Longitudinal determinants of bronchial responsiveness to inhaled histamine

Background and study objective: The point prevalence of bronchial hyperresponsiveness (BHR) is imperfectly associated with current asthma, possibly due to changes over time in bronchial responsiveness (BR). To evaluate cross-sectional and longitudinal determinants of BR, a population sample comprising 408 children and adolescents, aged 7 to 17 years at enrollment, was examined twice, 6 years apart. Methods: Case history was obtained by interview and questionnaire. BR to inhaled histamine, pulmonary function, and skin prick test reactivity were measured using standard techniques. Results: The point prevalence of BHR (the concentration of histamine causing a 20% decline in FEV1 <8 mg/mL) declined from childhood to early adulthood (25% and 6%, respectively; p<0.001); and similarly a decline in histamine dose-response slope was observed. At both surveys, prechallenge FEV1 percent predicted, asthma, and atopy, especially atopy to house dust mite (HDM), were important determinants for the degree of BR. After adjustment for prechallenge FEV1 percent predicted, no male-female difference was observed in degree of BR. Lower FEV1 percent predicted (p=0.003), asthma (p<0.001), higher degree of BR (p=0.003), and atopy to HDM (p=0.007) at enrollment predicted a higher degree of BR at the second survey (degree of BR at second survey adjusted for prechallenge FEV1). Furthermore, new asthma (p<0.001) and/or atopy to HDM (p=0.003) were associated with higher BR at the second survey. Confining the analysis to nonasthmatics showed that subjects with new or persistent atopy to NDM had significantly increased BR compared with nonatopic subjects; and, moreover, prechallenge FEV1 percent predicted was significantly correlated with BR. Conclusions: BR declines from childhood to early adulthood, possibly reflecting the increase in airway caliber. The level of FEV1 and atopy, especially to HDM, are important determinants for changes over time in level of BR, also in nonasthmatic subjects.