Anti-inflammatory medications for cystic fibrosis lung disease: selecting the most appropriate agent.
Anti-inflammatory medications for cystic fibrosis lung disease: selecting the most appropriate agent.
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DOI：
10.2165/00151829-200504040-00004
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发表时间：
2005-01-01
期刊：
影响因子：
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通讯作者：
Konstan, Michael W
中科院分区：
文献类型：
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作者：
Chmiel, James F;Konstan, Michael W
囊性纤维化（CF）的肺部疾病的特征在于气道阻塞、感染和炎症的自我维持循环。旨在减少炎症反应的治疗是一种相对较新的治疗策略。注意力主要集中在皮质类固醇和NSAID的治疗潜力上。虽然有益，但全身性皮质类固醇的使用受到其不可接受的不良反应的限制。目前尚不清楚吸入性糖皮质激素是否是一种可行的替代方案，尽管近年来其在CF中的使用急剧增加。高剂量布洛芬已被证明可以减缓CF肺病的进展，但尽管其具有良好的风险-效益特征，但其使用尚未被广泛采用。因此，其他抗炎方法正在研究中。由于炎症反应可以由许多刺激物触发，并且由于由这些刺激物激活的途径产生许多介质，因此存在过多的抗炎治疗靶点。特异性抗体、受体拮抗剂和反调节细胞因子，如白细胞介素（IL）-10和干扰素-γ，可抑制导致CF气道损伤性炎症的促炎介质，包括肿瘤坏死因子-α、IL-1 β和IL-8。CF中正在进行调节导致炎症介质产生的细胞内信号级联的分子的研究。对于已确诊疾病的患者，针对中性粒细胞产物（如DNA酶、抗氧化剂和蛋白酶抑制剂）的治疗方法的最新进展和预期进展有望限制炎症反应的后果。为了优化抗炎治疗，有必要了解这些药物在CF肺中的作用机制，以确定哪些药物最有益，并确定应在肺部疾病的年龄和阶段开始哪些治疗。希望仍然是纠正异常CF跨膜传导调节蛋白或基因替代疗法将是治愈性的。然而，基本缺陷的纠正也必须纠正失调的炎症反应才能有效。在那些旨在修复基本缺陷的治疗方法实现之前，限制炎症过程的影响对于减缓肺功能下降并从而延长CF患者的生存期将是重要的。
The lung disease of cystic fibrosis (CF) is characterized by a self-sustaining cycle of airway obstruction, infection, and inflammation. Therapies aimed at decreasing the inflammatory response represent a relatively new strategy for treatment. Attention has focused primarily upon the therapeutic potential of corticosteroids and NSAIDs. Although beneficial, the use of systemic corticosteroids is limited by their unacceptable adverse effects. It is unclear if inhaled corticosteroids are a viable alternative, although their use in CF has dramatically increased in recent years. High-dose ibuprofen has been shown to slow progression of CF lung disease, but its use has not been widely adopted despite a favorable risk-benefit profile. Thus, other anti-inflammatory approaches are under investigation. Since the inflammatory response can be triggered by many stimuli and since the pathways activated by these stimuli produce many mediators, there are a plethora of targets for anti-inflammatory therapeutics. Specific antibodies, receptor antagonists, and counter-regulatory cytokines, such as interleukin (IL)-10 and interferon-gamma, inhibit the pro-inflammatory mediators responsible for the damaging inflammation in the CF airway, including tumor necrosis factor-alpha, IL-1beta and IL-8. Studies of molecules that modulate intracellular signaling cascades that lead to the production of inflammatory mediators, are underway in CF. For patients with established disease, recent and projected advances in therapies that are directed at neutrophil products, such as DNase, antioxidants, and protease inhibitors, hold great promise for limiting the consequences of the inflammatory response. To optimize anti-inflammatory therapy, it is necessary to understand the mechanism of action of these agents in the CF lung to determine which agents will be most beneficial, and to determine which therapies should be initiated at what age and stage of lung disease. Hope remains that correction of the abnormal CF transmembrane conductance regulator protein or gene replacement therapy will be curative. However, correction of the basic defect must also correct the dysregulated inflammatory response in order to be effective. Until those therapies aimed at repairing the basic defect are realized, limiting the effects of the inflammatory process will be important in slowing the decline in lung function and thus prolonging survival in patients with CF.