Skip to main content
Top
Published in: Digestive Diseases and Sciences 10/2021

01-10-2021 | Eosinophilia | Original Article

Functional Dyspepsia and Duodenal Eosinophil Count and Degranulation: A Multiethnic US Veteran Cohort Study

Authors: M. Ellionore Järbrink-Sehgal, Jordan Sparkman, Alexander Damron, Marjorie M. Walker, Linda K. Green, Daniel G. Rosen, David Y. Graham, Hashem E. El-Serag

Published in: Digestive Diseases and Sciences | Issue 10/2021

Login to get access

Abstract

Background

Duodenal eosinophilia may play a role in functional dyspepsia (FD), but existing study results are conflicted. We investigated the association between duodenal eosinophils (count and degranulation) and FD symptoms, accounting for atopic conditions, medications, and seasonal variations.

Methods

In a cross-sectional study conducted in the Michael E. DeBakey VA Medical Center in Houston, Texas, we analyzed duodenal histopathology of 436 patient samples from a prospective cohort with a validated symptom survey data and chart reviews. FD was defined using Rome II symptom criteria. Eosinophil count was number per 5 high-power fields (HPF), and eosinophil degranulation was eosinophilic granules in the stroma both determined by two independent investigators.

Results

The study cohort was predominantly male (87.4%) with a mean age of 59.3 (standard deviation (SD) ± 9.8). Mean and median eosinophil counts were 75.5 (± 47.8) and 63 (IQR: 43, 101) per five HPF, respectively. Duodenal eosinophilia (defined as ≥ 63 per 5 HPF) and eosinophil degranulation were present in 50.5% and 23.1% of patient samples, respectively. FD was observed in 178 patients (41.7%), but neither the mean eosinophil count nor duodenal eosinophilia was associated with FD. Eosinophil degranulation was independently associated with FD overall (OR 1.74; 95% CI 1.08, 2.78; p = 0.02) and early satiety (OR 2.04; 95% CI 1.26, 3.30; p = 0.004).

Conclusions

In this large, ethnically diverse cohort of adult patients, we found no significant association between duodenal eosinophilia and FD. However, the presence of duodenal eosinophilic degranulation, an activated eosinophil marker, was significantly associated with FD, especially early satiety.
Appendix
Available only for authorised users
Literature
1.
go back to reference El-Serag HB, Talley NJ. Systemic review: the prevalence and clinical course of functional dyspepsia. Aliment Pharmacol Ther. 2004;19:643–654.CrossRef El-Serag HB, Talley NJ. Systemic review: the prevalence and clinical course of functional dyspepsia. Aliment Pharmacol Ther. 2004;19:643–654.CrossRef
2.
go back to reference Camilleri M, Dubois D, Coulie B, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US upper gastrointestinal study. Clin Gastroenterol Hepatol. 2005;3:543–552.CrossRef Camilleri M, Dubois D, Coulie B, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US upper gastrointestinal study. Clin Gastroenterol Hepatol. 2005;3:543–552.CrossRef
3.
go back to reference Dominitz JA, Provenzale D. Prevalence of dyspepsia, heartburn, and peptic ulcer disease in veterans. Am J Gastroenterol. 1999;94:2086–2093.CrossRef Dominitz JA, Provenzale D. Prevalence of dyspepsia, heartburn, and peptic ulcer disease in veterans. Am J Gastroenterol. 1999;94:2086–2093.CrossRef
4.
go back to reference El-Serag HB, Talley NJ. Health-related quality of life in functional dyspepsia. Aliment Pharmacol Ther. 2003;18:387–393.CrossRef El-Serag HB, Talley NJ. Health-related quality of life in functional dyspepsia. Aliment Pharmacol Ther. 2003;18:387–393.CrossRef
5.
go back to reference Talley NJ, Ford AC. Functional dyspepsia. N Engl J Med. 2015;373:1853–1863.CrossRef Talley NJ, Ford AC. Functional dyspepsia. N Engl J Med. 2015;373:1853–1863.CrossRef
6.
go back to reference Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003;98:783–788.CrossRef Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003;98:783–788.CrossRef
7.
go back to reference Talley NJ, Walker MM, Aro P, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin Gastroenterol Hepatol. 2007;5:1175–1183.CrossRef Talley NJ, Walker MM, Aro P, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin Gastroenterol Hepatol. 2007;5:1175–1183.CrossRef
8.
go back to reference Walker MM, Salehian SS, Murray CE, et al. Implications of eosinophilia in the normal duodenal biopsy-an association with allergy and functional dyspepsia. Aliment Pharmacol Ther. 2010;31:1229–1236.CrossRef Walker MM, Salehian SS, Murray CE, et al. Implications of eosinophilia in the normal duodenal biopsy-an association with allergy and functional dyspepsia. Aliment Pharmacol Ther. 2010;31:1229–1236.CrossRef
9.
go back to reference Walker MM, Aggarwal KR, Shim LS, et al. Duodenal eosinophilia and early satiety in functional dyspepsia: confirmation of a positive association in an Australian cohort. J Gastroenterol Hepatol. 2014;29:474–479.CrossRef Walker MM, Aggarwal KR, Shim LS, et al. Duodenal eosinophilia and early satiety in functional dyspepsia: confirmation of a positive association in an Australian cohort. J Gastroenterol Hepatol. 2014;29:474–479.CrossRef
10.
go back to reference Wang X, Li X, Ge W, et al. Quantitative evaluation of duodenal eosinophils and mast cells in adult patients with functional dyspepsia. Ann Diagn Pathol. 2015;19:50–56.CrossRef Wang X, Li X, Ge W, et al. Quantitative evaluation of duodenal eosinophils and mast cells in adult patients with functional dyspepsia. Ann Diagn Pathol. 2015;19:50–56.CrossRef
11.
go back to reference Genta RM, Sonnenberg A, Turner K. Quantification of the duodenal eosinophil content in adults: a necessary step for an evidence-based diagnosis of duodenal eosinophilia. Aliment Pharmacol Ther. 2018;47:1143–1150.CrossRef Genta RM, Sonnenberg A, Turner K. Quantification of the duodenal eosinophil content in adults: a necessary step for an evidence-based diagnosis of duodenal eosinophilia. Aliment Pharmacol Ther. 2018;47:1143–1150.CrossRef
12.
go back to reference Futagami S, Shindo T, Kawagoe T, et al. Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am J Gastroenterol. 2010;105:1835–1842.CrossRef Futagami S, Shindo T, Kawagoe T, et al. Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am J Gastroenterol. 2010;105:1835–1842.CrossRef
13.
go back to reference Binesh F, Akhondei M, Pourmirafzali H, et al. Determination of relative frequency of eosinophils and mast cells in gastric and duodenal mucosal biopsies in adults with non-ulcer dyspepsia. J Coll Physicians Surg Pak. 2013;23:326–329.PubMed Binesh F, Akhondei M, Pourmirafzali H, et al. Determination of relative frequency of eosinophils and mast cells in gastric and duodenal mucosal biopsies in adults with non-ulcer dyspepsia. J Coll Physicians Surg Pak. 2013;23:326–329.PubMed
14.
go back to reference Friesen CA, Kearns GL, Andre L, et al. Clinical efficacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia. J Pediatr Gastroenterol Nutr. 2004;38:343–351.CrossRef Friesen CA, Kearns GL, Andre L, et al. Clinical efficacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia. J Pediatr Gastroenterol Nutr. 2004;38:343–351.CrossRef
15.
go back to reference Collins MH, Capocelli K, Yang GY. Eosinophilic gastrointestinal disorders pathology. Front Med (Lausanne). 2017;4:261.CrossRef Collins MH, Capocelli K, Yang GY. Eosinophilic gastrointestinal disorders pathology. Front Med (Lausanne). 2017;4:261.CrossRef
16.
go back to reference Kramer JR, Fischbach LA, Richardson P, et al. Waist-to-hip ratio, but not body mass index, is associated with an increased risk of Barrett’s esophagus in white men. Clin Gastroenterol Hepatol. 2013;11(373–381):e1. Kramer JR, Fischbach LA, Richardson P, et al. Waist-to-hip ratio, but not body mass index, is associated with an increased risk of Barrett’s esophagus in white men. Clin Gastroenterol Hepatol. 2013;11(373–381):e1.
17.
go back to reference Drossman DA. Rome II. The functional gastrointestinal disorders. McLean, VA: Degnon Associates; 2000. Drossman DA. Rome II. The functional gastrointestinal disorders. McLean, VA: Degnon Associates; 2000.
18.
go back to reference Carrasco JL, Jover L. Estimating the generalized concordance correlation coefficient through variance components. Biometrics. 2003;59:849–858.CrossRef Carrasco JL, Jover L. Estimating the generalized concordance correlation coefficient through variance components. Biometrics. 2003;59:849–858.CrossRef
19.
go back to reference Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009;29:765–773.CrossRef Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009;29:765–773.CrossRef
20.
go back to reference Friesen CA, Neilan NA, Schurman JV, et al. Montelukast in the treatment of duodenal eosinophilia in children with dyspepsia: effect on eosinophil density and activation in relation to pharmacokinetics. BMC Gastroenterol. 2009;9:32.CrossRef Friesen CA, Neilan NA, Schurman JV, et al. Montelukast in the treatment of duodenal eosinophilia in children with dyspepsia: effect on eosinophil density and activation in relation to pharmacokinetics. BMC Gastroenterol. 2009;9:32.CrossRef
21.
go back to reference Lee MJ, Jung HK, Lee KE, et al. Degranulated eosinophils contain more fine nerve fibers in the duodenal mucosa of patients with functional dyspepsia. J Neurogastroenterol Motil. 2019;25:212–221.CrossRef Lee MJ, Jung HK, Lee KE, et al. Degranulated eosinophils contain more fine nerve fibers in the duodenal mucosa of patients with functional dyspepsia. J Neurogastroenterol Motil. 2019;25:212–221.CrossRef
22.
go back to reference Rothenberg ME, Hogan SP. The eosinophil. Ann Rev Immunol. 2006;24:147–174.CrossRef Rothenberg ME, Hogan SP. The eosinophil. Ann Rev Immunol. 2006;24:147–174.CrossRef
23.
go back to reference Hogan SP. Functional role of eosinophils in gastrointestinal inflammation. Immunol Allergy Clin North Am. 2009;29(129–40):xi. Hogan SP. Functional role of eosinophils in gastrointestinal inflammation. Immunol Allergy Clin North Am. 2009;29(129–40):xi.
24.
go back to reference McBrien CN, Menzies-Gow A. The biology of eosinophils and their role in asthma. Front Med (Lausanne). 2017;4:93.CrossRef McBrien CN, Menzies-Gow A. The biology of eosinophils and their role in asthma. Front Med (Lausanne). 2017;4:93.CrossRef
25.
go back to reference Desreumaux P, Bloget F, Seguy D, et al. Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis. Gastroenterology. 1996;110:768–774.CrossRef Desreumaux P, Bloget F, Seguy D, et al. Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis. Gastroenterology. 1996;110:768–774.CrossRef
26.
go back to reference Murch S. Allergy and intestinal dysmotility–evidence of genuine causal linkage? Curr Opin Gastroenterol. 2006;22:664–668.CrossRef Murch S. Allergy and intestinal dysmotility–evidence of genuine causal linkage? Curr Opin Gastroenterol. 2006;22:664–668.CrossRef
27.
go back to reference Akiho H, Deng Y, Blennerhassett P, et al. Mechanisms underlying the maintenance of muscle hypercontractility in a model of postinfective gut dysfunction. Gastroenterology. 2005;129:131–141.CrossRef Akiho H, Deng Y, Blennerhassett P, et al. Mechanisms underlying the maintenance of muscle hypercontractility in a model of postinfective gut dysfunction. Gastroenterology. 2005;129:131–141.CrossRef
Metadata
Title
Functional Dyspepsia and Duodenal Eosinophil Count and Degranulation: A Multiethnic US Veteran Cohort Study
Authors
M. Ellionore Järbrink-Sehgal
Jordan Sparkman
Alexander Damron
Marjorie M. Walker
Linda K. Green
Daniel G. Rosen
David Y. Graham
Hashem E. El-Serag
Publication date
01-10-2021
Publisher
Springer US
Keyword
Eosinophilia
Published in
Digestive Diseases and Sciences / Issue 10/2021
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-020-06689-2

Other articles of this Issue 10/2021

Digestive Diseases and Sciences 10/2021 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.