Evaluating CRMS/CFSPID phenotypes and outcomes: A retrospective study from a large UK cystic fibrosis centre

Abstract

Background: Cystic fibrosis transmembrane conductance regulator metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID) is a designation given following a positive newborn screen for cystic fibrosis (CF) when CF is not excluded but cannot be confirmed. We describe the long-term clinical outcomes of a CRMS/CFSPID cohort.

Methods: A retrospective, single centre study of children with a current or previous diagnosis of CRMS/CFSPID. Study period extended from February 1, 2007 to August 1, 2022. Baseline and longitudinal data were assessed.

Results: 30 children were designated as CRMS/CFSPID between 2007 and 2021. At baseline, 13 CFTR variants were identified, of which F508del and R117H 7T/9T were most common (occurring in 25 and 20 children respectively). Initial mean immunoreactive trypsinogen and sweat chloride were 82.8 mmol/L and 34.3 mmol/L respectively. During longitudinal assessment (n = 27), occurring over a mean duration of 8.5 years, five children progressed to CF at a mean age of 9.5 years. All children were pancreatic sufficient except one who reclassified to CF. Four isolated Pseudomonas aeruginosa and 12 isolated Staphylococcus aureus, of which one and two progressed to CF respectively. All recent Z-scores for weight and spirometry were above -2. Initial mean sweat chloride was higher in those who progressed to CF versus those who did not, although this did not reach statistical significance (38.4 mmol/L versus 32.0 mmol/L respectively, p = 0.105).

Conclusions: Most children with CRMS/CFSPID remained well with a low progression rate to CF. This supports a less intensive medical surveillance approach. Our results highlight the importance of assessment in a dedicated CRMS/CFSPID clinic during adolescence to detect progression to CF after 6 years of age.