Age-dependent pulmonary reactivity to house dust mite allergen: a model of adult-onset asthma? (1)
The main factors differentiating asthma phenotypes are atopic or nonatopic, Th2 or non-Th2 inflammation, symp- tom severity, sex, and age at disease onset. C57BL/6 mice primarily exhibit non-Th2- dominated immune responses but have the capacity to develop classic asthma-like responses, such as allergen-specific IgE, airway hyperresponsiveness (AHR), and eosinophilic airway inflammation.
An allergic response was induced via intranasal instillation. The mice were sensitized on days 1, 3, and 5 and challenged on days 12, 13, and 14
The 9-mo-old mice exhibited significantly increased inspiratory capacity and compliance and significantly decreased elastance and resistance in both central airway and small airway/peripheral tissue compared with their younger counterparts.
Between age groups, a significant difference in neutrophilia was seen in HDM-exposed mice, specifically, as 9-mo-old mice displayed higher counts.
EC200RL was significantly decreased in HDM-exposed, 9-mo- old (but not 3-mo-old) mice compared with their age-matched controls. For these older mice, EC200RL most strongly correlated with the number of eosinophils in BALF
Alveolar or pleural inflammation was not significantly different between groups.
All lung sections stained positively for IL-4, IL-13, IL-17, CD4, eotaxin-1, and IFN-g. For all target proteins, lungs of 9-mo-old HDM-exposed mice appeared to stain positively to a greater extent than lungs of all other groups.
One major phenotype presents as a perimenopausal change in females; this female-only study could serve as a unique model for that particular phenotype. Significant differences were observed between the middle-aged and young-adult control mice in all pulmonary function testing measurements, suggesting that there are age-related effects on pulmonary function, even in the absence of an allergen.