Air pollutants, genetic susceptibility and risk of incident idiopathic pulmonary fibrosis

Background Air 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. Our objective was to explore the associations of air pollutants with IPF risk and further assess the modification effect of genetic susceptibility.Methods We used land-use regression model estimated concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOX) and particulate matter (fine particulate matter with diameter <2.5 mu m (PM2.5) and particulate matter with diameter <10 mu m (PM10)). The polygenic risk score (PRS) was constructed using 13 independent single nucleotide polymorphisms. 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.Results Among 433 738 participants from the UK Biobank, the incidence of IPF was 27.45 per 100 000 person-years during a median follow-up of 11.78 years. The adjusted hazard ratios of IPF for each interquartile range increase in NO2, NOX and PM2.5 were 1.11 (95% CI 1.03-1.19), 1.07 (95% CI 1.01- 1.13) and 1.09 (95% CI 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 a high PRS and high air pollution had the highest risk of incident IPF compared with those with a low PRS and low air pollution (adjusted hazard ratio: NO2 3.94 (95% CI 2.77-5.60), NOX 3.08 (95% CI 2.21-4.27), PM2.5 3.65 (95% CI 2.60-5.13) and PM10 3.23 (95% CI 2.32-4.50)).Conclusion Long-term exposures to air pollutants may elevate the risk of incident IPF. There are additive effects of air pollutants and genetic susceptibility on IPF risk.

Automated summary

This study aimed to explore the association between air pollutants and the risk of idiopathic pulmonary fibrosis (IPF), as well as the modification effect of genetic susceptibility. The results showed that long-term exposure to air pollutants may increase the risk of incident IPF, with additive effects between air pollutants and genetic susceptibility.