{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:22:01Z","timestamp":1792092121261,"version":"4.4.0"},"reference-count":58,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Christiane Herzog Stiftung, Stuttgart, Germany","award":["2101 C-H-P"],"award-info":[{"award-number":["2101 C-H-P"]}]},{"name":"Christiane Herzog Stiftung, Stuttgart, Germany","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"Christiane Herzog Stiftung, Stuttgart, Germany","award":["CRC 1449"],"award-info":[{"award-number":["CRC 1449"]}]},{"name":"Mukoviszidose Institut gGmbH, Bonn","award":["2101 C-H-P"],"award-info":[{"award-number":["2101 C-H-P"]}]},{"name":"Mukoviszidose Institut gGmbH, Bonn","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"Mukoviszidose Institut gGmbH, Bonn","award":["CRC 1449"],"award-info":[{"award-number":["CRC 1449"]}]},{"name":"German Cystic Fibrosis Association Mukoviszidose e.V.","award":["2101 C-H-P"],"award-info":[{"award-number":["2101 C-H-P"]}]},{"name":"German Cystic Fibrosis Association Mukoviszidose e.V.","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"German Cystic Fibrosis Association Mukoviszidose e.V.","award":["CRC 1449"],"award-info":[{"award-number":["CRC 1449"]}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["2101 C-H-P"],"award-info":[{"award-number":["2101 C-H-P"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["CRC 1449"],"award-info":[{"award-number":["CRC 1449"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Research Foundation","award":["2101 C-H-P"],"award-info":[{"award-number":["2101 C-H-P"]}]},{"name":"German Research Foundation","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"German Research Foundation","award":["CRC 1449"],"award-info":[{"award-number":["CRC 1449"]}]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","award":["2101 C-H-P"],"award-info":[{"award-number":["2101 C-H-P"]}]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","award":["CRC 1449"],"award-info":[{"award-number":["CRC 1449"]}]},{"name":"BIH","award":["2101 C-H-P"],"award-info":[{"award-number":["2101 C-H-P"]}]},{"name":"BIH","award":["82DZL009B1"],"award-info":[{"award-number":["82DZL009B1"]}]},{"name":"BIH","award":["CRC 1449"],"award-info":[{"award-number":["CRC 1449"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CFTR modulator therapy with elexacaftor\/tezacaftor\/ivacaftor (ETI) has been approved for people with CF and at least one F508del allele in Europe. In the US, the ETI label has been expanded to 177 rare CFTR mutations responsive in Fischer rat thyroid cells, including G85E, but not N1303K. However, knowledge on the effect of ETI on G85E or N1303K CFTR function remains limited. In vitro effects of ETI were measured in primary human nasal epithelial cultures (pHNECs) of a G85E homozygous patient and an N1303K homozygous patient. Effects of ETI therapy in vivo in these patients were assessed using clinical outcomes, including multiple breath washout and lung MRI, and the CFTR biomarkers sweat chloride concentration (SCC), nasal potential difference (NPD) and intestinal current measurement (ICM), before and after initiation of ETI. ETI increased CFTR-mediated chloride transport in G85E\/G85E and N1303K\/N1303K pHNECs. In the G85E\/G85E and the N1303K\/N1303K patient, we observed an improvement in lung function, SCC, and CFTR function in the respiratory and rectal epithelium after initiation of ETI. The approach of combining preclinical in vitro testing with subsequent in vivo verification can facilitate access to CFTR modulator therapy and enhance precision medicine for patients carrying rare CFTR mutations.<\/jats:p>","DOI":"10.3390\/ijms241512365","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T11:04:38Z","timestamp":1690974278000},"page":"12365","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Personalized CFTR Modulator Therapy for G85E and N1303K Homozygous Patients with Cystic Fibrosis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1666-8924","authenticated-orcid":false,"given":"Simon Y.","family":"Graeber","sequence":"first","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH) at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-5239","authenticated-orcid":false,"given":"Anita","family":"Bal\u00e1zs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Ziegahn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-4031","authenticated-orcid":false,"given":"Tihomir","family":"Rubil","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Vitzthum","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linus","family":"Piehler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Drescher","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Seidel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Rohrbach","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jobst","family":"R\u00f6hmel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH) at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9090-7869","authenticated-orcid":false,"given":"Stephanie","family":"Thee","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH) at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4862-9487","authenticated-orcid":false,"given":"Julia","family":"Duerr","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2199","authenticated-orcid":false,"given":"Marcus A.","family":"Mall","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH) at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-8315","authenticated-orcid":false,"given":"Mirjam","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13353 Berlin, Germany"},{"name":"German Centre for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH) at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1183\/09031936.00228013","article-title":"CFTR: Cystic fibrosis and beyond","volume":"44","author":"Mall","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJMoa2100665","article-title":"Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes","volume":"385","author":"Barry","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","article-title":"Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: A double-blind, randomised, phase 3 trial","volume":"394","author":"Heijerman","year":"2019","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1164\/rccm.202202-0392OC","article-title":"Efficacy and Safety of Elexacaftor\/Tezacaftor\/Ivacaftor in Children 6 Through 11 Years of Age with Cystic Fibrosis Heterozygous for F508del and a Minimal Function Mutation: A Phase 3b, Randomized, Placebo-controlled Study","volume":"206","author":"Mall","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1164\/rccm.201910-1943SO","article-title":"Cystic Fibrosis: Emergence of Highly Effective Targeted Therapeutics and Potential Clinical Implications","volume":"201","author":"Mall","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S2213-2600(21)00454-9","article-title":"Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: A 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial","volume":"10","author":"Sutharsan","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1164\/rccm.202102-0509OC","article-title":"A Phase 3 Open-Label Study of ELX\/TEZ\/IVA in Children 6 Through 11 Years of Age With CF and at Least One F508del Allele","volume":"203","author":"Zemanick","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1164\/rccm.202201-0219OC","article-title":"Effects of Elexacaftor\/Tezacaftor\/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles","volume":"206","author":"Graeber","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1164\/rccm.202110-2249OC","article-title":"Effects of Elexacaftor\/Tezacaftor\/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles","volume":"205","author":"Graeber","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: A global perspective","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2202437","DOI":"10.1183\/13993003.02437-2022","article-title":"The French Compassionate Program of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del CFTR variant","volume":"61","author":"Burgel","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ebiom.2014.12.005","article-title":"Measurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis","volume":"2","author":"Awatade","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ensinck, M., De Keersmaecker, L., Heylen, L., Ramalho, A.S., Gijsbers, R., Farre, R., De Boeck, K., Christ, F., Debyser, Z., and Carlon, M.S. (2020). Phenotyping of Rare CFTR Mutations Reveals Distinct Trafficking and Functional Defects. Cells, 9.","DOI":"10.3390\/cells9030754"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.jcf.2018.05.011","article-title":"Physiological and pharmacological characterization of the N1303K mutant CFTR","volume":"17","author":"DeStefano","year":"2018","journal-title":"J. Cyst. Fibros."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2002774","DOI":"10.1183\/13993003.02774-2020","article-title":"Rescue of multiple class II CFTR mutations by elexacaftor+ tezacaftor+ivacaftor mediated in part by the dual activities of Elexacaftor as both corrector and potentiator","volume":"57","author":"Laselva","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e139983","DOI":"10.1172\/jci.insight.139983","article-title":"Allosteric folding correction of F508del and rare CFTR mutants by elexacaftor-tezacaftor-ivacaftor (Trikafta) combination","volume":"5","author":"Veit","year":"2020","journal-title":"JCI Insight"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1164\/rccm.202101-0090LE","article-title":"Elexacaftor\/Tezacaftor\/Ivacaftor Improved Clinical Outcomes in a Patient with N1303K-CFTR Based on In Vitro Experimental Evidence","volume":"204","author":"Huang","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","first-page":"101775","article-title":"Clinical efficacy of elexacaftor-tezacaftor-ivacaftor in an adolescent with homozygous G85E cystic fibrosis","volume":"40","author":"Stekolchik","year":"2022","journal-title":"Respir. Med. Case Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sadras, I., Kerem, E., Livnat, G., Sarouk, I., Breuer, O., Reiter, J., Gileles-Hillel, A., Inbar, O., Cohen, M., and Gamliel, A. (2023). Clinical and functional efficacy of elexacaftor\/tezacaftor\/ivacaftor in people with cystic fibrosis carrying the N1303K mutation. J. Cyst. Fibros., in press.","DOI":"10.1016\/j.jcf.2023.06.001"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"822437","DOI":"10.3389\/fimmu.2022.822437","article-title":"Age-Related Differences in Structure and Function of Nasal Epithelial Cultures From Healthy Children and Elderly People","volume":"13","author":"Balazs","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1164\/rccm.201710-1983OC","article-title":"Effects of Lumacaftor-Ivacaftor Therapy on Cystic Fibrosis Transmembrane Conductance Regulator Function in Phe508del Homozygous Patients with Cystic Fibrosis","volume":"197","author":"Graeber","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1164\/rccm.201507-1271LE","article-title":"Intestinal Current Measurements Detect Activation of Mutant CFTR in Patients with Cystic Fibrosis with the G551D Mutation Treated with Ivacaftor","volume":"192","author":"Graeber","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"00716","DOI":"10.1183\/23120541.00716-2021","article-title":"Novel CFTR modulator combinations maximise rescue of G85E and N1303K in rectal organoids","volume":"8","author":"Ensinck","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_26","unstructured":"US Food and Drug Administration (2023, July 16). Trikafta Label, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/217660s000lbl.pdf."},{"key":"ref_27","unstructured":"European Medical Agency (2023, July 16). Assessment Report Kaftrio. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/kaftrio-epar-public-assessment-report_en.pdf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1126\/science.7543698","article-title":"CFTR as a cAMP-dependent regulator of sodium channels","volume":"269","author":"Stutts","year":"1995","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0014-5793(96)00079-8","article-title":"Wild type but not Delta F508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes","volume":"381","author":"Mall","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_30","first-page":"G1274","article-title":"Cholinergic ion secretion in human colon requires coactivation by cAMP","volume":"275","author":"Mall","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2000946","DOI":"10.1183\/13993003.00946-2020","article-title":"ENaC inhibition in cystic fibrosis: Potential role in the new era of CFTR modulator therapies","volume":"56","author":"Mall","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1172\/JCI2729","article-title":"The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways","volume":"102","author":"Mall","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1165\/ajrcmb.23.6.4207","article-title":"Inhibition of amiloride-sensitive epithelial Na(+) absorption by extracellular nucleotides in human normal and cystic fibrosis airways","volume":"23","author":"Mall","year":"2000","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"L401","DOI":"10.1152\/ajplung.00431.2007","article-title":"Amiloride-insensitive Na+ and fluid absorption in the mammalian distal lung","volume":"294","author":"Yang","year":"2008","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1164\/rccm.202004-1200LE","article-title":"Comparison of Organoid Swelling and In Vivo Biomarkers of CFTR Function to Determine Effects of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation","volume":"202","author":"Graeber","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1136\/thoraxjnl-2011-200953","article-title":"Understanding the natural progression in %FEV1 decline in patients with cystic fibrosis: A longitudinal study","volume":"67","author":"Whitehead","year":"2012","journal-title":"Thorax"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/ppul.26180","article-title":"Variability of clinically measured lung clearance index in children with cystic fibrosis","volume":"58","author":"Frauchiger","year":"2023","journal-title":"Pediatr. Pulmonol."},{"key":"ref_38","first-page":"396","article-title":"CFTR Modulator Therapy in an Individual With Cystic Fibrosis Caused by a N1303K CFTR Variant and Infected With Mycobacterium abscessus","volume":"27","author":"Elson","year":"2022","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1056\/NEJMoa1807120","article-title":"VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles","volume":"379","author":"Keating","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Capurro, V., Tomati, V., Sondo, E., Renda, M., Borrelli, A., Pastorino, C., Guidone, D., Venturini, A., Giraudo, A., and Mandrup Bertozzi, S. (2021). Partial Rescue of F508del-CFTR Stability and Trafficking Defects by Double Corrector Treatment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105262"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1165\/rcmb.2016-0276MA","article-title":"Pharmacological Rescue of Conditionally Reprogrammed Cystic Fibrosis Bronchial Epithelial Cells","volume":"56","author":"Gentzsch","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.jaci.2021.02.008","article-title":"Chronic rhinosinusitis with nasal polyps is associated with impaired TMEM16A-mediated epithelial chloride secretion","volume":"147","author":"Salomon","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1164\/rccm.200605-642ST","article-title":"An official American Thoracic Society\/European Respiratory Society statement: Pulmonary function testing in preschool children","volume":"175","author":"Beydon","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3-95-yr age range: The global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"00408","DOI":"10.1183\/23120541.00408-2020","article-title":"Multicentre feasibility of multiple-breath washout in preschool children with cystic fibrosis and other lung diseases","volume":"6","author":"Stahl","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1164\/rccm.201604-0893OC","article-title":"Comparison of Lung Clearance Index and Magnetic Resonance Imaging for Assessment of Lung Disease in Children with Cystic Fibrosis","volume":"195","author":"Stahl","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1152\/japplphysiol.00338.2021","article-title":"Correction of sensor crosstalk error in Exhalyzer D multiple-breath washout device significantly impacts outcomes in children with cystic fibrosis","volume":"131","author":"Wyler","year":"2021","journal-title":"J. Appl. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1164\/rccm.201309-1659OC","article-title":"Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease","volume":"189","author":"Wielputz","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/j.ejrad.2011.02.045","article-title":"Morphologic and functional scoring of cystic fibrosis lung disease using MRI","volume":"81","author":"Eichinger","year":"2012","journal-title":"Eur. J. Radiol."},{"key":"ref_50","unstructured":"Naehrlich, L., Stuhrmann-Spangenberg, M., Barben, J., Bargon, J., Blankenstein, O., Bremer, W., Brunsmann, F., Buchholz, T., Ellemunter, H., and Fusch, C. (2023, June 21). S2-Konsensus-Leitlinie \u201cDiagnose der Mukoviszidose\u201d (AWMF 026-023). Available online: http:\/\/www.awmf.org\/leitlinien\/detail\/ll\/026-023.html."},{"key":"ref_51","unstructured":"LeGrys, V.A. (2019). Sweat Testing: Sample Collection and Quantitative Chloride Analysis, Approved Guideline, Clinical and Laboratory Standards Institute. [4th ed.]."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-61779-117-8_6","article-title":"Nasal potential difference measurements to assess CFTR ion channel activity","volume":"741","author":"Rowe","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1164\/rccm.201003-0382OC","article-title":"Clinical phenotype and genotype of children with borderline sweat test and abnormal nasal epithelial chloride transport","volume":"182","author":"Girodon","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Graeber, S.Y., Vitzthum, C., and Mall, M.A. (2021). Potential of Intestinal Current Measurement for Personalized Treatment of Patients with Cystic Fibrosis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11050384"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"G617","DOI":"10.1152\/ajpgi.2000.278.4.G617","article-title":"Defective cholinergic Cl(-) secretion and detection of K(+) secretion in rectal biopsies from cystic fibrosis patients","volume":"278","author":"Mall","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1053\/j.gastro.2004.07.006","article-title":"CFTR Cl- channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis","volume":"127","author":"Hirtz","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Roth, E.K., Hirtz, S., Duerr, J., Wenning, D., Eichler, I., Seydewitz, H.H., Amaral, M.D., and Mall, M.A. (2011). The K+ channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024445"},{"key":"ref_58","unstructured":"R Core Team (2018). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12365\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:24:36Z","timestamp":1760127876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,2]]},"references-count":58,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241512365"],"URL":"https:\/\/doi.org\/10.3390\/ijms241512365","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,2]]}}}