{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:34:32Z","timestamp":1788572072744,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tianjin Medical Key Specialty Construction Project","award":["TJYXZDXK-018A"],"award-info":[{"award-number":["TJYXZDXK-018A"]}]},{"name":"Tianjin Medical Key Specialty Construction Project","award":["2024TJMT001"],"award-info":[{"award-number":["2024TJMT001"]}]},{"name":"Tianjin Medical Key Specialty Construction Project","award":["TJWJ2024QN063"],"award-info":[{"award-number":["TJWJ2024QN063"]}]},{"name":"Tianjin Metrology Science and Technology Project","award":["TJYXZDXK-018A"],"award-info":[{"award-number":["TJYXZDXK-018A"]}]},{"name":"Tianjin Metrology Science and Technology Project","award":["2024TJMT001"],"award-info":[{"award-number":["2024TJMT001"]}]},{"name":"Tianjin Metrology Science and Technology Project","award":["TJWJ2024QN063"],"award-info":[{"award-number":["TJWJ2024QN063"]}]},{"name":"Tianjin Health Research Project","award":["TJYXZDXK-018A"],"award-info":[{"award-number":["TJYXZDXK-018A"]}]},{"name":"Tianjin Health Research Project","award":["2024TJMT001"],"award-info":[{"award-number":["2024TJMT001"]}]},{"name":"Tianjin Health Research Project","award":["TJWJ2024QN063"],"award-info":[{"award-number":["TJWJ2024QN063"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Air pollutants have both acute and chronic impacts on human health, affecting multiple systems and organs. While PM2.5 exposure is commonly assumed to be strongly associated with all respiratory diseases, this relationship has not been systematically analyzed. This study employed a two-sample Mendelian randomization approach to investigate the effects of PM2.5 on eight common lung diseases, using data from GWAS. Additionally, multivariable Mendelian randomization was applied to assess the direct effects of various air pollutants and the mediating roles of common factors such as BMI and smoking. At a significance threshold of 5\u00d710\u22128, PM2.5 showed a significant causal relationship with both asthma and COPD. When the screening threshold was relaxed to 5\u00d7 10\u22126, this exposure continued to demonstrate significant associations not only with asthma and COPD, but also with other respiratory diseases, including pneumonia, emphysema\/chronic bronchitis, and lung cancer. In the multivariable Mendelian randomization analysis, which controlled for smoking and bacterial infections, the association with pneumonia became non-significant, while the relationships with the other four diseases persisted. This study provides a systematic exploration of the relationship between PM2.5 and eight pulmonary diseases from a new perspective, deepening our understanding of the impact of air pollution on health and laying the foundation for future efforts to mitigate these effects.<\/jats:p>","DOI":"10.3390\/toxics12120851","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T05:06:53Z","timestamp":1732597613000},"page":"851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Relationship Between PM2.5 and Eight Common Lung Diseases: A Two-Sample Mendelian Randomization Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Yuhang","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Medical School, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin 300100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic, Tianjin Chest Hospital Affiliated to Tianjin University, Tianjin 300051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Medical School, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7175-6767","authenticated-orcid":false,"given":"Fang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Medical School, Tianjin University, Tianjin 300072, China"},{"name":"Department of Thoracic, Tianjin Chest Hospital Affiliated to Tianjin University, Tianjin 300051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xike","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Thoracic, Tianjin Chest Hospital Affiliated to Tianjin University, Tianjin 300051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Medical School, Tianjin University, Tianjin 300072, China"},{"name":"Department of Thoracic, Tianjin Chest Hospital Affiliated to Tianjin University, Tianjin 300051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2222-4657","authenticated-orcid":false,"given":"Daqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Medical School, Tianjin University, Tianjin 300072, China"},{"name":"Department of Thoracic, Tianjin Chest Hospital Affiliated to Tianjin University, Tianjin 300051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic, Tianjin Chest Hospital Affiliated to Tianjin University, Tianjin 300051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S2213-2600(14)70168-7","article-title":"Respiratory risks from household air pollution in low and middle income countries","volume":"2","author":"Gordon","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7520","DOI":"10.1002\/anie.200501122","article-title":"Atmospheric Aerosols: Composition, Transformation, Climate and Health Effects","volume":"44","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/ije\/dyt150","article-title":"Meta-analysis of the effects of indoor nitrogen dioxide and gas cooking on asthma and wheeze in children","volume":"42","author":"Lin","year":"2013","journal-title":"Int. J. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1080\/10473289.1997.10464074","article-title":"Fine Particles and Coarse Particles: Concentration Relationships Relevant to Epidemiologic Studies","volume":"47","author":"Wilson","year":"1997","journal-title":"J. Air Waste Manag. Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"483","DOI":"10.5114\/aoms.2010.14458","article-title":"Air pollution and non-respiratory health hazards for children","volume":"4","author":"Kelishadi","year":"2010","journal-title":"Arch. Med. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1078\/1438-4639-00306","article-title":"Health effects of particles in ambient air","volume":"207","author":"Kappos","year":"2004","journal-title":"Int. J. Hydrogen Environ. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107004","DOI":"10.1289\/EHP7246","article-title":"Fine Particulate Matter Exposure and Cancer Incidence: Analysis of SEER Cancer Registry Data from 1992\u20132016","volume":"128","author":"Coleman","year":"2020","journal-title":"Environ. Health Perspect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.envint.2011.03.003","article-title":"Ambient air pollution, climate change, and population health in China","volume":"42","author":"Kan","year":"2012","journal-title":"Environ. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ccl.2016.09.001","article-title":"Environmental Exposures and Cardiovascular Disease","volume":"35","author":"Rollins","year":"2017","journal-title":"Cardiol. Clin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.scitotenv.2016.11.147","article-title":"The burden of lung cancer mortality attributable to fine particles in China","volume":"579","author":"Guo","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1016\/j.scitotenv.2009.12.030","article-title":"An evaluation of resident exposure to respirable particulate matter and health economic loss in Beijing during Beijing 2008 Olympic Games","volume":"408","author":"Hou","year":"2010","journal-title":"Sci. Total Environ."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dong, G.-H., Chen, T., Liu, M.-M., Wang, D., Ma, Y.-N., Ren, W.-H., Lee, Y.L., Zhao, Y.-D., and He, Q.-C. (2011). Gender Differences and Effect of Air Pollution on Asthma in Children with and without Allergic Predisposition: Northeast Chinese Children Health Study. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022470"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11869-011-0145-4","article-title":"Long-term exposure to outdoor air pollution and the prevalence of asthma: Meta-analysis of multi-community prevalence studies","volume":"6","author":"Anderson","year":"2013","journal-title":"Air Qual. Atmos. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1802140","DOI":"10.1183\/13993003.02140-2018","article-title":"Air pollution, lung function and COPD: Results from the population-based UK Biobank study","volume":"54","author":"Doiron","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1016\/j.atmosenv.2011.02.066","article-title":"Spatial and temporal variation of chemical composition and mass closure of ambient coarse particulate matter (PM10\u20132.5) in the Los Angeles area","volume":"45","author":"Cheung","year":"2011","journal-title":"Atmos. Environ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.scitotenv.2019.05.470","article-title":"Short-term and long-term effects of PM2.5 on acute nasopharyngitis in 10 communities of Guangdong, China","volume":"688","author":"Zhang","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1097\/EDE.0b013e318294beaa","article-title":"Long- and Short-Term Exposure to PM2.5 and Mortality: Using Novel Exposure Models","volume":"24","author":"Kloog","year":"2013","journal-title":"Epidemiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: Genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Hemani","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a038984","DOI":"10.1101\/cshperspect.a038984","article-title":"Multivariable Mendelian Randomization and Mediation","volume":"11","author":"Sanderson","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ajhg.2011.11.029","article-title":"Five Years of GWAS Discovery","volume":"90","author":"Visscher","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11195","DOI":"10.1021\/es301948k","article-title":"Development of Land Use Regression Models for PM2.5, PM2.5 Absorbance, PM 10 and PM coarse in 20 European Study Areas; Results of the ESCAPE Project","volume":"46","author":"Eeftens","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"CRP CHD Genetics Collaboration Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e73218","DOI":"10.7554\/eLife.73218","article-title":"A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor","volume":"10","author":"Huang","year":"2021","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hemani, G., Tilling, K., and Davey Smith, G. (2017). Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet., 13.","DOI":"10.1101\/117101"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fu, S., Zhang, L., Ma, F., Xue, S., Sun, T., and Xu, Z. (2022). Effects of Selenium on Chronic Kidney Disease: A Mendelian Randomization Study. Nutrients, 14.","DOI":"10.3390\/nu14214458"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1093\/aje\/kwt084","article-title":"Efficient Design for Mendelian Randomization Studies: Subsample and 2-Sample Instrumental Variable Estimators","volume":"178","author":"Pierce","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"The LifeLines Cohort Study, The InterAct Consortium, kConFab\/AOCS Investigators, Endometrial Cancer Association Consortium, Ovarian Cancer Association Consortium, PRACTICAL consortium, Day, F.R., Thompson, D.J., Helgason, H., and Chasman, D.I. (2017). Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. Nat. Genet., 49, 834\u2013841.","DOI":"10.1038\/ng.3841"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur. J. Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1093\/aje\/kwu234","article-title":"Air Pollution and Acute Respiratory Infections Among Children 0\u20134 Years of Age: An 18-Year Time-Series Study","volume":"180","author":"Darrow","year":"2014","journal-title":"Am. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1080\/15287394.2014.922388","article-title":"Short-Term Effects of Fine Particulate Air Pollution on Hospital Admissions for Respiratory Diseases: A Case-Crossover Study in a Tropical City","volume":"77","author":"Tsai","year":"2014","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1289\/ehp.0901292","article-title":"Short-Term Effects of Air Pollution on Wheeze in Asthmatic Children in Fresno, California","volume":"118","author":"Mann","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/aje\/kwx166","article-title":"Long-Term PM2.5 Exposures and Respiratory, Cancer and Cardiovascular Mortality in American Older Adults","volume":"186","author":"Pun","year":"2017","journal-title":"Am. J. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1001\/jamainternmed.2022.4696","article-title":"Association of Particulate Matter Exposure With Lung Function and Mortality Among Patients With Fibrotic Interstitial Lung Disease","volume":"182","author":"Goobie","year":"2022","journal-title":"JAMA Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3322\/caac.21632","article-title":"Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations","volume":"70","author":"Turner","year":"2020","journal-title":"CA A Cancer J. Clin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.envres.2015.11.004","article-title":"The association between lung cancer incidence and ambient air pollution in China: A spatiotemporal analysis","volume":"144","author":"Guo","year":"2016","journal-title":"Environ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.scitotenv.2018.07.237","article-title":"Air pollution, land use, and complications of pregnancy","volume":"645","author":"Choe","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/s13046-022-02437-8","article-title":"PM2.5 promotes NSCLC carcinogenesis through translationally and transcriptionally activating DLAT-mediated glycolysis reprograming","volume":"41","author":"Chen","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/1091581816682224","article-title":"Effects of Components of PM2.5 Collected in Japan on the Respiratory and Immune Systems","volume":"36","author":"Honda","year":"2017","journal-title":"Int. J. Toxicol."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/12\/851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:39:30Z","timestamp":1760114370000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/12\/851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,26]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["toxics12120851"],"URL":"https:\/\/doi.org\/10.3390\/toxics12120851","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,26]]}}}