BackgroundAir pollutants are considered as non-negligible risk factors of idiopathic pulmonary fibrosis (IPF). However, the relationship between long-term air pollution and the incidence of IPF is unknown.ObjectiveTo explore the associations of air pollutants with IPF risk and further assess modification effect of genetic susceptibility.MethodsLand-use regression model estimated concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), and particulate matter (PM2.5 and PM10). The polygenic risk score (PRS) was constructed using 13 independent SNPs. The Cox proportional hazard models were used to evaluate the associations of air pollutants with IPF risk and further investigate the modification effect of genetic susceptibility. Additionally, absolute risk was calculated.ResultsAmong 433 738 participants from the UK Biobank, the incidence of IPF was 27.45/1 00 000 person-years during a median follow-up of 11.78 years. The adjusted hazard ratios (HRs) [95% confidence interval (CIs)] of IPF for each interquartile range increase in NO2, NOx, and PM2.5 were 1.11 (1.03, 1.19), 1.07 (1.01, 1.13), and 1.09 (1.02, 1.17), respectively. PM2.5 had the highest population attribution risk, followed by NOx and NO2. There were additive interactions between NO2, NOx and PM2.5 and genetic susceptibility. Participants with high PRS and high air pollution had the highest risk of incident IPF compared to those with low PRS and low air pollution [NO2: 3.94 (2.77, 5.60); NOx: 3.08 (2.21, 4.27); PM2.5: 3.65 (2.60, 5.13); PM10: 3.23 (2.32, 4.50)].ConclusionLong-term air pollutants exposures may elevate the risk of incident IPF. There are additive effects of air pollutants and genetic susceptibility on IPF risk.

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