Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment
Language English Country Netherlands Media print-electronic
Document type Clinical Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
30268371
DOI
10.1016/j.jcf.2018.08.013
PII: S1569-1993(18)30795-1
Knihovny.cz E-resources
- Keywords
- BMI, Biomarker, Cystic fibrosis, FEV(1), HE4, Ivacaftor, Sweat chloride,
- MeSH
- Chloride Channel Agonists therapeutic use MeSH
- Aminophenols therapeutic use MeSH
- Biomarkers analysis MeSH
- Quinolones therapeutic use MeSH
- Cystic Fibrosis * genetics physiopathology therapy MeSH
- Child MeSH
- Adult MeSH
- Body Mass Index MeSH
- Humans MeSH
- Drug Monitoring methods MeSH
- Mutation MeSH
- Sweat chemistry MeSH
- Cystic Fibrosis Transmembrane Conductance Regulator genetics MeSH
- WAP Four-Disulfide Core Domain Protein 2 analysis MeSH
- Respiratory Function Tests methods MeSH
- Retrospective Studies MeSH
- Forced Expiratory Volume drug effects MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Chloride Channel Agonists MeSH
- Aminophenols MeSH
- Biomarkers MeSH
- Quinolones MeSH
- ivacaftor MeSH Browser
- Cystic Fibrosis Transmembrane Conductance Regulator MeSH
- WAP Four-Disulfide Core Domain Protein 2 MeSH
- WFDC2 protein, human MeSH Browser
BACKGROUND: We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy. METHODS: In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1-6 months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI). RESULTS: After 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r = -0.5376; P < .001 and r = -0.3285; P < .001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β = -0.57, P = .019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581-0.863]; P = .029) were used as classifier, especially in the first 2 months of treatment (0.806 [95% CI 0.665-0.947]; P < .001). CONCLUSIONS: This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.
Cork Adult Cystic Fibrosis Centre Cork University Hospital Cork Ireland
Cystic Fibrosis Foundation Bethesda MD USA
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 Pediatrics University of Washington School of Medicine Seattle WA USA
Department of Preventive Medicine Faculty of Public Health University of Debrecen Debrecen Hungary
QIMR Berghofer Medical Research Institute and The Prince Charles Hospital Brisbane Australia
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