{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T18:27:04Z","timestamp":1794508024243,"version":"4.9.1"},"reference-count":18,"publisher":"BMJ","issue":"8","funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["REEVES21G0"],"award-info":[{"award-number":["REEVES21G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Elaine Galwey Memorial Research Bursary","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/501100016387","name":"Grifols","doi-asserted-by":"publisher","award":["Alpha-1 Laurells Training Award n\/a"],"award-info":[{"award-number":["Alpha-1 Laurells Training Award n\/a"]}],"id":[{"id":"10.13039\/501100016387","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012921","name":"Royal College of Surgeons in Ireland","doi-asserted-by":"publisher","award":["StAR MD programme n\/a"],"award-info":[{"award-number":["StAR MD programme n\/a"]}],"id":[{"id":"10.13039\/100012921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2023,4,6]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>\n                    Treatment with elexacaftor\/tezacaftor\/ivacaftor (ETI) has been shown to improve lung function in people with cystic fibrosis (PWCF). However, its biological effects remain incompletely understood. Here we describe alterations in pulmonary and systemic inflammation in PWCF following initiation of ETI. To address this, we collected spontaneously expectorated sputum and matching plasma from PWCF (n=30) immediately prior to ETI therapy, then again at 3 and 12 months. Within 3 months, PWCF demonstrated reduced activity of neutrophil elastase, proteinase three and cathepsin G, and decreased concentrations of interleukin (IL)\u22121\u03b2 and IL-8 in sputum, accompanied by decreased\n                    <jats:italic>Pseudomonas<\/jats:italic>\n                    burden and restoration of secretory leukoprotease inhibitor levels. Once treated with ETI, all airway inflammatory markers studied in PWCF had reduced to levels found in matched non-CF bronchiectasis controls. In PWCF with advanced disease, ETI resulted in decreased plasma concentrations of IL-6, C-reactive protein and soluble TNF receptor one as well as normalisation of levels of the acute phase protein, alpha-1 antitrypsin. These data clarify the immunomodulatory effects of ETI and underscore its role as a disease modifier.\n                  <\/jats:p>","DOI":"10.1136\/thorax-2022-219943","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T13:25:38Z","timestamp":1684502738000},"page":"835-839","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":138,"title":["Effect of elexacaftor\/tezacaftor\/ivacaftor on airway and systemic inflammation in cystic fibrosis"],"prefix":"10.1136","volume":"78","author":[{"given":"Michelle","family":"Casey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudie","family":"Gabillard-Lefort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ois\u00edn F","family":"McElvaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver J","family":"McElvaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-1641","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan C","family":"Heeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Gunaratnam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emer P","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5624-1338","authenticated-orcid":false,"given":"Mark P","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel G","family":"McElvaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"2024051320421095000_78.8.835.1","article-title":"Muco-obstructive lung diseases. Reply","volume":"381","author":"Boucher","year":"2019","journal-title":"N Engl J Med"},{"key":"2024051320421095000_78.8.835.2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901716"},{"key":"2024051320421095000_78.8.835.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301725"},{"key":"2024051320421095000_78.8.835.4","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2002.129847"},{"key":"2024051320421095000_78.8.835.5","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200703-044BR"},{"key":"2024051320421095000_78.8.835.6","doi-asserted-by":"publisher","DOI":"10.1038\/nm1690"},{"key":"2024051320421095000_78.8.835.7","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1164\/rccm.201905-1013OC","article-title":"Specific inhibition of the NLRP3 inflammasome as an antiinflammatory strategy in cystic fibrosis","volume":"200","author":"McElvaney","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2024051320421095000_78.8.835.8","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aav4634","article-title":"CFTR-pten-dependent mitochondrial metabolic dysfunction promotes pseudomonas aeruginosa airway infection","volume":"11","author":"Riquelme","year":"2019","journal-title":"Sci Transl Med"},{"key":"2024051320421095000_78.8.835.9","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S2213-2600(21)00103-X","article-title":"Interleukin-6: obstacles to targeting a complex cytokine in critical illness","volume":"9","author":"McElvaney","year":"2021","journal-title":"Lancet Respir Med"},{"key":"2024051320421095000_78.8.835.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32597-8"},{"key":"2024051320421095000_78.8.835.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908639"},{"key":"2024051320421095000_78.8.835.12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jcf.2018.06.001","article-title":"A specialized method of sputum collection and processing for therapeutic interventions in cystic fibrosis","volume":"18","author":"McElvaney","year":"2019","journal-title":"J Cyst Fibros"},{"key":"2024051320421095000_78.8.835.13","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-0693"},{"key":"2024051320421095000_78.8.835.14","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201609-1954OC"},{"key":"2024051320421095000_78.8.835.15","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.642180","article-title":"Ivacaftor reduces inflammatory mediators in upper airway lining fluid from cystic fibrosis patients with a G551D mutation: serial non-invasive home-based collection of upper airway lining fluid","volume":"12","author":"Mainz","year":"2021","journal-title":"Front Immunol"},{"key":"2024051320421095000_78.8.835.16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/ppul.26261","article-title":"Impact of elexacaftor-tezacaftor-ivacaftor on bacterial colonization and inflammatory responses in cystic fibrosis","volume":"58","author":"Sheikh","year":"2023","journal-title":"Pediatr Pulmonol"},{"key":"#cr-split#-2024051320421095000_78.8.835.17.1","doi-asserted-by":"crossref","unstructured":"Casey M , Gabillard-Lefort C , Fraughen D , et al . The impact of elexacaftor\/tezacaftor\/ivacaftor on the protease-antiprotease balance in cystic fibrosis airways. American Thoracic Society 2022 International Conference, May 13-18, 2022 - San Francisco, CA","DOI":"10.1164\/ajrccm-conference.2022.205.1_MeetingAbstracts.A1465"},{"key":"#cr-split#-2024051320421095000_78.8.835.17.2","doi-asserted-by":"crossref","unstructured":"May 2022:A1465 doi:10.1164\/ajrccm-conference.2022.205.1_MeetingAbstracts.A1465","DOI":"10.1164\/ajrccm-conference.2022.205.1_MeetingAbstracts.A1465"}],"container-title":["Thorax"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/thorax-2022-219943","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T23:56:48Z","timestamp":1715644608000},"score":1,"resource":{"primary":{"URL":"https:\/\/thorax.bmj.com\/lookup\/doi\/10.1136\/thorax-2022-219943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":18,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,7,13]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/thorax-2022-219943"],"URL":"https:\/\/doi.org\/10.1136\/thorax-2022-219943","relation":{},"ISSN":["0040-6376","1468-3296"],"issn-type":[{"value":"0040-6376","type":"print"},{"value":"1468-3296","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]}}}