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

Xuannian Li; Suqi Liu; Nan Jiang; Fei Xu; Huaman Liu; Xinhua Jia

doi:10.3389/fpubh.2024.1438974

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

Front Public Health. 2024 Sep 9:12:1438974. doi: 10.3389/fpubh.2024.1438974. eCollection 2024.

Authors

Xuannian Li¹, Suqi Liu¹, Nan Jiang¹, Fei Xu², Huaman Liu³, Xinhua Jia⁴

Affiliations

¹ The First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
² Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
³ Department of General Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
⁴ Department of Pneumology and Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

Abstract

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

Method: 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.

Result: 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.

Conclusion: 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.

Keywords: Mendelian randomization; air pollution; chronic respiratory diseases; inflammatory proteins; lung function.

MeSH terms

Air Pollutants* / adverse effects
Air Pollution / adverse effects
Chronic Disease
Environmental Exposure / adverse effects
Forced Expiratory Volume
Humans
Male
Mendelian Randomization Analysis*
Nitrogen Dioxide / adverse effects
Particulate Matter* / adverse effects
Respiratory Function Tests
Respiratory Tract Diseases / epidemiology

Substances

Air Pollutants
Particulate Matter
Nitrogen Dioxide

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by Research Foundation of Young Qihuang Scholars Training Project, Grant no. Qnqhxz-02 and Shandong Province Taishan Scholar Project, Grant no. No.tsqn202306393.