Persistent plasma and RBC fatty acid abnormalities in children and adolescents with cystic fibrosis on highly effective CFTR modulators.

BACKGROUND

Essential fatty acid deficiency (EFAD) is a common complication in people with cystic fibrosis (pwCF). While CFTR modulators (CFTRm) have become the standard of care, their effect on EFAD has been minimally explored. This study assesses the impact of CFTRm on fatty acid (FA) profiles in a large cohort of children/adolescents with CF and examines correlations with clinical outcomes.

METHODS

227 blood samples were collected from 163 pwCF (median age: 9.7 years). Most participants were F508del homozygous/compound heterozygous, clinically stable, pancreatic insufficient on enzyme replacement therapy, and receiving CFTRm. FAs were measured by gas chromatography-mass spectrometry.

RESULTS

FA abnormalities in CF were more pronounced in RBCs than in plasma. Low omega-6 linoleic acid (LA) was observed in 4.5 % and 11 % of plasma and RBC samples, respectively. 14.1 % of plasma and 33.9 % of RBC samples had elevated EFAD biomarkers (mead acid (MA) and/or T/T ratio). LA was lower in the participants ≥10 years old. Severe CFTR genotypes were associated with lower LA and higher MA and T/T ratio. In contrast, none of the pwCF with mild genotypes had laboratory findings suggestive of EFAD. There was no improvement in FAs on CFTRm. Elexacaftor/tezacaftor/ivacaftor was no more effective in correcting FA abnormalities than the older generation CFTRm.

CONCLUSION

Despite therapeutic and nutritional advances in CF treatment, EFAD remains prevalent and underrecognized in the CF population. The high risk of developing EFAD in pwCF with severe CFTR genotypes warrants the inclusion of the FA testing as a standard of care of these individuals.