Association of Particulate Matter Exposure With Lung Function and Mortality Among Patients With Fibrotic Interstitial Lung Disease
Authors: Goobie Gillian C. , Carlsten Christopher , Johannson Kerri A. , Khalil Nasreen , Marcoux Veronica , Assayag Deborah , Manganas Hélène , Fisher Jolene H. , Kolb Martin R. J. , Lindell Kathleen O. , Fabisiak James P. , Chen Xiaoping , Gibson Kevin F. , Zhang Yingze , Kass Daniel J. , Ryerson Christopher J. , Nouraie S. Mehdi 
Published: October 2022

Importance

Particulate matter 2.5 μm or less in diameter (PM2.5) is associated with adverse outcomes in idiopathic pulmonary fibrosis, but its association with other fibrotic interstitial lung diseases (fILDs) remains unclear.

Objective

To investigate the association of PM2.5 exposure with mortality and lung function among patients with fILD.

Design, Setting, and Participants

In this multicenter, international, prospective cohort study, patients were enrolled in the Simmons Center for Interstitial Lung Disease Registry at the University of Pittsburgh in Pittsburgh, Pennsylvania (Simmons cohort); 42 sites of the Pulmonary Fibrosis Foundation Registry (PFF cohort); and 8 sites of the Canadian Registry for Pulmonary Fibrosis (CARE-PF cohort). A total of 6683 patients were included (Simmons, 1424; PFF, 1870; and CARE-PF, 3389). Data were analyzed from June 1, 2021, to April 3, 2023.

Exposures

Exposure to PM2.5 and its constituents was estimated with hybrid models, combining satellite-derived aerosol optical depth with chemical transport models and ground-based PM2.5 measurements.

Main Outcomes and Measures

Multivariable linear regression tested associations of exposures with baseline forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO), and linear mixed models tested associations with lung function decline. Multivariable Cox models tested associations of 5-year time-varying exposures from enrollment to censoring with mortality or lung transplant. Multiconstituent analyses were performed with quantile-based g-computation. Models were adjusted for age, sex, smoking history, self-reported race, a socioeconomic covariate, and site (for PFF and CARE-PF only). Cohort effect estimates were meta-analyzed with clustering by cohort.

Results

Median follow-up across the 3 cohorts was 2.9 years (IQR, 1.5-4.5 years), with death for 28% of patients and lung transplant for 10% of patients. Of 6683 patients, 3653 were men (55%), 205 were Black (3.1%), and 5609 were White (84.0%). Median (IQR) age at enrollment was 66 (58-73) years. In Simmons, each 1-μg/m3 increase in 5-year preenrollment PM2.5 was associated with a lower estimated percentage baseline FVC, and each 1-μg/m3 increase in 5-year precensoring PM2.5 was associated with decreasing FVC and DLCO, but these associations were not observed in PFF or CARE-PF. In PFF, each 1-μg/m3 increase in 5-year preenrollment PM2.5 was associated with lower percentage baseline DLCO. In cohort-specific analyses, each 1-μg/m3 increase in 5-year time-varying PM2.5 exposure was associated with higher mortality or transplant rates in Simmons (hazard ratio [HR], 1.05 [95% CI, 1.01-1.09]; P = .02), but not the other cohorts (PFF HR, 1.02 [95% CI, 0.98-1.06]; P = .38; CARE-PF HR, 0.98 [95% CI, 0.96-1.01]; P = .16). Meta-analysis of pooled individual patient data from the 3 cohorts demonstrated an HR of 1.09 (95% CI, 1.05-1.13; P &amp;lt; .001) for each 1-μg/m3 increase in PM2.5. Increasing exposures to sulfate, ammonium, and black carbon PM2.5 constituents were also associated with higher rate of mortality or transplant in the meta-analysis, and multiconstituent models demonstrated that black carbon and sulfate were the primary drivers of the adverse mortality rates associated with the PM2.5 mixture.

Conclusions and Relevance

In this cohort study, exposure to PM2.5 was associated with worse lung function and mortality or transplant among some but not all patients with fILD. Sulfate, ammonium, and black carbon constituents were associated with the most potential risk, highlighting the need for reductions in human-derived sources of pollution.