The relationship between sweat chloride levels and mortality in cystic fibrosis varies by individual genotype

Abstract

There is significant variability in sweat chloride distribution across CFTR class 2-5 genotypes. The relationship between sweat chloride and mortality varies by genotype with a relatively strong relationship in R117H/F508del patients.

Cystic fibrosis year in review 2018, part 1

“…Only 35 patients were included, so additional study is needed . In patients enrolled in CFF PR, chloride values were found to vary both within and across mutation classes, and to demonstrate a relationship with mortality (except in type 1 mutations) …”

“…13 In patients enrolled in CFF PR, chloride values were found to vary both within and across mutation classes, and to demonstrate a relationship with mortality (except in type 1 mutations). 14 The methodology for sweat testing has been minimally altered since its early discovery and remains the gold standard diagnostic test for CF. With the development of advancing technology and significant use in studies of CFTR modulators, other modalities are being investigated.…”

Devil in the detail of newborn screening for cystic fibrosis

“…However, infants with higher NBS bloodspot IRT have higher sweat chloride concentrations than infants with identical CF genotypes and normal IRT results,16 suggesting that those detected through NBS have a different and potentially more severe phenotype. For individuals with p.Arg117His, increasing sweat chloride concentrations are associated with increased mortality,17 and those infants detected through NBS might be at increased risk of developing significant disease. It is ironic that ivacaftor, currently the most expensive medication for CF, has marketing authorisation for adults with the p.Arg117His mutation.…”

Strategies implemented in Paraguay for the neonatal detection, diagnosis and treatment of people with cystic fibrosis

“…La FQ es autosómica recesiva, causada por mutaciones en el gen que codifica para una proteína de membrana, denominada Regulador de Conductancia Transmembrana de FQ (CFTR, por sus siglas en inglés), para el que se han identificado más de 2.000 (14,15) mutaciones . La función de la proteína CFTR, es actuar como un canal regulador del transporte de cloruro, bicarbonato y agua en una variedad de tejidos (16) epiteliales .…”

“…Aunque se describe que la FQ compromete principalmente a la población caucásica actualmente se reconoce que ningún grupo étnico puede ser (14) considerado exento .…”