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We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).<\/jats:p>\n                  <jats:p>A transgenic mouse model of chronic type 2 pulmonary inflammation (I5\/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.<\/jats:p>\n                  <jats:p>\n                    Airspace enlargement was identified in I5\/hE2 mice and was dependent on eosinophils. Examination of I5\/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed,\n                    <jats:italic>in vitro<\/jats:italic>\n                    , that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5\/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4\/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1\u2005s.\n                  <\/jats:p>\n                  <jats:p>A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4\/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.<\/jats:p>","DOI":"10.1183\/13993003.01291-2018","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:25:14Z","timestamp":1549499114000},"page":"1801291","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":88,"title":["Eosinophil-derived IL-13 promotes emphysema"],"prefix":"10.1183","volume":"53","author":[{"given":"Alfred D.","family":"Doyle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manali","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"LeSuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler B.","family":"Bittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saif\u00a0M.","family":"Pasha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-8873","authenticated-orcid":false,"given":"Justin J.","family":"Frere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"Neely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6646-564X","authenticated-orcid":false,"given":"Jake A.","family":"Kloeber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly\u00a0P.","family":"Shim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei I.","family":"Ochkur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Svenningsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin\u00a0L.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Rank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Jacobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2019,2,6]]},"reference":[{"key":"2024102100482392000_53.5.1801291.1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2500\/aap.2015.36.3812","article-title":"Burden of chronic obstructive pulmonary disease: healthcare costs and beyond","volume":"36","author":"May","year":"2015","journal-title":"Allergy Asthma Proc"},{"key":"2024102100482392000_53.5.1801291.2","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.00009014"},{"key":"2024102100482392000_53.5.1801291.3","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.chest.2017.05.019","article-title":"New anti-eosinophil drugs for asthma and COPD: targeting the trait!","volume":"152","author":"Bel","year":"2017","journal-title":"Chest"},{"key":"2024102100482392000_53.5.1801291.4","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.jaci.2018.02.035","article-title":"Chronic obstructive pulmonary disease subpopulations and phenotyping","volume":"141","author":"Segal","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"2024102100482392000_53.5.1801291.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.05.011"},{"key":"2024102100482392000_53.5.1801291.6","first-page":"39","article-title":"Eosinophilic airway inflammation in COPD","volume":"1","author":"Saha","year":"2006","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"2024102100482392000_53.5.1801291.7","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S2213-2600(17)30217-5","article-title":"Eosinophils in COPD: just another biomarker?","volume":"5","author":"Bafadhel","year":"2017","journal-title":"Lancet Respir Med"},{"key":"2024102100482392000_53.5.1801291.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1411863"},{"key":"2024102100482392000_53.5.1801291.9","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1164\/rccm.201509-1869OC","article-title":"Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. 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