Boushey H A, Fahy J V
Cardiovascular Research Institute, University of California San Francisco 94143-0130, USA.
Environ Health Perspect. 1995 Sep;103 Suppl 6(Suppl 6):229-33. doi: 10.1289/ehp.95103s6229.
Results of studies of the epidemiology, physiology, histopathology, and cell biology of asthma have revised our conception of the disease. Epidemiologic studies have shown asthma to be an important cause of death, suffering, and economic hardship. Physiologic studies have shown that asthma is a chronic illness characterized by persistent bronchial hyperreactivity. Histopathologic studies have shown characteristic changes: epithelial damage, deposition of collagen beneath the basement membrane, eosinophilic and lymphocytic infiltration, and hypertrophy and hyperplasia of goblet cells, submucosal glands, and airway smooth muscle. Studies of the functions of cells in the airway mucosa suggest that asthma may be fundamentally mediated by a difference in the type of lymphocyte predominating in the airway mucosa but may also involve complex interactions among resident and migratory cells. Asthma may thus result from sensitization of a subpopulation of CD4+ lymphocytes, the Th2 subtype, in the airways. These lymphocytes produce a family of cytokines that favor IgE production and the growth and activation of mast cells and eosinophils, arming the airways with the mechanisms of response to subsequent reexposure to the allergen. This conceptual model has stimulated research along lines that will almost certainly lead to powerful new treatments, and it has already put current therapies in a new light, clarifying the role of antinflammatory agents, especially of inhaled corticosteroids. This conceptual model has some limitations: it ignores new evidence on the role of the mast cell in producing cytokines and depends on results of studies of the effects of inhalation of allergen, although most asthma exacerbations are provoked by viral respiratory infection. Preliminary studies suggest that viral infection and allergen inhalation may involve the activation of different pathways, with viral infection activating production of cytokines by airway epithelial cells. Similar study of the mechanisms activated by inhalation of air toxics may provide important clues as to how they might induce or exacerbate asthma.
哮喘的流行病学、生理学、组织病理学和细胞生物学研究结果修正了我们对该疾病的认识。流行病学研究表明，哮喘是导致死亡、痛苦和经济困难的重要原因。生理学研究表明，哮喘是一种以持续性支气管高反应性为特征的慢性疾病。组织病理学研究显示了特征性变化：上皮损伤、基底膜下胶原蛋白沉积、嗜酸性粒细胞和淋巴细胞浸润，以及杯状细胞、黏膜下腺体和气道平滑肌的肥大和增生。气道黏膜细胞功能研究表明，哮喘可能根本上是由气道黏膜中占主导地位的淋巴细胞类型差异介导的，但也可能涉及驻留细胞和迁移细胞之间的复杂相互作用。因此，哮喘可能是由气道中CD4+淋巴细胞亚群（Th2亚型）的致敏引起的。这些淋巴细胞产生一类细胞因子，有利于IgE的产生以及肥大细胞和嗜酸性粒细胞的生长和活化，使气道具备对随后再次接触过敏原的反应机制。这个概念模型激发了相关研究，几乎肯定会带来强大的新治疗方法，并且已经使当前的治疗方法有了新的认识，阐明了抗炎药物尤其是吸入性皮质类固醇的作用。这个概念模型有一些局限性：它忽略了肥大细胞在产生细胞因子方面作用的新证据，并且依赖于吸入过敏原效果的研究结果，尽管大多数哮喘发作是由病毒性呼吸道感染引发的。初步研究表明，病毒感染和吸入过敏原可能涉及不同途径的激活，病毒感染激活气道上皮细胞产生细胞因子。对吸入空气毒物激活机制的类似研究可能为它们如何诱发或加重哮喘提供重要线索。
