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

Am J Respir Crit Care Med. 2018 May 1;197(9):1136-1146. doi: 10.1164/rccm.201709-1807OC.

Abstract

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).

Keywords: ICS; LABA; treatment for COPD exacerbations.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use*
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists / therapeutic use*
  • Placebo Effect
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / prevention & control*
  • Respiratory Tract Infections / drug therapy*

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Muscarinic Antagonists

Associated data

  • ISRCTN/ISRCTN45572998