Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis

Silvia Gartner
ORCID logo ,
Jordi Roca-Ferrer
,
Paula Fernandez-Alvarez
,
Isabel Lima
,
Sandra Rovira-Amigo
,
Elena García-Arumí
,
Eduardo Tizzano
,
César Picado
* ORCID logo
Version 1 : Received: 4 January 2024 / Approved: 4 January 2024 / Online: 5 January 2024 (09:16:02 CET)

A peer-reviewed article of this Preprint also exists.

Gartner, S.; Roca-Ferrer, J.; Fernandez-Alvarez, P.; Lima, I.; Rovira-Amigo, S.; García-Arumi, E.; Tizzano, E.F.; Picado, C. Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis. J. Clin. Med. 2024, 13, 2050. Gartner, S.; Roca-Ferrer, J.; Fernandez-Alvarez, P.; Lima, I.; Rovira-Amigo, S.; García-Arumi, E.; Tizzano, E.F.; Picado, C. Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis. J. Clin. Med. 2024, 13, 2050.

Abstract

Previous studies found high but very variable levels of tetranor-PGEM and PGD-M (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF), which correlated with the severity of the CF transmembrane receptor (CFTR) genetic alteration. This study aims to assess the potential role of cyclooxygenase (COX)-1 and COX-2 genetic polymorphisms in the variability of PG production, and determine the potential role of PG metabolites as markers of symptoms severity and imaging findings. Thirty healthy subjects and 103 pwCF were included in the study. Clinical and radiological CF severity was evaluated using clinical scoring methods and the extent of bronchiectasis and air trapping were assessed by chest computed tomography (CT). Urine metabolites were measured using liquid chromatography/tandem mass spectrometry. The presence of variants in the COX-1 gen (PTGS1 639 C>A, PTGS1 762+14delA, and COX-2 gen: PTGS2-899G>C (-765G>C) and PTGS2 (8473T>C) were analysed. PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in healthy controls. There were also statistically significant differences between clinically mild and moderate disease and severe disease. Patients with bronchiectasis and/or air trapping had higher PGE-M levels than patients without these complications. The four polymorphisms did not associate with clinical severity, air trapping, bronchiectasis, or urinary PG levels. Taken together, the present study suggests that urinary PG level testing can be used as a biomarker of CF severity. We found no relationship between COX-1 and COX-2 genetic polymorphisms in the variability of PG production.

Keywords

cystic fibrosis; prostaglandin E2; prostaglandin D2; genetic polymorphisms; PTGS1; PTGS2; COX-1; COX-2

Subject

Medicine and Pharmacology, Pediatrics, Perinatology and Child Health

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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