Variable reduction in beta-adrenergic sweat secretion in cystic fibrosis heterozygotes.

Abstract

Because patients with cystic fibrosis (CF) consistently lack sweating response to isoproterenol (ISO) in vivo and in vitro, we studied to what extent beta-adrenergic defect is expressed in CF heterozygotes. To improve the sensitivity and accuracy of determining the sweating response to intradermal ISO (also containing theophylline and atropine), a water vapor analyzer was used, and the peak sweat rates attained after intradermal injection in the forearm of optimal concentrations of ISO and methacholine (MCH) were determined. The peak ISO sweat rate was further normalized by the peak MCH sweat rate in each individual and expressed as the relative ISO sweat ratemax (in percent). The relative ISO sweat ratemax was determined independent of age and sex and was unchanged after brief acclimatization. The mean relative ISO sweat ratemax of CF heterozygotes was significantly lower than that of controls (10.1% vs 19.5%); however, 21 of the 54 CF heterozygotes overlapped with controls, and the remainder of the CF heterozygotes fell below the arbitrary demarcation line drawn at the relative sweat rate of around 10%. Thus, although the ISO sweat test may not be a practical discrimination test for CF heterozygotes, knowledge of the diversity of beta-adrenergic sweating responses in CF heterozygotes will provide a useful data base for further understanding the possible linkage (or its absence) between the abnormal CF gene(s) (which may be identified by molecular biologists in the near future) and the abnormal intracellular process(es) that takes place during beta-adrenergic stimulation of the CF eccrine sweat gland.