Genetic Factors in Nonspecific Bronchial Hyperreactivity

We tested bronchial reactivity to carbachol in 50 asthmatics, healthy parents of 40 asthmatic children, and 70 healthy subjects with no personal or family history of asthma. Stepped doses of carbachol (0.1%) aerosol were given until a 50% drop in forced expiratory flow rate from 25% to 75% was observed, or until the subject had inhaled 80 of his or her own vital-capacity equivalent volumes of the aerosol. The area under the dose-response curve was computed. Histograms of the carbachol reactivity showed a bimodal distribution: 10% of normal subjects and 50% of nonasthmatic parents had values in the asthmatic range. In 85% of parent couples at least one of the two parents had bronchial reactivity without being asthmatic. Our findings suggest that bronchial reactivity to a cholinergic bronchoconstrictor indicates an autosomal-dominant pattern of inheritance.