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Individuals carrying a single cystic fibrosis transmembrane conductance regulator (CFTR) mutation exhibit partial CFTR dysfunction and are increasingly recognized as being at risk for CRS; however, the sinonasal phenotype and host\u2013pathogen interactions in CF carriers remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We characterized heterozygous\n                      <jats:italic>\u0394F508<\/jats:italic>\n                      CF rabbits (heterozygous,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a06) compared with wild\u2010type (WT) (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05). Baseline sinonasal structure was assessed by computed tomography and histology. CFTR function was measured by nasal potential difference (NPD) and Ussing chamber analysis of primary epithelial cultures, with or without CFTR modulators. Bacterial sinusitis was induced using\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      (PA14), followed by longitudinal imaging, bacterial quantification, histology, and PA14 RNA sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Heterozygous rabbits demonstrated significant sinus hypoplasia compared with WT (mm\n                      <jats:sup>3<\/jats:sup>\n                      : heterozygous 77.9\u00a0vs. WT 108.1\u00a0mm\n                      <jats:sup>3<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) without spontaneous sinusitis. NPD revealed \u223c50% reduction in chloride transport relative to WT (\u2206mV: heterozygous \u221215.5\u00a0vs. WT \u221235.8,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01). CFTR modulation partially restored chloride secretion in epithelial cells from heterozygous to \u223c80% of WT (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). Following\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      inoculation, heterozygous rabbits exhibited higher bacterial burden (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05), persistent radiographic opacification (week 4,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.01), and delayed histologic recovery. PA14 RNAseq revealed a distinct transcriptional profile in the heterozygous sinonasal environment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Heterozygous\n                      <jats:italic>\u0394F508<\/jats:italic>\n                      CF rabbits recapitulate key sinonasal features relevant to CF carriers, including reduced CFTR function, altered host defense, and impaired infection clearance. This model provides a translational platform for investigating CRS pathogenesis and evaluating CFTR\u2010targeted therapies in CF carriers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alr.70128","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:27:41Z","timestamp":1773005261000},"page":"788-796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering Cystic Fibrosis Carrier: Insights From a Heterozygous CFTR\u2010F508del Rabbit Model"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-8959","authenticated-orcid":false,"given":"Do\u2010Yeon","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Division of Otolaryngology Department of Surgery Veterans Affairs  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6910-8402","authenticated-orcid":false,"given":"Alexis E.","family":"McFeely","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Skinner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Hedvat","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of California at Los Angeles  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weslee","family":"Ping\u2010ay","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of California at Los Angeles  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8612-5442","authenticated-orcid":false,"given":"Daniel M.","family":"Beswick","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of California at Los Angeles  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin H.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3292-9167","authenticated-orcid":false,"given":"Bradford A.","family":"Woodworth","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head &amp; Neck Surgery University of Alabama at Birmingham  Birmingham Alabama USA"},{"name":"Gregory Fleming James Cystic Fibrosis Research Center University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Center For Advanced Models For Translational Sciences and Therapeutics University of Michigan Medical Center  Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2014.12.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2013.27.3960"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.05.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.04.015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.21053\/ceo.2023.00025"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02645-2020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.284.14.1814"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/coa.13875"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21874"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.23549"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00540"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.024"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.627666"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22290"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1227\/ons.0000000000000527"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22514"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21892"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22907"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.21798"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2010.24.3379"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2008.22.3125"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2007.21.3068"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/ajot.2000.9874"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3849"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914912117"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139813"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.152186"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2016.07.003"}],"container-title":["International Forum of Allergy &amp; 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