Eosinophils and mast cells as therapeutic targets in pediatric functional dyspepsia

Friesen, Craig A.; Schurman, Jennifer Verrill; Colombo, Jennifer; Abdel‐Rahman, Susan M.

doi:10.4292/wjgpt.v4.i4.86

Cited by 41 publications

(38 citation statements)

References 114 publications

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“…It is a common diagnosis in children with population prevalence estimates of 3.5% to 27% [1,2] . A number of biologic contributors to the generation of FD have been identified and include inflammation, electromechanical dysfunction (e.g., altered gastric emptying) and visceral hyperalgesia [3,4] . Melatonin, a hormone produced, in part, by the pineal gland, has a well-known role in regulation of sleep-wake cycles through its sleep promoting effects.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of melatonin on pediatric functional dyspepsia: A pilot study

Zybach

Friesen

Schurman

2016

WJGPT

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AIM:To study the effectiveness of melatonin vs placebo in children with functional dyspepsia (FD). METHODS:The study was conducted as a double blind, randomized, placebo controlled crossover trial. Subjects were aged 8-17 years and diagnosed with FD based on Rome Ⅲ criteria. All subjects had failed to respond to 4 wk of acid suppression. Subjects receive a continuous two weeks of placebo and a continuous two weeks of melatonin in an order blinded to the participant and the study team. A Global Clinical Score was obtained to assess changes in abdominal pain. Pain was self-reported to be worse (grade 1), no change (grade 2), moderate improvement (grade 3), good (grade 4; minimal pain and not interfering with daily activities), or excellent (grade 5; no pain), respectively. A positive clinical response was defined as a grade 3 or greater response. Subjects wore an actigraph to assess sleep during a one week baseline period and during each treatment period. Subjects' sleep latency and total sleep time were recorded throughout the duration of the study. RESULTS:Fourteen subjects were enrolled and 12 completed the study. One withdrew prior to starting both melatonin and placebo and the other before starting melatonin. A positive clinical response (grade 3-5) was achieved in 42% of subjects on melatonin vs 50% of subjects on placebo (NS). Effect size was calculated

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Section: Introductionmentioning

confidence: 99%

Therapeutic effect of melatonin on pediatric functional dyspepsia: A pilot study

Zybach

Friesen

Schurman

2016

WJGPT

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“…Anti-inflammatory agents and drugs aimed at decreasing allergic reactions are already being studied in functional dyspepsia. 9,10 Observational studies, while confirming the original observation of duodenal eosinophilia, need to give way to mechanistic studies that help us understand the pathogenesis of duodenal eosinophilia. Future studies will help determine if treating the eosinophilia, much as we treat eosinophilic oesophagitis, or restricting the diet will alleviate dyspeptic symptoms.…”

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confidence: 99%

Editorial: the diminishing returns of normalisation of the oesophageal mucosa

Genta¹

2017

Aliment Pharmacol Ther

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hampered by the lack of correlation between symptom improvement and changes in physiologic measures such as gastric emptying studies.A new direction in functional dyspepsia is the concept that the duodenum may be the source of symptoms. Observational studies show an increased number of eosinophils in duodenal biopsies obtained from adults and children with functional dyspepsia. [2][3][4] Other studies have shown an increase in mast cells in the mucosa and evidence of inflammation in the sub-mucosal nerves and ganglia in the upper gastrointestinal tract. 5An inflammatory reaction may trigger the accumulation of eosinophils in the duodenal mucosa. The trigger may be intrinsic through the brain-gut axis or extrinsic through ingested proteins or bacteria.During the inflammatory process, a number of cytokines are released and activate the eosinophils, which are then ready for degranulation.During the process of degranulation, nerve growth factor is released and may have an effect on the sensory nerves of the upper gastrointestinal tract. Other products of degranulation such as major basic proteins can affect smooth muscle function causing spasm. Studies have shown that children with atopy have duodenal eosinophilia and that challenge with cow's milk protein can generate dyspeptic symptoms. 6 Other studies have shown that inflammation, including eosinophilia, may be seen in patients with Helicobacter pylori infection. 7 The process by which extrinsic factors create duodenal eosinophilic infiltration is uncertain. One plausible postulate is that alterations in mucosal permeability allow food-based antigens and bacterial products exposure to the immune system. What are the implications for future treatments? Anti-inflammatory agents and drugs aimed at decreasing allergic reactions are already being studied in functional dyspepsia. 9,10 Observational studies, while confirming the original observation of duodenal eosinophilia, need to give way to mechanistic studies that help us understand the pathogenesis of duodenal eosinophilia. Future studies will help determine if treating the eosinophilia, much as we treat eosinophilic oesophagitis, or restricting the diet will alleviate dyspeptic symptoms. ACKNOWLEDGEMENTDeclaration of personal interests: Consultant Ironwood Pharmaceuticals.

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“…If this hypothesis is correct, then some patients with functional dyspepsia may have a response to therapy targeted at immune activation, but this remains to be established; however, preliminary data in children suggest that montelukast, a leukotriene-receptor antagonist, reduces symptoms. 49 Tr e atment of Func tiona l Dyspepsi a…”

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confidence: 99%