Arizona Respiratory Center and BIO5 Institute, University of Arizona, Tucson, AZ, USA.
Lancet. 2013 Oct 19;382(9901):1360-72. doi: 10.1016/S0140-6736(13)61536-6. Epub 2013 Sep 13.
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, offer hope to improve the quality of life and long-term prognosis of severe asthmatics with specific molecular phenotypes.
哮喘是一组异质性疾病,导致反复发作、可逆性支气管阻塞。虽然该病可在任何年龄发病,但大多数情况下,首发症状出现在儿童时期。哮喘具有很强的遗传成分,全基因组关联研究已经确定了几个基因的变异,这些变异略微增加了患病风险。哮喘常与对鼻病毒感染的易感性增加以及气道定植微生物群落组成的变化相关,但这些变化是疾病的原因还是后果尚不清楚。目前尚无经证实的预防策略;然而,早期生活中接触微生物产物(特别是在农业环境中)似乎可以预防哮喘的发现,为寻找此类暴露的替代物以预防哮喘提供了希望。遗传和免疫学研究表明,肺部常驻细胞,特别是与黏膜上皮相关的细胞,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方法,但对每日吸入药物的依从性有限是此类治疗成功的主要障碍。对常规治疗有抵抗的重度哮喘仍然是一个挑战,但新型生物疗法,如针对 IgE、白细胞介素 5 和白细胞介素 13 的人源化抗体,为改善特定分子表型的重度哮喘患者的生活质量和长期预后带来了希望。