Exposure to particulate matter 2.5 μm or less associated with adverse outcomes among patients with fibrotic interstitial lung disease

1. Increasing exposure to sulfate, nitrate, and ammonium particulate matter 2.5 μm (PM2.5 μm) constituents was associated with adverse outcomes among patients with fibrotic interstitial lung disease with respect to baseline severity, disease progression, and had increased mortality across all 3 cohorts.

2. A PM2.5 μm exposure of 8μg/m3 or more was associated with a hazard ratio for mortality of 4.40 in the Simmons cohort, 1.71 in the Pulmonary Fibrosis Foundation cohort, and 1.45 in the Canadian Registry for Pulmonary Fibrosis Foundation cohort.

Evidence Rating Level: 2 (Good)

Study Rundown: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of fibrotic interstitial lung disease (fILD), a group of pulmonary conditions characterized by dyspnea, radiographic pulmonary fibrosis and high mortality. Air pollution is known to be associated with IPF development and progression, and particulate matter 2.5 μm (PM_2.5) is estimated to be responsible for up to 8.9 million premature deaths annually. This multicenter prospective cohort study investigated the association of PM_2.5 exposure with mortality and lung function among patients with fILD. A total of 6683 patients with fILD were included from various registries, and data was analyzed from June 1, 2021, to August 2, 2022. The primary exposure was PM_2.5 and its constituents. The main measures were multivariable linear regression to test exposures 5 years before enrollment with baseline forced vital capacity (FVC) and diffusion capacity for carbon monoxide. A PM_{2.5 μm} exposure of 8μg/m³ or more was associated with a hazard ratio for mortality of 4.40 in the Simmons cohort, 1.71 in the Pulmonary Fibrosis Foundation cohort (PFF), and 1.45 in the Canadian Registry for Pulmonary Fibrosis Foundation cohort (CARE-PF). It was found that increasing exposure to sulfate, nitrate, and ammonium PM_{2.5 μm} constituents was associated with increased mortality across all cohorts. Meta-analyses further revealed that exposure to sulfate and ammonium was associated with the rate of decrease in FVC, diffusion capacity of carbon monoxide, and an association of increasing levels of PM_{2.5 μm}. A strength of this study was that it represents the largest and most geographically diverse evaluation of the associations between PM_{2.5 μm} and disease in patients with diverse forms of fILD. A limitation of this study was that pollution exposures were estimated at a patient’s most recent residential address but neglects to account for changes in address, leading to the potential risk of exposure misclassification.

Click to read the study in JAMA Internal Medicine

Relevant Reading: Air pollution and interstitial lung diseases: defining epigenomic effects

In-Depth [prospective cohort]: This study investigated the association of PM_{2.5 μm} exposure with mortality and lung function in patients with fILD. There was a total of 6683 patients in the cohort (3653 [55%] men, the median age at enrollment was 66 (58-73 years). The 3 cohorts included Simmons (n=1424), Pulmonary Fibrosis Foundation (n=1870), and the Canadian Registry for Pulmonary Fibrosis (n=3389).  The median follow-up across the 3 cohorts was 2.9 years (IQR, 1.5-4.5 years), which included 28% of patient death and 10% of patients had lung transplants. The main measures included a multivariable linear regression to test associations of exposures 5 years before enrollment with baseline forced vital capacity and diffusion capacity for carbon monoxide. Additionally, multivariable Cox models were used to test associations of exposure with a decrease in lung function. A PM_{2.5 μm} exposure of 8μg/m³ or more was associated with increased mortality, Simmons cohort (HR, 4.40 [95% CI, 3.51-5.51]; P <.001; PFF cohort HR, 1.71 [95% CI, 1.32-2.21] P < .001; CARE-PF cohort HR, 1.45 [95% CI, 1.18-1.79]; P <.001). In adjusted Simmons cohort models, it was found that an increase of 1μg/m³ in the 5-year pre-enrollment PM_{2.5 μm} level was associated with a 0.98% lower estimated percentage baseline FVC (95% CI, -1.45 to 0.50; P <.001), but was not shown to be significant in the PFF or CARE-PF cohorts. Upon evaluating the association of PM_{2.5 μm} and its constituents with a decrease in lung function, each increase of 1μg/m³ in 5-year precensoring PM_{2.5 μm} exposure in the Simmons cohort was associated with an additional 0.4% decrease in FVC percentage per year (95% CI, -0.53 to -0.27; P <.001), however, it was not observed in the PFF or CARE-PF cohorts.

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