{"doi":"10.1183/13993003.00182-2025","title":"Reduced lung fluid club cell secretory protein informs chronic lung allograft dysfunction risk","abstract":"Background 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 <8.63 ng·µg −1 ). Here, we aim to validate this association in an independent patient set from a prospective observational cohort. Methods 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 <8.63 ng·µg −1 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. Results BALF CCSP <8.63 ng·µg −1 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 ng·µg −1 , revealed that the threshold of 8.63 ng·µg −1 had the largest HR for CLAD. Iterative resampling demonstrated robust reproducibility of the association between BALF CCSP <8.63 ng·µg −1 and CLAD risk across the combined cohort. Biopsies corresponding to CCSP <8.63 ng·µg −1 had a pro-inflammatory profile. Conclusions Early post-transplant reductions in BALF CCSP identify lung recipients at increased CLAD risk and may associate with heightened allograft inflammation.","journal":"European Respiratory Journal","year":2025,"id":529429,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":398208,"name":"Jeremy M. Weber","orcid":"0000-0002-7221-8821","position":1,"is_corresponding":false},{"id":278240,"name":"Megan L. Neely","orcid":"0000-0002-0101-1081","position":2,"is_corresponding":false},{"id":796010,"name":"Nicholas O’Grady","orcid":"0000-0001-8711-7508","position":3,"is_corresponding":false},{"id":603106,"name":"Francine L. Kelly","orcid":null,"position":4,"is_corresponding":false},{"id":486981,"name":"Rachel A. Myers","orcid":"0000-0003-0086-8339","position":5,"is_corresponding":false},{"id":899174,"name":"Andrew Nagler","orcid":null,"position":6,"is_corresponding":false},{"id":1408710,"name":"Patrick D. McArthur","orcid":null,"position":7,"is_corresponding":false},{"id":380291,"name":"Courtney W. Frankel","orcid":"0000-0003-0821-5244","position":8,"is_corresponding":false},{"id":278246,"name":"John A. Belperio","orcid":"0000-0003-2379-5486","position":9,"is_corresponding":false},{"id":380290,"name":"Marie Budev","orcid":"0000-0003-1575-3980","position":10,"is_corresponding":false},{"id":380980,"name":"Matthew G. Hartwig","orcid":"0000-0001-8393-2791","position":11,"is_corresponding":false},{"id":247650,"name":"Tereza Martinu","orcid":"0000-0001-9234-6807","position":12,"is_corresponding":false},{"id":380292,"name":"John M. Reynolds","orcid":"0000-0003-4766-8852","position":13,"is_corresponding":false},{"id":381898,"name":"Pali D. Shah","orcid":null,"position":14,"is_corresponding":false},{"id":280833,"name":"L.G. Singer","orcid":"0000-0002-2693-8676","position":15,"is_corresponding":false},{"id":322834,"name":"Laurie D. Snyder","orcid":"0000-0002-5962-2184","position":16,"is_corresponding":false},{"id":896631,"name":"S. Samuel Weigt","orcid":null,"position":17,"is_corresponding":false},{"id":278245,"name":"Scott M. Palmer","orcid":"0000-0002-1370-3771","position":18,"is_corresponding":false},{"id":278237,"name":"Jamie L. Todd","orcid":"0000-0003-4247-3693","position":19,"is_corresponding":false},{"id":545935,"name":"Jeeyon Rim","orcid":"0009-0002-0416-2480","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:50:56.971987Z","pmid":"41309269","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}