Airway response to inhaled methacholine in healthy nonsmoking twins

The variability of maximum expiratory flows is genetically determined, and the airway response to chronic cigarette smoking is also influenced by genetic factors. In nonsmoking nonatopic healthy individuals there is a wide variability of acute airway responses to bronchoactive drugs. The present study was designed to investigate whether this variability might also be genetically determined. We tested this hypothesis by measuring the threshold of airway response to inhaled methacholine using a partial flow-volume curve as the index of response in 10 monozygotic (MZ) and 10 dizygotic (DZ) healthy nonsmoking pairs of twins. Methacholine aerosol was given in doubling doses from number 1 (0.031 mg/ml) to number 11 (32 mg/ml). The mean threshold (+/-SD) for the MZ twins was dose 4.5 +/- 2.4 and for the DZ twins was 7.2 +/- 2.0 (P = 0.0004). No explanation could be found for the difference in mean threshold between MZ and DZ twins. The mean intrapair difference in threshold (+/-SD) for the MZ twins was 2.7 +/- 1.6 doubling doses and for the DZ twins was 2.4 +/- 1.8 (P = 0.7). Slope of dose response to methacholine and intrapair differences were not different between MZ and DZ twins. The present study supports the view that environmental factors are more important than genetic factors in determining the variability of acute airway responsiveness to bronchoactive drugs in healthy nonsmoking individuals.