{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:15:42Z","timestamp":1787890542610,"version":"build-2784847793"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The 2019 Global Initiative for Asthma (GINA) report no longer recommended short\u2010acting beta\u2010agonists (SABA) monotherapy due to associated complications and a lack of anti\u2010inflammatory properties. This systematic review and meta\u2010analysis aimed to evaluate adverse outcomes associated with SABA overuse in patients with asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched for studies on SABA overuse (\u2265\u20093 SABA canisters\/year) in patients with asthma, from 1981 to November 2023. Randomized controlled trials (RCTs), cohort studies, and cross\u2010sectional studies were included. Pooled risk ratios (RRs) were calculated for dichotomous measures of all\u2010cause mortality and acute exacerbations using random\u2010effects models and Mantel\u2010Haenszel weighting. Subgroup analyses were conducted based on study design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Out of 626 records, 27 studies (2 RCTs, 1 prospective cohort study, 12 retrospective cohort studies, and 12 cross\u2010sectional studies) were included. SABA overuse (\u2265\u20093 SABA canisters\/year) was associated with significantly higher mortality (2743 of 130,629 in the overuse group versus 3534 of 300,451 in controls; RR\u2009=\u20092.04, 95% confidence interval, CI\u2009=\u20091.37\u20133.04;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and a significantly higher rate of acute exacerbations (60,320 of 165,271 in the overuse group versus 84,439 of 376,845 in controls; RR\u2009=\u20091.93, 95% CI\u2009=\u20091.24\u20133.03;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). An\u00a0increased risk of acute exacerbations was observed in retrospective cohort studies (RR\u2009=\u20091.88, 95% CI\u2009=\u20091.43\u20132.47;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and cross\u2010sectional studies (RR\u2009=\u20092.23, 95% CI\u2009=\u20091.04\u20134.77;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SABA overuse was associated with increased rates of mortality and acute exacerbations in patients with asthma, supporting guidelines that advise against SABA monotherapy\u00a0in asthma management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.16538","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T03:09:46Z","timestamp":1749524986000},"page":"1629-1646","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Adverse Outcomes Associated With Short\u2010Acting Beta\u2010Agonist Overuse in Asthma: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"80","author":[{"given":"Chia\u2010Ling","family":"Tsao","sequence":"first","affiliation":[{"name":"Center for Global Health, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"School of Medicine Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Yen","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Weiss Memorial Hospital  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Hsun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Maimonides Medical Center  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina Yi Jin","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda","family":"Phipatanakul","sequence":"additional","affiliation":[{"name":"Division of Immunology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana B.","family":"Ruran","sequence":"additional","affiliation":[{"name":"Division of Immunology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9394-4144","authenticated-orcid":false,"given":"Kevin Sheng\u2010Kai","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Global Health, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30925-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02094-2020"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(23)00230-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101936"},{"issue":"4","key":"e_1_2_8_6_1","first-page":"918","article-title":"Asthma Exacerbations: Pathogenesis, Prevention, and Treatment","volume":"5","author":"Castillo J. 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