{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:30:28Z","timestamp":1791095428980,"version":"4.1.0"},"reference-count":18,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"funder":[{"DOI":"10.13039\/501100000082","name":"Cystic Fibrosis Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000082","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000092","name":"Ontario Genomics Institute","doi-asserted-by":"publisher","award":["OGI-148"],"award-info":[{"award-number":["OGI-148"]}],"id":[{"id":"10.13039\/501100000092","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006126","name":"Hospital for Sick Children","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006126","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,3,8]]},"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In people with cystic fibrosis (pwCF), human nasal epithelial cell (HNEC) cultures can be used to assess response to CF transmembrane conductance regulator (CFTR) modulators. However, thresholds of\n                      <jats:italic>in vitro<\/jats:italic>\n                      responses that predict clinical benefit remain poorly understood. In this study we describe the concordance between\n                      <jats:italic>in vitro<\/jats:italic>\n                      response in HNECs and clinical outcomes in pwCF harbouring the F508del variant, treated with either lumacaftor\/ivacaftor, tezacaftor\/ivacaftor or elexacaftor\/tezacaftor\/ivacaftor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Response of HNECs to CFTR modulators was assessed by CFTR-mediated chloride current stimulated by forskolin or inhibited by CFTRinh-172 in both pwCF and healthy controls. Clinical response was defined as change in forced expiratory volume in 1\u2005s (FEV\n                      <jats:sub>1<\/jats:sub>\n                      ), lung clearance index (LCI), sweat chloride or respiratory domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) between baseline and within 3\u2005months after the start of modulator treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 58 unique\n                      <jats:italic>in vitro<\/jats:italic>\n                      \u2013clinical pairs,\n                      <jats:italic>in vitro<\/jats:italic>\n                      measures of functional rescue correlated with changes in FEV\n                      <jats:sub>1<\/jats:sub>\n                      , LCI and sweat chloride, but not CFQ-R. The concordance between\n                      <jats:italic>in vitro<\/jats:italic>\n                      response and clinical outcomes was highest when a composite outcome was used. For example, an\n                      <jats:italic>in vitro<\/jats:italic>\n                      response of 10% of healthy controls had positive and negative predictive values of 90.5% and 100%, respectively, for a clinical response in either FEV\n                      <jats:sub>1<\/jats:sub>\n                      , LCI or sweat chloride.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified thresholds of nasal epithelial cell theratype response in pwCF to predict clinical benefit from CFTR modulator therapy. The utility of this therapy testing platform to predict a clinical response improves when multiple clinical outcome measures are combined.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.01855-2024","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T08:00:21Z","timestamp":1744272021000},"page":"2401855","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Relationship between theratyping in nasal epithelial cells and clinical outcomes in people with cystic fibrosis"],"prefix":"10.1183","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4057-6592","authenticated-orcid":false,"given":"Felix","family":"Ratjen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Stanojevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarini","family":"Gunawardena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul 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J.","family":"Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Gonska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"2025070401550711000_65.6.2401855.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2216474"},{"key":"2025070401550711000_65.6.2401855.2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01959-2023"},{"key":"2025070401550711000_65.6.2401855.3","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00110-2023"},{"key":"2025070401550711000_65.6.2401855.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2019.06.010"},{"key":"2025070401550711000_65.6.2401855.5","doi-asserted-by":"publisher","DOI":"10.3390\/children10010004"},{"key":"2025070401550711000_65.6.2401855.6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094448"},{"key":"2025070401550711000_65.6.2401855.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2018.03.013"},{"key":"2025070401550711000_65.6.2401855.8","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02774-2020"},{"key":"2025070401550711000_65.6.2401855.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2020.07.015"},{"key":"2025070401550711000_65.6.2401855.10","doi-asserted-by":"publisher","DOI":"10.3390\/jpm10040209"},{"key":"2025070401550711000_65.6.2401855.11","doi-asserted-by":"publisher","DOI":"10.3390\/cells12081174"},{"key":"2025070401550711000_65.6.2401855.12","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02398-2021"},{"key":"2025070401550711000_65.6.2401855.13","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02437-2022"},{"key":"2025070401550711000_65.6.2401855.14","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01307-2022"},{"key":"2025070401550711000_65.6.2401855.15","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202110-2249OC"},{"key":"2025070401550711000_65.6.2401855.16","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202201-0219OC"},{"key":"2025070401550711000_65.6.2401855.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0394-6"},{"key":"2025070401550711000_65.6.2401855.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2018.01.008"}],"container-title":["European 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