Experimental and Computational Analysis of pMDI Aerosol Transport in Pediatric Airways: Impact of Inhalation Flow, Mucus Rheology, and Actuation Timing

Experimental and Computational Analysis of pMDI Aerosol Transport in Pediatric Airways: Impact of Inhalation Flow, Mucus Rheology, and Actuation Timing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Experimental and Computational Analysis of pMDI Aerosol Transport in Pediatric Airways: Impact of Inhalation Flow, Mucus Rheology, and Actuation Timing Farnia Dastoorian, Janusz Kozinski, Leila Pakzad This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6785337/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Effective drug delivery to the lungs of pediatric patients using pressurized metered-dose inhalers (pMDIs) requires a deep understanding of airflow and particle transport within the airways. This study examines airflow patterns and aerosol deposition in a pediatric mouth-throat (MT) model, incorporating a cystic fibrosis (CF) inhalation profile and simulating the presence of a mucus layer. A CT-derived pediatric MT model was 3D printed and integrated into a next-generation impactor (NGI) to evaluate drug deposition at a flow rate of 15 L/min , offering experimental validation of the computational fluid dynamics (CFD) model. Three different boundary conditions were used to represent the mucus layer, with the Eulerian Wall Film (EWF) approach demonstrating the highest accuracy. The study also explored the effects of a non-Newtonian, shear-thinning mucus layer on deposition behaviour. Large Eddy Simulation (LES) was employed to analyze airflow dynamics, while the Discrete Phase Model (DPM) was utilized to simulate particle transport and deposition. Higher flow rates increased wall shear stress, which enhanced shear-driven transport. Morris’s sensitivity analysis identified flow rate as the dominant factor, demonstrating a strong correlation with deposition efficiency ( r s = 0.87). Furthermore, the presence of shear-thinning mucus reduced secondary flows, induced asymmetric swirling, and increased the minimum particle size exiting the trachea by 60.2%, rising from 0.491 to 0.789 µm compared to Newtonian mucus. Synchronized actuation further achieved the highest delivery efficiency at 46% due to smooth aerosol entrainment during the buildup of the CF inhalation profile. This transient CF profile also resulted in a broader particle size distribution ranging from 0.78 to 20 µm , in comparison to constant flow rates of 7.5 and 15 L/min . pulmonary drug delivery CFD inhalation profile pMDI actuation timing Eulerian wall-film shear-thinning mucus Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6785337","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":469183539,"identity":"8984437c-879a-4a8d-9d2a-eee20f6ec813","order_by":0,"name":"Farnia Dastoorian","email":"","orcid":"","institution":"Lakehead University","correspondingAuthor":false,"prefix":"","firstName":"Farnia","middleName":"","lastName":"Dastoorian","suffix":""},{"id":469183541,"identity":"71407b21-9aef-469d-8f02-da8ed3fb6d2b","order_by":1,"name":"Janusz Kozinski","email":"","orcid":"","institution":"Lakehead University","correspondingAuthor":false,"prefix":"","firstName":"Janusz","middleName":"","lastName":"Kozinski","suffix":""},{"id":469183543,"identity":"d22889e4-11e0-4165-be5b-02b039e6108c","order_by":2,"name":"Leila Pakzad","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYBACPgYGZiDFLMfHwAZmMTYQ0sIG1WLMRrKWxDbitUg3Pzb8UWOd3sZ+LPFxQYWd7IYDzA8/4NUic8w4QeJYem4bT9ph4xlnko03HGAzlsCrRSLB+IAB2+HcNob0NmneNubEDQd4GAhoSf98IOHf4XQ2/uftv3n/1YO0MP/AryXHOOFg2+EENom0Y8y8DYdBWtjw2yJzptiwsS/dsE3iWbI0z7HjxjMPs5lZ4NPCL92+WfLHN2t5fv40w888NdWyfcebH9/ApwWLT5nxqseqZRSMglEwCkYBGgAAts5EspBfvkcAAAAASUVORK5CYII=","orcid":"","institution":"Lakehead University","correspondingAuthor":true,"prefix":"","firstName":"Leila","middleName":"","lastName":"Pakzad","suffix":""}],"badges":[],"createdAt":"2025-05-30 13:53:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6785337/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6785337/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86581533,"identity":"64f37e55-afb0-4304-a132-b4f3284c137b","added_by":"auto","created_at":"2025-07-12 22:01:22","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1761423,"visible":true,"origin":"","legend":"","description":"","filename":"PakzadManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6785337/v1_covered_f5e6f1c6-5bc4-4743-b902-374a63170a77.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Experimental and Computational Analysis of pMDI Aerosol Transport in Pediatric Airways: Impact of Inhalation Flow, Mucus Rheology, and Actuation Timing","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pulmonary drug delivery, CFD, inhalation profile, pMDI actuation timing, Eulerian wall-film, shear-thinning mucus","lastPublishedDoi":"10.21203/rs.3.rs-6785337/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6785337/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEffective drug delivery to the lungs of pediatric patients using pressurized metered-dose inhalers (pMDIs) requires a deep understanding of airflow and particle transport within the airways. This study examines airflow patterns and aerosol deposition in a pediatric mouth-throat (MT) model, incorporating a cystic fibrosis (CF) inhalation profile and simulating the presence of a mucus layer.\u003c/p\u003e \u003cp\u003eA CT-derived pediatric MT model was 3D printed and integrated into a next-generation impactor (NGI) to evaluate drug deposition at a flow rate of 15 \u003cem\u003eL/min\u003c/em\u003e, offering experimental validation of the computational fluid dynamics (CFD) model. Three different boundary conditions were used to represent the mucus layer, with the Eulerian Wall Film (EWF) approach demonstrating the highest accuracy. The study also explored the effects of a non-Newtonian, shear-thinning mucus layer on deposition behaviour. Large Eddy Simulation (LES) was employed to analyze airflow dynamics, while the Discrete Phase Model (DPM) was utilized to simulate particle transport and deposition.\u003c/p\u003e \u003cp\u003eHigher flow rates increased wall shear stress, which enhanced shear-driven transport. Morris\u0026rsquo;s sensitivity analysis identified flow rate as the dominant factor, demonstrating a strong correlation with deposition efficiency (\u003cem\u003er\u003c/em\u003e\u003csub\u003e\u003cem\u003es\u003c/em\u003e\u003c/sub\u003e = 0.87). Furthermore, the presence of shear-thinning mucus reduced secondary flows, induced asymmetric swirling, and increased the minimum particle size exiting the trachea by 60.2%, rising from 0.491 to 0.789 \u003cem\u003e\u0026micro;m\u003c/em\u003e compared to Newtonian mucus. Synchronized actuation further achieved the highest delivery efficiency at 46% due to smooth aerosol entrainment during the buildup of the CF inhalation profile. This transient CF profile also resulted in a broader particle size distribution ranging from 0.78 to 20 \u003cem\u003e\u0026micro;m\u003c/em\u003e, in comparison to constant flow rates of 7.5 and 15 \u003cem\u003eL/min\u003c/em\u003e.\u003c/p\u003e","manuscriptTitle":"Experimental and Computational Analysis of pMDI Aerosol Transport in Pediatric Airways: Impact of Inhalation Flow, Mucus Rheology, and Actuation Timing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-11 09:28:17","doi":"10.21203/rs.3.rs-6785337/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ba4c2a5c-a1c0-4dd0-8934-c51f2a48e348","owner":[],"postedDate":"June 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-12T21:53:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-11 09:28:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6785337","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6785337","identity":"rs-6785337","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}