Blasi F, Canonica G W, Miravitlles M
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Cardio-thoracic unit and Cystic Fibrosis Adult Center Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
Department of Biomedical Science, Personalized Medicine Clinic: Asthma & Allergy - Humanitas Clinical and Research Center, Humanitas University -Rozzano (Milano), Milan, Italy.
Respir Res. 2017 Jan 18;18(1):19. doi: 10.1186/s12931-017-0506-0.
As emphasized by international recommendations and largely confirmed by clinical experience, long-acting bronchodilators play a central role in the maintenance treatment of chronic obstructive pulmonary disease (COPD) due to their proven efficacy in reducing airflow obstruction and improving symptoms.
There are some important aspects to define with regard to inhalation therapy for COPD, particularly those concerning the selection criteria and the optimal use of long-acting bronchodilators. First of all, it needs to be determined in which patients and clinical situations monotherapy with one bronchodilator, such as a long-acting muscarinic antagonist (LAMA), should be considered adequate, and in which cases the use of combination therapies, such as the "double bronchodilation" with a LAMA and a long-acting β2-agonist (LABA), should be preferred. Another critical issue concerns the effect of the frequency of daily administration of inhaled agents on the control of symptoms during the 24 h. COPD symptoms are known to exhibit considerable circadian variability with worsening in the early morning, and a significant proportion of patients have disease-related sleep disorders which can adversely affect their quality of life. The worsening of symptoms in the early morning may be due, at least in part, to a reduction in airway caliber caused by an increased "cholinergic tone" at night. As such, the coverage of nighttime and early morning symptoms is a reasonable therapeutic goal, which can be achieved by many patients using LAMAs such as aclidinium bromide twice daily (BID). Therapeutic adherence is known to be a multifactorial phenomenon that is frequently affected by other aspects than dosing frequency, including the technical features and ease of use of the inhalers. To this end, it should be mentioned that certain new-generation inhalers such as Genuair® have been associated in clinical trials with higher patient preference.
In this work, in addition to presenting an overview of the main evidence on the efficacy of COPD treatment with the LAMA aclidinium bromide BID, we suggest some selection criteria for the monotherapy with one long-acting bronchodilator or the combination therapy with LAMA and LABA in COPD patients, with particular reference to specific clinical scenarios.
正如国际指南所强调且临床经验充分证实的那样,长效支气管扩张剂在慢性阻塞性肺疾病(COPD)的维持治疗中发挥着核心作用,因为其在减轻气流阻塞和改善症状方面的疗效已得到证实。
关于COPD的吸入治疗,有一些重要方面需要明确,特别是那些与长效支气管扩张剂的选择标准和最佳使用有关的方面。首先,需要确定在哪些患者和临床情况下,单一支气管扩张剂(如长效毒蕈碱拮抗剂(LAMA))的单药治疗应被视为足够,以及在哪些情况下应优先使用联合治疗,如LAMA与长效β2受体激动剂(LABA)的“双重支气管扩张”。另一个关键问题涉及吸入药物每日给药频率对24小时内症状控制的影响。已知COPD症状具有显著的昼夜变化,清晨时症状会加重,并且相当一部分患者患有与疾病相关的睡眠障碍,这会对他们的生活质量产生不利影响。清晨症状加重可能至少部分归因于夜间“胆碱能张力”增加导致气道口径减小。因此,覆盖夜间和清晨症状是一个合理的治疗目标,许多患者使用如阿地溴铵每日两次(BID)等LAMA即可实现。已知治疗依从性是一个多因素现象,除给药频率外,还经常受到其他方面的影响,包括吸入器的技术特点和易用性。为此,应该提到某些新一代吸入器,如Genuair®,在临床试验中与更高的患者偏好相关。
在这项工作中,除了概述使用阿地溴铵BID治疗COPD疗效的主要证据外,我们还针对COPD患者使用单一长效支气管扩张剂单药治疗或LAMA与LABA联合治疗提出了一些选择标准,特别参考了特定的临床情况。