Latorre M, Novelli F, Vagaggini B, Braido F, Papi A, Sanduzzi A, Santus P, Scichilone N, Paggiaro P
Cardio-Thoracic and Vascular Department, Pathophysiology Unit, University of Pisa, Italy.
Allergy and Respiratory Diseases Clinic, DIMI, University of Genoa, IRCS AOU San Martino-IST, Genoa, Italy.
Pulm Pharmacol Ther. 2015 Feb;30:44-50. doi: 10.1016/j.pupt.2014.10.006. Epub 2014 Nov 6.
Inhaled corticosteroids (ICS) are frequently recommended for the treatment of asthma and COPD, often in combination with long-acting beta2-agonists (LABA), depending on the severity of the disease and/or on the specific phenotype. Several ICS/LABA combinations are currently available that differ in their pharmacokinetic characteristics and dose of both components. Thus, this review assesses differences in the efficacy and the safety profiles of the ICS components in the two more frequently used ICS/LABA combinations (budesonide/formoterol and fluticasone/salmeterol) for the management of COPD. Whereas the basic mechanism of action is similar for all ICS (binding with the intracellular glucocorticoid receptor, which mediates both genomic and non genomic effects), the pharmacokinetic and characteristics of ICS are quite different in terms of receptor affinity, bioavailability, lipophilicity and drug persistence in the airways. Fluticasone persists longer in airway mucus and requires more time to dissolve in the lining fluid and then enter the airway wall, whereas budesonide is cleared more quickly from the airways. Comparative efficacy of the two major ICS/LABA combinations recommended for the treatment of COPD show similar efficacy in terms of reduction of exacerbations, improvement in forced expiratory volume in the first second (FEV1) and quality of life. One retrospective cohort study suggested a greater efficacy for the budesonide/formoterol combination on hospital or emergency department admissions, oral corticosteroid courses, and addition of tiotropium, and an observational real-life study reported a greater reduction of COPD exacerbations with budesonide/formoterol than with fluticasom/salmeterol combination. Among the potential side effects of chronic ICS treatment in patients with COPD, recently the use of fluticasone or fluticasone/salmeterol combination has been associated with a higher prevalence of pneumonia in the major long-term studies. On the other hand, no similar increased risk of pneumonia has been reported in patients with COPD treated with the budesonide/formoterol combination. A recent population-based cohort study from the Quebec database showed that the adjusted odds ratio for having severe pneumonia was higher for fluticasone (2.1) than for budesonide (1.17) or other ICS (1.41). Of the ICS studied, only fluticasone demonstrated a dose-related increase in risk of pneumonia in patients with COPD. This difference between fluticasone and budesonide may be explained by the longer retention of fluticasone in the airways, with potentially greater inhibition of type-1 innate immunity. Therefore, the risk:benefit ratio should be evaluated thoroughly when choosing an ICS/LABA combination for patients with COPD.
吸入性糖皮质激素（ICS）常用于治疗哮喘和慢性阻塞性肺疾病（COPD），通常根据疾病严重程度和/或特定表型与长效β2受体激动剂（LABA）联合使用。目前有几种ICS/LABA组合，其药代动力学特征和两种成分的剂量各不相同。因此，本综述评估了两种更常用的ICS/LABA组合（布地奈德/福莫特罗和氟替卡松/沙美特罗）中ICS成分在COPD管理中的疗效和安全性差异。虽然所有ICS的基本作用机制相似（与细胞内糖皮质激素受体结合，介导基因组和非基因组效应），但ICS在受体亲和力、生物利用度、亲脂性和气道内药物持久性方面的药代动力学和特性有很大差异。氟替卡松在气道黏液中持续时间更长，需要更多时间溶解在衬液中，然后进入气道壁，而布地奈德从气道清除得更快。推荐用于治疗COPD的两种主要ICS/LABA组合的比较疗效显示，在减少急性加重、改善第一秒用力呼气量（FEV1）和生活质量方面具有相似的疗效。一项回顾性队列研究表明，布地奈德/福莫特罗组合在住院或急诊科就诊、口服糖皮质激素疗程以及加用噻托溴铵方面疗效更佳，一项观察性现实生活研究报告称，与氟替卡松/沙美特罗组合相比，布地奈德/福莫特罗组合能更有效地减少COPD急性加重。在COPD患者长期使用ICS治疗的潜在副作用中，最近在主要的长期研究中，使用氟替卡松或氟替卡松/沙美特罗组合与肺炎的较高患病率相关。另一方面，使用布地奈德/福莫特罗组合治疗的COPD患者未报告类似的肺炎风险增加。魁北克数据库最近一项基于人群的队列研究表明，氟替卡松（2.1）导致严重肺炎的校正比值比高于布地奈德（1.17）或其他ICS（1.41）。在所研究的ICS中，只有氟替卡松在COPD患者中显示出与剂量相关的肺炎风险增加。氟替卡松和布地奈德之间的这种差异可能是由于氟替卡松在气道中保留时间更长，对1型固有免疫的抑制作用可能更大。因此，为COPD患者选择ICS/LABA组合时，应全面评估风险效益比。
