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

Rationale: While 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.

Objective: 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 one year of follow-up in the IPF-PRO Registry, a prospective observational registry that enrolled individuals with IPF at 46 US sites from June 2014 to October 2018. Five-year average pollution exposures (PM_2.5, NO₂, O₃) prior to enrollment date were estimated at participants' residential addresses with validated national spatio-temporal models. Multivariable regression models estimated associations between pollution exposure and physiologic measurements (FVC, DL_CO, supplemental oxygen use at rest) and quality of life measurements (St. George's Respiratory Questionnaire [SGRQ], EuroQoL, Cough and Sputum Assessment Questionnaire) at enrollment. Cox proportional hazard models estimated associations between pollutants and a composite outcome of death, lung transplant, or >10% absolute decline in FVC % 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 Whites, 76% were male, mean (SD) age was 70 (7.7) years. In fully adjusted analyses, higher PM_2.5 exposure was associated with worse quality of life per SGRQ activity score (3.48 [95% confidence interval (CI) 0.64, 6.32] per 2µg/m³ PM_2.5) and EuroQoL scores (-0.04 [95%CI -0.06, -0.01] per 2µg/m³ PM_2.5), and lower FVC % predicted and lower DL_CO% 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 % predicted at enrollment, although this effect was attenuated in multi-pollutant models. There was no association between NO₂ and enrollment measures, between pollution exposure and one-year outcomes, or evidence for gene-environment interactions.

Conclusion: 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.