Espel JC, et al. - This study was undertaken to assess the genotype-specific link between sweat chloride and mortality in cystic fibrosis. Findings revealed that across CFTR class 2–5 genotypes, sweat chloride distribution significantly varied. Researchers observed that the link between sweat chloride and mortality varied by genotype and they noted a relatively strong relationship in R117H/F508del patients.

Methods

• Researchers analyzed the CFF Patient Registry and included all patients in the registry between 1996 and 2012 with at least one F508del allele.
• They excluded patients without a documented genotype or plausible sweat chloride level.
• Time to mortality during the observation period was the primary outcome.
• Using the 3 most prevalent alleles in each of 5 classes, they assessed 15 genotypes.
• Using Kaplan-Meier curves, log-rank tests, and multivariable Cox PH models, they compared subgroups of sweat chloride.
• In addition, researchers used area under the receiver operating characteristic curves to assess the overall predictive value of sweat chloride on mortality.

Results

• Inclusion criteria was fulfilled by 18,893 subjects.
• Findings demonstrated that across genotypes in patients with class 1 mutations, sweat chloride distribution was similar, but it was significantly different across genotypes in mutation classes 2–5.
• A link between sweat chloride and mortality was exhibited by the R117H/F508del genotype patients (HR: 1.32 for every 10 mmol/L increase in sweat chloride [95% CI 1.12–1.54].
• In addition, data reported significant associations in patients with F508del/F508del, I507del/F508del, G551D/F508del and 2789 + 5G → A/F508del genotypes, though the clinical relevance for these genotypes was not clear.