{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:51:35Z","timestamp":1791363095575,"version":"4.3.1"},"reference-count":34,"publisher":"The Royal Society","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009193","name":"Royal Society of New Zealand Marsden Fund","doi-asserted-by":"publisher","award":["UOA2223"],"award-info":[{"award-number":["UOA2223"]}],"id":[{"id":"10.13039\/501100009193","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Venegas\u2013Winkler model is a seminal model in asthma pathophysiology, providing both a conceptual and quantitative framework for extending a posited bistability between open and closed states at the level of the individual, terminal airway to the lung as a whole. In doing so, it offers an explanation for the characteristic ventilation heterogeneity (or clustered ventilation defects) seen in asthma. The terminal airway bistability is based on the Anafi\u2013Wilson model, and this is embedded and extended into a symmetric bifurcating airway tree, in which an enforced tidal volume target and an imposed degree of airway smooth-muscle activation interact to generate spatially structured ventilation patterns. Here, we provide the first open-source implementation of the Venegas\u2013Winkler bronchoconstriction cascade model and use it to identify several previously undescribed properties: both the tree depth and wall thickness assumptions affect the bifurcation onset, tidal volume and acinar elastance assumptions require careful interpretation for a model at sub-lung scale and airway geometry assumptions strongly affect driving pressures and bifurcation cascade characteristics.<\/jats:p>","DOI":"10.1098\/rsos.261168","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:10:58Z","timestamp":1791331858000},"source":"Crossref","is-referenced-by-count":0,"title":["Self-organized ventilation defects in asthma: insights and open-source implementation of the Venegas\u2013Winkler model"],"prefix":"10.1098","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5903-5484","authenticated-orcid":false,"given":"Graham M.","family":"Donovan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"2026100704094910100_RSOS261168C1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nature03490","article-title":"Self-organized patchiness in asthma as a prelude to catastrophic shifts","volume":"434","author":"Venegas","year":"2005","journal-title":"Nature"},{"key":"2026100704094910100_RSOS261168C2","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1152\/jappl.2001.91.3.1185","article-title":"Airway stability and heterogeneity in the constricted lung","volume":"91","author":"Anafi","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"2026100704094910100_RSOS261168C3","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1152\/japplphysiol.00041.2007","article-title":"Complex airway behavior and paradoxical responses to bronchoprovocation","volume":"103","author":"Winkler","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"2026100704094910100_RSOS261168C4","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1152\/japplphysiol.01401.2009","article-title":"Dynamics of tidal volume and ventilation heterogeneity under pressure-controlled ventilation during bronchoconstriction: a simulation study","volume":"109","author":"Wongviriyawong","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"2026100704094910100_RSOS261168C5","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1152\/japplphysiol.01163.2010","article-title":"Self-organized patterns of airway narrowing","volume":"110","author":"Winkler","year":"2011","journal-title":"J. Appl. 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Physiol."},{"key":"2026100704094910100_RSOS261168C9","doi-asserted-by":"crossref","first-page":"e112443","DOI":"10.1371\/journal.pone.0112443","article-title":"Deep inspiration and the emergence of ventilation defects during bronchoconstriction: a computational study","volume":"9","author":"Golnabi","year":"2014","journal-title":"PLoS ONE"},{"key":"2026100704094910100_RSOS261168C10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1152\/japplphysiol.00466.2014","article-title":"Pendelluft in the bronchial tree","volume":"117","author":"Greenblatt","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"2026100704094910100_RSOS261168C11","unstructured":"Greenblatt\n              EJ\n            \n          . 2014Quantifying patchy ventilation: from experiments to mechanistic models. Master's thesis, Massachusetts Institute of Technology, Cambridge, MA, USA."},{"key":"2026100704094910100_RSOS261168C12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ddmod.2014.02.008","article-title":"Mathematical modeling of ventilation defects in asthma","volume":"15","author":"Winkler","year":"2015","journal-title":"Drug Discov. Today Dis. Models"},{"key":"2026100704094910100_RSOS261168C13","first-page":"011005","article-title":"Airway transmural pressures in an airway tree during bronchoconstriction in asthma","volume":"2","author":"Winkler","year":"2019","journal-title":"J. Eng. Sci. Med. Diagn. Ther."},{"key":"2026100704094910100_RSOS261168C14","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.21037\/atm-22-5095","article-title":"Mechanisms of airway remodeling converge at the critical point of bronchoconstriction in asthma","volume":"10","author":"Winkler","year":"2022","journal-title":"Ann. Transl. 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