Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
Respir Med. 2023 Nov-Dec;219:107439. doi: 10.1016/j.rmed.2023.107439. Epub 2023 Oct 24.
Nocturnal and early morning symptoms are common and uncomfortable in many patients with COPD, and are likely to affect their long-term outcomes. However, it is still debated whether it is better to give 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 h, 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 the most studies of the available LAMA/LABA combinations in terms of impact on daytime and nocturnal symptoms.
夜间和清晨症状在许多 COPD 患者中很常见且令人不适，并且可能会影响他们的长期预后。然而，对于有症状的 COPD 患者，长效支气管扩张剂是每日一次给药还是每日两次给药更好，目前仍存在争议。自主神经张力的昼夜节律与气道口径之间的功能联系解释了为什么在慢性气道疾病中，支气管扩张剂的给药时间在不同的生物学（昼夜）时间给药会产生不同的效果。然而，给药时间也取决于要使用的支气管扩张剂的药理学特征。由于每日一次与每日两次长效支气管扩张剂产生的支气管扩张作用在 24 小时内存在差异，因此根据患者对夜间进一步支气管扩张的需求，选择长效支气管扩张剂可能会根据特定患者的偏好进行定制。这对于那些在夜间或清晨出现呼吸症状的人特别有帮助。与安慰剂相比，夜间支气管扩张剂给药始终与动态呼吸力学和吸气神经驱动的持续整夜改善相关。目前的证据表明，夜间和清晨症状的控制最好通过在晚上服用 LAMA 来处理。相比之下，似乎白天症状更适合使用 LABA。因此，可以推测，联合使用 LAMA 和 LABA 可以更好地改善支气管扩张和控制症状。LAMA 和 LABA 都必须迅速起效。在现有的 LAMA/LABA 组合中，阿地溴铵/福莫特罗（每日两次）组合在日间和夜间症状方面的研究最多。
