Air pollution, genetic factors, and chronic rhinosinusitis: A prospective study in the UK Biobank

Background: Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition that manifests in two primary subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While previous studies indicate a correlation between air pollution and CRS, the role of genetic predisposition in this relationship remains largely unexplored. We hypothesized that higher air pollution exposure would lead to the development of CRS, and that genetic susceptibility might modify this association. Methods: This cohort study involving 367,298 adult participants from the UK Biobank, followed from March 2006 to October 2021. Air pollution metrics were estimated at residential locations using land-use regression models. Cox proportional hazard models were employed to explore the associations between air pollution exposure and CRS, CRSwNP, and CRSsNP. A polygenic risk score (PRS) was constructed to evaluate the joint effect of air pollution and genetic predisposition on the development of CRS. Results: We found that the risk of CRS increased under long-term exposure to PM_2.5 [the hazard ratios (HRs) with 95 % CIs: 1.59 (1.26–2.01)], PM₁₀ [1.64 (1.26–2.12)], NO₂ [1.11 (1.04–1.17)], and NO_x [1.18 (1.12–1.25)], respectively. These effects were more pronounced among participants with CRSwNP, although the differences were not statistically significant. Additionally, we found that the risks for CRS and CRSwNP increased in a graded manner among participants with higher PRS or higher exposure to PM_2.5, PM₁₀, or NO_x concentrations. However, no multiplicative or additive interactions were observed. Conclusions: Long-term exposure to air pollution increases the risk of CRS, particularly CRSwNP underscoring the need to prioritize clean air initiatives and environmental regulations.