{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T21:03:24Z","timestamp":1788642204482,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Obstructive sleep apnoea (OSA) worsens asthma control. Oxygen desaturation increases oxidative stress, contributing to corticosteroid insensitivity, a hallmark of severe asthma. This study investigated the impact of hypoxaemia and reactive oxygen species on corticosteroid responsiveness in asthma with OSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Asthmatic patients with apnoea\u2013hypopnoea index (AHI)\u2009\u2265\u20095\u2009h\n                      <jats:sup>\u22121<\/jats:sup>\n                      were classified as OSA. Interleukin (IL)\u20108 and IL\u20106 production by peripheral blood mononuclear cells (PBMCs), serum cytokines, oxidative stress markers and nuclear histone deacetylase 2 (HDAC2) were quantified by enzyme\u2010linked immunosorbent assay. HDAC2 and hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) expression were evaluated by Western blotting and flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Compared with non\u2010OSA asthmatics, OSA patients used higher inhaled corticosteroid doses and had increased serum thiobarbituric acid\u2010reactive substances and 8\u2010hydroxy\u20102\u2010deoxyguanosine, but lower superoxide dismutase and total antioxidant capacity. HDAC2 was lower in OSA PBMCs and in non\u2010OSA PBMCs exposed to 5% O\u2082 than in normoxia. HDAC2 was correlated inversely with AHI, corticosteroid dose, serum IL\u20108, oxidative stress, baseline production of IL\u20108\/IL\u20106 and dexamethasone\u2010induced IL\u20108 suppression. Dexamethasone inhibited TNF\u2010\u03b1\u2010induced IL\u20108 and lipopolysaccharide (LPS)\u2010induced IL\u20106 in non\u2010OSA PBMCs, but not in OSA PBMCs. HDAC2 inhibitor CAY10683 impaired corticosteroid action, while N\u2010acetylcysteine and inhibitors of HIF\u20101\u03b1 (CAY10585) or phosphoinositide 3\u2010kinase (LY294002) restored HDAC2 and corticosteroid sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>OSA is associated with oxidative stress, reduced HDAC2, and corticosteroid insensitivity in asthma. Antioxidants may help restore corticosteroid efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70157","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T02:35:01Z","timestamp":1754361301000},"page":"5790-5802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Corticosteroid insensitivity in asthma associated with obstructive sleep apnoea: Role of oxidative stress and histone acetylation"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-8702","authenticated-orcid":false,"given":"Chun\u2010Yu","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Thoracic Medicine Chang Gung Memorial Hospital, Linkou Branch  Taoyuan Taiwan"},{"name":"College of Medicine Chang Gung University  Taoyuan 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