{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:33:49Z","timestamp":1791380029887,"version":"4.3.3"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"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":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bronchial thermoplasty is a relatively new but seemingly effective treatment in subjects with asthma who do not respond to conventional therapy. Although the favored mechanism is ablation of the airway smooth muscle layer, because bronchial thermoplasty treats only a small number of central airways, there is ongoing debate regarding its precise method of action. Our aim in the present study was to elucidate the underlying method of action behind bronchial thermoplasty. We employed a combination of extensive human lung specimens and novel computational methods. Whole left lungs were acquired from the Prairie Provinces Fatal Asthma Study. Subjects were classified as control (n\u2009=\u200931), nonfatal asthma (n\u2009=\u200932), or fatal asthma (n\u2009=\u200925). Simulated lungs for each group were constructed stochastically, and flow distributions and functional indicators (e.g., resistance) were quantified both before and after a 75% reduction in airway smooth muscle in the \u201cthermoplasty-treated\u201d airways. Bronchial thermoplasty triggered global redistribution of clustered flow patterns wherein structural changes to the treated central airways led to a reopening cascade in the small airways and significant improvement in lung function via reduced spatial heterogeneity of flow patterns. This mechanism accounted for progressively greater efficacy of thermoplasty with both severity of asthma and degree of muscle activation, broadly consistent with existing clinical findings. We report a probable mechanism of action for bronchial thermoplasty: alteration of lung-wide flow patterns in response to structural alteration of the treated central airways. This insight could lead to improved therapy via patient-specific, tailored versions of the treatment\u2014as well as to implications for more conventional asthma therapies.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0011oc","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T16:59:40Z","timestamp":1524070780000},"page":"355-362","source":"Crossref","is-referenced-by-count":61,"title":["Unraveling a Clinical Paradox: Why Does Bronchial Thermoplasty Work in Asthma?"],"prefix":"10.1093","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5903-5484","authenticated-orcid":false,"given":"Graham M.","family":"Donovan","sequence":"first","affiliation":[{"name":"Department of Mathematics, University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Elliot","sequence":"additional","affiliation":[{"name":"West Australian Sleep Disorders Research Institute, Department of Pulmonary Physiology and Sleep Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis H. Y.","family":"Green","sequence":"additional","affiliation":[{"name":"Airway Inflammation Group, Snyder Institute of Chronic Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan L.","family":"James","sequence":"additional","affiliation":[{"name":"West Australian Sleep Disorders Research Institute, Department of Pulmonary Physiology and Sleep Medicine, and"},{"name":"Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Noble","sequence":"additional","affiliation":[{"name":"School of Human Sciences and"},{"name":"Centre for Neonatal Research and Education, School of Paediatrics and Child Health, The University of Western Australia, Subiaco, Western Australia, 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