{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:12:55Z","timestamp":1776852775725,"version":"3.51.2"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Department of Pediatrics at the University of Pittsburgh"},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL149693"],"award-info":[{"award-number":["HL149693"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Pediatrics at the University of Pittsburgh"},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL149693"],"award-info":[{"award-number":["HL149693"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Elexacaftor\/tezacaftor\/ivacaftor (ETI) has had a substantial positive impact for people living with cystic fibrosis (pwCF). However, there can be substantial variability in efficacy, and we lack adequate biomarkers to predict individual response. We thus aimed to identify transcriptomic profiles in nasal respiratory epithelium that predict clinical response to ETI treatment. We obtained nasal epithelial samples from pwCF before ETI initiation and performed a transcriptome-wide analysis of baseline gene expression to predict changes in forced expiratory volume in 1 second (\u0394FEV1), year\u2019s best FEV1 (\u0394ybFEV1), and body mass index (\u0394BMI). Using the top differentially expressed genes, we generated transcriptomic risk scores (TRSs) and evaluated their predictive performance. The study included 40 pwCF \u22656 years of age (mean, 27.7 [SD, 15.1] years; 40% female). After ETI initiation, FEV1 improved by \u22655% in 22 (61.1%) participants, and ybFEV1 improved by \u22655% in 19 (50%). TRSs were constructed using top overexpressed and underexpressed genes for each outcome. Adding the \u0394FEV1 TRS to a model with age, sex, and baseline FEV1 increased the area under the receiver operating characteristic curve (AUC) from 0.41 to 0.88, the \u0394ybFEV1 TRS increased the AUC from 0.51 to 0.88, and the \u0394BMI TRS increased the AUC from 0.46 to 0.92. Average accuracy was thus \u223c85% in predicting the response to the three outcomes. Results were similar in models further adjusted for F508del zygosity and previous CFTR modulator use. In conclusion, we identified nasal epithelial transcriptomic profiles that help accurately predict changes in FEV1 and BMI with ETI treatment. These novel TRSs could serve as predictive biomarkers for clinical response to modulator treatment in pwCF.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0103oc","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T12:05:55Z","timestamp":1721390755000},"page":"730-739","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":9,"title":["Nasal Epithelium Transcriptomics Predict Clinical Response to Elexacaftor\/Tezacaftor\/Ivacaftor"],"prefix":"10.1093","volume":"71","author":[{"given":"Molin","family":"Yue","sequence":"first","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8245-1961","authenticated-orcid":false,"given":"Daniel J.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"},{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina M.","family":"Gaietto","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"},{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1202-044X","authenticated-orcid":false,"given":"Franziska J.","family":"Rosser","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"},{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Qoyawayma","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle L.","family":"Manni","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"},{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael M.","family":"Myerburg","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Pilewski","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6139-5320","authenticated-orcid":false,"given":"Juan C.","family":"Celed\u00f3n","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"},{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7196-8703","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Medicine, University of Pittsburgh Medical Center Children\u2019s Hospital of Pittsburgh, and"},{"name":"Cystic Fibrosis Center, University of Pittsburgh, Pittsburgh, Pennsylvania; 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