Site of Airflow Obstruction during Early and Late Phase Asthmatic Responses to Allergen Bronchoprovocation

Abstract

Chronic asthma and late asthmatic responses (LAR) are associated with local inflammation which might be expected to produce airflow obstruction in small airways and to increase nonspecific airway reactivity. In contrast, early asthmatic responses (EAR) are primarily bronchospastic and probably involve more central airways. We challenged 17 nonsmoking, mildly asthmatic atopic subjects with allergen bronchoprovocation and measured changes in spirometry (FEV1) over the next 24 hours. Each subject also performed a helium-oxygen (He-O2) flow-volume loop before challenge (baseline), during the EAR, and six hours and 24 hours after challenge to measure the effect of gas density on flow rates at midvital capacity. Twelve subjects had both an EAR and a LAR; five subjects had only a LAR. Of these 17 subjects, 15 were initially density dependent, while only two were density independent. During the EAR, 13 percent of the density dependent population had significant decreases in delta Vmax 50 percent; 47 percent had significant decreases during LAR. The He-O2 flow data analyzed at specified time points after challenge revealed significant decreases in the mean delta Vmax 50 percent at six hours in those who had only a LAR (p less than 0.01). In those who had a dual airway response, density dependence increased during the EAR, but decreased at six and significantly at 24 hours (p less than 0.05) postchallenge. There was a strong trend for the severity of the LAR (measured by changes in FEV1) to be directly related to the total decrease in delta Vmax 50 percent during the LAR. We conclude that late asthmatic responses occur frequently after a single antigenic bronchial challenge and can be associated with persistent symptoms. The LAR were often associated with a decrease in density dependence of maximal expiratory airflow, and therefore, may involve small airways.