Thirty Years of Sweat Chloride Testing at One Referral Center

Abstract

ObjectiveTo conduct a descriptive analysis of the sweat test (ST), associating ST results with epidemiological data, CFTR (cystic fibrosis transmembrane conductance regulator) mutations and reasons to indicate the ST, as well as correlating sweat sodium and sweat chloride concentrations in subjects.MethodsRetrospective survey and descriptive analysis of 5,721 ST at a university referral center.ResultsThe inclusion of the subjects was based on clinical data related with cystic fibrosis (CF) phenotype. The samples were grouped by (i) sweat chloride concentrations (mEq/L): <30: 3,249/5,277 (61.6%); ≥30 to <60: 1,326/5,277 (25.1%); ≥60: 702/5,277 (13.3%) and (ii) age: (Group A––GA) 0 to <6 months; (Group B––GB) ≥6 months to <18 years; (Group C––GC) ≥18 years. Digestive symptoms showed higher prevalence ratio for the CF diagnosis as well as association between younger age and higher values of sweat chloride, sweat sodium, and chloride/sodium ratio. The indication of ST due to respiratory symptoms was higher in GB and associated with greater age, lower values of sweat chloride, sweat sodium, and chloride/sodium ratio. There was higher prevalence of ST with sweat chloride levels <30 mEq/L in GB, ≥60 mEq/L in GC, and with borderline level in GB. There was positive correlation between sweat sodium and sweat chloride. Sweat chloride/sweat sodium and sweat sodium–sweat chloride indexes showed association with sex, reason for ST indication, and CFTR mutations. Sex alters some values presented in the ST. The number of ST/year performed before and after the newborn screening implementation was the same; however, we observed a higher number of borderlines values. A wide spectrum of CFTR mutation was found. Severe CFTR mutations and F508del/F508del genotype were associated with highest probability of ST chloride levels ≥60 mEq/L, and the absence of CFTR mutations identified was associated with borderline ST and respiratory symptoms.ConclusionsST data showed wide variability dependent on age, sex, reason for examination indication, CFTR mutations, and weight of the collected sweat sample. Sweat sodium concentration is directly correlated with sweat chloride levels and it could be used as a quality parameter.

Evaluation of continuous constant current and continuous pulsed current in sweat induction for cystic fibrosis diagnosis

“…In the literature, we did not have a consensus regarding the maximum value to sweat weight where we can consider the sweat test as acceptable to CF diagnosis. Also, as previously reported by us and discussed in our present data, we found a negative correlation between sweat weight and concentration of chloride [ 26 ]. In this scenario, we believe that this fact is not important when the final sweat weight is bigger than 75 mg until values around 100 mg, but when we have a highest sweat weight, a major influence in concentration of chloride can be achieved and representing an alteration in the classification of the patient, mainly, in cases, with normal or borderline values in sweat test.…”

“…In our data, a large number of the evaluated individuals had a change in the outcome of the CF diagnosis, considering the increase in sweat weight collected in the sweat test. At the same time, we showed that there is a negative correlation between the chloride ion and the sweat weight, and this fact was observed in the literature [ 26 ], but other studies should be performed to close the idea behind this issue. Thus, the sweat test should be redone even when a sweat value was obtained according to the guidelines (≥ 75 mg) and there was still clinical suspicion and/or positive neonatal screening.…”

Novel, rare and common pathogenic variants in the CFTR gene screened by high-throughput sequencing technology and predicted by in silico tools

“…All patients were attended at the Referral Center of a University Hospital and had equal access to: (i) genetic counseling, (ii) tools for diagnosis and functional analysis of CFTR, (iii) outpatient and therapeutic management, (iv) availability of drugs and (v) psychological support. Sweat tests were performed in outpatient settings 15 . Induction of sweating and sweat collection were performed according to the Gibson-Cooke method (1959) 16 , and chloride concentration was quantified by titrations with mercury nitrate 17–20 .…”

Liver Failure in a Chinese Cystic Fibrosis Child With Homozygous R553X Mutation

“…The patient suffered from bronchiectasis, but no significant change was found in the chest CT between 2014 and 2016. Although we did not obtain results of the sweat test, a previous study identified that several damaging CFTR mutations, including homozygous F508del/F508del mutations, were associated with high sweat chloride levels exceeding 60 mEq/L (36). Therefore, the sweat test is an important tool for CF diagnosis, particularly in the absence of the identification of mutations in the CFTR gene.…”