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Non\u2010eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non\u2010eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies. The cystic fibrosis transmembrane conductance regulator (CFTR) is dysregulated in multiple respiratory diseases including cystic fibrosis and chronic obstructive pulmonary disease and has proven a valuable therapeutic target. We hypothesized that the CFTR may also play a role in non\u2010eosinophilic asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patient\u2010derived human bronchial epithelial cells (hBECs) were isolated and differentiated at the air\u2010liquid interface. Single cell RNA\u2010sequencing (scRNAseq) was used to identify epithelial cell subtypes and transcriptional activity. Ion transport was investigated with Ussing chambers and immunofluorescent quantification of ionocyte abundance in human airway epithelial cells and murine models of asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified that hBECs from patients with non\u2010eosinophilic asthma had reduced CFTR function, and did not differentiate into CFTR\u2010expressing ionocytes compared to those from eosinophilic asthma or healthy donors. Similarly, ionocytes were also diminished in the airways of a murine model of neutrophilic\u2010dominant but not eosinophilic asthma. Treatment of hBECs from healthy donors with a neutrophilic asthma\u2010like inflammatory cytokine mixture led to a reduction in ionocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inflammation\u2010induced loss of CFTR\u2010expressing ionocytes in airway cells from non\u2010eosinophilic asthma may represent a key feature of disease pathogenesis and a novel drug target.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/resp14833-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/resp.14833","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T02:00:48Z","timestamp":1727920848000},"page":"25-40","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inflammation\u2010induced loss of\n                    <scp>CFTR<\/scp>\n                    \u2010expressing airway ionocytes in non\u2010eosinophilic asthma"],"prefix":"10.1111","volume":"30","author":[{"given":"Ling","family":"Chen","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy University of Newcastle  Newcastle New South Wales Australia"},{"name":"Immune Health Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"A. Hoefel","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy University of Newcastle  Newcastle New South Wales Australia"},{"name":"Immune Health Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4947-5918","authenticated-orcid":false,"given":"Prabuddha S.","family":"Pathinayake","sequence":"additional","affiliation":[{"name":"Immune Health Program Hunter Medical Research Institute  New Lambton Heights New South Wales Australia"},{"name":"School of Medicine and Public Health University of Newcastle  Newcastle New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-7025","authenticated-orcid":false,"given":"Andrew","family":"Reid","sequence":"additional","affiliation":[{"name":"Immune Health Program Hunter Medical Research Institute  New Lambton 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