Clinical and Laboratory Standards Institute C34—Sweat Testing: Specimen Collection and Quantitative Chloride Analysis describes methods for performing sweat testing for cystic fibrosis diagnosis. Sweat stimulation, collection, and quantitative measurement of sweat chloride are described, along with results evaluation and reporting, QA, and method validation.

CLSI C34-Ed4 replaces the previous edition of the approved guideline, CLSI C34-A3, published in 2009. Several changes were made in this edition, including: 

• Moved procedures for gauze or filter paper collection and analysis to Appendix A because many of these systems are no longer manufactured 

• Moved the procedure for sweat chloride analysis using a chloridometer with individual titration vials and the coiled tubing collector to Appendix B because that chloridometer is no longer manufactured 

• Expanded discussion of sweat testing in infants following a positive newborn screening test 

• Updated reference intervals for sweat chloride concentration CLSI C34 was revised in 2024 under the Limited Revision Process and replaces the 4th edition of the guideline, which was published in 2019. Several changes were made in this edition, including: 

• Updating language on sweat stimulation, specimen collection, analysis, and interpretation 

• Including conditions that may necessitate consultation with a specialist, such as implanted devices, broken or damaged skin, history of epilepsy or seizures, or pregnancy

CLSI C34 provides recommendations for sweat stimulation by pilocarpine iontophoresis (specific precautions are noted), sweat collection in filter paper or gauze (see Appendix A) or in a commercial sweat collector using coiled tubing (see Appendix B), and quantitative chloride measurement. The procedure for sweat chloride (chloride ion [Cl–]) determination using coulometric titration is described. Sweat conductivity screening methods are also mentioned. Sweat chloride test results evaluation, including reference intervals and diagnostic criteria, is described, with an emphasis on sweat chloride testing for newborn cystic fibrosis (CF) screening. Validation studies and QA techniques are discussed, along with analytical and biological error sources. 

The intended users of CLSI C34 are laboratory and clinical personnel responsible for collecting sweat specimens, measuring sweat chloride, and evaluating and reporting sweat test results. 

Procedures for gauze or filter paper collection and analysis, which are less often performed, are located in Appendix A because many of these systems are no longer manufactured. Other methods for measuring sweat electrolytes after pilocarpine iontophoresis exist but are not included in CLSI C34. Some of these methods have significant documented analytical problems, as well as limited diagnostic application.