1. Inhaled dual bronchodilator therapy did not reduce respiratory symptom points in tobacco-exposed persons with preserved lung function. 

2. Compared to placebo, there was no difference in lung function measures in those treated with bronchodilators.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Tobacco smoke is an established cause of chronic obstructive pulmonary disease (COPD), resulting in reduced forced expiratory volume in 1 second (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 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. At 12 weeks, no significant differences were observed in the St. George’s Respiratory Questionnaire (SGRQ) symptom assessment score, FEV1, and inspiratory capacity between the treatment and the placebo group. The study limitations included a limited follow-up period and dose limits as approved by the Food and Drug Adminstration. 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 symptoms.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: The current study was a multicenter randomized controlled trial that assessed the efficacy of dual long-acting bronchodilator therapy in treating tobacco-exposed patients with preserved lung function. Persons between 40 and 80 years of age 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. Exclusion criteria included asthma, other concomitant lung disease, and the current use of combination maintenance therapy. In the modified intention-to-treat analysis, 471 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 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, 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group achieved the primary outcome (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; p=0.65). The mean change from baseline in the FEV1 was 0.04L (95% CI, 0.01 to 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 to 0.18) in the treatment group and 0.02L (95% CI, -0.03 to 0.08). Treatment failure was uncommon in both groups. Despite the limited follow-up period, these results showed that dual bronchodilator therapy did not relieve respiratory symptoms in tobacco-exposed patients with preserved lung function.

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