{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T06:55:46Z","timestamp":1773471346892,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Combining inhaled corticosteroids (ICSs), long\u2010acting \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists (LABAs) and long\u2010acting muscarinic antagonists (LAMAs) is recommended to treat severe forms of asthma and chronic obstructive pulmonary disease (COPD). Clinical benefits have been demonstrated for ICS\/LABA\/LAMA combinations. This study characterized the interaction between the ICS beclomethasone dipropionate, the LABA formoterol fumarate and the LAMA glycopyrronium bromide in human airways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Human passively sensitized airways and bronchi from COPD donors were stimulated with histamine or carbachol. Tissues were incubated overnight with beclomethasone and then treated with formoterol and glycopyrronium, alone or in triple combination. The interaction was assessed by using Bliss Independence and Unified Theory theorems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Beclomethasone\/formoterol\/glycopyrronium combination synergistically relaxed medium bronchi and small airways. Beclomethasone\/formoterol\/glycopyrronium combination at 100:6:12.5 combination ratio was a balanced drug mixture leading to very strong synergistic effect on relaxation of medium bronchi (Combination Index: from 0.042 to 0.96) and middle to very strong synergy in small airways (Combination Index: from 0.018 to 0.310). The synergy was related with the activation of intracellular glucocorticoid receptors and G<jats:sub>s\u03b1<\/jats:sub>subunit G\u2010protein of \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptors, leading to the modulation of cyclic AMP\u2010dependent PKA pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Triple beclomethasone\/formoterol\/glycopyrronium combination induces synergistic bronchorelaxant effect in medium and small human airways, at least in<jats:italic>ex vivo<\/jats:italic>experiments. Further research is needed to confirm these findings in clinical studies in patients with asthma or COPD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14909","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T11:34:38Z","timestamp":1572348878000},"page":"1150-1163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide: Synergy of triple combination therapy on human airway smooth muscle<i>ex vivo<\/i>"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-5040","authenticated-orcid":false,"given":"Paola","family":"Rogliani","sequence":"first","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine University of Rome \u201cTor Vergata\u201d Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Gabriella","family":"Matera","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology, Department of Experimental Medicine University of Campania \u201cLuigi Vanvitelli\u201d Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Facciolo","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit Regina Elena National Cancer Institute Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clive","family":"Page","sequence":"additional","affiliation":[{"name":"Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Cazzola","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine University of Rome \u201cTor Vergata\u201d Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-069X","authenticated-orcid":false,"given":"Luigino","family":"Calzetta","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Medicine, Department of Experimental Medicine University of Rome \u201cTor Vergata\u201d Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(84)90150-6"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2018.12.016"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.05.020"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.03.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0770-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2018.1442216"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0306OC"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2015.11.004"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01586-2018"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.10"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704617"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(85)90401-7"},{"key":"e_1_2_11_17_1","volume-title":"Global initiative for asthma (GINA). 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