Advancements in Sweat Testing Techniques for Cystic Fibrosis: From Classical to Novel Methods

ABSTRACT Background Sweat testing remains central to the diagnosis of cystic fibrosis (CF), with the sweat chloride test (SCT) serving as the gold standard since 1959. However, SCT has important limitations, including restricted availability in low‐ and middle‐income countries (LMICs), difficulty obtaining adequate sweat samples in infants, and diagnostically ambiguous intermediate results. Methods This narrative review summarizes established and emerging sweat‐based diagnostic approaches for CF, with a focus on their clinical utility, limitations, and relevance across different healthcare settings. Results SCT remains the reference method for confirming CF, but sweat conductivity has emerged as a practical screening tool, particularly in LMICs, because of its simplicity, low sample requirement, and high sensitivity. Advanced CFTR functional assays, including nasal potential difference and intestinal current measurement, provide sensitive assessment of CFTR dysfunction but are technically demanding and largely restricted to specialized centers. The β‐adrenergic sweat test offers a promising in vivo alternative for evaluating CFTR‐mediated sweat secretion and may help distinguish CF, CFTR‐related disorders, carriers, and unaffected individuals. Emerging technologies, such as wearable sweat sensors, microneedle‐based sweat induction systems, and other noninvasive approaches, may further expand diagnostic possibilities. Conclusion Combining accessible screening tools with functional and emerging sweat‐based methods may improve CF diagnosis, particularly in LMICs and diagnostically challenging cases.