Allergen-sensitzation and environmental exposures in early life interact synergistically to alter lung growth

哮喘的发展是遗传易感性和环境暴露之间复杂相互作用的结果。在珀斯，大约40%的6岁儿童对吸入性过敏原过敏，然而，其中只有一半患有哮喘。因此，过敏性致敏本身不足以发展为持续性哮喘。第二次打击，与肺部炎症在生命早期，增加这种风险几倍。第二次打击可能来自病毒感染或其他炎症刺激，如暴露于香烟烟雾，空气污染物和汽车尾气排放。第二次撞击的时机可能很重要，特别是如果它是早期的，而肺部仍在生长和发育。本项目的目的是研究过敏原致敏和暴露于环境危害之间的相互作用，在生命早期使用小鼠模型过敏性炎症。我们将检验这一假设，即早期过敏性致敏和病毒感染的结合改变了肺的生长、气道功能和气道高反应性，然而，暴露于空气污染物不能提供诱发持续性哮喘所需的“第二次打击”。确定病毒感染和环境污染在生命早期的作用可能为我们提供一种干预策略，可以预防呼吸功能和气道高反应性的终身变化。

Asthma develops as the result of complex interactions between genetic susceptibilities and environmental exposures. Approximately 40% of 6-year-old children in Perth are sensitized to inhaled allergens, however, only half of these have asthma. Allergic sensitization per se is therefore insufficient for the development of persistent asthma. A second hit, associated with lung inflammation in early life, increases this risk several fold. This second hit could come from viral infection or from other inflammatory stimuli such as exposure to cigarette smoke, air pollutants and vehicle exhaust emissions. The timing of this second hit may well be important, particularly if it is early while the lungs are still growing and developing. The aim of this project is to examine interactions between allergen sensitization and exposure to environmental hazards in early life using a mouse model of allergic inflammation. We will test the hypothesis that the combination of allergic sensitization and viral infections in early life alter lung growth, airway function and airway hyperresponsiveness, however, exposure to air pollutants can not provide the 'second hit required to induce persistent asthma. Determining the role viral infection and environmental pollution have early in life may provide us with a strategy for intervention that could prevent life-long changes in respiratory function and airway hyperresponsiveness.