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characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma\/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1\/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies.<\/jats:p>","DOI":"10.3390\/ijms24129913","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:59:57Z","timestamp":1686279597000},"page":"9913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["COPD Patients Exhibit Distinct Gene Expression, Accelerated Cellular Aging, and Bias to M2 Macrophages"],"prefix":"10.3390","volume":"24","author":[{"given":"Camila Oliveira","family":"da Silva","sequence":"first","affiliation":[{"name":"Laboratory of Histocompatibility and Cryopreservation, University of the State of Rio de Janeiro, Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4952-2278","authenticated-orcid":false,"given":"Jeane","family":"de Souza Nogueira","sequence":"additional","affiliation":[{"name":"Laboratory of Histocompatibility and Cryopreservation, University of the State of Rio de Janeiro, Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-3651","authenticated-orcid":false,"given":"Adriana Paulino","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"University Center of Valencia (UNIFAA), Rio de Janeiro 27600-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Victoni","sequence":"additional","affiliation":[{"name":"VetAgro Sup, University of Lyon, APCSe, 69280 Marcy l\u2019\u00c9toile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Prudente","family":"B\u00e1rtholo","sequence":"additional","affiliation":[{"name":"Department of Thorax, University of the State of Rio de Janeiro, Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-0753","authenticated-orcid":false,"given":"Cl\u00e1udia Henrique","family":"da Costa","sequence":"additional","affiliation":[{"name":"Department of Thorax, University of the State of Rio de Janeiro, Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Monte Alto","family":"Costa","sequence":"additional","affiliation":[{"name":"Tissue Repair Laboratory, University of the State of Rio de Janeiro, Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1868-9905","authenticated-orcid":false,"given":"Samuel dos Santos","family":"Valen\u00e7a","sequence":"additional","affiliation":[{"name":"Laboratory of Redox Biology, ICB, Federal University of Rio de Janeiro, Rio de Janeiro 21941-853, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3075-0630","authenticated-orcid":false,"given":"Martina","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, GRIAC, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-1821","authenticated-orcid":false,"given":"Lu\u00eds Crist\u00f3v\u00e3o","family":"Porto","sequence":"additional","affiliation":[{"name":"Laboratory of Histocompatibility and Cryopreservation, University of the State of Rio de Janeiro, Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1183\/09031936.00082507","article-title":"Definition, epidemiology and natural history of COPD","volume":"30","author":"Viegi","year":"2007","journal-title":"Eur. 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