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 [PM2.5], 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 PM2.5 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 PM2.5) and EuroQoL scores (-0.04 [95% CI, -0.06, -0.01] per 2 μg/m3 PM2.5), 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 PM2.5 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).

Rationale: Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited.Objectives: To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF.Methods: The study population included all 1,156 randomized patients in two clinical trials of IFN-gamma 1b. FVC and other measures of functional status were measured at screening or baseline and 24-week intervals thereafter. Reliability was assessed based on two proximal measures of FVC, validity was assessed based on correlations between FVC and other measures of functional status, and responsiveness was assessed based on the relationship between 24-week changes in FVC and other measures of functional status. Distribution-based and anchor-based methods were used to estimate the MCID.Measurements and Main Results: Correlation of percent-predicted FVC between measurements(mean interval, 18 d) was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters were generally weak, with the strongest observed correlation between FVC and carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between change in FVC and changes in other parameters were slightly stronger (range, r = 0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold higher (P, 0.001) in patients with a 24-week decline in FVC between 5% and 10%. The estimated MCID was 2-6%.Conclusions: FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference.