Particulate Matter Associations with Lung Function in Pulmonary Sarcoidosis

<b>Rationale:</b> Sarcoidosis is a multisystem disease with pulmonary manifestations in >90% of patients. Environmental exposures are associated with sarcoidosis incidence, but the impact on clinical outcomes remains understudied. <b>Objectives:</b> To evaluate the association of exposures to ambient particulate matter [Formula: see text]2.5 μm in diameter (PM_2.5) with lung function outcomes in pulmonary sarcoidosis. <b>Methods:</b> PM_2.5 and constituent exposures were obtained by matching monthly satellite-derived hybrid measurements to each patient's residential address obtained from the time of enrollment, averaged over 5 years before registry enrollment and censoring. Linear models evaluated associations of pollutants with baseline lung function (FEV₁, FVC, FEV₁/FVC ratio, and Dl_CO). Linear mixed effects models analyzed associations of pollutants with rates of lung function change (FEV₁, FVC, and Dl_CO change per year of follow-up). <b>Measurements and Main Results:</b> Two prospectively enrolled cohorts of mostly middle-aged, White, and nonsmoking adults with specialist-diagnosed pulmonary sarcoidosis were used. The U.S. cohort (<i>n</i> = 400) experienced higher 5-year preenrollment median PM_2.5 exposures (12.3 μg/m³) than the Canadian cohort (<i>n</i> = 112) (8.0 μg/m³). Each 1-μg/m³ increase in PM_2.5 was associated with 0.93% predicted lower baseline FEV₁ (95% confidence interval, -1.76 to -0.10; <i>P</i> = 0.03) and 1.53% predicted lower FVC (95% confidence interval, -2.26 to -0.79; <i>P</i> < 0.001) in the U.S. cohort, but the associations were not significant in the Canadian cohort. PM_2.5, sulfate, nitrate, and ammonium were associated with accelerated FEV₁, FVC, and Dl_CO decline in the U.S. cohort. <b>Conclusions:</b> PM_2.5 was associated with worse pulmonary disease severity and progression in a higher-exposure cohort, highlighting the importance of exposure disparities in this population.