{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:56:11Z","timestamp":1793318171659,"version":"4.5.0"},"reference-count":37,"publisher":"European Respiratory Society (ERS)","issue":"5","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515010406, 2024A1515030252, 2025A1515012432"],"award-info":[{"award-number":["2023A1515010406, 2024A1515030252, 2025A1515012432"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Municipal Key Research and Development Program","award":["2025B03J0115"],"award-info":[{"award-number":["2025B03J0115"]}]},{"name":"the Clinical Research Program of Nanfang Hospital, Southern Medical University","award":["2023CR008"],"award-info":[{"award-number":["2023CR008"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82370029, 82570037"],"award-info":[{"award-number":["82370029, 82570037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2026,3,24]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Fractional exhaled nitric oxide (\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      ) reflects type 2 airway inflammation, yet the prognostic utility of longitudinal\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      changes in COPD remains unclear. We aim to explore whether 6-month\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      variation patterns predict subsequent moderate-to-severe exacerbations in COPD patients receiving triple therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We prospectively evaluated COPD patients receiving triple inhaled therapy from 2023 to 2024. Four\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      -related variables were used to derive\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      variation phenotypes\n                      <jats:italic>via<\/jats:italic>\n                      K-means unsupervised clustering.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three distinct\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      -variation phenotypes were identified: a High\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      -Persistently Elevated subtype (Cluster 1, 11.2%), a High\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      -Declining subtype (Cluster 2, 20.3%) and a Low\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      -Stable subtype (Cluster 3, 68.5%). During 6\u201312\u2005months of follow-up, 75 patients (33.8%) experienced a moderate-to-severe exacerbation. Compared with Cluster 3, both Cluster 1 (OR 6.97, 95% CI 2.38\u201320.47) and Cluster 2 (OR 20.08, 95% CI 7.01\u201357.58) were independently associated with future exacerbations (p&lt;0.001). The final prediction model incorporating\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      variation phenotypes demonstrated excellent discrimination (AUC 0.889) and provided greater net clinical benefit than models using traditional clinical predictors alone (p=0.004). Subgroup analyses revealed consistent effect sizes across categories of age, prior-year exacerbations, baseline FEV\n                      <jats:sub>1<\/jats:sub>\n                      % predicted, symptom burden, smoking status and proportion of days covered, supporting the robustness and internal consistency of the\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      -variation phenotyping approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Short-term longitudinal\n                      <jats:italic>F<\/jats:italic>\n                      <jats:sub>ENO<\/jats:sub>\n                      variation over 6\u2005months was independently associated with future moderate-to-severe exacerbations in COPD patients receiving triple therapy, supporting risk stratification and hypothesis generation for future interventional studies rather than direct treatment guidance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.01774-2025","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T17:00:25Z","timestamp":1776358825000},"page":"01774-2025","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Short-term longitudinal variation in exhaled nitric oxide fraction predicts future moderate-to-severe exacerbations in COPD patients on triple therapy: a prospective cohort study"],"prefix":"10.1183","volume":"12","author":[{"given":"Zhaoqian","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junrao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiling","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"2026090101501761000_12.5.01774-2025.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01273-9"},{"key":"2026090101501761000_12.5.01774-2025.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2019.12.014"},{"key":"2026090101501761000_12.5.01774-2025.3","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.2147\/COPD.S513573","article-title":"Characteristics and outcomes of people with COPD who experience exacerbations while on inhaled triple therapy: results of the SIRIUS I cohort study in the US (2015\u20132019)","volume":"20","author":"Nordon","year":"2025","journal-title":"Int J Chronic Obstr Pulmon Dis"},{"key":"2026090101501761000_12.5.01774-2025.4","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (GOLD) . The global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2024. https:\/\/goldcopd.org\/archived-reports\/"},{"key":"2026090101501761000_12.5.01774-2025.5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.9120-11ST"},{"key":"2026090101501761000_12.5.01774-2025.6","doi-asserted-by":"crossref","first-page":"5753524","DOI":"10.1155\/2022\/5753524","article-title":"Understanding the cellular sources of the fractional exhaled nitric oxide (FeNO) and its role as a biomarker of type 2 inflammation in asthma","volume":"2022","author":"Escamilla-Gil","year":"2022","journal-title":"Biomed Res Int"},{"key":"2026090101501761000_12.5.01774-2025.7","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.3390\/diagnostics13081428","article-title":"Update on the role of FeNO in asthma management","volume":"13","author":"Murugesan","year":"2023","journal-title":"Diagnostics (Basel)"},{"key":"2026090101501761000_12.5.01774-2025.8","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01457-2017"},{"key":"2026090101501761000_12.5.01774-2025.9","doi-asserted-by":"crossref","first-page":"108134","DOI":"10.1016\/j.rmed.2025.108134","article-title":"Short term exacerbation risk and exhaled nitric oxide in COPD","volume":"243","author":"Romero-Linares","year":"2025","journal-title":"Resp Med"},{"key":"2026090101501761000_12.5.01774-2025.10","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.2147\/COPD.S165780","article-title":"Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis","volume":"13","author":"Lu","year":"2018","journal-title":"Int J Chronic Obstr Pulmon Dis"},{"key":"2026090101501761000_12.5.01774-2025.11","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/15412555.2018.1482532","article-title":"Value of exhaled nitric oxide (FeNO) and eosinophilia during the exacerbations of chronic obstructive pulmonary disease requiring hospital admission","volume":"15","author":"R\u00edo","year":"2018","journal-title":"COPD"},{"key":"2026090101501761000_12.5.01774-2025.12","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/resp.14439","article-title":"Variability of fractional exhaled nitric oxide is associated with the risk and aetiology of COPD exacerbations","volume":"28","author":"Schumann","year":"2023","journal-title":"Respirology"},{"key":"2026090101501761000_12.5.01774-2025.13","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.3390\/jpm12111906","article-title":"Fractional exhaled nitric oxide (FeNO) in patients with stable chronic obstructive pulmonary disease: short-term variability and potential clinical implications","volume":"12","author":"Ambrosino","year":"2022","journal-title":"J Pers Med"},{"key":"2026090101501761000_12.5.01774-2025.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(96)00236-3"},{"key":"2026090101501761000_12.5.01774-2025.15","doi-asserted-by":"crossref","first-page":"107634","DOI":"10.1016\/j.rmed.2024.107634","article-title":"Development and validation of a prediction score to assess the risk of incurring in COPD-related exacerbations: a population-based study in primary care","volume":"227","author":"Lapi","year":"2024","journal-title":"Resp Med"},{"key":"2026090101501761000_12.5.01774-2025.16","first-page":"201","article-title":"A score to predict short-term risk of COPD exacerbations (SCOPEX)","volume":"10","author":"Make","year":"2015","journal-title":"Int J Chronic Obstr"},{"key":"2026090101501761000_12.5.01774-2025.17","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-214644"},{"key":"2026090101501761000_12.5.01774-2025.18","doi-asserted-by":"crossref","first-page":"1611947","DOI":"10.3389\/fmed.2025.1611947","article-title":"Analysis of exhaled nitric oxide and its influencing factors in patients with chronic obstructive pulmonary disease","volume":"12","author":"Shen","year":"2025","journal-title":"Front Med (Lausanne)"},{"key":"2026090101501761000_12.5.01774-2025.19","first-page":"3037","article-title":"The relationship of fractional exhaled nitric oxide in patients with AECOPD","volume":"18","author":"Xu","year":"2023","journal-title":"Int J Chronic Obstr"},{"key":"2026090101501761000_12.5.01774-2025.20","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1556\/APhysiol.100.2013.016","article-title":"Relationship between exhaled nitric oxide and the frequency of severe acute exacerbation of COPD: 3-year follow-up","volume":"100","author":"Antus","year":"2013","journal-title":"Acta Physiol Hung"},{"key":"2026090101501761000_12.5.01774-2025.21","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2147\/JAA.S289592","article-title":"Annual fractional exhaled nitric oxide measurements and exacerbations in severe asthma","volume":"13","author":"Abe","year":"2020","journal-title":"J Asthma Allergy"},{"key":"2026090101501761000_12.5.01774-2025.22","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/resp.14474","article-title":"Is FeNOtyping in COPD the path to precision medicine?","volume":"28","author":"Flynn","year":"2023","journal-title":"Respirology"},{"key":"2026090101501761000_12.5.01774-2025.23","doi-asserted-by":"crossref","first-page":"1591052168","DOI":"10.1177\/17534666251335800","article-title":"Eosinophils in chronic obstructive pulmonary disease","volume":"19","author":"Vanetti","year":"2025","journal-title":"Ther Adv Respir Dis"},{"key":"2026090101501761000_12.5.01774-2025.24","doi-asserted-by":"crossref","first-page":"2408466","DOI":"10.1080\/07853890.2024.2408466","article-title":"Eosinophilic inflammation: a key player in COPD pathogenesis and progression","volume":"56","author":"Lee","year":"2024","journal-title":"Ann Med"},{"key":"2026090101501761000_12.5.01774-2025.25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2008.02969.x"},{"key":"2026090101501761000_12.5.01774-2025.26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s12931-022-02123-5","article-title":"Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review","volume":"23","author":"Hurst","year":"2022","journal-title":"Resp Res"},{"key":"2026090101501761000_12.5.01774-2025.27","doi-asserted-by":"crossref","first-page":"106725","DOI":"10.1016\/j.rmed.2021.106725","article-title":"Exacerbation history, severity of dyspnoea and maintenance treatment predicts risk of future exacerbations in patients with COPD in the general population","volume":"192","author":"Marott","year":"2022","journal-title":"Resp Med"},{"key":"2026090101501761000_12.5.01774-2025.28","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1186\/s40001-025-03042-z","article-title":"Prediction of 12-month exacerbation-related readmission in hospitalized patients with COPD: a single-center study in China","volume":"30","author":"Zhang","year":"2025","journal-title":"Eur J Med Res"},{"key":"2026090101501761000_12.5.01774-2025.29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41533-024-00361-2","article-title":"Medication adherence halves COPD patients\u2019 hospitalization risk: evidence from Swiss health insurance data","volume":"34","author":"Bischof","year":"2024","journal-title":"NPJ Prim Care Resp Med"},{"key":"2026090101501761000_12.5.01774-2025.30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4046\/trd.2019.0050","article-title":"Exhaled nitric oxide in patients with stable chronic obstructive pulmonary disease: clinical implications of the use of inhaled corticosteroids","volume":"83","author":"Jo","year":"2020","journal-title":"Tuberc Respir Dis"},{"key":"2026090101501761000_12.5.01774-2025.31","doi-asserted-by":"crossref","first-page":"107682","DOI":"10.1016\/j.rmed.2024.107682","article-title":"Correlation of fractional exhaled nitric oxide (FeNO) and clinical outcomes in patients with chronic obstructive pulmonary disease: a prospective cohort study","volume":"229","author":"Keeratichananont","year":"2024","journal-title":"Resp Med"},{"key":"2026090101501761000_12.5.01774-2025.32","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1164\/rccm.202303-0455CI","article-title":"Targeting type 2 inflammation and epithelial alarmins in chronic obstructive pulmonary disease: a biologics outlook","volume":"208","author":"Rabe","year":"2023","journal-title":"Am J Resp Crit Care"},{"key":"2026090101501761000_12.5.01774-2025.33","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.3390\/biomedicines10092128","article-title":"Blood eosinophils and exhaled nitric oxide: surrogate biomarkers of airway eosinophilia in stable COPD and exacerbation","volume":"10","author":"Antus","year":"2022","journal-title":"Biomedicines"},{"key":"2026090101501761000_12.5.01774-2025.34","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1111\/all.16447","article-title":"Exhaled nitric oxide and sputum eosinophils are complementary tools for diagnosing occupational asthma","volume":"80","author":"Doyen","year":"2025","journal-title":"Allergy"},{"key":"2026090101501761000_12.5.01774-2025.35","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.3390\/cells12212518","article-title":"Exhaled nitric oxide as biomarker of type 2 diseases","volume":"12","author":"Maniscalco","year":"2023","journal-title":"Cells-Basel"},{"key":"2026090101501761000_12.5.01774-2025.36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2303951"},{"key":"2026090101501761000_12.5.01774-2025.37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S2213-2600(24)00324-2","article-title":"Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe chronic obstructive pulmonary disease (COURSE): a randomised, placebo-controlled, phase 2a trial","volume":"13","author":"Singh","year":"2025","journal-title":"Lancet Resp Med"}],"container-title":["ERJ Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/23120541.01774-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:50:31Z","timestamp":1788252631000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/23120541.01774-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,9,1]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1183\/23120541.01774-2025"],"URL":"https:\/\/doi.org\/10.1183\/23120541.01774-2025","relation":{},"ISSN":["2312-0541"],"issn-type":[{"value":"2312-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]}}}