{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:10:03Z","timestamp":1790075403707,"version":"4.0.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Budesonide\/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease. Combining these medications may provide additional benefits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the efficacy and tolerability of budesonide\/formoterol added to tiotropium in patients eligible for inhaled corticosteroid\/long-acting \u03b22-agonist combination therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this 12-week, randomized, double-blind, parallel-group, multicenter study, after a 2-week run-in, 660 subjects (75% male; mean age, 62 yr; FEV1, 1.1 L; 38% predicted normal), 40 years of age or older, received tiotropium (18 \u03bcg once daily) plus either budesonide\/formoterol (320\/9 \u03bcg) (n = 329) or placebo (n = 331) twice daily.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Clinic predose (primary outcome) and postdose FEV1, predose and postdose forced vital capacity and inspiratory capacity, and health status were measured. Other outcomes included daily measurements taken at home (pre- and postdose morning FEV1 and peak expiratory flow, morning symptoms and activities, and morning reliever use), severe exacerbations, and tolerability. Over the treatment period, budesonide\/formoterol plus tiotropium significantly increased predose FEV1 by 6% (65 ml) and postdose by 11% (123 and 131 ml at 5 and 60 min postdose, respectively) versus tiotropium alone (both P &amp;lt; 0.001). Other outcomes all significantly improved with budesonide\/formoterol plus tiotropium versus tiotropium alone. The number of severe exacerbations decreased by 62% (rate ratio, 0.38; 95% confidence interval, 0.25\u20130.57; P &amp;lt; 0.001). Both treatments were well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with chronic obstructive pulmonary disease, budesonide\/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function, health status, morning symptoms and activities, and reduces severe exacerbations.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT00496470).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200904-0492oc","type":"journal-article","created":{"date-parts":[[2009,7,30]],"date-time":"2009-07-30T22:00:38Z","timestamp":1248991238000},"page":"741-750","source":"Crossref","is-referenced-by-count":277,"title":["Efficacy and Tolerability of Budesonide\/Formoterol Added to Tiotropium in Patients with Chronic Obstructive Pulmonary 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Peterson","sequence":"additional","affiliation":[{"name":"AstraZeneca Research and Development Lund, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Polanowski","sequence":"additional","affiliation":[{"name":"AstraZeneca Research and Development Lund, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Kessler","sequence":"additional","affiliation":[{"name":"Department of Pneumology, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,10,15]]},"reference":[{"key":"2026032100090777800_BIB1","year":"2008"},{"key":"2026032100090777800_BIB2","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1183\/09031936.02.00240902","volume":"19","year":"2002","journal-title":"Eur Respir 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