title: Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.
abstract: Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA).
  
  
  
  This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites.
  
  
  
  Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo.
  
  
  
  Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation.
authors.affiliation: Department of Pediatrics, Division of Pediatric Pulmonary, Allergy, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States. Electronic address: michael.g.oconnor@vanderbilt.edu.
authors.forename: Michael Glenn
authors.initials: MG
authors.lastname: O'Connor
authors.affiliation: Department of Pediatrics, Division of Pediatric Gastroenterology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Kelly
authors.initials: K
authors.lastname: Thomsen
authors.affiliation: Department of Pediatrics, Division of Pediatric Pulmonary, Allergy, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Rebekah F
authors.initials: RF
authors.lastname: Brown
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TN, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Laposata
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Seegmiller
mesh_terms: D000293:Adolescent; D016718:Arachidonic Acid / Q000097:blood; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000097:blood / Q000178:diet therapy* / Q000652:urine; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D006801:Humans; D019787:Linoleic Acid / Q000097:blood; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D011453:Prostaglandins / Q000652:urine*; D016896:Treatment Outcome
chemical_list: D005227:Fatty Acids; D011453:Prostaglandins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C060526:7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid; D019787:Linoleic Acid
keywords: Cystic fibrosis; DHA; Fatty acids; Prostaglandin E