{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:17:43Z","timestamp":1792426663031,"version":"4.5.0"},"reference-count":40,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2025,2,15]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Some patients with severe asthma have persistent type-2 inflammation despite being treated with high-dose inhaled corticosteroids (ICS). The variability in ICS deposition between patients with severe asthma is not well-understood and could contribute to this persistence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To characterise and compare model-predicted deposition of fine-particle and extrafine-particle ICS in patients with severe asthma based on biomarkers of type-2 inflammation, airway morphology and airway function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-eight patients with severe asthma performed full-inspiration and full-expiration chest CT on the same day that biomarkers of type-2 inflammation were measured. Functional respiratory imaging and computational fluid dynamics were used to simulate and predict intrathoracic, central and peripheral airway deposition, and central-to-peripheral airway deposition (C:P) ratio of fine-particle ICS (fluticasone-propionate HFA) (ICS<jats:sub>FP<\/jats:sub>) and extrafine-particle ICS (beclomethasone-dipropionate HFA) (ICS<jats:sub>EFP<\/jats:sub>). CT-derived wall area percent (WA%), lumen area (LA) and mucus burden were quantified to characterise airway morphology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Simulated deposition of ICS<jats:sub>EFP<\/jats:sub>was higher than ICS<jats:sub>FP<\/jats:sub>in the intrathoracic, central and peripheral airways (all p&lt;0.0001). Greater WA% and smaller LA were correlated with greater C:P ratio of ICS<jats:sub>FP<\/jats:sub>(r=0.60, p=0.0068; r=\u22120.60, p=0.0072) and ICS<jats:sub>EFP<\/jats:sub>(r=0.54, p=0.028; r=\u22120.54, p=0.026). Participants with elevated sputum eosinophils had a greater C:P ratio, irrespective of particle size (ICS<jats:sub>FP<\/jats:sub>, p=0.045; ICS<jats:sub>EFP<\/jats:sub>, p=0.021).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In severe asthma patients with thicker airway walls, narrower airway lumens and elevated biomarkers of type-2 inflammation, a smaller ratio of ICS<jats:sub>FP<\/jats:sub>reached the peripheral airways. ICS<jats:sub>EFP<\/jats:sub>did not fully mitigate this. Patient-specific airway morphology may impact regional ICS deposition and contribute to persistent inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1136\/thorax-2024-222444","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T19:44:06Z","timestamp":1743104646000},"page":"425-432","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Computational fluid dynamics model predictions of inhaled corticosteroid deposition in patients with severe asthma"],"prefix":"10.1136","volume":"80","clinical-trial-number":[{"clinical-trial-number":"nct03884842","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03455686","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Nandhitha","family":"Ragunayakam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Thakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosein","family":"Sadafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Venegas Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonni","family":"Friedlander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Kjarsgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dvorkin-Gheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-7211","authenticated-orcid":false,"given":"Manali","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrna B","family":"Dolovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben R","family":"Lavon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Inman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-1863","authenticated-orcid":false,"given":"Sarah","family":"Svenningsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"2025061605400835000_80.7.425.1","unstructured":"GINA Main Report . 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