Tobacco smoke is an established cause of COPD, resulting in reduced FEV1 relative to forced vital capacity (FVC) not reversible by bronchodilators. Some tobacco exposed individuals whose lung function is preserved as measured by spirometry also exhibit respiratory symptoms similar to those with COPD. Although it has been found that
airway-wall thickening, and mucus concentration may contribute to these symptoms, independent from lung function, it remains unclear if bronchodilators are beneficial in this patient population.
The current study, published in The New England Journal of Medicine, was a multicenter randomized controlled trial to determine if a dual therapy of long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrrolate could improve respiratory symptoms in tobacco exposed individuals with preserved lung function. Participants (N=471) aged 40-80 who currently or previously smoked cigarettes with at least a 10-pack-year history, had respiratory symptoms as defined by the COPD Assessment Test score of at least 10, and preserved lung function as measured by spirometry were included.
In the modified intention-to-treat analysis, participants were randomized 1:1 to receive either indacaterol 27.5µg combined with glycopyrrolate 15.6µg or a placebo for 12 weeks. The primary outcome was an improvement by at least four points in the St. George’s Respiratory Questionnaire (SGRQ) score without treatment failure, which is defined as an increase in lower respiratory symptoms necessitating treatment with a long-acting bronchodilator,
glucocorticoid, or antibiotic.
Overall, at 12 weeks, 56.4% of participants in the treatment group and 59.0% in the placebo group achieved the primary outcome (difference, -2.6 percentage points: 95% CI, -11.6 to 6.3). The mean change from baseline in the FEV1 was 0.04L (95% CI, 0.01-0.08) in the treatment group and -0.01L (95% CI, -0.04 to 0.02) in the placebo group, while the mean change in inspiratory capacity was 0.12L (95% CI, 0.07- 0.18) in the treatment group and 0.02L (95% CI, -0.03 to 0.08). Treatment failure was uncommon in both groups.
At 12 weeks, no significant differences were observed in the SGRQ symptom assessment score, FEV1, and inspiratory capacity between groups.
Limitations of this study included a less than adequate follow-up period and dose limits as approved by the FDA. Nevertheless, these results showed that for tobacco-exposed patients with preserved lung function, the current dual bronchodilator regimen did not result in the abatement of their respiratory symptom.
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