{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:05:13Z","timestamp":1778133913107,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3 Catalana de Pneumologia (FUCAP)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Previous studies found high but very variable levels of tetranor-PGEM and PGDM (urine metabolites of prostaglandin (PG) E2 and PGD2, respectively) in persons with cystic fibrosis (pwCF). This study aims to assess the role of cyclooxygenase COX-1 and COX-2 genetic polymorphisms in PG production and of PG metabolites as potential markers of symptoms\u2019 severity and imaging findings. Methods: A total of 30 healthy subjects and 103 pwCF were included in this study. Clinical and radiological CF severity was evaluated using clinical scoring methods and chest computed tomography (CT), respectively. Urine metabolites were measured using liquid chromatography\/tandem mass spectrometry. Variants in the COX-1 gene (PTGS1 639 C&gt;A, PTGS1 762+14delA and COX-2 gene: PTGS2-899G&gt;C (-765G&gt;C) and PTGS2 (8473T&gt;C) were also analyzed. Results: PGE-M and PGD-M urine concentrations were significantly higher in pwCF than in 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. Conclusions: These results suggest that urinary PG level testing can be used as a biomarker of CF severity. COX genetic polymorphisms are not involved in the variability of PG production.<\/jats:p>","DOI":"10.3390\/jcm13072050","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T10:58:31Z","timestamp":1712055511000},"page":"2050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8190-5092","authenticated-orcid":false,"given":"Silvia","family":"Gartner","sequence":"first","affiliation":[{"name":"Unidad de Neumolog\u00eda Pedi\u00e1trica y Fibrosis Qu\u00edstica, Hospital Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Roca-Ferrer","sequence":"additional","affiliation":[{"name":"Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaciones en Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2695-3531","authenticated-orcid":false,"given":"Paula","family":"Fernandez-Alvarez","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica Cl\u00ednica y Molecular, Hospital Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Medicina Gen\u00e9tica, Vall d\u2019Hebr\u00f3n Institut de Recerca VHIR, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Lima","sequence":"additional","affiliation":[{"name":"Unidad de Neumolog\u00eda Pedi\u00e1trica y Fibrosis Qu\u00edstica, Hospital Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Rovira-Amigo","sequence":"additional","affiliation":[{"name":"Unidad de Neumolog\u00eda Pedi\u00e1trica y Fibrosis Qu\u00edstica, Hospital Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Garc\u00eda-Arumi","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica Cl\u00ednica y Molecular, Hospital Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Medicina Gen\u00e9tica, Vall d\u2019Hebr\u00f3n Institut de Recerca VHIR, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo F.","family":"Tizzano","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica Cl\u00ednica y Molecular, Hospital Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Medicina Gen\u00e9tica, Vall d\u2019Hebr\u00f3n Institut de Recerca VHIR, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7400-4993","authenticated-orcid":false,"given":"C\u00e9sar","family":"Picado","sequence":"additional","affiliation":[{"name":"Hospital Clinic, Universitat de Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaciones en Red de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"ref_1","unstructured":"(2011, April 25). Available online: http:\/\/www.genet.sickkids.on.ca\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/S2213-2600(16)00023-0","article-title":"Progress in therapies for cystic fibrosis","volume":"4","author":"Amaral","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1053\/j.gastro.2010.09.046","article-title":"Type of CFRT mutations determines risk of pancreatitis in patients with cystic fibrosis","volume":"140","author":"Ooi","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_4","first-page":"1178","article-title":"Genetic determination of exocrine pancreatic function in cystic fibrosis","volume":"50","author":"Kristidis","year":"1992","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1148\/radiol.2533090418","article-title":"Cystic fibrosis genotype and assessing rates of decline in pulmonary status","volume":"253","author":"Cleveland","year":"2009","journal-title":"Radiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1136\/thx.2004.031153","article-title":"Genotype-phenotype correlation for pulmonary function in cystic fibrosis","volume":"60","author":"Mata","year":"2005","journal-title":"Thorax"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1002\/ppul.23217","article-title":"Risk factors for lung function decline in a large cohort of young cystic fibrosis patients","volume":"50","author":"Cogen","year":"2015","journal-title":"Pediatr. Pulmonol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1136\/thx.50.12.1301","article-title":"Genetic and clinical features of patients with cystic fibrosis diagnosed after the age of 16 years","volume":"50","author":"Gran","year":"1995","journal-title":"Thorax"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1183\/09031936.96.09112207","article-title":"Genotype-phenotype relationships in a cohort of adult cystic fibrosis patients","volume":"9","author":"Hubert","year":"1996","journal-title":"Eur. Respir. J."},{"key":"ref_10","first-page":"1006","article-title":"Cystic fibrosis: The delta508 mutation does not lead to an exceptional severe phenotype. A cohort study","volume":"152","author":"Borgo","year":"1993","journal-title":"J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/aje\/kwh083","article-title":"Association between initial disease presentation, lung disease outcomes, and survival in patient with cystic fibrosis","volume":"159","author":"Lai","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000029497","article-title":"Genotype and phenotype in cystic fibrosis","volume":"67","author":"Zielenski","year":"2000","journal-title":"Respiration"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jcf.2015.03.003","article-title":"Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy","volume":"14","author":"Cantin","year":"2015","journal-title":"J. Cyst. Fibros."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jcf.2006.12.001","article-title":"Early inflammation in the airways of the cystic fibrosis foetus","volume":"6","author":"Verhaeghe","year":"2007","journal-title":"J. Cyst. Fibros."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shrestha, N., McCarron, A., Rout-Pitt, N., Donnelley, M., Parsons, D.W., and Hryciw, D.H. (2022). Essential Fatty Acid Deficiency in Cystic Fibrosis Disease Progression: Role of Genotype and Sex. Nutrients, 14.","DOI":"10.3390\/nu14214666"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1056\/NEJMoa021218","article-title":"Association of cystic fibrosis with abnormalities in fatty acid metabolism","volume":"350","author":"Freedman","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.freeradbiomed.2012.05.001","article-title":"Metabolomic profiling of regulatory lipid mediators in sputum from adult cystic fibrosis patients","volume":"53","author":"Yang","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev.biochem.69.1.145","article-title":"Cyclooxygenases: Structural, cellular and molecular biology","volume":"69","author":"Smith","year":"2000","journal-title":"Ann. Rev. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1136\/thx.2004.039842","article-title":"Upregulation of COX-1 and COX-2 in nasal polyps in cystic fibrosis","volume":"61","author":"Pujols","year":"2006","journal-title":"Thorax"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.plefa.2016.08.011","article-title":"Elevated prostaglandin E metabolites and abnormal fatty acids at baseline in pediatric patients: A pilot study","volume":"113","author":"Thomsen","year":"2016","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.plefa.2013.06.001","article-title":"Quantification of major urinary metabolites of PGE2 and PGD2 in cystic fibrosis: Correlation with disease severity","volume":"89","author":"Jabr","year":"2013","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"L816","DOI":"10.1152\/ajplung.00466.2004","article-title":"Impact of CFTR delta508 mutation on prostaglandin E2 production and type IIA phospholipase A2 expression by pulmonary epithelial cells","volume":"289","author":"Medjane","year":"2005","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1002\/jcp.23020","article-title":"CFRT negatively regulates cyclooxygenase-2-PGE2 positive feedback loop in inflammation","volume":"227","author":"Chen","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Borot, F., Vieu, D.V., Faure, G., Fritsch, J., Colas, J., and Moriceau, S. (2009). Eicosanoid Release Is Increased by Membrane Destabilization and CFTR Inhibition in Calu-3 Cells. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007116"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16083","DOI":"10.3390\/ijms150916083","article-title":"Abnormal unsaturated fatty acid metabolism in cystic fibrosis: Biochemical mechanisms and clinical implications","volume":"15","author":"Seegmiller","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1111\/febs.12457","article-title":"CFTR: A hub for kinases and crosstalk of cAMP and Ca2+","volume":"280","author":"Kunzelmann","year":"2013","journal-title":"FEBS J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/BF03208862","article-title":"Prostaglandin-endoperoxide synthase genes COX1 and COX2\u2014Novel modifiers of disease severity in cystic fibrosis patients","volume":"51","author":"Czerska","year":"2010","journal-title":"J. Appl. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1469-1809.2006.00310.x","article-title":"Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry","volume":"71","author":"Alonso","year":"2006","journal-title":"Ann. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/j.1536-4801.1984.tb08613.x","article-title":"Hypothesis revisited. Cystic fibrosis: A disturbance of water and electrolyte movement of exocrine secretory tissue associated with altered prostaglandin (PGE2) metabolism","volume":"3","author":"Anderson","year":"1984","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_30","first-page":"80","article-title":"Progression of lung disease on computed tomography and pulmonary function tests in children and adults with cystic fibrosis","volume":"61","author":"Lindblad","year":"2006","journal-title":"Thorax"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1097\/MCP.0000000000000209","article-title":"Evolution of cystic fibrosis lung function in the early years","volume":"21","author":"Bush","year":"2015","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ejrad.2011.01.114","article-title":"Radiological abnormalities associated with Aspergillus colonization in a cystic fibrosis population","volume":"81","author":"McMahon","year":"2012","journal-title":"Eur. J. Radiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1378\/chest.10-1152","article-title":"Bronchiectasis and pulmonary exacerbations in children and young adults with cystic fibrosis","volume":"140","author":"Loeve","year":"2011","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1136\/thx.2008.110908","article-title":"The spectrum of structural abnormalities on CT scans from patients with CF with severe advanced lung disease","volume":"64","author":"Loeve","year":"2009","journal-title":"Thorax"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1183\/09031936.00137612","article-title":"Impact of bronchiectasis and trapped air on quality of life and exacerbations in cystic fibrosis","volume":"42","author":"Tepper","year":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.jcf.2020.01.010","article-title":"Airway profile of bioactive lipids predicts early progression of lung disease in cystic fibrosis","volume":"19","author":"Horati","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jcf.2016.07.006","article-title":"The effects of ivacaftor on CF fatty acid metabolism: An analysis from the GOAL study","volume":"16","author":"Seegmiller","year":"2017","journal-title":"J. Cyst. Fibros."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2050\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:22:22Z","timestamp":1760106142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,2]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jcm13072050"],"URL":"https:\/\/doi.org\/10.3390\/jcm13072050","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,2]]}}}