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In human bronchi combining these drugs elicits a positive interaction, thus we aimed to characterize this information further in equine isolated airways stimulated by electrical field stimulation (EFS) and using the Concentration\u2010Reduction Index (CRI) and Combination Index (CI) equations. The drugs were administered alone and together by reproducing ex vivo the concentration\u2010ratio delivered by the currently available fixed\u2010dose combination (1:1). The single agents elicited a significant (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) concentration\u2010dependent reduction in the EFS\u2010induced contractility, that was synergistically improved (CI 0.18) when administered in combination (0.9 logarithms more potent, 24% more effective than the monocomponents). The drugs mixture allowed a reduction in the concentration of olodaterol from \u22431 to \u22432.3 logarithms. A favorable CRI was detected also for tiotropium bromide, whose concentration can be reduced \u22431 logarithm at medium effect levels, remaining positive up to submaximal relaxant effect in the presence of olodaterol. The combination of tiotropium bromide\/olodaterol allows the reduction in the concentration of the monocomponents to achieve airway smooth muscle relaxation, thus potentially decreases the risk of adverse events when these drugs are used to treat severe asthmatic horses.<\/jats:p>","DOI":"10.1111\/jvp.12504","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T06:47:05Z","timestamp":1522133225000},"page":"546-554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combining long\u2010acting bronchodilators with different mechanisms of action: A pharmacological approach to optimize bronchodilation of equine airways"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-069X","authenticated-orcid":false,"given":"L.","family":"Calzetta","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine and Surgery University of Rome \u201cTor Vergata\u201d Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Rogliani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Surgery University of Rome \u201cTor Vergata\u201d Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Pistocchini","sequence":"additional","affiliation":[{"name":"CDVet Laboratorio Analisi Veterinarie Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Mattei","sequence":"additional","affiliation":[{"name":"Department of Biology Centro Servizi Interdipartimentale\u2010STA University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Cito","sequence":"additional","affiliation":[{"name":"ASL Roma 2 UOC Tutela Igienico Sanitaria Degli Alimenti di Origine Animale Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Alfonsi","sequence":"additional","affiliation":[{"name":"ASL Roma 2 UOC Igiene Degli Allevamenti e Delle Produzioni Zootecniche Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Page","sequence":"additional","affiliation":[{"name":"The Sackler Institute of Pulmonary Pharmacology Institute of Pharmaceutical Science King's College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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