{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:34:05Z","timestamp":1791196445863,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Severe asthma is a major public health issue throughout the world. Increased bronchial smooth muscle (BSM) mass, a characteristic feature of airway remodeling in severe asthma, is associated with resistance to high-intensity treatment and poor prognosis. In vitro, the Ca2+-channel blocker gallopamil decreased the proliferation of BSM cells from patients with severe asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We conducted a double-blind, randomized, placebo-controlled study to evaluate the effect of gallopamil on airway remodeling in patients with severe asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Subjects received either gallopamil (n\u2009=\u200916) or placebo (n\u2009=\u200915) for 1 year and were monitored for an additional 3-month period. Airway remodeling was analyzed at baseline and after treatment phase using both fiberoptic bronchoscopy and computed tomography scan. The primary end point was the BSM area. Secondary end points included normalized BSM thickness and frequency of asthma exacerbations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>BSM area was reduced in the gallopamil group (baseline vs. end of treatment) but was unchanged in the placebo group. Between-group differences in BSM area were not significantly different in gallopamil versus placebo groups. By contrast, between-group differences in normalized BSM thickness were significantly different between the two groups. The mean number of exacerbations per month was not different during the treatment phase in gallopamil versus placebo group but was significantly lower in patients previously treated with gallopamil during the follow-up period. There were no differences between the groups with respect to overall side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gallopamil treatment for 12 months reduces BSM remodeling and prevents the occurrence of asthma exacerbations.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 00896428).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201410-1874oc","type":"journal-article","created":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T10:24:17Z","timestamp":1422527057000},"page":"876-883","source":"Crossref","is-referenced-by-count":77,"title":["Calcium Channel Blocker Reduces Airway Remodeling in Severe Asthma. A Proof-of-Concept Study"],"prefix":"10.1093","volume":"191","author":[{"given":"Pierre-Olivier","family":"Girodet","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Dournes","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Thumerel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"Begueret","sequence":"additional","affiliation":[{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre Dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annaig","family":"Ozier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Dupin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Trian","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Montaudon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Laurent","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Marthan","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Berger","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, D\u00e9partement de Pharmacologie, CIC1401, Bordeaux, France"},{"name":"INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Bordeaux, France; and"},{"name":"CHU de Bordeaux, CIC1401, Service d'Exploration Fonctionnelle Respiratoire, Service d'Imagerie Diagnostique et Th\u00e9rapeutique, Service d'Anatomopathologie, Service de Chirurgie Thoracique, Service de Cardiologie, Pessac, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,15]]},"reference":[{"key":"2026032100224180100_bib1","doi-asserted-by":"crossref","first-page":"b494","DOI":"10.1136\/bmj.b494","article-title":"Difficult to treat asthma in adults","volume":"338","author":"Currie","year":"2009","journal-title":"BMJ"},{"key":"2026032100224180100_bib2","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/S0140-6736(13)61536-6","article-title":"Asthma","volume":"382","author":"Martinez","year":"2013","journal-title":"Lancet"},{"key":"2026032100224180100_bib3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jaci.2009.03.049","article-title":"Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction","volume":"124","author":"Kaminska","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"2026032100224180100_bib4","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1164\/rccm.200905-0745OC","article-title":"T cells localize with proliferating smooth muscle alpha-actin+ cell compartments in asthma","volume":"182","author":"Ramos-Barb\u00f3n","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100224180100_bib5","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1164\/ajrccm.164.3.2010109","article-title":"Airway smooth muscle cell proliferation is increased in asthma","volume":"164","author":"Johnson","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100224180100_bib6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.pharmthera.2011.02.001","article-title":"Airway remodeling in asthma: new mechanisms and potential for pharmacological intervention","volume":"130","author":"Girodet","year":"2011","journal-title":"Pharmacol Ther"},{"key":"2026032100224180100_bib7","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1056\/NEJMoa021660","article-title":"Dysfunctional interaction of C\/EBPalpha and the glucocorticoid receptor in asthmatic bronchial smooth-muscle cells","volume":"351","author":"Roth","year":"2004","journal-title":"N Engl J Med"},{"key":"2026032100224180100_bib8","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1084\/jem.20070956","article-title":"Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma","volume":"204","author":"Trian","year":"2007","journal-title":"J Exp Med"},{"key":"2026032100224180100_bib9","year":"2012"},{"key":"2026032100224180100_bib10","first-page":"309","article-title":"Guidelines for methacholine and exercise challenge testing-1999","volume":"161","author":"Crapo","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100224180100_bib11","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1164\/ajrccm.162.6.ats9-00","article-title":"Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions","volume":"162","author":"American Thoracic Society","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100224180100_bib12","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/S0140-6736(02)11679-5","article-title":"Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial","volume":"360","author":"Green","year":"2002","journal-title":"Lancet"},{"key":"2026032100224180100_bib13","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1126\/science.1079368","article-title":"Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide","volume":"299","author":"Nisoli","year":"2003","journal-title":"Science"},{"key":"2026032100224180100_bib14","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1183\/09031936.99.14613949","article-title":"Assessment of bronchial inflammation using an automated cell recognition system based on colour analysis","volume":"14","author":"Berger","year":"1999","journal-title":"Eur Respir J"},{"key":"2026032100224180100_bib15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1164\/rccm.201105-0915OC","article-title":"Role of YKL-40 in bronchial smooth muscle remodeling in asthma","volume":"185","author":"Bara","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100224180100_bib16","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1148\/radiol.2353040121","article-title":"Airway wall thickness in cigarette smokers: quantitative thin-section CT assessment","volume":"235","author":"Berger","year":"2005","journal-title":"Radiology"},{"key":"2026032100224180100_bib17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1148\/radiol.2422060029","article-title":"Assessment of airways with three-dimensional quantitative thin-section CT: in vitro and in vivo validation","volume":"242","author":"Montaudon","year":"2007","journal-title":"Radiology"},{"key":"2026032100224180100_bib18","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0140-6736(86)90837-8","article-title":"Statistical methods for assessing agreement between two methods of clinical measurement","volume":"1","author":"Bland","year":"1986","journal-title":"Lancet"},{"key":"2026032100224180100_bib19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1136\/bmj.313.7048.41","article-title":"Measurement error and correlation coefficients","volume":"313","author":"Bland","year":"1996","journal-title":"BMJ"},{"key":"2026032100224180100_bib20","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1056\/NEJMoa064707","article-title":"Asthma control during the year after bronchial thermoplasty","volume":"356","author":"Cox","year":"2007","journal-title":"N Engl J Med"},{"key":"2026032100224180100_bib21","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1165\/rcmb.2013-0029OC","article-title":"Estimating airway smooth muscle cell volume and number in airway sections. Sources of variability","volume":"50","author":"Jones","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032100224180100_bib22","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1164\/ajrccm.187.1.107b","article-title":"Airway compliance studied by lumen area changes alone cannot discriminate between collapsibility and elasticity","volume":"187","author":"Dournes","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100224180100_bib23","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1148\/radiol.2533090303","article-title":"Bronchial measurements in patients with asthma: comparison of quantitative thin-section CT findings with those in healthy subjects and correlation with pathologic findings","volume":"253","author":"Montaudon","year":"2009","journal-title":"Radiology"},{"key":"2026032100224180100_bib24","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1183\/09031936.00019810","article-title":"Pathophysiology of bronchial smooth muscle remodelling in asthma","volume":"36","author":"Bara","year":"2010","journal-title":"Eur Respir J"},{"key":"2026032100224180100_bib25","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1304048","article-title":"Dupilumab in persistent asthma with elevated eosinophil levels","volume":"368","author":"Wenzel","year":"2013","journal-title":"N Engl J Med"},{"key":"2026032100224180100_bib26","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1046\/j.1365-2125.2000.00115.x","article-title":"Pharmacokinetics and pharmacodynamics of R- and S-gallopamil during multiple dosing","volume":"49","author":"Gross","year":"2000","journal-title":"Br J Clin Pharmacol"},{"key":"2026032100224180100_bib27","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1136\/hrt.70.3.252","article-title":"Heart rate variability in time and frequency domains: effects of gallopamil, nifedipine, and metoprolol compared with placebo","volume":"70","author":"Schweizer","year":"1993","journal-title":"Br Heart J"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/191\/8\/876\/67215956\/ajrccm_191_8_876.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/191\/8\/876\/67215956\/ajrccm_191_8_876.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:22:52Z","timestamp":1774066972000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/191\/8\/876\/8505005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2015,4,15]]},"published-print":{"date-parts":[[2015,4,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201410-1874oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,4]]},"published":{"date-parts":[[2015,4]]}}}