Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study

Abstract

Background 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). Methods 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 to 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. Results 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. Conclusions 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.

Impact of omega‐3 supplementation on children and adolescents patients with cystic fibrosis: A systematic review and meta‐analysis of randomized‐controlled trials

“…For the reasons listed above, 14 of the investigations were dropped. Finally, the quantitative meta‐analysis contained 12 trials with 13 treatment arms that satisfied the qualifying requirements 6,8,17–26 …”

The fatty acid imbalance of cystic fibrosis exists at birth independent of feeding in pig and ferret models

“…Note that none of these mechanisms are mutually exclusive, and any combination might contribute to the fatty acid abnormalities in CF. Oral supplementation with docosahexaenoic acid or linoleic acid raises plasma concentrations in CF patients [95,96]. Linoleic acid supplementation restores normal growth to children with CF whereas provision of excess calories alone is not sufficient [96][97][98].…”

Low linoleic and high docosahexaenoic acids in a severe phenotype of transgenic cystic fibrosis mice

“…One possible explanation to this discrepancy might be if AA is excessively liberated from membranes 16 and transformed to eicosanoids. 21,49,50 A compensatory upregulation of the enzyme systems would also increase transformation to DHA, which is considered more efficient in rodents than in humans. 51 The difference in DHA with time between male and female is in agreement with the well-known increased capacity of female to synthesize DHA.…”