{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:02:59Z","timestamp":1779692579743,"version":"3.53.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Background<\/jats:title>\n \n Chronic Obstructive Pulmonary Disease (COPD) is characterized by a progressive deterioration of lung function, which occurs at its fastest rate in the early stages (GOLD I-II). Preliminary clinical investigation has suggested that\n Cordyceps militaris<\/jats:italic>\n capsules can improve post-bronchodilator forced expiratory volume in 1\u00a0s (FEV\n 1<\/jats:sub>\n ) in mild-to-moderate COPD. However, previous studies were limited by the absence of placebo control. Therefore, this trial is designed to evaluate the efficacy and safety of\n Cordyceps militaris<\/jats:italic>\n capsules versus placebo in improving post-bronchodilator FEV\n 1<\/jats:sub>\n in patients with mild-to-moderate stable COPD.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This study is a multi-center, randomized, double-blind, placebo-controlled clinical trial involving 160 eligible patients aged between 40 and 85\u00a0years. After a 1-week run-in period, participants are randomized in a 1:1 ratio to receive either\n Cordyceps militaris<\/jats:italic>\n capsules or placebo capsules for 24\u00a0weeks, and are followed for an additional 24\u00a0weeks. The primary outcome measure is the change in post-bronchodilator FEV\n 1<\/jats:sub>\n . Secondary outcome measures comprise additional lung function parameters, such as pre-bronchodilator FEV\n 1<\/jats:sub>\n , pre- and post-bronchodilator measures of forced vital capacity (FVC), FEV\n 1<\/jats:sub>\n \/FVC ratio, mid-expiratory flow (MMEF), forced expiratory flow 75% (FEF75), forced expiratory flow 50% (FEF50). In addition, frequency of acute exacerbations, time to the first acute exacerbation, COPD Assessment Test (CAT), Cough and Sputum Assessment Questionnaire (CASA-Q), EuroQol five-dimension five-level questionnaire (EQ-5D-5L), and Modified Medical Research Council dyspnea scale (mMRC) are also included.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This study is designed to evaluate the therapeutic potential of\n Cordyceps militaris<\/jats:italic>\n capsules and to provide a traditional Chinese medicine intervention for preserving lung function in mild-to-moderate stable COPD.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n https:\/\/www.chictr.org.cn\/<\/jats:ext-link>\n , ChiCTR2400086743, identifier, ChiCTR2400086743.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1775068","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:06:23Z","timestamp":1779689183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating Cordyceps militaris capsules on post-bronchodilator FEV1 decline in patients with COPD: a study protocol for double-blind, randomized, placebo-controlled trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Siqi","family":"Lin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianming","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiting","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanbin","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yan","sequence":"additional","affiliation":[{"name":"China-Japan Friendship Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangming","family":"Dong","sequence":"additional","affiliation":[{"name":"Nanfang Hospital Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaofeng","family":"Zhan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Hospital of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xiao","sequence":"additional","affiliation":[{"name":"The Second People\u2019s Hospital of Baiyun and Guangzhou","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, China"]},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangdong Provincial Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaci.2016.05.011","article-title":"Inflammatory mechanisms in patients with chronic obstructive pulmonary disease","volume":"138","author":"Barnes","year":"2016","journal-title":"J. Allergy. Clin. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s12931-018-0882-0","article-title":"What have we learned from observational studies and clinical trials of mild to moderate COPD?","volume":"19","author":"Barrecheguren","year":"2018","journal-title":"Respir. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1080\/17476348.2016.1188693","article-title":"UPLIFT study - understanding potential long-term impacts on function with tiotropium - and sub-analyses. Bibliographic resume of the obtained results","volume":"10","author":"Callejas","year":"2016","journal-title":"Expert Rev. Respir. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1164\/rccm.202005-1854OC","article-title":"Pharmacotherapy and lung function decline in patients with chronic obstructive pulmonary disease. A systematic review","volume":"203","author":"Celli","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B1","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3760\/cma.j.cn112147-20210109-00031","article-title":"Guidelines for the diagnosis and management of chronic obstructive pulmonary disease (revised version 2021)","volume":"44","year":"2021","journal-title":"Chin. J. Tuberc. Respir. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019","volume":"396","author":"Collaborators","year":"2020","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1016\/S0140-6736(24)00367-2","article-title":"Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the global burden of disease study 2021","volume":"403","author":"Collaborators","year":"2024","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.fitote.2010.07.010","article-title":"Medicinal uses of the mushroom cordyceps militaris: current state and prospects","volume":"81","author":"Das","year":"2010","journal-title":"Fitoterapia"},{"key":"B10","doi-asserted-by":"publisher","first-page":"D1404","DOI":"10.1093\/nar\/gkae1037","article-title":"HERB 2.0: an updated database integrating clinical and experimental evidence for traditional Chinese medicine","volume":"53","author":"Gao","year":"2025","journal-title":"Nucleic. acids. Res."},{"key":"B11","unstructured":"Global Strategy for Prevention. Diagnosis and Management of COPD: 2024\n \n \n 2024"},{"key":"B35","unstructured":"Global Strategy for Prevention. Diagnosis and Management of COPD: 2025\n \n \n 2025"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.2147\/COPD.S296696","article-title":"A systematic literature review of the humanistic burden of COPD","volume":"16","author":"Hurst","year":"2021","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"987","DOI":"10.4049\/jimmunol.1001861","article-title":"FOXO3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease","volume":"187","author":"Hwang","year":"2011","journal-title":"J. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1002\/ptr.4655","article-title":"A new isoflavone glycitein 7-O-beta-D-glucoside 4''-O-methylate, isolated from Cordyceps militaris grown on germinated soybeans extract, inhibits EGF-Induced mucus hypersecretion in the human lung mucoepidermoid cells","volume":"26","author":"Kim","year":"2012","journal-title":"Phytother. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.4046\/trd.2016.79.3.121","article-title":"Strategies for management of the early chronic obstructive lung disease","volume":"79","author":"Lee","year":"2016","journal-title":"Tuberc. Respir. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/jebm.12578","article-title":"Guidelines of integrated Chinese and Western medicine for diagnosis and treatment of chronic obstructive pulmonary disease (2022)","volume":"16","author":"Li","year":"2023","journal-title":"J. Evid.-Based Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e70091","DOI":"10.1111\/jebm.70091","article-title":"The effectiveness of yong chong cao capsule in patients with mild to severe COPD: a multi-center, randomized, double-blinded, active-controlled trial","volume":"18","author":"Li","year":"2025","journal-title":"J. Evid.-Based Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e14184","DOI":"10.1016\/j.heliyon.2023.e14184","article-title":"Development of an efficient method for separation and purification of cordycepin from liquid fermentation of Cordyceps militaris and analysis of cordycepin antitumor activity","volume":"9","author":"Liu","year":"2023","journal-title":"Heliyon"},{"key":"B19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.fitote.2018.05.010","article-title":"The genus cordyceps: an extensive review of its traditional uses, phytochemistry and pharmacology","volume":"129","author":"Olatunji","year":"2018","journal-title":"Fitoterapia"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e069679","DOI":"10.1136\/bmj-2021-069679","article-title":"Burden of chronic obstructive pulmonary disease and its attributable risk factors in 204 countries and territories, 1990-2019: results from the global burden of disease study 2019","volume":"378","author":"Safiri","year":"2022","journal-title":"BMJ"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e2412043","DOI":"10.4014\/jmb.2412.12043","article-title":"The inhibitory effects of Cordyceps militaris ARA301 extract on lipopolysaccharide-induced lung injury in vivo","volume":"35","author":"Seong","year":"2025","journal-title":"J. Microbiol. Biotechnol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1136\/thoraxjnl-2018-212665","article-title":"12-month randomised controlled trial of ginseng extract for moderate COPD","volume":"74","author":"Shergis","year":"2019","journal-title":"Thorax"},{"key":"B23","doi-asserted-by":"publisher","first-page":"CD010744","DOI":"10.1002\/14651858.CD010744.pub2","article-title":"Smoking cessation for people with chronic obstructive pulmonary disease","volume":"2016","author":"van Eerd","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1056\/NEJMoa1105482","article-title":"Changes in forced expiratory volume in 1 second over time in COPD","volume":"365","author":"Vestbo","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"6134593","DOI":"10.1155\/2016\/6134593","article-title":"Herbal medicine Cordyceps sinensis improves health-related quality of life in moderate-to-severe asthma","volume":"2016","author":"Wang","year":"2016","journal-title":"Evid.-based Complement. Altern. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"rgaf114","DOI":"10.1093\/jpp\/rgaf114","article-title":"Study on the potential mechanism of Cordyceps militaris in chronic obstructive pulmonary disease via integrating metabolomics and network pharmacology","volume":"78","author":"Wang","year":"2026","journal-title":"J. Pharm. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e150473","DOI":"10.1172\/JCI150473","article-title":"The lung microbiome: progress and promise","volume":"131","author":"Whiteside","year":"2021","journal-title":"J. Clin. Invest."},{"key":"B9","doi-asserted-by":"publisher","first-page":"100161","DOI":"10.59717\/j.xinn-med.2025.100161","article-title":"Respiratory health outcomes and treatment of patients with mild-to-moderate COPD not eligible for previous major randomized controlled trials","volume":"3","author":"Wu","year":"2025","journal-title":"Innovation Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1749-8546-9-20","article-title":"Panax ginseng therapy for chronic obstructive pulmonary disease: a clinical trial protocol and pilot study","volume":"9","author":"Wu","year":"2014","journal-title":"Chin. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1172\/JCI60132","article-title":"SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice","volume":"122","author":"Yao","year":"2012","journal-title":"J. Clin. Invest."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4903671","DOI":"10.1155\/2019\/4903671","article-title":"Effectiveness and safety of oral Cordyceps sinensis on stable COPD of GOLD stages 2-3: systematic review and meta-analysis","volume":"2019","author":"Yu","year":"2019","journal-title":"Evid.-based Complement. Altern. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1136\/thorax-2023-220436","article-title":"Distinct trajectories of lung function from childhood to mid-adulthood","volume":"79","author":"Zhang","year":"2024","journal-title":"Thorax"},{"key":"B32","doi-asserted-by":"publisher","first-page":"119701","DOI":"10.1016\/j.jep.2025.119701","article-title":"Cordyceps militaris alleviates COPD by regulating amino acid metabolism, gut microbiota and short chain fatty acids","volume":"346","author":"Zhang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1056\/NEJMoa1700228","article-title":"Tiotropium in early-stage chronic obstructive pulmonary disease","volume":"377","author":"Zhou","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"117076","DOI":"10.1016\/j.jpba.2025.117076","article-title":"Integrating proteomics, metabolomics, and network pharmacology to investigate the mechanism of cordyceps sinensis in the treatment of COPD rats","volume":"266","author":"Zhou","year":"2025","journal-title":"J. Pharm. Biomed. Anal."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1775068\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:06:29Z","timestamp":1779689189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1775068\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":35,"alternative-id":["10.3389\/fphar.2026.1775068"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1775068","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"article-number":"1775068"}}