Background: Limiting allergen exposure in the sensitization phase has been proposed as a means of primary prevention of asthma, but its effectiveness is debated. Hypothesis: Primary prevention of asthma is more effective in limiting asthma symptoms in young guinea pigs compared with adults, whether males or females. Methods: The following experimental groups were used: young/young, sensitized and challenged before sexual maturity; young/adult, sensitized young and challenged after sexual maturity; adult/adult, sensitized and challenged after sexual maturity. Males and females were sensitized intraperitoneally with varying doses of ovalbumin (OVA) and challenged intratracheally with a constant OVA dose. Cellular infiltration into lung and lavage fluid as well as airway hyperresponsiveness to intravenous methacholine was determined 24 h later. Results: In unsensitized animals, density of resident inflammatory cells as well as baseline pulmonary function differed with age and sex. Maximum OVA-induced eosinophilia in females occurred at a lower sensitizing dose of OVA than in males, and the slopes of the dose-response relationship differed significantly between sexes. Young females had more pronounced increases in eosinophils compared with some adult treatment groups. The concentrations of OVA-specific antibodies were not directly related to differences in cellular infiltration. Airway hyperresponsiveness to methacholine challenge was observed in all treatment groups. Conclusion: Young animals require major reductions in allergen exposure compared with adults to effectively limit airway inflammation in primary prevention. Heterogeneity of asthma symptoms seen with age and sex suggests that primary prevention by limiting allergen exposure or treatment with anti-inflammatory or bronchodilator drugs may be more effective strategies for specific age and gender populations.

Previous studies in a guinea pig model of asthma have suggested that age and sex contribute both to the profile of asthma symptoms, i.e., asthma heterogeneity, as well as to the success of primary prevention strategies. The present study investigated the contributions of age and sex to the severity of central vs. peripheral airway hyperresponsiveness as well as to the effectiveness of secondary preventions strategies for asthma as modeled in the guinea pig. Experimental groups: Young/Young, sensitized and challenged before sexual maturity; Young/Adult, sensitized young and challenged after sexual maturity; Adult/Adult, sensitized and challenged after sexual maturity. Males and females were sensitized IP with 0.5 mg/kg ovalbumin (OVA) and challenged intratracheally with varying doses of OVA. Cellular infiltration into lung and lavage fluid, OVA specific IgG 1 as well as airway hyperresponsiveness to intravenous methacholine were determined 24 hr later. Airway hyperresponsiveness in central airways and peripheral lung was assessed by measurement of airway resistance, tissue damping and tissue elastance. Airway hyperresponsiveness with allergen sensitization and challenge was evident in male and female Adult/Adult animals and male Young/Young animals. Airway hyperresponsiveness in female Young/Young animals was not significant, despite marked airway eosinophilia. Changes in tissue elastance were more evident in OVA treated Adult/Adult compared to Young/Young animals. As allergen exposure decreased, a reduction in inflammation was seen in young females before other age sex groups. OVA induced increases in eosinophils were more pronounced in Young/Adult compared to Adult/Adult animals. Our results suggest that in asthmatic children, females may clinically Received 21 August 2006; accepted 27 October 2006. Address correspondence to Jean F. Regal, Department of Biochemistry and Molecular Biology, Medical School Duluth, University of Minnesota, 1035 University Dr., Duluth, Minnesota 55812, USA; e-mail: jregal@d.umn.edu benefit most from secondary prevention strategies to limit allergen exposure. In adult asthmatics, changes in tissue elastance may be significant, and secondary prevention strategies may be more effective in those sensitized as children compared to those sensitized as adults.