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

Feipeng Cui, Yu Sun, Junqing Xie, Dankang Li, Mingyang Wu, Lulu Song, Yonghua Hu, Yaohua Tian
European Respiratory Journal 2023 61: 2200777; DOI: 10.1183/13993003.00777-2022
Feipeng Cui
1Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
2Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
6Feipeng Cui and Yu Sun contributed equally to this work
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Yu Sun
3Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
6Feipeng Cui and Yu Sun contributed equally to this work
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Junqing Xie
4Center for Statistics in Medicine, NDORMS, The Botnar Research Centre, University of Oxford, Oxford, UK
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Dankang Li
1Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
2Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
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Mingyang Wu
1Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
2Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
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Lulu Song
1Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
2Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
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Yonghua Hu
5Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
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Yaohua Tian
1Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
2Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
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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 (NOx) and particulate matter (fine particulate matter with diameter <2.5 μm (PM2.5) 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, NOx and PM2.5 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. PM2.5 had the highest population attribution risk, followed by NOx and NO2. There were additive interactions between NO2, NOx and PM2.5 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), NOx 3.08 (95% CI 2.21–4.27), PM2.5 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.

Abstract

Long-term exposures to air pollutants were significantly associated with increased risk of incident idiopathic pulmonary fibrosis (IPF). Associations between air pollutants and risk of incident IPF were strengthened by genetic susceptibility to IPF. https://bit.ly/3BUDT7k

Footnotes

  • Author contributions: Feipeng Cui, Yu Sun, Junqing Xie and Yaohua Tian conceived the idea for the study, planned and carried out all the statistical analyses, and drafted the manuscript. Dankang Li, Mingyang Wu, Lulu Song and Yonghua Hu advised on all statistical aspects and interpreted the data. Yaohua Tian provided a critical review of the manuscript. All authors read the manuscript and approved the final version of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted, had full access to all the data in the study, and agrees to be accountable for all aspects of the work.

  • This article has an editorial commentary: https://doi.org/10.1183/13993003.02113-2022

  • Conflict of interest: The authors disclose that there are no potential competing financial interests or personal relationships that could affect the work reported in this article.

  • Received April 13, 2022.
  • Accepted September 6, 2022.
  • Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org
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Air pollutants, genetic susceptibility and risk of incident idiopathic pulmonary fibrosis
Feipeng Cui, Yu Sun, Junqing Xie, Dankang Li, Mingyang Wu, Lulu Song, Yonghua Hu, Yaohua Tian
European Respiratory Journal Feb 2023, 61 (2) 2200777; DOI: 10.1183/13993003.00777-2022

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Air pollutants, genetic susceptibility and risk of incident idiopathic pulmonary fibrosis
Feipeng Cui, Yu Sun, Junqing Xie, Dankang Li, Mingyang Wu, Lulu Song, Yonghua Hu, Yaohua Tian
European Respiratory Journal Feb 2023, 61 (2) 2200777; DOI: 10.1183/13993003.00777-2022
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