Search

The sweat test has been used for more than 50 years for the diagnosis of cystic fibrosis (CF) and remains an important diagnostic test in the genomic era. The currently used reference intervals for sweat electrolytes are applied to all patients regardless of age or sex. We performed a systematic review to summarise the studies with published reference values of sweat electrolyte concentrations for the diagnosis of CF. The MEDLINE (from 1950), EMBASE (from 1980) and PubMed (from 1950) databases were searched for English language studies. An abstract was also found by hand-searching. The search generated 1136 articles that matched the search key terms. Of these, 17 studies that contained data on sweat electrolyte concentrations were included in the analysis. Among these, seven studies did not perform the sweat test in accordance with current international and Australian guidelines. Of the ten remaining studies, four reported both the sweat sodium and chloride concentrations and six reported sweat chloride concentration only. A major limitation of these studies was the subject selection. Most recruited patients with various medical conditions including respiratory diseases or undefined recruitment criteria, whilst some did not report the subjects' age and some had small subject numbers. Only one study performed mutation analysis to determine carrier status. No study used appropriate statistical analysis to develop a sweat chloride reference interval. The literature review yielded no studies that reliably developed reference intervals for sweat electrolyte concentrations. The limitations of the studies highlight the need for reliable age-related reference intervals for sweat electrolyte concentrations in healthy subjects.

Cystic fibrosis (CF) is the most common inherited disorder of childhood. The diagnosis of CF has traditionally been based on clinical features with confirmatory evidence by sweat electrolyte analysis. Since 1989 it has been possible to also use gene mutation analysis to aid the diagnosis. Cloning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has advanced our understanding of CF, in particular the molecular basis of an expanded CF phenotype. However, because there are over 1000 mutations and 200 polymorphisms, many without recognised effects on CFTR, the molecular diagnosis can be troublesome. This has necessitated measurement of CFTR function with renewed interest in the sweat test. This review provides an overview of the clinical features of CF, the diagnosis and complex genetics. We provide a detailed discussion of the structure and function of CFTR and the classification of CFTR mutations. Sweat electrolyte analysis is discussed, from the physiology of sweating to the rigours of a properly performed sweat test and its interpretation. With this information it is possible to understand the relevance of the sweat test in the genomic era.