{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:56:18Z","timestamp":1789584978567,"version":"build-2803163510"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0522604 \/ 2024ZD0522600 to S Li"],"award-info":[{"award-number":["2024ZD0522604 \/ 2024ZD0522600 to S Li"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0522604 \/ 2024ZD0522600 to S Li"],"award-info":[{"award-number":["2024ZD0522604 \/ 2024ZD0522600 to S Li"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82173182"],"award-info":[{"award-number":["82173182"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Program of Sichuan","award":["2023NSFSC1939"],"award-info":[{"award-number":["2023NSFSC1939"]}]},{"DOI":"10.13039\/501100019014","name":"Chengdu Science and Technology Project","doi-asserted-by":"crossref","award":["2023-YF09-00039-SN"],"award-info":[{"award-number":["2023-YF09-00039-SN"]}],"id":[{"id":"10.13039\/501100019014","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Disruption of parasympathetic pulmonary nerves, which release acetylcholine and trigger airway smooth muscle constriction, has been shown to improve lung function and alleviate symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the current targeted lung denervation (TLD) mono-polar radiofrequency (RF) ablation system has the potential for structural improvement to enhance the generalizability and safety of the TLD procedure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop a novel TLD multi-polar RF ablation for COPD treatment and evaluate its feasibility, safety, and efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the preclinical study, we performed TLD in vitro (porcine lung and liver model) to validate its feasibility and in vivo (dogs and sheep) to ensure its safety and preliminary efficacy. Subsequently, we conducted a first-in-man study to evaluate TLD in patients with COPD forced expiratory volume in 1\u00a0s (FEV\n                      <jats:sub>1<\/jats:sub>\n                      )\/forced vital capacity (FVC) (FEV\n                      <jats:sub>1<\/jats:sub>\n                      \/FVC\u2009&lt;\u20090.70; FEV\n                      <jats:sub>1<\/jats:sub>\n                      20%\u201360% predicted) with three energy settings (12\u00a0W, 14\u00a0W, and 16\u00a0W). The primary safety endpoint was the occurrence of any adverse events or serious adverse events deemed related to the TLD device or the procedure. The efficacy endpoints included the instrument and technical success rates of the TLD procedures, as well as changes in lung function, exercise capacity assessments, and health-related quality of life.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In vitro experiments demonstrated that using ice-cold saline irrigation reduced the temperature at the ablation point compared to room-temperature saline (44\u00a0\u00b0C vs. 63\u00a0\u00b0C). The ablation range was 6\u20138\u00a0mm when the single electrode power was 12\u201316\u00a0W, coinciding with the distribution of peribronchial nerves. In the in vivo experiments, we confirmed the feasibility of performing TLD in dogs without causing esophageal injury. In sheep, the bronchoscopy and histological examinations showed airway epithelial restitution within a one-year follow-up. Postprocedural pulmonary airway resistance was reduced by approximately 30% with a sustained 30% decrease in axonal staining. In the first-in-man study, the nine patients included reported good tolerance with a success instrument rate of 100% and a technical success rate of 88.9%. FEV\n                      <jats:sub>1<\/jats:sub>\n                      increased by 160\u2009\u00b1\u2009120 mL at 6 months post-TLD and 80\u2009\u00b1\u2009150 mL at 12 months post-TLD from baseline. The patients\u2019 motor ability and quality of life scores showed improvement but returned to baseline levels by the twelfth month.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrated the feasibility of the novel TLD multi-polar RF ablation system in COPD patients. Its safety and clinical efficacy require further validation in larger patient cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>\n                      ChiCTR2100047843 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chictr.org.cn\/\" ext-link-type=\"uri\">http:\/\/www.chictr.org.cn\/<\/jats:ext-link>\n                      ). Registration date: 27 June, 2021.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-026-03496-7","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T02:53:22Z","timestamp":1768272802000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel targeted lung denervation multi-polar radiofrequency ablation system for moderate to severe COPD patients: a translational study"],"prefix":"10.1186","volume":"27","author":[{"given":"Rui","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchun","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoju","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaige","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liheng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenhui","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengming","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"3496_CR1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1164\/rccm.201204-0596PP","volume":"187","author":"J Vestbo","year":"2013","unstructured":"Vestbo J, Hurd SS, Agust\u00ed AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the Diagnosis, Management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187:347\u201365. https:\/\/doi.org\/10.1164\/rccm.201204-0596PP.","journal-title":"Am J Respir Crit Care Med"},{"key":"3496_CR2","unstructured":"Gold Reports. Glob. Initiat. Chronic Obstr. Lung Dis. - GOLD. 2020. https:\/\/goldcopd.org\/gold-reports\/. Accessed 27 Jul 2025. Cited 27 Jul\u00a02025."},{"key":"3496_CR3","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1513\/pats.200504-043SR","volume":"2","author":"KE Belmonte","year":"2005","unstructured":"Belmonte KE. Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease. Proc Am Thorac Soc Am Thorac Soc - PATS. 2005;2:297\u2013304. https:\/\/doi.org\/10.1513\/pats.200504-043SR.","journal-title":"Proc Am Thorac Soc Am Thorac Soc - PATS"},{"key":"3496_CR4","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/0002-9343(86)90470-5","volume":"81","author":"ER Bleecker","year":"1986","unstructured":"Bleecker ER. Cholinergic and neurogenic mechanisms in obstructive airways disease. Am J Med. 1986;81:93\u2013102. https:\/\/doi.org\/10.1016\/0002-9343(86)90470-5.","journal-title":"Am J Med"},{"key":"3496_CR5","doi-asserted-by":"publisher","first-page":"476","DOI":"10.3390\/biom13030476","volume":"13","author":"F Gomes","year":"2023","unstructured":"Gomes F, Cheng S-L, Pathophysiology. Therapeutic Targets, and future therapeutic alternatives in COPD: focus on the importance of the cholinergic system. Biomolecules Multidisciplinary Digit Publishing Inst. 2023;13:476. https:\/\/doi.org\/10.3390\/biom13030476.","journal-title":"Biomolecules Multidisciplinary Digit Publishing Inst"},{"key":"3496_CR6","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.rmed.2007.11.003","volume":"102","author":"F Lavorini","year":"2008","unstructured":"Lavorini F, Magnan A, Christophe Dubus J, Voshaar T, Corbetta L, Broeders M, et al. Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD. Respir Med. 2008;102:593\u2013604. https:\/\/doi.org\/10.1016\/j.rmed.2007.11.003.","journal-title":"Respir Med"},{"key":"3496_CR7","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s00408-015-9832-5","volume":"194","author":"EJ Zaccone","year":"2016","unstructured":"Zaccone EJ, Undem BJ. Airway vagal neuroplasticity associated with respiratory viral infections. Lung. 2016;194:25\u20139. https:\/\/doi.org\/10.1007\/s00408-015-9832-5.","journal-title":"Lung"},{"key":"3496_CR8","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1046\/j.1365-2125.2003.01892.x","volume":"56","author":"NR Labiris","year":"2003","unstructured":"Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003;56:588\u201399. https:\/\/doi.org\/10.1046\/j.1365-2125.2003.01892.x.","journal-title":"Br J Clin Pharmacol"},{"key":"3496_CR9","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1136\/thx.8.2.116","volume":"8","author":"OA Abbott","year":"1953","unstructured":"Abbott OA, Hopkins WA, Van Fleit WE, Robinson JS. A new approach to pulmonary emphysema. Thorax. 1953;8:116\u201332. https:\/\/doi.org\/10.1136\/thx.8.2.116.","journal-title":"Thorax"},{"key":"3496_CR10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1152\/japplphysiol.00565.2018","volume":"126","author":"JP Hummel","year":"2019","unstructured":"Hummel JP, Mayse ML, Dimmer S, Johnson PJ. Physiologic and histopathologic effects of targeted lung denervation in an animal model. J Appl Physiol. 2019;126:67\u201376. https:\/\/doi.org\/10.1152\/japplphysiol.00565.2018.","journal-title":"J Appl Physiol"},{"key":"3496_CR11","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12931-020-01383-3","volume":"21","author":"ML Mayse","year":"2020","unstructured":"Mayse ML, Norman HS, Peterson AD, Rouw KT, Johnson PJ. Targeted lung denervation in sheep: durability of denervation and long-term histologic effects on bronchial wall and peribronchial structures. Respir Res. 2020;21:117. https:\/\/doi.org\/10.1186\/s12931-020-01383-3.","journal-title":"Respir Res"},{"key":"3496_CR12","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1159\/000500463","volume":"98","author":"A Valipour","year":"2019","unstructured":"Valipour A, Shah PL, Pison C, Ninane V, Janssens W, Perez T, et al. Safety and dose study of targeted lung denervation in Moderate\/Severe COPD patients. Respiration. 2019;98:329\u201339. https:\/\/doi.org\/10.1159\/000500463.","journal-title":"Respiration"},{"key":"3496_CR13","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1164\/rccm.201903-0624OC","volume":"200","author":"D-J Slebos","year":"2019","unstructured":"Slebos D-J, Shah PL, Herth FJF, Pison C, Schumann C, H\u00fcbner R-H, et al. Safety and adverse events after targeted lung denervation for symptomatic moderate to severe chronic obstructive pulmonary disease (AIRFLOW). A multicenter randomized controlled clinical trial. Am J Respir Crit Care Med. 2019;200:1477\u201386. https:\/\/doi.org\/10.1164\/rccm.201903-0624OC.","journal-title":"Am J Respir Crit Care Med"},{"key":"3496_CR14","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.2147\/COPD.S158748","volume":"13","author":"A Valipour","year":"2018","unstructured":"Valipour A, Asadi S, Pison C, Jondot M, Kessler R, Benneddif K, et al. Long-term safety of bilateral targeted lung denervation in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:2163\u201372. https:\/\/doi.org\/10.2147\/COPD.S158748.","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"3496_CR15","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1136\/thoraxjnl-2014-206146","volume":"70","author":"D-J Slebos","year":"2015","unstructured":"Slebos D-J, Klooster K, Koegelenberg CFN, Theron J, Styen D, Valipour A, et al. Targeted lung denervation for moderate to severe COPD: a pilot study. Thorax. 2015;70:411\u20139. https:\/\/doi.org\/10.1136\/thoraxjnl-2014-206146.","journal-title":"Thorax"},{"key":"3496_CR16","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12931-021-01664-5","volume":"22","author":"C Pison","year":"2021","unstructured":"Pison C, Shah PL, Slebos D-J, Ninane V, Janssens W, Perez T, et al. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes. Respir Res. 2021;22:62. https:\/\/doi.org\/10.1186\/s12931-021-01664-5.","journal-title":"Respir Res"},{"key":"3496_CR17","doi-asserted-by":"publisher","unstructured":"Shah PL, Slebos D-J, Sue R, Bhatt SP, Ghattas C, Strange C et al. Randomized Sham Controlled Trial of Targeted Lung Denervation in Patients with COPD (AIRFLOW-3). Am J Respir Crit Care Med. American Thoracic Society - AJRCCM; 2025. https:\/\/doi.org\/10.1164\/rccm.202502-0404OC. Cited 31 Oct 2025.","DOI":"10.1164\/rccm.202502-0404OC"},{"key":"3496_CR18","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1136\/thorax.56.11.880","volume":"56","author":"PW Jones","year":"2001","unstructured":"Jones PW. Health status measurement in chronic obstructive pulmonary disease. Thorax. 2001;56:880\u20137. https:\/\/doi.org\/10.1136\/thorax.56.11.880.","journal-title":"Thorax"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-026-03496-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-026-03496-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-026-03496-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T14:41:41Z","timestamp":1770648101000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12931-026-03496-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":18,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3496"],"URL":"https:\/\/doi.org\/10.1186\/s12931-026-03496-7","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"assertion":[{"value":"7 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This animal study was approved by the Ethical Committee of WestPoint Innovation Center (Ethical Approval number: IAC21110101, IAC22041801), and treatment of the animals was in accordance with the Animal Welfare Act of 1966 and all efforts were made to minimize animal suffering and to use the minimum number of animals necessary to produce reliable scientific data. This clinical study was approved by Ethical Committee of West China Hospital of Sichuan University (Ethical Approval number: 2021-426) and in accordance with the Declaration of Helsinki (1996), Good Clinical Practice guidelines, and local requirements. The trial was registered on the Chinese Clinical Trial Registry (chiCTR.gov, No. ChiCTR2100047843, 27 June, 2021). The date of enrolment of the first research participant was 15 September, 2021. Patients or their representatives provided signed informed consent forms before participation in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"50"}}