B-204 Continued Reduction in Sweat Chloride Concentrations in an Elderly Cystic Fibrosis Patient

Background Cystic fibrosis (CF) is the result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes for the CFTR chloride ion channel. As a result, there is reduced chloride reabsorption into cells causing mucous impaction in the lungs and elevated chloride concentrations in sweat. Sweat chloride testing is a common diagnostic tool for CF. Here, we report a case where decreased sweat chloride concentrations were observed continuously with an investigation of the cause. Methods The sweat samples of a 74-year-old female patient were collected after iontophoresis using the Macroduct collector, and sweat chloride concentrations were measured using coulombic titration with a ChloroChek Chloridometer. The first sweat chloride measurements were made on 10/17/2023. Then, measurements were made on 11/9/2024 and 12/17/2024. Results The first (and repeat) testing on 10/17/2023, 11/9/2024, and 12/17/2024 yielded sweat chloride concentrations of 45 (50), 34 (34), and 24 (24) mM, respectively. Chart review revealed c.3846G>A (W1282X) and c.1210-11T>G (5T-12TG) mutations on the CTFR gene tested in an outside hospital. The patient started Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy, a CFTR protein modulator therapy, allowing for better chloride ion transport on 10/18/2024. After ETI treatment, the patient’s sweat chloride concentrations were decreased from 45 (50) mM to 34 (34) mM within 1 month, and to 24 (24) mM within 2 months. The patient also experienced a reduction in coughing, sputum purulence, chest pain, and oxygen dependency. Furthermore, the patient experienced increased energy and tolerance to exercise, but lung infections were still present. Conclusion Our investigation indicates that the patient’s gradual decrease in sweat chloride concentration is due to ETI therapy. Clinical laboratorians should be aware that the uncommon late onset of cystic fibrosis can happen and be treated in elderly patients without an early diagnosis. For these patients, an investigation is needed to determine whether the inconsistent sweat chloride concentrations during serial testing are the results of therapy.