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Multicenter Study
. 2022 Dec 1;182(12):1248-1259.
doi: 10.1001/jamainternmed.2022.4696.

Association of Particulate Matter Exposure With Lung Function and Mortality Among Patients With Fibrotic Interstitial Lung Disease

Gillian C Goobie  1   2   3 , Christopher Carlsten  4   5 , Kerri A Johannson  6 , Nasreen Khalil  4 , Veronica Marcoux  7 , Deborah Assayag  8 , Hélène Manganas  9 , Jolene H Fisher  10 , Martin R J Kolb  11 , Kathleen O Lindell  2   12 , James P Fabisiak  13 , Xiaoping Chen  2   14 , Kevin F Gibson  2   14 , Yingze Zhang  14 , Daniel J Kass  2   14 , Christopher J Ryerson  4   15 , S Mehdi Nouraie  14
Affiliations
Multicenter Study

Association of Particulate Matter Exposure With Lung Function and Mortality Among Patients With Fibrotic Interstitial Lung Disease

Gillian C Goobie et al. JAMA Intern Med. .

Erratum in

  • Error in Figure 2.
    [No authors listed] [No authors listed] JAMA Intern Med. 2022 Dec 1;182(12):1331. doi: 10.1001/jamainternmed.2022.5683. JAMA Intern Med. 2022. PMID: 36469031 Free PMC article. No abstract available.

Abstract

Importance: Particulate matter 2.5 μm or less in diameter (PM2.5) is associated with adverse outcomes for patients with idiopathic pulmonary fibrosis, but its association with other fibrotic interstitial lung diseases (fILDs) and the association of PM2.5 composition with adverse outcomes remain 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; 42 sites of the Pulmonary Fibrosis Foundation Registry; and 8 sites of the Canadian Registry for Pulmonary Fibrosis. A total of 6683 patients with fILD were included (Simmons, 1424; Pulmonary Fibrosis Foundation, 1870; and Canadian Registry for Pulmonary Fibrosis, 3389). Data were analyzed from June 1, 2021, to August 2, 2022.

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 was used to test associations of exposures 5 years before enrollment with baseline forced vital capacity and diffusion capacity for carbon monoxide. Multivariable Cox models were used to test associations of exposure in the 5 years before censoring with mortality, and linear mixed models were used to test associations of exposure with a decrease in lung function. Multiconstituent analyses were performed with quantile-based g-computation. Cohort effect estimates were meta-analyzed. Models were adjusted for age, sex, smoking history, race, a socioeconomic variable, and site (only for Pulmonary Fibrosis Foundation and Canadian Registry for Pulmonary Fibrosis cohorts).

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 the 6683 patients in the cohort, 3653 were men (55%), 205 were Black (3.1%), and 5609 were White (84.0%). Median (IQR) age at enrollment across all cohorts was 66 (58-73) years. A PM2.5 exposure of 8 μg/m3 or more was associated with a hazard ratio for mortality of 4.40 (95% CI, 3.51-5.51) in the Simmons cohort, 1.71 (95% CI, 1.32-2.21) in the Pulmonary Fibrosis Foundation cohort, and 1.45 (95% CI, 1.18-1.79) in the Canadian Registry for Pulmonary Fibrosis cohort. Increasing exposure to sulfate, nitrate, and ammonium PM2.5 constituents was associated with increased mortality across all cohorts, and multiconstituent models demonstrated that these constituents tended to be associated with the most adverse outcomes with regard to mortality and baseline lung function. Meta-analyses revealed consistent associations of exposure to sulfate and ammonium with mortality and with the rate of decrease in forced vital capacity and diffusion capacity of carbon monoxide and an association of increasing levels of PM2.5 multiconstituent mixture with all outcomes.

Conclusions and relevance: This cohort study found that exposure to PM2.5 was associated with baseline severity, disease progression, and mortality among patients with fILD and that sulfate, ammonium, and nitrate constituents were associated with the most harm, highlighting the need for reductions in human-derived sources of pollution.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Goobie reported receiving grants from Boehringer Ingelheim and the Pulmonary Fibrosis Foundation (PFF) during the conduct of the study. Dr Johannson reported receiving nonfinancial support and personal fees from Boehringer Ingelheim; personal fees from Hoffman-La Roche, Pliant Therapeutics, the Three Lakes Foundation, and Thyron SAB; grants from the University of Calgary Cumming School of Medicine, the Three Lakes Foundation, and the Pulmonary Fibrosis Society of Calgary; and grants from the University Hospital Foundation outside the submitted work. Dr Marcoux reported receiving grants from Boehringer Ingelheim Canada outside the submitted work and during the conduct of the study; grants and personal fees from Hoffman-La Roche and AstraZeneca; personal fees from Boehringer Ingelheim Canada and Roche; and grants from the University of Saskatchewan, the Royal University Hospital Foundation, and Roche. Dr Assayag reported receiving personal fees and grants from Boehringer Ingelheim and Novartis and personal fees from Hoffman-La Roche outside the submitted work. Dr Manganas reported receiving grants from Hoffman-La Roche, Galapagos Pharma, and BMS Pharma outside the submitted work; grants from the University of British Columbia during the conduct of the study; grants from Boehringer Ingelheim Pharma; honoraria for educational events from the Boehringer Ingelheim Advisory Board; and personal fees from Boehringer Ingelheim Pharma. Dr Fisher reported receiving grants from the Canadian PFF and Boehringer Ingelheim during the conduct of the study (Boehringer Ingelheim provides funding to the University of British Columbia for the Canadian Registry for Pulmonary Fibrosis [CARE-PF]; the University of British Columbia subsequently provides funding to each CARE-PF site) and personal fees from Boehringer Ingelheim and AstraZeneca outside of the submitted work. Dr Kolb reported receiving grants from Boehringer Ingelheim during the conduct of the study; personal fees from Boehringer Ingelheim, Algernon, Hoffman-La Roche, Horizon, CSL Behring, LabCorp, Nitto Denko, BMS, United Therapeutics, and Bellerophon Therapeutics outside the submitted work; and personal fees and grants from GSK, Gilead, Actelion, RespiVert, Genoa, Alkermes, Pharmaxis, Prometric, Indalo, and Third Pole outside the submitted work. Dr Fabisiak reported receiving funding from the Heinz Endowments. Dr Zhang reported receiving a grant from the National Institutes of Health (NIH) and grants from Boehringer Ingelheim and PFF during the conduct of the study. Dr Kass reported receiving grants from the NIH, grants from Boehringer Ingelheim and PFF during the conduct of the study, and collaborative research funding from Regeneron Pharmaceuticals outside the submitted work. Dr Ryerson reported receiving personal fees and grants from Boehringer Ingelheim and Hoffman-La Roche outside the submitted work. Dr Nouraie reported receiving a grant from Boehringer Ingelheim during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Distribution and Constituent Composition of Particulate Matter 2.5 μm or Less in Diameter (PM2.5) Across 3 Cohorts
A, A representative year (2005) for PM2.5 level, with Simmons Center for Interstitial Lung Disease Registry (ILD) referral center indicated with a yellow circle, Pulmonary Fibrosis Foundation (PFF) Registry referral centers indicated with blue circles, and Canadian Registry for Pulmonary Fibrosis (CARE-PF) ILD referral centers with red circles. The PM2.5 and its constituent component estimates are accurate to 0.01° by 0.01° (approximately 1.1 km2 at the equator), with mean monthly estimates available across North America from 2000 to 2018. B, Proportion of median total PM2.5 mass that each constituent component makes up in each cohort. C, Data are broken down by each constituent component (measured in micrograms per meter cubed) across each cohort. Asterisks shown in Quebec and Alaska reflect wildfires that occurred in those locations in 2005, highlighting how high PM2.5 levels during such exceptional events may increase yearly mean values of exposures in these remote, rural regions. BC indicates black carbon; NH4+, ammonium; NO3−, nitrate; OM, organic matter; SO42−, sulfate; and SS, sea salt.
Figure 2.
Figure 2.. Survival by Exposures to Low (<8 μg/m3) vs High (≥8 μg/m3) Levels of Particulate Matter 2.5 μm or Less in Diameter (PM2.5) 5 Years Before Censoring
Kaplan-Meier survival curves for associations of exposures to PM2.5 total mass in the 5 years before censoring, in which death and transplant are considered composite outcomes. Hazard ratios (HRs) reported for dichotomized and continuous models are adjusted for age at enrollment, sex, race, smoking history, a socioeconomic variable, and site (Pulmonary Fibrosis Foundation Registry and Canadian Registry for Pulmonary Fibrosis only). A, Simmons Center for Interstitial Lung Disease Registry: continuous PM2.5 exposure (HR, 1.33 [95% CI, 1.29-1.36]; P < .001) and PM2.5 level of 8 μg/m3 or higher (HR, 4.40 [95% CI, 3.51-5.51]; P < .001). B, Pulmonary Fibrosis Foundation Registry: continuous PM2.5 exposure (HR, 1.20 [95% CI, 1.10-1.31]; P < .001) and PM2.5 level of 8 μg/m3 or higher (HR, 1.71 [95% CI, 1.32-2.21]; P < .001). C, Canadian Registry for Pulmonary Fibrosis: continuous PM2.5 exposure (HR, 1.00 [95% CI, 0.96-1.05]; P = .89) and PM2.5 level of 8 μg/m3 or higher (HR, 1.45 [95% CI, 1.18-1.79]; P < .001).
Figure 3.
Figure 3.. Tornado Plots of Association of Constituents of Particulate Matter 2.5 μm or Less in Diameter With Mortality in Multipollutant Models
Results are reported from adjusted quantile-based g-computation Cox proportional hazards survival models in which 5-year precensoring estimates for SO42−, NO3−, NH4+, BC, OM, SS, and soil were included. All models were adjusted for age at enrollment, sex, race, smoking history, a socioeconomic variable, and site (for the Pulmonary Fibrosis Foundation Registry and Canadian Registry for Pulmonary Fibrosis). Bars going in the harmful direction are displayed in light brown, and bars going in the beneficial direction are displayed in light blue. The sum of all positive weights equals 1, and that of all negative weights equals −1 (ie, effect size cannot be directly compared between positive and negative weights). Hazard ratios for 1-quantile increase in overall mixture are 2.19 (95% CI, 1.93-2.48) for the Simmons Center for Interstitial Lung Disease Registry (A), 2.76 (95% CI, 2.15-3.54) for the Pulmonary Fibrosis Foundation Registry (B), and 2.29 (95% CI, 2.02-2.61) for the Canadian Registry for Pulmonary Fibrosis (C) (all P < .001). BC indicates black carbon; NH4+, ammonium; NO3−, nitrate; OM, organic matter; SO42−, sulfate; and SS, sea salt.
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