Persistent plasma and RBC fatty acid abnormalities in children and adolescents with cystic fibrosis on highly
Tatiana Yuzyuk1, Catherine M McDonald2, Kayode Balogun3
1Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA; ARUP Institute of Clinical & Experimental Pathology, Salt Lake City, UT, USA.
Insights
Essential fatty acid deficiency (EFAD) remains common in cystic fibrosis (CF) patients despite CFTR modulator (CFTRm) therapy. Testing for EFAD is recommended, especially for those with severe CFTR genotypes, as current treatments do not improve fatty acid profiles.
Area of Science:
- Biochemistry
- Clinical Nutrition
- Pediatric Pulmonology
Background:
- Essential fatty acid deficiency (EFAD) is a frequent complication in people with cystic fibrosis (pwCF).
- The impact of CFTR modulators (CFTRm) on EFAD in pwCF is not well understood.
- This study investigates CFTRm's effect on fatty acid (FA) profiles and clinical outcomes in children and adolescents with CF.
Purpose of the Study:
- To assess the impact of CFTR modulators on fatty acid profiles in a large cohort of children and adolescents with cystic fibrosis.
- To examine correlations between fatty acid profiles and clinical outcomes in this population.
- To determine if CFTR modulators improve fatty acid abnormalities in pwCF.
Main Methods:
- Collected 227 blood samples from 163 pwCF (median age: 9.7 years).
- Participants were mostly F508del homozygous/compound heterozygous, clinically stable, pancreatic insufficient, and on enzyme replacement therapy and CFTRm.
- Measured fatty acids using gas chromatography-mass spectrometry.
Main Results:
- FA abnormalities were more pronounced in red blood cells (RBCs) than plasma.
- 14.1% of plasma and 33.9% of RBC samples showed elevated EFAD biomarkers (mead acid and/or T/T ratio).
- Severe CFTR genotypes correlated with lower linoleic acid (LA) and higher EFAD biomarkers; no EFAD was seen in mild genotypes. CFTR modulators did not improve FA profiles.
Conclusions:
- EFAD is prevalent and underrecognized in the CF population, despite advances in treatment and nutrition.
- Individuals with severe CFTR genotypes have a high risk of EFAD.
- Routine FA testing should be considered for pwCF, particularly those with severe CFTR genotypes.
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.
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