Topical eye treatment with p-blocker abolishes sweat secretion triggered by intradermal isoprenaline plus aminophylline: a clinical observation

Abstract

Objectives: Two new versions of the sweat test have recently been developed with claimed advantages of being sensitive enough to quantify residual CFTR function and to measure efficacy of basic therapies. Methods: Rates of water evaporation (kg water/hr/m2 ) and of volume of sweat per gland (nL/min) were measured in a healthy female, 61 yrs, following the reported test protocols. Results: Cholinergic stimulation gave normal results (maximal evaporimetric response 5 min after intradermal injection of carbachol: 95.1 kg water/hr/m2 and gland secretion rate obtained 10 min after methacholine injection: 1.8 nL/min). However, the β-adrenergic (isoprenaline plus aminophylline) stimulation, induced in the presence of atropine to block cholinergic stimulation, was abolished (β-adrenergic/cholinergic ratio: 0 and 5.8% of the normal values for evaporimetry and bubble test, respectively), eliciting a diagnosis of CF. The results were confirmed by repeating each test at least twice. Sweat chloride after pilocarpine iontophoresis using a coulometric method was 24 mmol/L. PCR-based screening showed no CFTR mutation. History of current medications possibly interfering with the pharmacological agents used during the tests revealed long-term (>12 yrs) treatment of a well-controlled primary angle closure glaucoma consisting on a daily topical use of β-blocker carteol 2% (1 drop/left eye). No apparent symptom of β-blocker intoxication is present (heart rate: 66 beats/min, regular sinus rhythm, no symptom of asthma). Conclusion: Much attention should be paid to the use of medications that may interfere with the pharmacological steps of the β-secretion tests. The clinical observation confirms the proof-of-concept that the second phase of both tests directly evaluates β-adrenergic sweat production that is very sensitive to β-blocker treatment, even at topical eye use, leading to false positive test results