data from September 12, 2001, through December 31, 2021. Joint longitudinal survival models evaluated the association of baseline FEV₁ and change in FEV₁ from baseline with all-cause and cancer-cause mortality adjusted for age, race/ethnicity, height, smoking, work assignment (firefighters vs. emergency medical service providers), and WTC exposure. Results: By December 31, 2021, 607 of the 12,264 individuals in the cohort (4.9%) had died (crude rate = 259.5 per 100,000 person-years), and 190 of 12,264 (1.5%) had died from cancer (crude rate = 81.2 per 100,000 person-years). Baseline FEV₁ was >80% predicted in 10,970 of the 12,264 (89.4%); final FEV₁ was >80% in 9,996 (81.5%). Lower FEV₁ at baseline was associated with greater risk for all-cause mortality (hazard ratio [HR] per liter = 2.32; 95% confidence interval [95% CI] = 1.98–2.72) and cancer-cause mortality (HR per liter = 1.99; 95% CI = 1.49–2.66). Longitudinally, each 100-ml/yr decrease in FEV₁ was associated with an 11% increase in all-cause mortality (HR = 1.11; 95% CI = 1.06–1.15) and a 7% increase in cancer-cause mortality (HR = 1.07; 95% CI = 1.00–1.15). Compared with FEV₁ decrease,64 ml/yr, those with FEV₁ decrease >64 ml/yr had higher all-cause (HR = 2.91; 95% CI = 2.37–3.56) and cancer-cause mortality (HR = 2.68; 95% CI = 1.90–3.79). Conclusions: Baseline FEV₁ and longitudinal FEV₁ decrease are associated with increased risk of all-cause and cancer-cause mortality in a previously healthy occupational cohort, the majority of whom had normal lung function, after intense exposure to dust/smoke. Further investigation is needed to define pathways by which lung function impacts mortality after an irritant exposure.