In the RETHINC study, 535 people with a tobacco-smoking history of at least 10 years and preserved lung function did not benefit from dual bronchodilator therapy compared with placebo. Participants had respiratory symptoms at baseline and preserved lung function as indicated by spirometry-measured forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use.
“In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the [St. George’s Respiratory Questionnaire] score (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 investigators write. “The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and −0.09 percentage points (95% CI, −1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, −0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo.”
Editorial: “On the basis of this trial and other studies, it is clear that spirometry cannot be used to identify persons with a history of smoking who are at high risk for disease progression because the test is too insensitive in detecting small-airway disease,” writes an editorialist. “Forced oscillometry, the lung-clearance index (also known as the multiple-breath washout test), and imaging-based methods such as parametric response mapping with the use of computed tomography and functional and microstructural magnetic resonance imaging show promise for the detection of small-airway disease before the onset of airflow limitation on spirometry. Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough. Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”