Human epididymis protein 4 (HE4) plasma concentration inversely correlates with the improvement of cystic fibrosis lung disease in p.Phe508del-CFTR homozygous cases treated with the CFTR modulator lumacaftor/ivacaftor combination
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
37087300
DOI
10.1016/j.jcf.2023.04.001
PII: S1569-1993(23)00091-7
Knihovny.cz E-zdroje
- Klíčová slova
- Biomarker, Cystic fibrosis, HE4, Lumacaftor/ivacaftor, Sweat chloride, ppFEV1,
- MeSH
- aktivátory chloridových kanálů terapeutické užití MeSH
- aminofenoly terapeutické užití MeSH
- aminopyridiny terapeutické užití MeSH
- benzodioxoly terapeutické užití MeSH
- cystická fibróza * diagnóza farmakoterapie genetika MeSH
- dítě MeSH
- fixní kombinace léků MeSH
- homozygot MeSH
- lidé MeSH
- mutace MeSH
- protein CFTR genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aktivátory chloridových kanálů MeSH
- aminofenoly MeSH
- aminopyridiny MeSH
- benzodioxoly MeSH
- CFTR protein, human MeSH Prohlížeč
- fixní kombinace léků MeSH
- ivacaftor MeSH Prohlížeč
- lumacaftor MeSH Prohlížeč
- protein CFTR MeSH
BACKGROUND: We previously documented that elevated HE4 plasma concentration decreased in people with CF (pwCF) bearing the p.Gly551Asp-CFTR variant in response to CFTR modulator (CFTRm) ivacaftor (IVA), and this level was inversely correlated with the FEV1% predicted values (ppFEV1). Although the effectiveness of lumacaftor (LUM)/IVA in pwCF homozygous for the p.Phe508del-CFTR variant has been evaluated, plasma biomarkers were not used to monitor treatment efficacy thus far. METHODS: Plasma HE4 concentration was examined in 68 pwCF drawn from the PROSPECT study who were homozygous for the p.Phe508del-CFTR variant before treatment and at 1, 3, 6 and 12 months after administration of LUM/IVA therapy. Plasma HE4 was correlated with ppFEV1 using their absolute and delta values. The discriminatory power of delta HE4 was evaluated for the detection of lung function improvements based on ROC-AUC analysis and multiple regression test. RESULTS: HE4 plasma concentration was significantly reduced below baseline following LUM/IVA administration during the entire study period. The mean change of ppFEV1 was 2.6% (95% CI, 0.6 to 4.5) by 6 months of therapy in this sub-cohort. A significant inverse correlation between delta values of HE4 and ppFEV1 was observed especially in children with CF (r=-0.7053; p<0.0001). Delta HE4 predicted a 2.6% mean change in ppFEV1 (AUC: 0.7898 [95% CI 0.6823-0.8972]; P < 0.0001) at a cut-off value of -10.7 pmol/L. Moreover, delta HE4 independently represented the likelihood of being a responder with ≥ 5% delta ppFEV1 at 6 months (OR: 0.89, 95% CI: 0.82-0.95; P = 0.001). CONCLUSIONS: Plasma HE4 level negatively correlates with lung function improvement assessed by ppFEV1 in pwCF undergoing LUM/IVA CFTRm treatment.
Department of Laboratory Medicine Faculty of Medicine University of Debrecen Debrecen Hungary
Department of Pediatrics Faculty of Medicine University of Debrecen Debrecen Hungary
Department of Preventive Medicine Faculty of Public Health University of Debrecen Debrecen Hungary
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