Duodenal Eosinophils and Mast Cells in Functional Dyspepsia: A Systematic Review and Meta-Analysis of Case-Control Studies

Ayesha Shah; Thomas Fairlie; Georgia Brown; Michael P Jones; Guy D Eslick; Kerith Duncanson; Nikhil Thapar; Simon Keely; Natasha Koloski; Mohit Shahi; Marjorie M Walker; Nicholas J Talley; Gerald Holtmann

doi:10.1016/j.cgh.2022.01.014

Duodenal Eosinophils and Mast Cells in Functional Dyspepsia: A Systematic Review and Meta-Analysis of Case-Control Studies

Clin Gastroenterol Hepatol. 2022 Oct;20(10):2229-2242.e29. doi: 10.1016/j.cgh.2022.01.014. Epub 2022 Feb 3.

Authors

Affiliations

¹ Faculty of Medicine, Faculty of Health and Behavioural Sciences, The University of Queensland, Queensland, Australia; Department of Gastroenterology and Hepatology, Queensland, Australia; Department of Anatomical Pathology, Princess Alexandra Hospital, Queensland, Australia.
² School of Medicine and Public Health, Hunter Medical Research Institute, The University of Newcastle, Newcastle, Australia.
³ Department of Psychology, Macquarie University, Sydney, New South Wales, Australia.
⁴ Faculty of Medicine, Faculty of Health and Behavioural Sciences, The University of Queensland, Queensland, Australia; Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Queensland, Australia.
⁵ Faculty of Medicine, Faculty of Health and Behavioural Sciences, The University of Queensland, Queensland, Australia; Department of Gastroenterology and Hepatology, Queensland, Australia; School of Medicine and Public Health, Hunter Medical Research Institute, The University of Newcastle, Newcastle, Australia.
⁶ Faculty of Medicine, Faculty of Health and Behavioural Sciences, The University of Queensland, Queensland, Australia; Department of Anatomical Pathology, Princess Alexandra Hospital, Queensland, Australia.
⁷ Faculty of Medicine, Faculty of Health and Behavioural Sciences, The University of Queensland, Queensland, Australia; Department of Gastroenterology and Hepatology, Queensland, Australia. Electronic address: g.holtmann@uq.edu.au.

PMID: 35123088
DOI: 10.1016/j.cgh.2022.01.014

Abstract

Background & aims: This study explored the link between duodenal eosinophils and mast cells in patients with functional dyspepsia (FD).

Methods: MEDLINE (PubMed) and Embase electronic databases were searched until June 2021 for case-control studies reporting duodenal eosinophils and mast cells in FD. Pooled standardized mean difference (SMD), odds ratio, and 95% CIs of duodenal eosinophils and mast cells in FD patients and controls were calculated, using a random-effects model.

Results: Twenty-two case-control studies with 1108 FD patients and 893 controls were identified. Duodenal eosinophils (SMD, 1.29; 95% CI, 0.85-1.73; P = .0001) and mast cells (SMD, 2.11; 95% CI, 1.14-3.07; P = .0001) were increased in FD patients compared with controls. Substantial heterogeneity was found (I² = 93.61, P = .0001; and I² = 96.69, P = .0001, respectively) and visual inspection of funnel plots confirmed publication bias. Degranulation of duodenal eosinophils was significantly higher in FD patients compared with controls (odds ratio, 3.78; 95% CI, 6.76-4.48; P = .0001), without statistically significant heterogeneity. We conducted a sensitivity analysis for duodenal eosinophils, by including only high-quality studies, and the results remained unchanged (SMD, 1.73; 95% CI, 1.06-2.40; P = .0001), with substantial heterogeneity. Postinfectious FD patients had increased duodenal eosinophils compared with controls (SMD, 3.91; 95% CI, 1.32-6.51; P = .001) and FD patients without any history of infection (SMD, 1.42; 95% CI, 0.88-1.96; P = .001). Helicobacter pylori-negative FD patients had significantly higher duodenal eosinophils compared with controls (SMD, 3.98; 95% CI, 2.13-5.84; P = .0001), with substantial heterogeneity. No significant difference in duodenal eosinophils was seen according to FD subtypes.

Conclusions: This meta-analysis suggests a link between duodenal microinflammation and FD. However, the quality of evidence is very low, largely owing to the unexplained heterogeneity and serious risk of publication bias in all comparative analyses. Thus, causality remains uncertain and further studies are required.

Keywords: Eosinophils; Functional Dyspepsia; Functional Gastrointestinal Disorders; Irritable Bowel Syndrome; Mast Cells; Meta-Analysis; Systematic Review.

Publication types

Meta-Analysis
Review
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Duodenum
Dyspepsia*
Eosinophilia*
Eosinophils
Humans
Mast Cells