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

哮喘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岁儿童对吸入过敏原敏感，然而，这些人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。第二次发作与早期肺部炎症有关，会使这种风险增加几倍。第二次感染可能来自病毒感染或其他炎性刺激，如暴露在香烟烟雾、空气污染物和汽车尾气中。第二次撞击的时机很可能很重要，特别是如果它是早期的，而肺部仍在生长和发育。该项目的目的是使用过敏性炎症的小鼠模型来检查过敏原致敏和早期暴露于环境危害之间的相互作用。我们将测试这一假设，即早期过敏反应和病毒感染的组合改变了肺生长、呼吸道功能和呼吸道高反应性，然而，暴露在空气污染物中并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所起的作用可能为我们提供一种干预策略，可以防止呼吸功能和呼吸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.