{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T10:44:37Z","timestamp":1762771477643,"version":"build-2065373602"},"reference-count":40,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2024A02001"],"award-info":[{"award-number":["GZNL2024A02001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370036; 82170034"],"award-info":[{"award-number":["82370036; 82170034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2019B020227006"],"award-info":[{"award-number":["2019B020227006"]}]},{"name":"Clinical Research Foundation of Guangzhou Medical University","award":["2017-160"],"award-info":[{"award-number":["2017-160"]}]},{"name":"Incubative Project for Innovation Team of Guangzhou Medical University","award":["2017-159"],"award-info":[{"award-number":["2017-159"]}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2025,5,11]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Asthmatic cough may not respond well to corticosteroids. The underlying mechanisms and heterogeneity of cough variant asthma (CVA) remain poorly understood. The objectives of the present study were to explore airway immunological mechanisms and identify molecular endotypes in CVA by analysing sputum transcriptomics, clinical and pathophysiological characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RNA sequencing and cytokine measurement were performed on sputum samples from newly diagnosed patients with CVA (n=72), classic asthma (CA) (n=28) and healthy controls (HC) (n=28). Patients with CVA were treated and followed-up for 6\u2005months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The majority of differentially expressed genes in CVA\n                      <jats:italic>versus<\/jats:italic>\n                      HC overlapped with those identified in CA\n                      <jats:italic>versus<\/jats:italic>\n                      HC. However, the type 2 immunity co-expression network in CVA was lower than that in CA. Based on sputum transcriptomics profiles, two endotypes of CVA were identified: mixed-inflammatory CVA (n=40) and pauci-inflammatory CVA (n=32). Mixed-inflammatory CVA showed higher inflammation-related gene set signatures compared to both pauci-inflammatory CVA and HC. Mixed-inflammatory CVA also showed elevated levels of eosinophils, neutrophils, type 2, type 1 and type 3 cytokines in sputum compared to HC. Conversely, pauci-inflammatory CVA had slightly elevated sputum eosinophils, but no significant gene signatures and cytokine differences compared to HC. During 6\u2005months\u2019 follow-up, pauci-inflammatory CVA showed a trend of less complete resolution in cough (56.2%\n                      <jats:italic>versus<\/jats:italic>\n                      80.0%, p=0.0553) compared to mixed-inflammatory CVA. Kaplan\u2013Meier analysis found significantly higher cough persistence in pauci-inflammatory\n                      <jats:italic>versus<\/jats:italic>\n                      mixed-inflammatory CVA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CVA exhibits overlapping but distinct airway transcriptomics profiles compared to CA. Two distinct molecular endotypes are identified in CVA, presenting different clinical and pathophysiological features.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.01303-2024","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T12:55:14Z","timestamp":1751547314000},"page":"01303-2024","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of two distinct molecular endotypes in cough-variant asthma based on sputum transcriptomics and clinical pathophysiological features"],"prefix":"10.1183","volume":"11","author":[{"given":"Wenzhi","family":"Zhan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yadong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6462-6676","authenticated-orcid":false,"given":"Jiaxing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5376-8230","authenticated-orcid":false,"given":"Ruchong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanrong","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangtao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dejun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7393-2664","authenticated-orcid":false,"given":"Mei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongchang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanshan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kefang","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"2025111002401205000_11.6.01303-2024.1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/S2213-2600(23)00187-X","article-title":"Cough and cough hypersensitivity as treatable traits of asthma","volume":"11","author":"Lai","year":"2023","journal-title":"Lancet Respir Med"},{"key":"2025111002401205000_11.6.01303-2024.2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jpsychores.2015.03.011","article-title":"Cough variant asthma patients are more depressed and anxious than classic asthma patients","volume":"79","author":"Saito","year":"2015","journal-title":"J Psychosom Res"},{"key":"2025111002401205000_11.6.01303-2024.3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.2147\/JIR.S343411","article-title":"Inflammatory phenotypes of cough variant asthma as response predictors to anti-asthmatic therapy","volume":"15","author":"Rybka-Fraczek","year":"2022","journal-title":"J Inflamm Res"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.4","DOI":"10.1378\/chest.10-0132"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.5","DOI":"10.21037\/jtd.2018.09.153"},{"key":"2025111002401205000_11.6.01303-2024.6","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1378\/chest.12-0441","article-title":"A prospective, multicenter survey on causes of chronic cough in China","volume":"143","author":"Lai","year":"2013","journal-title":"Chest"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.7","DOI":"10.1016\/S0140-6736(08)60595-4"},{"key":"2025111002401205000_11.6.01303-2024.8","doi-asserted-by":"crossref","first-page":"807385","DOI":"10.3389\/fmed.2021.807385","article-title":"Clinical and inflammatory characteristics of the Chinese APAC cough variant asthma cohort","volume":"8","author":"Lai","year":"2022","journal-title":"Front Med"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.9","DOI":"10.1111\/j.1398-9995.2005.00609.x"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.10","DOI":"10.1183\/09031936.98.11051064"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.11","DOI":"10.21037\/jtd-20-2026"},{"key":"2025111002401205000_11.6.01303-2024.12","doi-asserted-by":"crossref","first-page":"399","DOI":"10.4168\/aair.2020.12.3.399","article-title":"Understanding the molecular mechanisms of asthma through transcriptomics","volume":"12","author":"Park","year":"2020","journal-title":"Allergy Asthma Immunol Res"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.13","DOI":"10.1016\/j.jaci.2017.06.037"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.14","DOI":"10.1016\/j.jaci.2023.02.031"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.15","DOI":"10.1164\/rccm.201807-1291OC"},{"key":"2025111002401205000_11.6.01303-2024.16","doi-asserted-by":"crossref","first-page":"104782","DOI":"10.1016\/j.phrs.2020.104782","article-title":"Biologics or immunotherapeutics for asthma?","volume":"158","author":"Tay","year":"2020","journal-title":"Pharmacol Res"},{"key":"2025111002401205000_11.6.01303-2024.17","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.jaci.2019.03.027","article-title":"IL-17-high asthma with features of a psoriasis immunophenotype","volume":"144","author":"\u00d6stling","year":"2019","journal-title":"J Allergy Clin Immunol"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.18","DOI":"10.2174\/092986711795328337"},{"key":"2025111002401205000_11.6.01303-2024.19","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.jaci.2023.04.017","article-title":"Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data","volume":"152","author":"Zhan","year":"2023","journal-title":"J Allergy Clin Immunol"},{"unstructured":"Global Initiative for Asthma (GINA) . Global Strategy for Asthma Management and Prevention. 2024 Update. 2024. Date last accessed: 12 March 2025. www.ginasthma.org","key":"2025111002401205000_11.6.01303-2024.20"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.21","DOI":"10.1186\/s13059-014-0550-8"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.22","DOI":"10.1186\/1471-2105-9-559"},{"key":"2025111002401205000_11.6.01303-2024.23","first-page":"100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.24","DOI":"10.1186\/1471-2105-14-7"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.25","DOI":"10.1016\/j.jaci.2013.12.1091"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.26","DOI":"10.1016\/j.jaci.2013.07.036"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.27","DOI":"10.1016\/j.cell.2021.02.016"},{"key":"2025111002401205000_11.6.01303-2024.28","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1111\/cea.13992","article-title":"Non-asthmatic eosinophilic bronchitis is characterized by proximal airway eosinophilic inflammation as compared with classic asthma and cough variant asthma","volume":"51","author":"Zhang","year":"2021","journal-title":"Clin Exp Allergy"},{"key":"2025111002401205000_11.6.01303-2024.29","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s12931-022-02104-8","article-title":"Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China","volume":"23","author":"Zhou","year":"2022","journal-title":"Respir Res"},{"key":"2025111002401205000_11.6.01303-2024.30","doi-asserted-by":"crossref","first-page":"L1074","DOI":"10.1152\/ajplung.00531.2020","article-title":"RSV infection potentiates TRPV1-mediated calcium transport in bronchial epithelium of asthmatic children","volume":"320","author":"Harford","year":"2021","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.31","DOI":"10.1007\/s00408-015-9832-5"},{"key":"2025111002401205000_11.6.01303-2024.32","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/S2213-2600(18)30150-4","article-title":"The heterogeneity of chronic cough: a case for endotypes of cough hypersensitivity","volume":"6","author":"Mazzone","year":"2018","journal-title":"Lancet Respir Med"},{"key":"2025111002401205000_11.6.01303-2024.33","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/resp.12748","article-title":"Eosinophilic airway inflammation is common in subacute cough following acute upper respiratory tract infection","volume":"21","author":"Lai","year":"2016","journal-title":"Respirology"},{"key":"2025111002401205000_11.6.01303-2024.34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jaip.2023.09.015","article-title":"Increased risk of new-onset asthma after COVID-19: a nationwide population-based cohort study","volume":"12","author":"Kim","year":"2024","journal-title":"J Allergy Clin Immunol Pract"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.35","DOI":"10.1183\/13993003.02135-2016"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.36","DOI":"10.1046\/j.1365-2222.2003.01788.x"},{"key":"2025111002401205000_11.6.01303-2024.37","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.jaip.2019.11.006","article-title":"T2-\u201clow\u201d asthma: overview and management strategies","volume":"8","author":"Fitzpatrick","year":"2020","journal-title":"J Allergy Clin Immunol Pract"},{"key":"2025111002401205000_11.6.01303-2024.38","doi-asserted-by":"crossref","first-page":"101903","DOI":"10.1016\/j.pupt.2020.101903","article-title":"Determinants of response to bronchodilator in patients with cough variant asthma \u2013 a randomized, single-blinded, placebo-controlled study","volume":"61","author":"Yi","year":"2020","journal-title":"Pulm Pharmacol Ther"},{"doi-asserted-by":"publisher","key":"2025111002401205000_11.6.01303-2024.39","DOI":"10.1053\/rmed.2002.1460"},{"key":"2025111002401205000_11.6.01303-2024.40","doi-asserted-by":"crossref","first-page":"101854","DOI":"10.1016\/j.pupt.2019.101854","article-title":"Interfering with airway nerves in cough associated with asthma","volume":"59","author":"Niimi","year":"2019","journal-title":"Pulm Pharmacol Ther"}],"container-title":["ERJ Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/23120541.01303-2024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T10:40:19Z","timestamp":1762771219000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/23120541.01303-2024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,3]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,11,10]]},"published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1183\/23120541.01303-2024"],"URL":"https:\/\/doi.org\/10.1183\/23120541.01303-2024","relation":{},"ISSN":["2312-0541"],"issn-type":[{"type":"electronic","value":"2312-0541"}],"subject":[],"published":{"date-parts":[[2025,7,3]]}}}