Center for Health and the Environment, University of California , Davis, California.
Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana.
Am J Physiol Lung Cell Mol Physiol. 2019 May 1;316(5):L757-L763. doi: 10.1152/ajplung.00468.2018. Epub 2019 Mar 6.
Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had ) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and ) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.
哮喘是一种由过敏原敏感性、炎症、性别和发病年龄等因素区分的异质性疾病。小鼠模型被广泛用于研究过敏性哮喘的早期生命发育。然而，生命后期依赖年龄的过敏原反应相对研究较少，缺乏广泛接受的模型。为了区分对普遍存在的屋尘螨（HDM）的依赖年龄的反应，3 月龄和 9 月龄雌性 C57BL/6 小鼠被随机分为两组，每组通过鼻腔内滴注接受 HDM 或磷酸盐缓冲盐水（对照）进行致敏和激发阶段。激发后 24 小时，所有小鼠进行肺功能测试和乙酰甲胆碱激发。收集支气管肺泡灌洗液（BALF）评估细胞差异，右肺叶固定、切片并进行组织病理学和免疫组织化学染色。两个年龄组对 HDM 暴露均表现出强烈的炎症/过敏反应。然而，只有 9 月龄的 HDM 暴露小鼠与年龄匹配的对照组相比表现出显著的气道高反应性。与年轻对照组相比，这些 HDM 暴露的小鼠还表现出组织细支气管炎、血管周围炎和 BALF 中性粒细胞计数显著增加，并且与所有其他组相比，免疫染色程度显著增加。本研究提出了一种成人发病哮喘的潜在模型，特别是针对特应性、围绝经期女性表型。我们的研究结果表明，肺功能随年龄下降，并且该成年亚组的炎症特征是混合的，而不是简单的特应性、Th2 反应。该模型可能会增强我们对年龄如何影响老年亚组中哮喘样症状发展的理解。
