Is it preferable to administer a bronchodilator once- or twice-daily when treating COPD?

• Published in: Respiratory medicine 2023-11, Vol.219, p.107439-107439, Article 107439
• Main Authors: Matera, Maria Gabriella, Rinaldi, Barbara, Ambrosio, Concetta, Cazzola, Mario
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma - drug therapy; Bronchodilator Agents; COPD; Drug Combinations; Humans; LABAs; LAMAs; Muscarinic Antagonists; Once-daily; Pulmonary Disease, Chronic Obstructive; Symptom variability; Twice-daily
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2023.107439

Night-time and early morning symptoms are common and uncomfortable in many patients with COPD, and likely to negatively influence their long-term outcomes. However, it is still debated whether it is preferable to administer long-acting bronchodilators once- or twice-daily to symptomatic COPD patients. The functional link between circadian rhythms of autonomic tone and airway calibre explains why the timing of administration of bronchodilators in chronic airway diseases can induce different effects when taken at different biological (circadian) times. However, the timing also depends on the pharmacological characteristics of the bronchodilator to be used. Because the profile of bronchodilation produced by once-daily vs. twice-daily long-acting bronchodilators differs throughout 24 hours, selecting long-acting bronchodilators may be customized to specific patient preferences based on the need for further bronchodilation in the evening. This is especially helpful for people who experience respiratory symptoms at night or early morning. Compared to placebo, evening bronchodilator administration is consistently linked with persistent overnight improvements in dynamic respiratory mechanics and inspiratory neural drive. The current evidence indicates that nocturnal and early morning symptoms control is best handled by a LAMA taken in the evening. In contrast, it seems preferable to use a LABA for daytime symptoms. Therefore, it can be speculated that combining a LAMA with a LABA can improve bronchodilation and control symptoms better. Both LAMA and LABA must be rapid in their onset of action. Aclidinium/formoterol, a twice-daily combination, is, among the available LAMA/LABA combinations, the most studied in terms of impact on daytime and night-time symptoms. •An important question when treating a patient suffering from COPD is whether it is preferable to administer a bronchodilator on a once- or twice-daily basis.•The twice-daily dosing of bronchodilators should be considered as a useful approach at least for the symptomatic treatment of COPD because there is a progressive attempt to shift attention towards controlling nocturnal symptoms and those present on awakening, which epidemiological studies indicate to be the most troublesome for COPD patients.•Unfortunately, due to a lack of information from adequate large studies, we are still unable to conclude, even indirectly, whether twice-daily administration of bronchodilators may be preferable to the once-daily