Asthma
Asthma
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DOI：
10.1016/s0140-6736(13)61536-6
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发表时间：
2013-10-19
期刊：
影响因子：
168.9
通讯作者：
Vercelli, Donata
中科院分区：
文献类型：
--
作者：
Martinez, Fernando D.;Vercelli, Donata
哮喘是一组异质性疾病，可导致复发性、可逆性支气管阻塞。尽管这种疾病可以在任何年龄开始，但大多数情况下，最初的症状出现在儿童时期。哮喘有很强的遗传因素，全基因组关联研究已经确定了一些基因的变异，这些变异会略微增加患病风险。哮喘通常与鼻病毒感染的易感性增加以及呼吸道微生物群落组成的变化有关，但这些变化是该疾病的原因还是结果尚不清楚。目前尚无行之有效的预防策略；然而，生命早期接触微生物产品，特别是在农业环境中，似乎可以预防哮喘，这一发现为利用这种接触的替代物来预防这种疾病带来了希望。遗传和免疫学研究指出，肺驻留细胞（尤其是与粘膜上皮相关的细胞）的反应缺陷是哮喘发病机制的关键因素。吸入皮质类固醇仍然是治疗轻度和中度哮喘的主要手段，但每日吸入药物的坚持有限是此类治疗成功的主要障碍。常规治疗难治的严重哮喘仍然是一个挑战，但新的生物疗法，例如针对 IgE、白细胞介素 5 和白细胞介素 13 的人源化抗体，为改善具有特定分子表型的严重哮喘患者的生活质量和长期预后带来了希望。
Asthma is a heterogeneous group of conditions that result in recurrent, reversible bronchial obstruction. Although the disease can start at any age, the first symptoms occur during childhood in most cases. Asthma has a strong genetic component, and genome-wide association studies have identified variations in several genes that slightly increase the risk of disease. Asthma is often associated with increased susceptibility to infection with rhinoviruses and with changes in the composition of microbial communities colonising the airways, but whether these changes are a cause or consequence of the disease is unknown. There is currently no proven prevention strategy; however, the finding that exposure to microbial products in early life, particularly in farming environments, seems to be protective against asthma offers hope that surrogates of such exposure could be used to prevent the disease. Genetic and immunological studies point to defective responses of lung resident cells, especially those associated with the mucosal epithelium, as crucial elements in the pathogenesis of asthma. Inhaled corticosteroids continue to be the mainstay for the treatment of mild and moderate asthma, but limited adherence to daily inhaled medication is a major obstacle to the success of such therapy. Severe asthma that is refractory to usual treatment continues to be a challenge, but new biological therapies, such as humanised antibodies against IgE, interleukin 5, and interleukin 13, off er hope to improve the quality of life and long-term prognosis of severe asthmatics with specific molecular phenotypes.