ß-adrenergic sweat test in children with inconclusive cystic fibrosis diagnosis: Do we need new reference ranges?

ABSTRACT

BACKGROUND: Investigating inconclusive cystic fibrosis (CF) diagnosis in children is difficult without advanced cystic fibrosis transmembrane conductance regulator (CFTR) function tests. This study investigated the utility of beta (ß)-adrenergic sweat test to exclude CF in participants with inconclusive diagnosis (CF suspects) in South Africa. METHODS: ß-adrenergic sweat test and sweat chloride tests (SCT) were performed simultaneously in CF suspects and adult controls (healthy, CFTR heterozygotes and CF). Cholinergic and ß-adrenergic induced sweat rate was measured by evaporimetry (transepithelial water loss [TEWL] g H2 O/m2 /h) following intradermal injections. Next-generation sequencing of CFTR was performed in CF suspects. CF diagnosis was defined by genotype. RESULTS: Thirty-seven controls (10 healthy, 14 CF, 13 CFTR heterozygotes) and 32 CF suspects (26 children; 6 adults) were enrolled. Six were excluded from formal analyses due to ß-adrenergic sweat test failure. In adults, evaporimetry was superior to SCT for diagnosis of CF with ß-adrenergiccholinergic ratio TEWL ≤ 0.05 achieving 100% sensitivity and specificity. Twenty-two CF suspect children (age range 3.4-15.6 years) completed ß-adrenergic sweat testing of which none had CF confirmed by genotyping ß-adrenergiccholinergic ratio > 0.05 successfully excluded CF in all but one child who was CFTR heterozygous. Median peak ß-adrenergic TEWL and ß-adrenergiccholinergic ratio in CFTR negative and CFTR heterozygous children was significantly lower than adult controls. CONCLUSION: ß-adrenergic sweat test is more accurate than SCT for excluding CF in children with inconclusive diagnosis. Established reference ranges for ß-adrenergic sweat test may not be suitable for children due to lower ß-adrenergic sweat secretion compared to adults.