{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:47:58Z","timestamp":1793742478630,"version":"4.6.1"},"reference-count":33,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC-CSF-MR\/V029460\/1"],"award-info":[{"award-number":["MRC-CSF-MR\/V029460\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000362","name":"Asthma and Lung UK","doi-asserted-by":"publisher","award":["AUK-WAPG22\/100005"],"award-info":[{"award-number":["AUK-WAPG22\/100005"]}],"id":[{"id":"10.13039\/501100000362","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JP Moulton Charitable Foundation","award":["no specific grant number"],"award-info":[{"award-number":["no specific grant number"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2024,12,27]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Asthma demonstrates a robust daily rhythm, with airflow obstruction and airway inflammation peaking overnight. Aligning the timing of drug administration with rhythms in disease (chronotherapy) may improve therapeutic efficacy. We aimed to evaluate the impact of dosage timing for inhaled corticosteroids in asthma.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>\nThis is a randomised three-way crossover trial. Participants with mild to moderate atopic asthma were randomised to beclometasone dipropionate: (1) 400 \ufffdg once daily between 08:00 and 09:00 (OD\n<jats:sub>AM<\/jats:sub>\n); (2) 400 \ufffdg once daily between 15:00 and 16:00 (OD\n<jats:sub>PM<\/jats:sub>\n); and (3) 200 \ufffdg twice daily between 08:00 and 09:00 and between 20:00 and 21:00 (BD) for 28 days, with a 2 week washout period in between treatment periods. Six-hourly spirometry and biomarkers were measured over 24 hours following the run-in period and at the end of each treatment period.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>\nOf 25 participants, 21 completed all regimens. OD\n<jats:sub>PM<\/jats:sub>\nwas superior in improving 22:00 FEV\n<jats:sub>1<\/jats:sub>\n(median (IQR): +160 (+70, +270) ml) compared with OD\n<jats:sub>AM<\/jats:sub>\n(-20 (-80, +230) ml) and BD (+80 (-20, +200) ml). OD\n<jats:sub>PM<\/jats:sub>\nresulted in better overnight (22:00 and 04:00) suppression in blood eosinophil counts compared with BD and OD\n<jats:sub>AM<\/jats:sub>\n. All regimens improved asthma control and reduced fractional exhaled nitric oxide and serum cortisol levels with no difference among dosing regimens.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>\nOD\n<jats:sub>PM<\/jats:sub>\nbetter suppresses the nocturnal dip in lung function and peak of blood eosinophil counts compared with BD and OD\n<jats:sub>AM<\/jats:sub>\n; this was without an increase in adverse events. Future trials are warranted to validate these findings in real-life settings and to determine which population may best benefit from chronotherapy.\n<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/thorax-2024-222073","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T20:50:16Z","timestamp":1744750216000},"page":"504-511","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["The impact of dosage timing for inhaled corticosteroids in asthma: a randomised three-way crossover trial"],"prefix":"10.1136","volume":"80","author":[{"given":"Ran","family":"Wang","sequence":"first","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester, UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-3246","authenticated-orcid":false,"given":"Robert","family":"Maidstone","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester, UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"},{"name":"Medicines Evaluation Unit, Wythenshawe, Greater Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ray","sequence":"additional","affiliation":[{"name":"NIHR Oxford Biomedical Research Centre, Oxford, UK"},{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"Loudon","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2733-6666","authenticated-orcid":false,"given":"Angela","family":"Simpson","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester, UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9990-9446","authenticated-orcid":false,"given":"Hannah Jane","family":"Durrington","sequence":"additional","affiliation":[{"name":"NIHR Manchester Biomedical Research Centre, Manchester, UK"},{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"2025071508200898000_80.8.504.1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-216421"},{"key":"2025071508200898000_80.8.504.2","first-page":"239","article-title":"Nocturnal asthma: a study in general practice","volume":"39","author":"Turner-Warwick","year":"1989","journal-title":"J R Coll Gen Pract"},{"key":"2025071508200898000_80.8.504.3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.6064.808"},{"key":"2025071508200898000_80.8.504.4","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/141.1.33"},{"key":"2025071508200898000_80.8.504.5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201807-1289LE"},{"key":"2025071508200898000_80.8.504.6","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.14d29.x"},{"key":"2025071508200898000_80.8.504.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(99)70527-0"},{"key":"2025071508200898000_80.8.504.8","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.5.2002058"},{"key":"2025071508200898000_80.8.504.9","doi-asserted-by":"crossref","DOI":"10.1183\/23120541.00161-2023","article-title":"Identification of diurnal rhythmic blood markers in bronchial asthma","volume":"9","author":"Krakowiak","year":"2023","journal-title":"ERJ Open Res"},{"key":"2025071508200898000_80.8.504.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(97)70272-0"},{"key":"2025071508200898000_80.8.504.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(95)70073-0"},{"key":"2025071508200898000_80.8.504.12","doi-asserted-by":"publisher","DOI":"10.1378\/chest.105.6.1732"},{"key":"2025071508200898000_80.8.504.13","unstructured":"British National Formulary, Available: https:\/\/bnf.nice.org.uk [Accessed 31 Jan 2024]."},{"key":"2025071508200898000_80.8.504.14","unstructured":"Global Initiative for Asthma (GINA) Main Report, 2023. 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