{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T22:28:11Z","timestamp":1778797691358,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T00:00:00Z","timestamp":1483920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30\u2010DK072517"],"award-info":[{"award-number":["P30\u2010DK072517"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32\u2010GM007546"],"award-info":[{"award-number":["T32\u2010GM007546"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Rationale<\/jats:title><jats:p>Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, decreases sweat chloride concentration, and improves pulmonary function in 6% of cystic fibrosis (CF) patients with specific <jats:italic>CFTR<\/jats:italic> mutations. Ivacaftor increases chloride transport in many other <jats:italic>CFTR<\/jats:italic> mutations in non\u2010human cells, if CFTR is in the epithelium. Some CF patients have CFTR in the epithelium with residual CFTR function. The effect of ivacaftor in these patients is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a series of randomized, crossover N\u2010of\u20101 trials of ivacaftor and placebo in CF patients \u22658 years old with potential residual CFTR function (intermediate sweat chloride concentration, pancreatic sufficient, or mild bronchiectasis on chest CT). Human nasal epithelium (HNE) was obtained via nasal brushing and cultured. Sweat chloride concentration change was the in vivo outcome. Chloride current change in HNE cultures with ivacaftor was the in vitro outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three subjects had decreased sweat chloride concentration (\u221214.8 to \u221240.8\u2009mmol\/L, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Two subjects had unchanged sweat chloride concentration. Two subjects had increased sweat chloride concentration (+23.8 and +27.3\u2009mmol\/L, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001); both were heterozygous for A455E and pancreatic sufficient. Only subjects with decreased sweat chloride concentration had increased chloride current in HNE cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Some CF patients with residual CFTR function have decreased sweat chloride concentration with ivacaftor. Increased chloride current in HNE cultures among subjects with decreased sweat chloride concentrations may predict clinical response to ivacaftor. Ivacaftor can increase sweat chloride concentration in certain mutations with unclear clinical effect. <jats:bold>Pediatr Pulmonol. 2017;52:472\u2013479.<\/jats:bold> \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.23659","type":"journal-article","created":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T15:51:59Z","timestamp":1483977119000},"page":"472-479","source":"Crossref","is-referenced-by-count":53,"title":["In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N\u2010of\u20101 studies"],"prefix":"10.1002","volume":"52","author":[{"given":"Meghan E.","family":"McGarry","sequence":"first","affiliation":[{"name":"Pediatric Pulmonology Department of Pediatrics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Illek","sequence":"additional","affiliation":[{"name":"Children's Hospital Oakland Research Institute Oakland California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ngoc P.","family":"Ly","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonology Department of Pediatrics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorna","family":"Zlock","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Olshansky","sequence":"additional","affiliation":[{"name":"Children's Hospital Oakland Research Institute Oakland California"},{"name":"College of Pharmacy Touro University Vallejo California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney","family":"Moreno","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonology Department of Pediatrics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter E.","family":"Finkbeiner","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis W.","family":"Nielson","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonology Department of Pediatrics University of California San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2011.12.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904709106"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105787108"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-05-0240"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909825"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105185"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-0239"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201301-0153OC"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201503-0578OC"},{"key":"e_1_2_10_11_1","unstructured":"MossRB FlumePA ElbornJS CookeJ RoweSM McColleySA RubensteinRC PilewskiJ HigginsM.2014. 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