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

Abstract

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 (NO _x ) and particulate matter (fine particulate matter with diameter <2.5 μm (PM_2.5) and particulate matter with diameter <10 μm (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, NO _x and PM_2.5 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. PM_2.5 had the highest population attribution risk, followed by NO _x and NO₂. There were additive interactions between NO₂, NO _x and PM_2.5 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), NO _x 3.08 (95% CI 2.21-4.27), PM_2.5 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.