Primary prevention of asthma: age and sex influence sensitivity to allergen-induced airway inflammation and contribute to asthma heterogeneity in Guinea pigs.
BACKGROUND
Limiting allergen exposure in the sensitization phase has been proposed as a means of primary prevention of asthma, but its effectiveness is debated.


OBJECTIVE
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.


CONCLUSIONS
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.
Regal
Jean F
JF
Department of Biochemistry and Molecular Biology, Medical School Duluth, University of Minnesota, Duluth, 55812, USA. jregal@d.umn.edu
Regal
Ronald R
RR
Meehan
Jessica L
JL
Mohrman
Margaret E
ME
D000367:Age Factors; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D004804:Eosinophils / Q000737:chemistry; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000276:immunology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D011322:Primary Prevention; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012737:Sex Factors
D000485:Allergens; D010047:Ovalbumin