{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:32:34Z","timestamp":1791639154826,"version":"4.3.4"},"reference-count":33,"publisher":"European Respiratory Society (ERS)","issue":"4","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["002339321 \u2013 Todd"],"award-info":[{"award-number":["002339321 \u2013 Todd"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["003781AB322 \u2013Todd"],"award-info":[{"award-number":["003781AB322 \u2013Todd"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["PALMER19AB0"],"award-info":[{"award-number":["PALMER19AB0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI113315"],"award-info":[{"award-number":["U01AI113315"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,10,6]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Lung transplant recipients with lower club cell secretory protein (CCSP) levels in bronchoalveolar lavage fluid (BALF) early post-transplantation are at increased risk for chronic lung allograft dysfunction (CLAD). For CLAD risk stratification, we previously identified a potential risk threshold for reduced CCSP (protein-normalised CCSP &lt;8.63\u2005ng\u00b7\u00b5g\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Here, we aim to validate this association in an independent patient set from a prospective observational cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Total protein and CCSP were quantified in 1481 BALF samples collected over the first post-transplant year from 353 patients (validation cohort). A Cox model tested the association between time to first CCSP &lt;8.63\u2005ng\u00b7\u00b5g\n                      <jats:sup>\u22121<\/jats:sup>\n                      and CLAD. If this threshold did not validate, we prespecified combining the discovery and validation cohorts to rederive a reduced CCSP risk threshold considering a larger number of CLAD events. In a subset, gene expression analyses were performed on allograft biopsies to examine molecular alterations at the time of reduced CCSP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BALF CCSP &lt;8.63\u2005ng\u00b7\u00b5g\n                      <jats:sup>\u22121<\/jats:sup>\n                      in the first post-transplant year was not significantly associated with CLAD in the validation cohort (hazard ratio (HR) 1.41; p=0.208). However, in the combined cohort, a dense grid search, including the previously identified threshold of 8.63\u2005ng\u00b7\u00b5g\n                      <jats:sup>\u22121<\/jats:sup>\n                      , revealed that the threshold of 8.63\u2005ng\u00b7\u00b5g\n                      <jats:sup>\u22121<\/jats:sup>\n                      had the largest HR for CLAD. Iterative resampling demonstrated robust reproducibility of the association between BALF CCSP &lt;8.63\u2005ng\u00b7\u00b5g\n                      <jats:sup>\u22121<\/jats:sup>\n                      and CLAD risk across the combined cohort. Biopsies corresponding to CCSP &lt;8.63\u2005ng\u00b7\u00b5g\n                      <jats:sup>\u22121<\/jats:sup>\n                      had a pro-inflammatory profile.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early post-transplant reductions in BALF CCSP identify lung recipients at increased CLAD risk and may associate with heightened allograft inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.00182-2025","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T17:10:14Z","timestamp":1764263414000},"page":"2500182","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Reduced lung fluid club cell secretory protein informs chronic lung allograft dysfunction risk"],"prefix":"10.1183","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0416-2480","authenticated-orcid":false,"given":"Jeeyon G.","family":"Rim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan L.","family":"Neely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8711-7508","authenticated-orcid":false,"given":"Nicholas","family":"O'Grady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francine L.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Nagler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"McArthur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney W.","family":"Frankel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Belperio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Budev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew G.","family":"Hartwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Martinu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pali D.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianne G.","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie D.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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