On the fetal origin of asthma: Effect of maternal allergen exposure on the airway responses of the guinea pig offspring later in life

Abstract

ON THE AIRWAY RESPONSES OF THE GUINEA PIG OFFSPRING LATER IN LIFE EGLE BYTAUTIENE, YURI VEDERNIKOV, WILLIAM MANER, MONICA LONGO, GARY DV HANKINS, GARLAND D. ANDERSON, GEORGE SAADE, University of Texas Medical Branch, Obstetrics & Gynecology/Maternal Fetal Medicine, Galveston, Texas OBJECTIVE: Epidemiological and experimental studies support a fetal origin for cardiovascular adult diseases. The familial and epidemiological characteristics of asthma may also be explained by a fetal origin. Our objective was to determine the effect of maternal exposure to allergens on the airway responses of offspring later in life using a well-characterized animal model for asthma research. STUDY DESIGN: 3 months old guinea pig offspring born to ovalbuminsensitized and nonsensitized mothers were tested for sensitivity to ovalbumin by intracutaneous injections. They were then anesthetized and ventilated via an endotracheal cannula connected to an ultrasonic nebulizer for antigen delivery, and to a transducer for measurement of pressure at the airway opening (PAO). After obtaining basal PAO, ovalbumin was nebulized for 1 min. After stabilization, ovalbumin was nebulized again after pretreatment with ketotifen (histamine H1 receptor antagonist). PAO was expressed as a percent change from basal PAO. Bronchoalveolar fluid (BALF) was collected 3 hours after first exposure to ovalbumin and eosinophil count was obtained. Student t test was used for analysis (significance: p!0.05). RESULTS: Skin thickening and erythema at the site of ovalbumin injection developed in all the offspring born to sensitized mothers, indicating an acute hypersensitivity reaction to antigen, but in none of the offspring of nonsensitized mothers. Exposure to aerosolized ovalbumin significantly increased PAO in the offspring born to sensitized mothers, indicating bronchoconstriction, and this response was completely abolished by ketotifen. Ovalbumin and ketotifen had no effect in pups of nonsensitized mothers. The number of eosinophils was significantly increased in BALF from offspring born to sensitized mothers compared with offspring born to non-sensitized mothers. CONCLUSION: Maternal exposure to allergen programs the fetus for hypersensitivity reaction to the same allergen later in life. Adult conditions related to environmental exposure to allergens, such as asthma, may have a fetal origin. SMFM Abstracts S175