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Age and Sex Influences on Airway Hyperresponsiveness

Objective. The precise relationship between age and gender and their influence on airway reactivity has not been clearly defined. Previous studies of age and gender influences on airway reactivity have been confounded by environmental influences such as cigarette smoking. The objective of this study was to examine the effect of age and gender on airway reactivity in C57BL/6 mice housed under controlled conditions, independent of confounding environmental factors. Methods. Mice were separated into four experimental groups based on age and gender: males at 6 and 12 weeks of age and females at 6 and 12 weeks of age. Airway reactivity to inhaled methacholine was examined in each group. Results. Significant differences in methacholine-induced airway reactivity were observed between the sexes at both age groups. At 6 weeks of age, the males demonstrated a significantly increased airway reactivity to methacholine as compared to females (p <.001). Paradoxically, at 12 weeks of age, the males demonstrated a significantly lower response to methacholine as compared to females (p <.001). Hence the relationship between age and airway reactivity is markedly different in males as compared to females. Examination of intragender differences revealed that in female mice, airway reactivity increased significantly with age (p <.001). In contrast, males demonstrated a significant reduction in airway reactivity with age (p <.001). Conclusion. These findings demonstrate important differences in airway reactivity related to age and gender that are observed independent of any environmental influences. Furthermore, these findings highlight the importance of careful age and sex matching in studies of airway reactivity.