Intensified Therapy with Inhaled Corticosteroids and Long-Acting β2-Agonists at the Onset of Upper Respiratory Tract Infection to Prevent Chronic Obstructive Pulmonary Disease Exacerbations. A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial
1Clinic of Respiratory Medicine and Pulmonary Cell Research, and5Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland2Department of Biomedicine, University of Basel, Basel, Switzerland3University of Basel, Basel, Switzerland4Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland6Lindenhof Hospital, Bern, Switzerland7Pneumology Department, GIGA I3 research group, University of Liege, CHU Liege, Belgium; and8Swiss Tropical and Public Health Institute, Basel, Switzerland
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Rationale:The efficacy of intensified combination therapy with inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA) at the onset of upper respiratory tract infection (URTI) symptoms in chronic obstructive pulmonary disease (COPD) is unknown.Objectives:To evaluate whether intensified combination therapy with ICS/LABA, at the onset of URTI symptoms, decreases the incidence of COPD exacerbation occurring within 21 days of the URTI.Methods:A total of 450 patients with stable, moderate to very severe COPD, were included in this investigator-initiated and -driven, double-blind, randomized, placebo-controlled study. At inclusion, patients were assigned to open-labeled low-maintenance dose ICS/LABA. Each patient was randomized either to intensified-dose ICS/LABA or placebo and instructed to start using this medication only in case of a URTI, at the onset of symptoms, twice daily, for 10 days.Measurements and Main Results:The incidence of any exacerbation following a URTI was not significantly decreased in the ICS/LABA group, as compared with placebo (14.6% vs. 16.2%; hazard ratio, 0.77; 95% confidence interval, 0.46-1.33; P = 0.321) but the risk of severe exacerbation was decreased by 72% (hazard ratio, 0.28; 95% confidence interval, 0.11-0.74%; P = 0.010). In the stratified analysis, effect size was modified by disease severity, fractional exhaled nitric oxide, and the body mass index-airflow obstruction-dyspnea, and exercise score. Compared with the stable period, evidence of at least one virus was significantly more common at URTI, 10 days after URTI, and at exacerbation.Conclusions:Intensified combination therapy with ICS/LABA for 10 days at URTI onset did not decrease the incidence of any COPD exacerbation but prevented severe exacerbation. Patients with more severe disease had a significant risk reduction for any exacerbation.Clinical trial registered with www.isrctn.com (ISRCTN45572998).