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It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at 2 concentrations, low (11.0\u2009\u00b1\u20091.89\u2009mg\/m3) and high (23.7\u2009\u00b1\u20090.077\u2009mg\/m3), over a 2-week period. Whole-body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24\u2009h after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only 1 gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae040","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T04:57:49Z","timestamp":1711601869000},"page":"332-348","source":"Crossref","is-referenced-by-count":4,"title":["Repeated exposure to eucalyptus wood smoke alters pulmonary gene and metabolic profiles in male Long-Evans rats"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-4265","authenticated-orcid":false,"given":"Samuel J","family":"Cochran","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Ohio State University Wexner Medical Center , Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3383-8446","authenticated-orcid":false,"given":"Katelyn","family":"Dunigan-Russell","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Ohio State University Wexner Medical Center , Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1100-1786","authenticated-orcid":false,"given":"Grace M","family":"Hutton","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Ohio State University Wexner Medical Center , Columbus, Ohio 43210,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4032-9663","authenticated-orcid":false,"given":"Helen","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education, U.S. Environmental Protection Agency, Center for Public Health and Environmental Assessment , Research Triangle Park, North Carolina 27711,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4562-4479","authenticated-orcid":false,"given":"Mette C","family":"Schladweiler","sequence":"additional","affiliation":[{"name":"Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2090-0677","authenticated-orcid":false,"given":"Dean P","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University , Atlanta, Georgia 30322,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda C","family":"Williams","sequence":"additional","affiliation":[{"name":"Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna A","family":"Fisher","sequence":"additional","affiliation":[{"name":"Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3070-6704","authenticated-orcid":false,"given":"M Ian","family":"Gilmour","sequence":"additional","affiliation":[{"name":"Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4220-2490","authenticated-orcid":false,"given":"Janice A","family":"Dye","sequence":"additional","affiliation":[{"name":"Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8889-3477","authenticated-orcid":false,"given":"M Ryan","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University , Atlanta, Georgia 30322,","place":["USA"]},{"name":"Atlanta Veterans Affairs Healthcare System , Decatur, Georgia 30033,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-7886","authenticated-orcid":false,"given":"Colette N","family":"Miller","sequence":"additional","affiliation":[{"name":"Cardiopulmonary and Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27711,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-0697","authenticated-orcid":false,"given":"Kymberly 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