Duodenal eosinophilia and early satiety in functional dyspepsia: Confirmation of a positive association in an <scp>A</scp>ustralian cohort

Walker, Marjorie M.; Aggarwal, K.; Shim, Lisa; Bassan, Milan S.; Kalantar, Jamshid S.; Weltman, Martin; Jones, Michael; Powell, Nick; Talley, Nicholas J.

doi:10.1111/jgh.12419

Cited by 145 publications

(153 citation statements)

References 45 publications

(99 reference statements)

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“…1) were increased in patients with functional dyspepsia and correlated with symptom intensity and impaired gastric emptying, suggesting that gastric disturbances in functional dyspepsia could, in fact, be secondary to duodenal inflammation 94 . Together with data of increased duodenal eosinophilia 90,91,95,96 , these studies have demonstrated that low-grade mucosal inflammation plays a key part in the pathogenesis of functional dyspepsia. Increased CD4 + T helper 2 (T H 2) cell response is a potent producer of key cytokines (IL-4, IL-5 and IL-13) that are involved in recruiting and activating eosinophils and mast cells 97 .…”

Section: Gastroduodenal Inflammationmentioning

confidence: 63%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

253

247

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| Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation. NATURE REVIEWS | DISEASE PRIMERS VOLUME 3 | ARTICLE NUMBER 17081 | 1 PRIMER © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .standard therapy for gastro -oesophageal reflux disease. Paediatric dyspeptic symptoms are being addressed in a separate classification effort 10 . This Primer covers functional dyspepsia in adults only, although we sporadically refer to paediatric functional dyspepsia when similarities exist. EpidemiologyThe population prevalence of functional dyspepsia is quite variable across the globe, with overall high numbers (10-40%) in Western countries and low numbers (5-30%) in Asia, independent of the respective functional dyspepsia definitions 11 . A large-scale health and nutrition survey from France 12 (which involved >35,000 people) identified that 15% of individuals had suspected functional dyspepsia, 28% had irritable bowel syndrome (IBS) and 6% had both. The population of patients who are affected by both IBS and functional dyspepsia has been reported to range between 10% and 27% in previous studies 13 and to approach 30% in popu lation samples; it could be even higher in specific populations 14,15 . This observation has given rise to the term 'overlap syndrome' (REF. 13), which calls into question the sensitivity and specificity of the Rome criteria, at least for IBS and functional dyspepsia. This argument is also supported by the observation that patients with functional dyspepsia m...

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Section: Gastroduodenal Inflammationmentioning

confidence: 63%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

253

247

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show abstract

“…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. …”

mentioning

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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“…S1 in the Supplementary Appendix). [36][37][38] Duodenal eosinophilia has been linked to smoking and to symptoms of early satiety and pain; barrier disruption and increased duodenal permeability have been documented. 36,39 In some cases, mast cells that can recruit eosinophils have also been observed in functional dyspepsia, but the patient population that was studied included patients with both functional dyspepsia and the irritable bowel syndrome.…”

mentioning

confidence: 99%

“…[36][37][38] Duodenal eosinophilia has been linked to smoking and to symptoms of early satiety and pain; barrier disruption and increased duodenal permeability have been documented. 36,39 In some cases, mast cells that can recruit eosinophils have also been observed in functional dyspepsia, but the patient population that was studied included patients with both functional dyspepsia and the irritable bowel syndrome. 39 Further evidence linking intestinal inflammation to functional dyspepsia is provided by the finding of enhanced small-bowel homing T lymphocytes that are positive for both α 4 β 7 integrin and chemokine receptor 9 in patients with functional dyspepsia -a finding that has been significantly associated with the release of cytokines (including tumor necrosis factor α), a greater severity of symptoms, and delayed gastric emptying, 40 thus implicating the duodenum in gastric disorders.…”

mentioning

confidence: 99%