Selgrade MaryJane K, Plopper Charles G, Gilmour M Ian, Conolly Rory B, Foos Brenda S P
National Health and Environmental Effects Research Laboratory, North California, USA.
J Toxicol Environ Health A. 2008;71(3):196-207. doi: 10.1080/15287390701597897.
Adults and children may have different reactions to inhalation exposures due to differences in target tissue doses following similar exposures, and/or different stages in lung growth and development. In the case of asthma and allergy both the developing immune system and initial encounters with common allergens contribute to this differential susceptibility. Asthma, the most common chronic childhood disease, has significant public health impacts and is characterized by chronic lung inflammation, reversible airflow obstruction, and immune sensitization to allergens. Animal studies described here suggest that air pollutants exacerbate asthma symptoms and may also play a role in disease induction. Changes characteristic of asthma were observed in rhesus monkeys sensitized to house dust mite antigen (HDMA) as infants and exposed repeatedly thereafter to ozone (O3) and HDMA. O3 exposure compromised airway growth and development and exacerbated the allergen response to favor intermittent airway obstruction and wheeze. In Brown Norway rats a variety of air pollutants enhanced sensitization to HDMA such that symptoms elicited in response to subsequent allergen challenge were more severe. Although useful for assessing air pollutants effects on initial sensitization, the rodent immune system is immature at birth relative to humans, making this model less useful for studying differential effects between adults and children. Because computational models available to address children's inhalation exposures are limited, default adjustments and their associated uncertainty will continue to be used in children's inhalation risk assessment. Because asthma is a complex (multiple genes, phenotypes, organ systems) disease, this area is ripe for systems biology approaches.
由于相似暴露后靶组织剂量的差异，和/或肺生长发育阶段的不同，成人和儿童对吸入暴露可能有不同反应。就哮喘和过敏而言，发育中的免疫系统以及与常见过敏原的初次接触都会导致这种易感性差异。哮喘是儿童最常见的慢性疾病，对公共卫生有重大影响，其特征为慢性肺部炎症、可逆性气流阻塞以及对过敏原的免疫致敏。此处描述的动物研究表明，空气污染物会加剧哮喘症状，还可能在疾病诱发中起作用。在幼年时对屋尘螨抗原（HDMA）致敏、此后反复暴露于臭氧（O₃）和HDMA的恒河猴身上观察到了哮喘的特征性变化。暴露于O₃会损害气道生长发育，并加剧过敏原反应，导致间歇性气道阻塞和喘息。在棕色挪威大鼠中，多种空气污染物增强了对HDMA的致敏作用，使得对后续过敏原激发产生的症状更严重。尽管啮齿动物免疫系统模型对于评估空气污染物对初始致敏的影响有用，但相对于人类而言，其出生时免疫系统不成熟，使得该模型在研究成人和儿童的差异影响方面用处较小。由于用于处理儿童吸入暴露的计算模型有限，在儿童吸入风险评估中仍将继续使用默认调整及其相关不确定性。由于哮喘是一种复杂（多基因、多表型、多器官系统）疾病，该领域很适合采用系统生物学方法。
