Preventing COPD Exacerbations in Upper Respiratory Tract Infections

Short-term intensified combination therapy with inhaled corticosteroids/long-acting beta agonists (LABAs) at the onset of an upper respiratory tract infection (URTI) leads to a significant reduction in severe exacerbations in patients with chronic obstructive pulmonary disease (COPD), according to the results of the Swedish PREVENT study published in the American Journal of Respiratory and Critical Care Medicine. 

The investigators found that a short-term increase in ICS/LABA dosing at the onset of URTI reduced the incidence of severe exacerbations by 72% (hazard ratio [HR], 0.28; 95% CI, 0.11-0.74; P =.010) in a population of 450 patients with COPD already receiving a low maintenance dose of ICS/LABA.

Although the incidence of any exacerbation following a URTI was not significantly decreased in the overall ICS/LABA group compared with placebo (14.6% vs 16.2%; HR, 0.77; 95% CI, 0.46-1.33; P =.321), patients with severe airflow limitation (FEV₁ ≤50%) had a 77% reduced risk of any exacerbation (HR, 0.23; 95% CI, 0.09-0.61; P =.003). Further, in patients with more severe disease the risk for any exacerbation was reduced by 76% (HR, 0.24; 95% CI, 0.11-0.54; P <.001) with intensified ICS/LABA therapy. 

The investigators noted that the intensified ICS/LABA regimen had greater efficacy in reducing exacerbations in patients with higher levels of fractional exhaled nitric oxide (FeNO) at a stable state. They suggested that FeNO might be increased in the subgroup of patients with COPD with predominantly eosinophilic airway inflammation, which tends to respond to glucocorticoids, as opposed to neutrophilic inflammation.  However, they cautioned that larger studies would be necessary to narrow the confidence intervals.

Potential limitations of the study included the relatively small number of patients and the low number of exacerbations, which could have led to an underestimation of the efficacy of intensified ICS/LABA therapy due to a beta error.

This intervention significantly reduced the risk for severe exacerbations in all patients and the risk for any exacerbation in patients with more severe disease, with potential implications for the treatment of patients with COPD.

Reference

Stolz D, Hirsch HH, Schilter D, et al. Intensified therapy with inhaled corticosteroids and LABA at the onset of URTI to prevent COPD exacerbations — a multicentre, randomised, double-blind, placebo-controlled trial [published online December 21, 2017]. Am J Respir Crit Care Med. 2017. doi:10.1164/rccm.201709-1807OC