Sixty-five years since the New York heat wave: advances in sweat testing for cystic fibrosis

The sweat test remains important as a diagnostic test for cystic fibrosis (CF) and has contributed greatly to our understanding of CF as a disease of epithelial electrolyte transport. The standardization of the sweat test, by Gibson and Cooke [Gibson and Cooke (1959) Pediatrics 1959;23:5], followed observations of excessive dehydration amongst patients with CF and confirmed the utility as a diagnostic test. Quantitative pilocarpine iontophoresis remains the gold standard for sweat induction, but there are a number of collection and analytical methods. The pathophysiology of electrolyte transport in sweat was described by Quinton [Quinton (1983) Nature 1983;301:421-422], and this complemented the developments in genetics that discovered the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial-based electrolyte transport protein. Knowledge of CF has since increased rapidly and further developments in sweat testing include: new collection methods, further standardization of the technique with international recommendations and age related reference intervals. More recently, sweat chloride values have been used as proof of effect for the new drugs that activate CFTR. However, there remain issues with adherence to sweat test guidelines in many countries and there are gaps in our knowledge, including reference intervals for some age groups and stability of sweat samples in transport. Furthermore, modern methods of elemental quantification need to be explored as alternatives to the original analytical methods for sweat electrolyte measurement. The purpose of this review is therefore to describe the development of the sweat test and consider future directions.