Patients with two identified mutations in the CFTR gene do not usually show normal sweat values in their tests. CF patients show proportionately elevated values for both sodium and chloride electrolytes; with a difference between them, that does not usually exceed 15 mEq/L. In CF, sweat sodium concentration is usually lower than sweat chloride concentration, and the opposite relationship is observed in individuals without CF [18].
In this study, this parameter was used to assess the quality of ST. When comparing the quality of ST with gender, it was observed that the numbers of correct tests were greater in males than females. A possible explanation is the fact that women produce lower sweat volume due to the constitution of their sweat glands. Men have fewer active sweat glands, but higher sweating rate per gland. Women show lower cholinergic and β-adrenergic sweat secretion rates than men [8, 9].
The comparison between the quality and results of ST for CF diagnosis showed a higher number of incorrect tests in the chloride concentration range of 40 to 60 mEq/L, known as borderline range for the ST, as determined by Gibson and Cooke [14]. Some studies approach the need to assess the test results with age-related reference intervals [1, 2, 11, 12, 19]. Patients with clinical CF and chloride levels in ST between 30 and 59 mEq/L may have two mutations in the CFTR gene [12, 20].
Sweat chloride reference value between 30 and 59 mEq/L is associated with borderline range, depending on the individual’s age, and it may possibly include individuals with Transmembrane Conductance Regulator Related Metabolic Syndrome. It is estimated that 8 to 15 % of subjects in this group may receive delayed diagnosis of CF and the initial clinical presentation of CF may be confused with other respiratory diseases [21, 22].
According to the Cystic Fibrosis Foundation, CF is likely to be diagnosed when chloride concentration is greater than or equal to 60 mEq/L in two-sample ST. For infants up to six months of age, CF is very unlikely to be diagnosed when the chloride concentration is equal to or less than 29 mEq/L; as well as for individuals older than six months of age, when chloride concentration is equal to or less than 39 mEq/L. In our study, a greater number of incorrect tests were observed in the age group over 18 years. It appears that sweat chloride peaked in adults over 18 years of age, suggesting that the borderline value of 60 mEq/L to diagnose CF may not be sensitive for all age groups [2]. During the first 24 h after birth, sweat electrolyte values may be transiently elevated in normal infants, followed rapid decline of electrolytes in the first days of life. Moreover, it can be difficult to obtain adequate amount of sweat during the first weeks after birth, especially in preterm infants [23].
The concentration of electrolytes in the sweat increases with age and healthy adults may have chloride levels above 60 mEq/L [24, 25]. Furthermore, at the time of interpretation of ST, it should be considered that some rare CFTR gene may be related to borderline or negative values ST [18, 25].
In addition to CF, some diseases may cause increased concentrations of sweat chloride, and most diseases can be differentiated based on clinical presentations. Some examples include: atopic dermatitis, hypogammaglobulinemia, glycogen storage disease type I, mucopolysaccharidosis type I, nephrogenic diabetes insipidus, pseudohypoaldosteronism, celiac disease, adrenal insufficiency, and untreated hypothyroidism. False positive result may occur in case of malnutrition, dehydration, skin conditions (eczema or rash) and ST technical errors during induction, collection and measure of chloride and sodium concentrations [18, 25].
False negative result is related to the presence of edema, use of mineralocorticoid, collection and analysis of insufficient amount of sweat, and other technical problems [25, 26]. Sweat sample was collected by experienced personnel in accordance with international guidelines and internal quality control procedures, in order to minimize possible methodological errors and misdiagnosis, as some symptoms may resemble those of CF.
There were two limitations to this study. First, this study did not include controls: all subjects were referred to ST due to their clinical manifestations, positive newborn screening results for CF, or family history. Second, it was not possible to confirm a diagnosis of CF for all patients using a genetic study. However, the data including CFTR mutations was included in the present manuscript and showed similar results as the first analysis for all exams performed.