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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10459033" target="_blank" >RIV/00064203:_____/23:10459033 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/23:10459033

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SUJeS8t2Sm" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SUJeS8t2Sm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jcf.2023.04.001" target="_blank" >10.1016/j.jcf.2023.04.001</a>

Result language

angličtina

Original language name

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

Original language description

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&lt;0.0001). Delta HE4 predicted a 2.6% mean change in ppFEV1 (AUC: 0.7898 [95% CI 0.6823-0.8972]; P &lt; 0.0001) at a cut-off value of -10.7 pmol/L. Moreover, delta HE4 independently represented the likelihood of being a responder with &gt;= 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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30101 - Human genetics

Project

<a href="/en/project/LM2018132" target="_blank" >LM2018132: The National Center for Medical Genomic</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Cystic Fibrosis

ISSN

1569-1993

e-ISSN

1873-5010

Volume of the periodical

22

Issue of the periodical within the volume

6

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

8

Pages from-to

1085-1092

UT code for WoS article

001129085700001

EID of the result in the Scopus database

2-s2.0-85153208380