Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function

Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary

“…Yet, people with pre-COPD so defined should already be considered “patients” because they suffer symptoms and/or have functional and/or structural abnormalities. Currently, there is no evidence on what the best treatment is for these patients [ 68 ]. There urgently is a need for randomized controlled trials, both in patients with “Pre-COPD”, and in young people with COPD [ 69 ].…”

Contemporary Concise Review 2022: Chronic obstructive pulmonary disease

“…In the larger RETHINC trial, 471 smokers with normal spirometry were randomized to either 12 weeks indacaterol/glycopyrrolate or placebo. Although there were small significant changes in lung function in the BD group, health status was unaffected 51 . By contrast, combining long‐acting beta‐agonist and anti‐muscarinic properties in a single molecule is now possible and the novel compound navafenterol proved to be at least as effective as the dual BD combinations in reducing symptoms and improving lung function 52 …”

The Importance of Early Chronic Obstructive Pulmonary Disease: A Lecture from 2022 Asian Pacific Society of Respirology

“…Based on the assumption that a majority of symptomatic smokers will eventually develop COPD [ 42 ], many in clinical practice are treating symptomatic smokers with preserved spirometry with anti-COPD therapies such as inhaled corticosteroids (ICS) or long acting bronchodilators [ 41 ]. A recent randomized controlled trial of symptomatic smokers with preserved spirometry, Redefining Therapy in Early COPD (RETHINC), showed that a 12-week treatment of a long acting beta-2 agonist/long acting muscarinic antagonist (LABA/LAMA) combination did not improve patients’ symptoms or quality of life [ 43 ]. The LABA/LAMA combination improved FEV1 in this population by approximately 40 mL, which is lower than approximately 200 mL improvement, which has been observed in patients with GOLD 2 or 3 COPD [ 44 ].…”

“…It should also be noted that the “placebo effect” is very strong in symptomatic smokers with preserved spirometry. In the RETHINC trial, for example, the average improvement in the St. George’s Respiratory Questionnaire (SGRQ) score and the CAT score over 12 weeks was 8.9 and 4.5 points, respectively, in the placebo group [ 43 ]. As the minimal clinically important difference for SGRQ is 4 points and that for CAT is 2 points, a majority of symptomatic smokers in the placebo group felt significantly better at 3 months of follow-up even without any treatment than they did at baseline.…”

“…Thus, future trials evaluating new approaches or novel therapies for symptomatic smokers with preserved spirometry should carefully consider the strong “placebo” effect in their design [ 44 ]. Moreover, in the RETHINC trial, the predominant symptoms in smokers with preserved spirometry were cough and sputum production (i.e., “smokers’ cough”) rather than exertional dyspnea with 70% reporting a history of chronic bronchitis (based on the CAT) [ 43 ]. This may have important implications in the choice of therapeutics for future evaluation.…”