Long-Term Air Pollution Exposure and Severity of Idiopathic Pulmonary Fibrosis: Data from the Idiopathic Pulmonary Fibrosis Prospective Outcomes (IPF-PRO) Registry.

Abstract

Rationale: Although exposure to air pollution is a known risk factor for adverse pulmonary outcomes, its impact in individuals with idiopathic pulmonary fibrosis (IPF) is less well understood. Objectives: To investigate the effects of long-term exposure to air pollution on disease severity and progression in patients with IPF and to determine whether genomic factors, such as MUC5B promoter polymorphism or telomere length, modify these associations. Methods: We performed analyses at enrollment and after 1 year of follow-up in the IPF-PRO (Idiopathic Pulmonary Fibrosis Prospective Outcomes) Registry, a prospective observational registry that enrolled individuals with IPF at 46 U.S. sites from June 2014 to October 2018. Five-year average pollution exposures (particulate matter ≤2.5 μm in aerodynamic diameter [PM_2.5], nitrogen dioxide, ozone) before the enrollment date were estimated at participants' residential addresses with validated national spatiotemporal models. Multivariable regression models estimated associations between pollution exposure and physiologic measurements (forced vital capacity [FVC], diffusing capacity of the lung for carbon monoxide, supplemental oxygen use at rest) and quality-of-life measurements (St. George's Respiratory Questionnaire, EuroQoL, Cough and Sputum Assessment Questionnaire) at enrollment. Cox proportional hazards models estimated associations between pollutants and a composite outcome of death, lung transplant, or >10% absolute decline in FVC percent predicted in the year after enrollment. Models were adjusted for individual-level and spatial confounders, including proxies for disease onset. Gene-environment interactions with MUC5B and telomere length were assessed. Results: Of 835 participants, 94% were non-Hispanic White individuals, 76% were male, and the mean (standard deviation) age was 70 (7.7) years. In fully adjusted analyses, higher PM_2.5 exposure was associated with worse quality of life per St. George's Respiratory Questionnaire activity score (3.48 [95% confidence interval (CI), 0.64, 6.32] per 2 μg/m³ PM_2.5) and EuroQoL scores (-0.04 [95% CI, -0.06, -0.01] per 2 μg/m³ PM_2.5), as well as lower FVC percent predicted and lower diffusing capacity of the lung for carbon monoxide percent predicted at enrollment_. Each 3 parts per billion difference in O₃ exposure was associated with a 1.57% (95% CI, 0.15, 2.98) higher FVC percent predicted at enrollment, although this effect was attenuated in multipollutant models. There was no association between nitrogen dioxide and enrollment measures or between pollution exposure and 1-year outcomes and no evidence for gene-environment interactions. Conclusions: In the IPF-PRO Registry, long-term exposure to PM_2.5 was associated with worse quality of life and lung function at enrollment, but not with short-term disease progression or mortality. There was no evidence of effect modification by interaction of genomic factors with pollution. The reason for the unexpected relationship between O₃ exposure and higher FVC is unclear. Clinical trial registered with www.clinicaltrials.gov (NCT01915511).