{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:27:04Z","timestamp":1792002424248,"version":"4.4.0"},"reference-count":68,"publisher":"The Royal Society","issue":"11","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["R. Soc. Open Sci."],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>Airway constriction and blockage in obstructive lung diseases cause ventilation heterogeneity and create barriers to effective drug deposition. Established computational particle-deposition models have not accounted for these impacts of disease. We present a new particle-deposition model that calculates ventilation based on the resistance of each airway, such that ventilation responds to airway constriction. The model incorporates distal airway constrictions representative of cystic fibrosis, allowing us to investigate the resulting impact on patterns of deposition. Unlike previous models, our model predicts how constrictions affect deposition in airways throughout the lungs, not just in the constricted airways. Deposition is reduced in airways directly distal and proximal to constrictions. When constrictions are clustered together, central-airways deposition can increase significantly in regions away from constrictions, but distal-airways deposition in those regions remains largely unchanged. We use our model to calculate lung clearance index (LCI), a clinical measure of ventilation heterogeneity, after applying constrictions of varying severities in one lobe. We find an increase in LCI coinciding with significantly reduced deposition in the affected lobe. Our results show how the model provides a framework for development of computational tools that capture the impacts of airway disease, which could significantly affect predictions of regional dosing.<\/jats:p>","DOI":"10.1098\/rsos.241108","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T04:09:26Z","timestamp":1730952566000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Non-local impact of distal airway constrictions on patterns of inhaled particle deposition"],"prefix":"10.1098","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9158-0930","authenticated-orcid":true,"given":"James D.","family":"Shemilt","sequence":"first","affiliation":[{"name":"Department of Mathematics, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-0058","authenticated-orcid":true,"given":"Alex","family":"Horsley","sequence":"additional","affiliation":[{"name":"Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7246-8660","authenticated-orcid":true,"given":"Jim M.","family":"Wild","sequence":"additional","affiliation":[{"name":"POLARIS, Imaging Sciences, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0172-6578","authenticated-orcid":true,"given":"Oliver E.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9558-1554","authenticated-orcid":true,"given":"Alice B.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5913-735X","authenticated-orcid":true,"given":"Carl A.","family":"Whitfield","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Manchester, Manchester, UK"},{"name":"Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2007.02.009"},{"key":"e_1_3_7_3_2","article-title":"Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis","volume":"11","author":"Smith S","year":"2022","unstructured":"Smith S, Rowbotham NJ. 2022 Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst. Rev. 11, CD001021. (doi:10.1002\/14651858.CD001021.pub4)","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00245-3"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.21154"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2011.0916"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01892.x"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/140.5.1317"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.118.4.1069"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2013.1064"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03490"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2023.29086.jgv"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2009.0772"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2016.1359"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1975.38.1.77"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8240(80)80060-7"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(03)00080-2"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/faat.1995.1144"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/02786820119122"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2016.01.018"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2022.106050"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/08958370600748687"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2006.01.002"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2011.05.007"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/cnm.2847"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-90509-8"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2020.105647"},{"key":"e_1_3_7_28_2","article-title":"In silico high-resolution whole lung model to predict the locally delivered dose of inhaled drugs","author":"Grill MJ","year":"2023","unstructured":"Grill MJ et al. 2023 In silico high-resolution whole lung model to predict the locally delivered dose of inhaled drugs. Ar.Xiv (doi:10.48550\/arXiv.2307.04757)","journal-title":"Ar.Xiv"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.05.009"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.10100322"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.1586\/17476348.2016.1136216"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2006.01.011"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2007.06.004"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2015.11.027"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2016.09.009"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2012.06.031"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208049"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-208948"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00520.2004"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1963.18.3.519"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2020.0253"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(70)90094-0"},{"key":"e_1_3_7_43_2","first-page":"78","article-title":"Pressure-volume curves of the respiratory system","volume":"50","author":"Harris RS","year":"2005","unstructured":"Harris RS. 2005 Pressure-volume curves of the respiratory system. Respir. Care 50, 78\u201398.","journal-title":"Respir. Care"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2012.01.042"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1258\/jrsm.2009.s19003"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1080\/02786829708965417"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-8502(72)90090-0"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-8502(05)80003-5"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2006.09.007"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2016.01.019"},{"key":"e_1_3_7_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092200410"},{"key":"e_1_3_7_52_2","unstructured":"Guennebaud G et al. 2010 Eigen v3. See http:\/\/eigen.tuxfamily.org."},{"key":"e_1_3_7_53_2","unstructured":"ARA Inc. 2015 Multiple-path particle dosimetry model. See https:\/\/www.ara.com\/products\/multiple-path-particle."},{"key":"e_1_3_7_54_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00821-2018"},{"key":"e_1_3_7_55_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2112059"},{"key":"e_1_3_7_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2009.01.025"},{"key":"e_1_3_7_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-8502(86)90035-2"},{"key":"e_1_3_7_58_2","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.06697"},{"key":"e_1_3_7_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/cnm.2787"},{"key":"e_1_3_7_60_2","unstructured":"Reynolds D Lee J. 1979 Modeling study of the pressure-flow relationship of the bronchial tree (abstract). Federation Proceedings 38 1444."},{"key":"e_1_3_7_61_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1982.52.1.44"},{"key":"e_1_3_7_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/cnm.2577"},{"key":"e_1_3_7_63_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1479-5876-12-S2-S5","article-title":"Computational modeling of the obstructive lung diseases asthma and COPD","volume":"12","author":"Burrowes KS","year":"2014","unstructured":"Burrowes KS, Doel T, Brightling C. 2014 Computational modeling of the obstructive lung diseases asthma and COPD. J. Transl. Med. 12 (Suppl. 2), 1\u20138. (doi:10.1186\/1479-5876-12-S2-S5)","journal-title":"J. Transl. Med."},{"key":"e_1_3_7_64_2","doi-asserted-by":"publisher","DOI":"10.1089\/jam.2004.17.278"},{"key":"e_1_3_7_65_2","unstructured":"UoM Lung Modelling Group. 2024 A computational model of ventilation gas\/particle transport and deposition in lung airway networks. See https:\/\/github.com\/UoM-Lung-Modelling-Group\/NetLungVPD\/tree\/v0.1."},{"key":"e_1_3_7_66_2","unstructured":"Shemilt J Whitfield C. 2024 Non-local impact of distal airway constrictions on patterns of inhaled particle deposition. Zenodo. doi:10.5281\/zenodo.10998702"},{"key":"e_1_3_7_67_2","unstructured":"Whitfield C. 2020 CarlWhitfield\/Space_filling_tree: space filling airway branching algorithm (v1.0.1). Zenodo. (doi:10.5281\/zenodo.3709073)"},{"key":"e_1_3_7_68_2","doi-asserted-by":"crossref","unstructured":"Whitfield C. 2020 Spectral graph theory efficiently characterises ventilation heterogeneity in airway networks (Dataset). Zenodo. (doi:10.5281\/zenodo.3709105)","DOI":"10.1101\/2020.04.15.042416"},{"key":"e_1_3_7_69_2","unstructured":"Shemilt J Horsley A Wild J Jensen O Thompson A Whitfield C. 2024 Supplementary material from: Non-local impact of distal airway constrictions on patterns of inhaled particle deposition. FigShare. (doi:10.6084\/m9.figshare.c.7523282)"}],"container-title":["Royal Society Open Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.241108","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsos.241108","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsos.241108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T04:09:39Z","timestamp":1730952579000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsos.241108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":68,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1098\/rsos.241108"],"URL":"https:\/\/doi.org\/10.1098\/rsos.241108","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSOS.241108\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.241108\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.241108\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.241108\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOS.241108\/v1\/review2","asserted-by":"object"}]},"ISSN":["2054-5703"],"issn-type":[{"value":"2054-5703","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-03","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"241108"}}