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• W4200345487 abstract "ViewpointLast Word on Viewpoint: Small airways vs. large airways in asthma: time for a new perspective—Size does not matter: airway interactions determine respiratory dys(function)Graham M. Donovan and Peter B. NobleGraham M. DonovanDepartment of Mathematics, The University of Auckland, Auckland, New Zealand and Peter B. NobleSchool of Human Sciences, The University of Western Australia, Crawley, Western Australia, AustraliaPublished Online:13 Dec 2021https://doi.org/10.1152/japplphysiol.00781.2021MoreSectionsPDF (149 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat to the editor: The range of responses to our Viewpoint (1) calling for a re-evaluation of how airway size is scrutinized in asthma has helped to clarify several important points. Although there appears to be relative consensus that the dichotomy between “small” and “large” airways is not particularly useful, it is less clear what paradigm should replace this in either a research or clinical context. Drs. Lutchen and Winkler (2) pose the question not in terms of generic behavior based on airway size, but rather the specific airways involved in each patient. This, we think, is the right question, but without a straightforward answer. Dr. Bayat (2) describes the potential role of functional imaging in service of this goal, and indeed, the relative stability over time of hyperpolarized gas MRI ventilation distributions (e.g. Ref. 3) supports the notion of specific structural defects largely determining the functional outcomes. The obstacle, as outlined by Drs. Bossé and Winkler (2), is complexity within a subject or patient. Indeed, recent efforts to identify specific airways for treatment using functional imaging (4) has demonstrated that although this approach has promise, mapping functional defects to specific structural abnormalities is challenging (5) because airways do not function in isolation, but instead are coupled by airflow and parenchymal interdependence. Hence, trying to interpret the results of functional assays in terms of specific, localized structural abnormalities may carry a substantial error margin.We acknowledge and support the need for any new perspective to propagate to the clinic, as called for by Drs Verbanck, Brusasco, O’Sullivan, and colleagues, and Thamrin and colleagues (2). As but one example, it is unclear if prioritizing aerosol delivery to the “small” airways is appropriate if we cannot be certain that the origin of the defect lies within the lung periphery. There is an urgent need to understand the outputs of new diagnostic methods, such of those offered by Dr. O’Sullivan and colleagues, and Drs. Foy and Siddiqui (2), and adopt those with adequate diagnostic power into clinical practice.Finally, several authors took up our call regarding the uncertainty of airway compliance and how it varies across the airway tree. The modeling outputs (1) were based on relatively small changes in the compliance difference between the peripheral and central airways; however, Dr. Eskandari (2) goes further and suggests that the relationship may be inverted (i.e., peripheral airways are stiffer than the central airways—at least in pigs). If so, this would certainly have notable functional consequences; we can only hope that we will soon have the data to better resolve this important question.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the authors.AUTHOR CONTRIBUTIONSG.M.D. and P.B.N. drafted manuscript; edited and revised manuscript; and approved final version of manuscript.REFERENCES1. Donovan GM, Noble PB. Small airways vs large airways in asthma: time for a new perspective. J Appl Physiol (1985). doi:10.1152/japplphysiol.00403.2021.Link | Google Scholar2. Verbanck S, Bossé Y, Bayat S, Lutchen KR, Thamrin C, Chapman DG, King GG, Brusasco V, O’Sullivan CF, Nilsen K, Prisk GK, Thompson BR, Foy BH, Siddiqui S, Winkler T, Eskandari M, Parameswaran H. Commentaries on viewpoint: small airways vs large airways in asthma: time for a new perspective. J Appl Physiol (1985). doi:10.1152/japplphysiol.00762.2021.Link | Google Scholar3. de Lange EE, Altes TA, Patrie JT, Battiston JJ, Juersivich AP, Mugler JP III, Platts-Mills TA. Changes in regional airflow obstruction over time in the lungs of patients with asthma: evaluation with 3He MR imaging. Radiology 250: 567–575, 2009.doi:10.1148/radiol.2502080188.Crossref | PubMed | ISI | Google Scholar4. Hall CS, Quirk JD, Goss CW, Lew D, Kozlowski J, Thomen RP, Woods JC, Tustison NJ, Mugler JP III, Gallagher L, Koch T, Schechtman KB, Ruset IC, Hersman FW, Castro M. Single-session bronchial thermoplasty guided by 129Xe magnetic resonance imaging. A pilot randomized controlled clinical trial. Am J Respir Crit Care Med 202: 524–534, 2020. doi:10.1164/rccm.201905-1021OC. Crossref | PubMed | ISI | Google Scholar5. Donovan GM, Elliot JG, Boser SR, Green FHY, James AL, Noble PB. Patient-specific targeted bronchial thermoplasty: predictions of improved outcomes with structure-guided treatment. J Appl Physiol (1985) 126: 599–606, 2019. doi:10.1152/japplphysiol.00951.2018. Link | ISI | Google ScholarAUTHOR NOTESCorrespondence: G. M. Donovan (g.[email protected]ac.nz). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Related ArticlesCommentaries on Viewpoint: Small airways vs. large airways in asthma: time for a new perspective 13 Dec 2021Journal of Applied PhysiologySmall airways vs large airways in asthma: time for a new perspective 13 Dec 2021Journal of Applied Physiology More from this issue > Volume 131Issue 6December 2021Pages 1849-1849 Crossmark Copyright & PermissionsCopyright © 2021 the American Physiological Society.https://doi.org/10.1152/japplphysiol.00781.2021PubMed34898286History Received 16 November 2021 Accepted 16 November 2021 Published online 13 December 2021 Published in print 1 December 2021 Metrics" @default.
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