{"doi":"10.1183/13993003.00441-2023","title":"Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease","abstract":"Background Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD). Methods A retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure. Results The discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL <10th percentile of normal. fHP and uILD patients with LTL <10th percentile experienced reduced survival when exposed to either mycophenolate or azathioprine in the discovery cohort (mortality hazard ratio (HR) 4.97, 95% CI 2.26–10.92; p<0.001) and replication cohort (mortality HR 4.90, 95% CI 1.74–13.77; p=0.003). Immunosuppressant exposure was not associated with differential survival in patients with LTL ≥10th percentile. There was a significant interaction between LTL <10th percentile and immunosuppressant exposure (discovery p interaction =0.013; replication p interaction =0.011). Low event rate and prevalence of LTL <10th percentile precluded subgroup analyses for CTD-ILD. Conclusion Similar to IPF, fHP and uILD patients with age-adjusted LTL <10th percentile may experience reduced survival when exposed to immunosuppression.","journal":"European Respiratory Journal","year":2023,"id":317911,"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":71,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":285949,"name":"Ayodeji Adegunsoye","orcid":"0000-0002-7015-9610","position":1,"is_corresponding":false},{"id":285958,"name":"Justin M. Oldham","orcid":"0000-0003-4957-8869","position":2,"is_corresponding":false},{"id":263005,"name":"Julia Kozlitina","orcid":"0000-0001-7720-2290","position":3,"is_corresponding":false},{"id":473637,"name":"Nicole Garcia","orcid":"0000-0002-1619-3359","position":4,"is_corresponding":false},{"id":1024936,"name":"Maria Poonawalla","orcid":null,"position":5,"is_corresponding":false},{"id":722954,"name":"R. Strykowski","orcid":"0000-0001-7827-6152","position":6,"is_corresponding":false},{"id":285951,"name":"A. Linderholm","orcid":"0000-0002-8561-3089","position":7,"is_corresponding":false},{"id":65485,"name":"Brett Ley","orcid":null,"position":8,"is_corresponding":false},{"id":285954,"name":"Shwu‐Fan Ma","orcid":"0000-0002-3058-9480","position":9,"is_corresponding":false},{"id":278242,"name":"Imre Noth","orcid":"0000-0001-9846-5030","position":10,"is_corresponding":false},{"id":285957,"name":"Mary E. Strek","orcid":"0000-0002-7671-1023","position":11,"is_corresponding":false},{"id":3386,"name":"Paul J. Wolters","orcid":"0000-0002-3108-6164","position":12,"is_corresponding":false},{"id":314479,"name":"Christine Kim Garcia","orcid":"0000-0002-0771-1249","position":13,"is_corresponding":false},{"id":314478,"name":"Chad A. Newton","orcid":"0000-0001-5256-9029","position":14,"is_corresponding":false},{"id":621910,"name":"David Zhang","orcid":"0000-0002-2983-9796","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:06:55.884740Z","pmid":"37591536","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":[]}