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吸入性糖皮质激素和大环内酯类药物疗法在支气管扩张症中起作用吗?

Is there a role for inhaled corticosteroids and macrolide therapy in bronchiectasis?

作者信息

King Paul

机构信息

Monash University, Department of Medicine, Monash Medical Centre, Melbourne, Victoria, Australia.

出版信息

Drugs. 2007;67(7):965-74. doi: 10.2165/00003495-200767070-00002.

Abstract

Bronchiectasis is characterised by permanent dilatation of the bronchi that arises from chronic inflammation predominantly caused by bacterial infection. This condition remains a major cause of excess respiratory morbidity and treatment is generally only partly successful. There is an urgent need for improved anti-inflammatory medication to treat bronchiectasis. Two potentially useful therapies are inhaled corticosteroids (ICS) and macrolides. The clinical trials that have been performed in bronchiectasis with these two medications can be considered to be preliminary data. This article reviews the anti-inflammatory properties, clinical efficacy and adverse effects of ICS and macrolides.ICS have a large number of potent anti-inflammatory properties. ICS remain the first-line treatment in asthma, reduce exacerbations in chronic obstructive pulmonary disease, and may improve lung function and symptoms in cystic fibrosis (CF). Four small clinical trials have assessed the effect of high-dose ICS on bronchiectasis. The main reported effect of these trials was a reduction in sputum volume and this may be a marker of decreased airway inflammation. Other possible benefits included decreased cough and sputum inflammatory cells/biomarkers. ICS have a relatively high prevalence of local adverse effects, and may be associated with ocular complications and osteoporosis. These adverse effects can be minimised by prescribing low doses of the medication. Macrolides have both antibacterial and immunomodulatory properties. Macrolides have less marked immunosuppressive properties than corticosteroids, and effects include decreasing mucous production, inhibiting virulence factors and biofilm formation of Pseudomonas aeruginosa, decreasing leukocyte numbers and altering inflammatory mediator release. Macrolides have been shown to be extremely effective in the treatment of diffuse panbronchiolitis, improve lung function and symptoms in asthma and CF, and reduce nasal polyps and secretions in sinusitis. Five small clinical trials have assessed the effect of macrolides on bronchiectasis. Reported benefits include reduced sputum volume, improved lung function and better symptom control. Macrolides are generally well tolerated, although they do have a number of drug interactions. There are concerns about the development of resistance, especially to non-tuberculous mycobacteria, with prolonged macrolide use. The evidence available suggests that both medications have a role in the management of bronchiectasis. More definitive trials of ICS and macrolides in bronchiectasis will clarify the likely benefit of these therapies.

摘要

支气管扩张症的特征是支气管永久性扩张,其由主要由细菌感染引起的慢性炎症所致。这种病症仍然是导致呼吸系统发病率过高的主要原因,并且治疗通常仅部分成功。迫切需要改进抗炎药物来治疗支气管扩张症。两种可能有用的疗法是吸入性糖皮质激素(ICS)和大环内酯类药物。在支气管扩张症中使用这两种药物进行的临床试验可被视为初步数据。本文综述了ICS和大环内酯类药物的抗炎特性、临床疗效及不良反应。

ICS具有大量强效抗炎特性。ICS仍是哮喘的一线治疗药物,可减少慢性阻塞性肺疾病的急性加重,并且可能改善囊性纤维化(CF)患者的肺功能和症状。四项小型临床试验评估了高剂量ICS对支气管扩张症的影响。这些试验报告的主要效果是痰液量减少,这可能是气道炎症减轻的一个指标。其他可能的益处包括咳嗽减轻以及痰液炎症细胞/生物标志物减少。ICS局部不良反应的发生率相对较高,并且可能与眼部并发症和骨质疏松症有关。通过开具低剂量药物可将这些不良反应降至最低。

大环内酯类药物具有抗菌和免疫调节特性。大环内酯类药物的免疫抑制特性不如糖皮质激素明显,其作用包括减少黏液分泌、抑制铜绿假单胞菌的毒力因子和生物膜形成、减少白细胞数量以及改变炎症介质释放。大环内酯类药物已被证明在治疗弥漫性泛细支气管炎方面极为有效,可改善哮喘和CF患者的肺功能及症状,并减少鼻窦炎患者的鼻息肉和分泌物。五项小型临床试验评估了大环内酯类药物对支气管扩张症的影响。报告的益处包括痰液量减少、肺功能改善和症状控制更好。大环内酯类药物一般耐受性良好,尽管它们确实存在一些药物相互作用。长期使用大环内酯类药物会引发对耐药性产生的担忧,尤其是对非结核分枝杆菌的耐药性。现有证据表明这两种药物在支气管扩张症的管理中都有作用。关于ICS和大环内酯类药物在支气管扩张症方面更具权威性的试验将阐明这些疗法可能带来的益处。

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