Causal effects of air pollutants on lung function and chronic respiratory diseases: a Mendelian randomization study

Our study aims to clarify the causality between air pollutants and lung function, chronic respiratory diseases, and the potential mediating effects of inflammatory proteins.

We employed Mendelian Randomization (MR) analysis with comprehensive instrumental variables screening criteria to investigate the effects of air pollutants on lung function and chronic lung diseases. Our study incorporated genetic instruments for air pollutants, ensuring F-statistics above 20.86. A total of 18 MR analyses were conducted using the inverse-variance weighted approach, along with heterogeneity and pleiotropy tests to validate the results. Mediated MR analysis was utilized to evaluate the inflammatory proteins mediating the effects of air pollutants.

MR analysis demonstrated significant causal interactions of particulate matter 2.5 (PM_2.5), PM₁₀, and Nitrogen dioxide (NO₂) with lung function decline. Specifically, PM₁₀ negatively affected forced expiratory volume in one second (FEV₁) (OR: 0.934, 95% CI: 0.904-0.965, p = 4.27 × 10^-5), forced vital capacity (FVC) (OR: 0.941, 95% CI: 0.910-0.972, p = 2.86 × 10^-4), and FEV₁/FVC (OR: 0.965, 95% CI: 0.934-0.998, p = 0.036). PM_2.5 and NO₂ were identified as potential risk factors for impairing FEV₁ (OR: 0.936, 95% CI: 0.879-0.998, p = 0.042) and FEV₁/FVC (OR: 0.943, 95% CI: 0.896-0.992, p = 0.024), respectively. For chronic respiratory diseases, PM_2.5 and NO₂ were associated with increased COPD incidence (OR: 1.273, 95% CI: 1.053-1.541, p = 0.013 for PM_2.5; OR: 1.357, 95% CI: 1.165-1.581, p = 8.74 × 10^-5 for NO₂). Sensitivity analyses confirmed the robustness of these findings, with no significant heterogeneity or horizontal pleiotropy detected.

Our study ascertained the causal correlations of air pollutants with lung function and COPD, emphasizing the importance of reducing air pollution. Interleukin-17A mediates the reduction of FEV₁ and FVC by PM₁₀, revealing potential therapeutic targets.