Evaluation of New System for β-adrenergic Sweat Test in the Context of Stratification of Patient With Cystic Fibrosis

Cystic fibrosis (CF) is a rare genetic disease affecting 1 baby in 2,850 live births in Belgium and associated with high morbidity and mortality. CF is caused by CFTR mutations resulting in loss-of-function of the CFTR protein. It leads to dramatic abnormalities in transepithelial ion transport and the production of thick mucus obstructing airways and duct lumens of exocrine glands. The gold standard for CF diagnosis is an accurate Gibson and Cooke sweat test which is very sensitive to lost or abrogated CFTR function, but shows a logarithmic relationship between sweat Cl - content and CFTR function: e.g. a 5% residual CFTR function is associated with sweat Cl- concentrations found below the diagnostic threshold (<60 mmol/L). Consequently, diagnosing CF is challenging in borderline cases and/or in the presence of CFTR mutations not recognized as disease-causing (CFTR2 data base; https://cftr2.org/). Contrary to routine sweat test measuring the CFTR-mediated reabsorption of Cl- in the sweat duct, beta-adrenergic sweat secretion test (BAST) measures CFTR mediated secretion of Cl- in the secretory coil of the sweat gland . Sato and Sato discovered in the early 1980s that CFTR-mediated sweat secretion can be stimulated with β-adrenergic agonists if the thermoregulative cholinergic sweat secretion is simultaneously inhibited with atropine . β-adrenergic sweat secretion was absent in people with CF (pwCF) and half-maximal in healthy heterozygous carriers of CFTR mutation (HTZ). Therefore, BAST seems to be a highly sensitive CFTR bioassay suitable for screening of CFTR dysfunction, monitoring the efficacy of new therapeutic interventions and differential diagnosis of exocrine pancreatic sufficient-CF, CFTR-Related disease and cystic fibrosis screen positive and finallyinconclusive diagnosis. BAST detect the relative improvement due to a novel treatment, while at the same time show that the levels did not return to a normal range. The available measurement range can thus be used to assess the individual response to therapeutic interventions, but can also be used to stratify patients in the intermediate range of activity, which fall into a spectrum, ranging from a severe loss of function in classical cystic fibrosis to the cystic fibrosis related disease with a relatively lowered activity.