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靶向治疗阻塞性气道疾病中的支气管炎。

Targeted therapy of bronchitis in obstructive airway diseases.

机构信息

Firestone Institute for Respiratory Health, St Joseph's Healthcare & Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

出版信息

Pharmacol Ther. 2013 Dec;140(3):213-22. doi: 10.1016/j.pharmthera.2013.07.001. Epub 2013 Jul 8.

Abstract

Guidelines for the management of obstructive airway diseases do not emphasize the measurement of bronchitis to indicate appropriate treatments or monitor response to treatment. Bronchitis is the central component of airway diseases and contributes to symptoms, physiological and structural abnormalities. It can be measured directly and reliably by quantitative assay of spontaneous or induced sputum. The measurement is reproducible, valid, and responsive to treatment and to changes in disease status. Bronchitis may be eosinophilic, neutrophilic, mixed, or paucigranulocytic (eosinophils and neutrophils not elevated). Eosinophilic bronchitis is usually a Th2 driven process and therefore a sputum eosinophilia of greater than 3% usually indicates a response to treatment with corticosteroids or novel therapies directed against Th2 cytokines such as IL-4, IL-5 and IL-13. Neutrophilic bronchitis which is a non-Th2 driven disease is generally a predictor of response to antibiotics and may be a predictor to therapies targeted at pathways that lead to neutrophil recruitment such as IL-8 (eg anti-CXCR2), IL-17 (eg anti-IL17) etc. Paucigranulocytic disease may not warrant anti-inflammatory therapy. Several novel monoclonals and small molecule antagonists have been evaluated in clinical trials with variable results and several more are likely to be discovered in the near future. The success of these agents will depend on appropriate patient selection by accurate phenotyping or characterization of bronchitis.

摘要

气道疾病管理指南并未强调通过测量支气管炎来指示适当的治疗或监测治疗反应。支气管炎是气道疾病的核心组成部分,会导致症状、生理和结构异常。通过对自发性或诱导性痰液进行定量检测,可以直接且可靠地测量支气管炎。该测量具有可重复性、有效性,并可响应治疗以及疾病状况的变化。支气管炎可能是嗜酸性粒细胞性、中性粒细胞性、混合性或寡细胞性(嗜酸性粒细胞和中性粒细胞不升高)。嗜酸性粒细胞性支气管炎通常是 Th2 驱动的过程,因此痰液嗜酸性粒细胞计数大于 3%通常表明对皮质类固醇或针对 Th2 细胞因子(如 IL-4、IL-5 和 IL-13)的新型治疗有反应。中性粒细胞性支气管炎是非 Th2 驱动的疾病,通常对抗生素有反应,也可能是针对导致中性粒细胞募集的途径的治疗的预测指标,如 IL-8(如抗 CXCR2)、IL-17(如抗 IL-17)等。寡细胞性疾病可能不需要抗炎治疗。一些新型单克隆抗体和小分子拮抗剂已在临床试验中进行了评估,结果各不相同,未来可能会发现更多。这些药物的成功将取决于通过准确表型或表征支气管炎来进行适当的患者选择。

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