{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:43:11Z","timestamp":1791582191238,"version":"4.3.4"},"reference-count":27,"publisher":"European Respiratory Society (ERS)","issue":"1","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["Unrestricted grant"],"award-info":[{"award-number":["Unrestricted grant"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2023,5,22]]},"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant, but modest, clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle cell (ASMC) area in COPD is associated with ICS responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, Global Initiative for Chronic Obstructive Lung Disease stage B\u2013D, underwent bronchoscopy with endobronchial biopsy. Patients were divided into groups A and B, with high ASMC area (HASMC: &gt;20% of the bronchial tissue area) and low ASMC area (LASMC: \u226420% of the bronchial tissue area), respectively, and followed a run-in period of 6\u2005weeks on open-label triple inhaled therapy with aclidinium (ACL)\/formoterol (FOR)\/budesonide (BUD) (400\/12\/400\u2005\u03bcg twice daily). Subsequently, patients were randomised to receive either ACL\/FOR\/BUD or ACL\/FOR\/placebo and followed for 12\u2005months. The primary end-point of the study was the difference in post-bronchodilator forced expiratory volume in 1\u2005s (FEV\n                      <jats:sub>1<\/jats:sub>\n                      ) over 12\u2005months between patients with LASMC and HASMC receiving or not receiving ICS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In patients with LASMC, ACL\/FOR\/BUD did not significantly improve FEV\n                      <jats:sub>1<\/jats:sub>\n                      over 12\u2005months, as compared to ACL\/FOR\/placebo (p=0.675). However, in patients with HASMC, ACL\/FOR\/BUD significantly improved FEV\n                      <jats:sub>1<\/jats:sub>\n                      , as compared to ACL\/FOR\/placebo (p=0.020). Over 12\u2005months, the difference of FEV\n                      <jats:sub>1<\/jats:sub>\n                      change between the ACL\/FOR\/BUD group and the ACL\/FOR\/placebo group was 50.6\u2005mL\u00b7year\n                      <jats:sup>\u22121<\/jats:sup>\n                      within the group of patients with LASMC and 183.0\u2005mL\u00b7year\n                      <jats:sup>\u22121<\/jats:sup>\n                      within the group of patients with HASMC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>COPD patients with \u0397ASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.<\/jats:p>\n                  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