{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T19:10:23Z","timestamp":1738264223613,"version":"3.35.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>In this paper, we present a new computational framework for the simulation of airway resistance, the fraction of exhaled nitric oxide, and the diffusion capacity for nitric oxide in healthy and unhealthy lungs. Our approach is firstly based on a realistic representation of the geometry of healthy lungs as a function of body mass, which compares well with data from the literature, particularly in terms of lung volume and alveolar surface area. The original way in which this geometry is created, including an individual definition of the airways in the first seven generations of the lungs, makes it possible to consider the heterogeneous nature of the lungs in terms of perfusion and ventilation. In addition, a geometry can be easily modified to simulate various abnormalities, local or global (constriction, inflammation, perfusion defect). The natural variability of the lungs at constant body mass is also considered. The computational framework includes the possibility to simulate, on a given (possibly modified) geometry, a test to measure the flow resistance of the lungs (including its component due to the not fully developed flow in the first generations of lungs), a test to measure the concentration of nitric oxide in the exhaled air, and a test to measure the diffusion capacity for nitric oxide. This is implemented in the framework by solving different transport equations (momentum and convection\/diffusion) describing these tests. Through numerous simulations, we demonstrate the ability of our model to reproduce results from the literature, both for healthy lungs and lungs of patients with asthma or chronic obstructive pulmonary disease. Such a computational framework, through the possibilities of numerous and rapid tests that it allows, sheds new light on experimental data by providing information on the phenomena that take place in the distal generations of the lungs, which are difficult to access with imaging.<\/jats:p>","DOI":"10.1371\/journal.pone.0311667","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T18:32:29Z","timestamp":1738261949000},"page":"e0311667","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A new computational framework for simulating airway resistance, fraction of exhaled nitric oxide, and diffusing capacity for nitric oxide"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3021-0207","authenticated-orcid":true,"given":"Benoit","family":"Haut","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyril","family":"Karamaoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-8601","authenticated-orcid":true,"given":"Cl\u00e9ment","family":"Rigaut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"pone.0311667.ref001","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.resp.2008.02.010","article-title":"Gas and aerosol mixing in the acinus","volume":"1963","author":"A. Tsuda","year":"2008","journal-title":"Respiratory Physiology and Neurobiology"},{"key":"pone.0311667.ref002","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-87553-3","volume-title":"Morphometry of the human lung","author":"E. R. Weibel","year":"1963"},{"key":"pone.0311667.ref003","author":"J. B. West","year":"2011","edition":"9"},{"key":"pone.0311667.ref004","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1126\/science.1223012","article-title":"A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia","volume":"337","author":"B. Button","year":"2012","journal-title":"Science"},{"key":"pone.0311667.ref005","doi-asserted-by":"crossref","first-page":"S212","DOI":"10.1016\/j.prrv.2006.04.199","article-title":"Physiology of mucus clearance","volume":"7","author":"M. King","year":"2006","journal-title":"Paediatric Respiratory Reviews"},{"key":"pone.0311667.ref006","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/S0140-6736(13)61536-6","article-title":"Asthma","volume":"328","author":"F. D. Martinez","year":"2013","journal-title":"Lancet"},{"key":"pone.0311667.ref007","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/S0140-6736(06)69290-8","article-title":"Asthma: defining of the persistent adult phenotypes","volume":"368","author":"S. E. Wenzel","year":"2006","journal-title":"Lancet"},{"key":"pone.0311667.ref008","article-title":"Global Initiative for Chronic Obstructive Lung Disease\u2014GOLD","author":"GOLD","year":"2024"},{"issue":"1","key":"pone.0311667.ref009","article-title":"Fractional exhaled nitric oxide as a determinant for the clinical course of asthma: a systematic review","volume":"8","author":"C. Suppli Ulrik","year":"2021","journal-title":"European Clinical Respiratory Journal"},{"issue":"4","key":"pone.0311667.ref010","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14748","article-title":"Lung diffusing capacity for nitric oxide and carbon monoxide following mild-to-severe COVID-19","volume":"9","author":"G. Barisione","year":"2021","journal-title":"Physiological Reports"},{"key":"pone.0311667.ref011","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1378\/chest.13-1875","article-title":"Impulse oscillometry: interpretation and practical applications","volume":"146","author":"S. Bickel","year":"2014","journal-title":"Chest"},{"key":"pone.0311667.ref012","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1056\/NEJMoa043596","article-title":"Use of exhaled nitric oxide measurements to guide treatment in chronic asthma","volume":"352","author":"A. D. Smith","year":"2005","journal-title":"New England Journal of Medecine"},{"key":"pone.0311667.ref013","first-page":"12466","article-title":"Volumetric versus distortional deformation in rat lungs","author":"S. Neelakantan","year":"2023","journal-title":"Proceedings of SPIE\u2014The International Society for Optical Engineering"},{"key":"pone.0311667.ref014","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1440-1843.2011.02117.x","article-title":"Quantitative pulmonary imaging using computed tomography and magnetic resonance imaging","volume":"17","author":"G. Washko","year":"2012","journal-title":"Respirology"},{"issue":"1","key":"pone.0311667.ref015","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-23424-0","article-title":"Lung topology characteristics in patients with chronic obstructive pulmonary disease","volume":"8","author":"F. Belchi","year":"2018","journal-title":"Scientific Reports"},{"issue":"3","key":"pone.0311667.ref016","doi-asserted-by":"crossref","DOI":"10.1002\/nbm.3448","article-title":"Diffusion lung imaging with hyperpolarized Gas MRI","volume":"30","author":"D. A. Yablonskiy","year":"2017","journal-title":"NMR in biomedicine"},{"issue":"191","key":"pone.0311667.ref017","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2022.0062","article-title":"Computational lung modelling in respiratory medicine","volume":"19","author":"S. Neelakantan","year":"2022","journal-title":"Journal of The Royal Society Interface"},{"key":"pone.0311667.ref018","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3389\/fphys.2016.00255","article-title":"Modeling of the nitric oxide transport in the human lungs","volume":"7","author":"C. Karamaoun","year":"2016","journal-title":"Frontiers in Physiology"},{"key":"pone.0311667.ref019","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/japplphysiol.00530.2017","article-title":"A new role for the exhaled nitric oxide as a functional marker of peripheral airway caliber changes: a theoretical study","volume":"124","author":"C. Karamaoun","year":"2018","journal-title":"Journal of Applied Physiology"},{"key":"pone.0311667.ref020","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nature02287","article-title":"An optimal bronchial tree may be dangerous","volume":"427","author":"B. Mauroy","year":"2004","journal-title":"Nature"},{"key":"pone.0311667.ref021","doi-asserted-by":"crossref","first-page":"488","DOI":"10.3389\/fphys.2019.00488","article-title":"Interplay between optimal ventilation and gas transport in a model of the human lung","volume":"10","author":"F. Noel","year":"2019","journal-title":"Frontiers in physiology"},{"key":"pone.0311667.ref022","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1152\/jappl.1973.35.3.401","article-title":"Gas transport in the human lung","volume":"35","author":"M. Paiva","year":"1973","journal-title":"Journal of Applied Physiology"},{"key":"pone.0311667.ref023","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0034-5687(70)90094-0","article-title":"The prediction of pressure drop and variation of resistance within the human bronchial airways","volume":"9","author":"T. J. Pedley","year":"1970","journal-title":"Respiration Physiology"},{"key":"pone.0311667.ref024","doi-asserted-by":"crossref","DOI":"10.1063\/5.0038706","article-title":"Wall shear stress distribution in a compliant airway tree","volume":"33","author":"J. Stephano","year":"2021","journal-title":"Physics of Fluids"},{"key":"pone.0311667.ref025","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1152\/japplphysiol.00044.2002","article-title":"Modeling of impact of gas molecular diffusion on nitric oxide expired profile","volume":"94","author":"A. Van Muylem","year":"2003","journal-title":"Journal of Applied Physiology"},{"key":"pone.0311667.ref026","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fphys.2020.570015","article-title":"Modeling of the transport and exchange of a gas species in lungs with an asymmetric branching pattern. Application to nitric oxide","volume":"11","author":"A. Buess","year":"2020","journal-title":"Frontiers in Physiology"},{"key":"pone.0311667.ref027","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1152\/japplphysiol.00984.2010","article-title":"An anatomical and functional model of the human tracheobronchial tree","volume":"110","author":"M. Florens","year":"2011","journal-title":"Journal of Applied Physiology"},{"key":"pone.0311667.ref028","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1152\/japplphysiol.00520.2004","article-title":"CT-based geometry analysis and finite element models of the human and ovine bronchial tree","volume":"97","author":"M. H. Tawhai","year":"2004","journal-title":"Journal of Applied Physiology"},{"issue":"17","key":"pone.0311667.ref029","doi-asserted-by":"crossref","DOI":"10.1103\/PhysRevLett.106.178104","article-title":"Optimal branching asymmetry of hydrodynamic pulsatile trees","volume":"106","author":"M. Florens","year":"2011","journal-title":"Physical Review Letters"},{"key":"pone.0311667.ref030","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1152\/japplphysiol.00097.2016","article-title":"Regional gas transport in the heterogeneous lung during oscillatory ventilation","volume":"121","author":"J. Herrmann","year":"2016","journal-title":"Journal of Applied Physiology"},{"key":"pone.0311667.ref031","article-title":"Energy dissipation in an asymmetric tracheobronchial tree tree: a CFD analysis","author":"A. Buess","year":"2017","journal-title":"in Proceedings of the 27th CANCAM, Sherbrooke"},{"key":"pone.0311667.ref032","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/j.jbiomech.2007.12.019","article-title":"Computational model of airflow in upper 17 generations of human respiratory tract","volume":"41","author":"T. Gemci","year":"2008","journal-title":"Journal of Biomechanics"},{"key":"pone.0311667.ref033","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/02786826.2016.1254721","article-title":"Caillibotte, \u00abThe influence of lung volume during imaging on CFD within realistic airway models,\u00bb","volume":"51","author":"I. Katz","year":"2017","journal-title":"Aerosol Science and Technology"},{"key":"pone.0311667.ref034","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s10439-014-1074-9","article-title":"A numerical study of heat and water vapor transfer in MDCT-based human airway models","volume":"42","author":"D. Wu","year":"2014","journal-title":"Annals of Biomedical Engineering"},{"key":"pone.0311667.ref035","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1126\/science.276.5309.122","article-title":"A general model for the origin of allometric scaling laws in biology","volume":"276","author":"G. B. West","year":"1997","journal-title":"Science"},{"issue":"1","key":"pone.0311667.ref036","first-page":"111","article-title":"The Impact of Airway Obstruction on Feno Values in Asthma Patients","volume":"12","author":"A. Michils","year":"2024","journal-title":"The Journal of Allergy and Clinical Immunology: In Practice"},{"issue":"2","key":"pone.0311667.ref037","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1152\/jappl.1998.85.2.653","article-title":"A two-compartment model of pulmonary nitric oxide exchange dynamics","volume":"85","author":"N. M. Tsoukias","year":"1985","journal-title":"Journal of Applied Physiology"},{"key":"pone.0311667.ref038","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1183\/09031936.00001414","article-title":"Microgravity and the respiratory system","volume":"43","author":"G. K. Prisk","year":"2014","journal-title":"European Respiratory Journal"},{"issue":"2","key":"pone.0311667.ref039","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00962-2016","article-title":"Standardisation and application of the single-breath determination of nitric oxide uptake in the lung","volume":"49","author":"G. S. Zavorsky","year":"2017","journal-title":"European Respiratory Journal"},{"key":"pone.0311667.ref040","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.resp.2017.02.006","article-title":"The measurement of DLNO and DLCO: A manufacturer\u2019s perspective","volume":"241","author":"X. Giraud","year":"2017","journal-title":"Respiratory Physiology & Neurobiology,"},{"issue":"4","key":"pone.0311667.ref041","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1113\/jphysiol.1915.sp001710","article-title":"The diffusion of gases through the lungs of man","volume":"49","author":"M. Krogh","year":"1915","journal-title":"The Journal of Physiology"},{"key":"pone.0311667.ref042","volume-title":"Enqu\u00eate de sant\u00e9 par examen belge 2018","author":"J. Van der Heyden","year":"2019"},{"issue":"1","key":"pone.0311667.ref043","article-title":"Tennis Courts in the Human Body: A Review of the Misleading Metaphor in Medical Literature","volume":"14","author":"A. Ananda Rao","year":"2022","journal-title":"Cureus"},{"key":"pone.0311667.ref044","doi-asserted-by":"crossref","DOI":"10.1186\/s12931-019-1237-1","article-title":"Han, \"Relationship between diffusion capacity and small airway abnormality in COPDGene","volume":"20","author":"R. N. Criner","year":"2019","journal-title":"Respiratory Research"},{"key":"pone.0311667.ref045","first-page":"15","article-title":"Whole-body plethysmography","volume":"31","author":"M. Goldman","year":"2005","journal-title":"European Respiratory Monograph"},{"issue":"6","key":"pone.0311667.ref046","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3109\/15412555.2010.528087","article-title":"Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity","volume":"7","author":"A. Deesomchok","year":"2010","journal-title":"COPD"},{"key":"pone.0311667.ref047","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1164\/ajrccm.161.4.9903111","article-title":"Airway nitric oxide diffusion in asthma: Role in pulmonary function and bronchial responsiveness","volume":"161","author":"P. E. Silkoff","year":"2000","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"3","key":"pone.0311667.ref048","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1378\/chest.123.3.751","article-title":"Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma","volume":"123","author":"L. J. Dupont","year":"2003","journal-title":"Chest"},{"key":"pone.0311667.ref049","first-page":"868","volume-title":"European Respiratory Journal","author":"G. Ramesh","year":"2001"},{"issue":"5","key":"pone.0311667.ref050","first-page":"340","article-title":"Neutrophils and Asthma","volume":"19","author":"J. Monteseir\u00edn","year":"2009","journal-title":"Journal of Investigational Allergology and Clinical Immunology"},{"issue":"1","key":"pone.0311667.ref051","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.rmed.2005.03.041","article-title":"Asthma-related resource use and cost by GINA classification of severity in three European countries","volume":"100","author":"E. Van Ganse","year":"2006","journal-title":"Respiratory Medicine"},{"key":"pone.0311667.ref052","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2023.1184784","article-title":"GOLD stage-specific phenotyping of emphysema and airway disease using quantitative computed tomography","volume":"10","author":"P. Konietzke","year":"2023","journal-title":"Frontiers in Medicine"},{"key":"pone.0311667.ref053","first-page":"12928","article-title":"In-silico CT lung phantom generated from finite-element mesh","author":"S. Neelakantan","year":"2024","journal-title":"Proceedings of SPIE\u2014The International Society for Optical Engineering"},{"key":"pone.0311667.ref054","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.jcis.2014.09.036","article-title":"A comprehensive analysis of the evaporation of a liquid spherical drop","volume":"438","author":"B. Sobac","year":"2015","journal-title":"Journal of Colloid and Interface Science"},{"key":"pone.0311667.ref055","first-page":"19","article-title":"Moreau, \u00abTrach\u00e9e: anatomie, physiologie, endoscopie et imagerie,\u00bb","author":"M. Hitier","year":"2013","journal-title":"EMC\u2014Oto-rhino-laryngologie"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0311667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T18:32:49Z","timestamp":1738261969000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0311667"}},"subtitle":[],"editor":[{"given":"James","family":"West","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0311667","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]}}}