A simplified cyclic adenosine monophosphate-mediated sweat rate test for quantitative measure of cystic fibrosis transmembrane regulator (CFTR) function

Objective: Sweat production is stimulated by both cholinergic and β-adrenergic pathways in the sweat gland secretory coil. β-Adrenergic pathwav-mediated sweating is absent in cystic fibrosis (CF) because cyclic adenosine monophosphate (cAMP)-mediated chloride transport through the cystic fibrosis transmembrane regulator (CFTR) is disrupted. We report the development of a rapid, reproducible, macroscopic, and quantitative methodology to test the hypothesis that β-adrenergic sweat rate discriminates among 3 different CFTR phenotypes - CE heterozygote CF carriers, and non-CF. Study design: Intradermal injection of a mixture of 50 μmol/L isoproterenol, 5 mmol/L aminophylline (to potentiate the β-adrenergic stimulation), and 140 μmol/L atropine (to block potential cholinergic stimulation) in lactated Ringer's solution was performed in duplicate on one forearm. A single injection of 0.5 mmol/L methacholine to stimulate sweat production by the cholinergic pathway was performed on the other forearm. Sweat rate was determined as the amount of sweat collected on filter paper over 20 minutes. Results and conclusions: Median cAMP-mediated sweat rates were 1.45 mg/20 min (CF, n = 29), 2.55 mg/20 min (CF heterozygote carriers, n = 30), and 3.65 mg/20 min (non-CE n = 30) and were significantly different in all 3 groups (P = .0001, Kruskal-Wallis test). Methacholine-stimulated sweat rates were similar for all 3 groups. The cAMP-mediated sweat rate test may be a useful endpoint for studies of new agents to increase the function of CFTR.