Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children.

Humans Bangladesh / epidemiology Pakistan / epidemiology Zambia / epidemiology Cohort Studies Child Female Male Infant Child, Preschool Duodenum / pathology United States / epidemiology Biopsy Intestinal Diseases / pathology Celiac Disease / pathology Intestinal Mucosa / pathology Goblet Cells / pathology Child Nutrition Disorders / epidemiology

Paneth cells child health crypts enteropathy global health goblet cells intestine malnutrition stunting villi

Journal

The American journal of clinical nutrition

ISSN: 1938-3207

Titre abrégé: Am J Clin Nutr

Pays: United States

ID NLM: 0376027

Informations de publication

Date de publication:
Sep 2024

Historique:

received: 06 09 2023

revised: 19 02 2024

accepted: 22 02 2024

medline: 20 9 2024

pubmed: 20 9 2024

entrez: 20 9 2024

Statut: ppublish

Résumé

Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses. We set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia ("EED") with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as "normal") or celiac disease. Five gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner's glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value. Biopsies from the duodenal bulb showed higher intramucosal Brunner's gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner's glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan. This scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED.

Sections du résumé

BACKGROUND BACKGROUND

Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses.

OBJECTIVES OBJECTIVE

We set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia ("EED") with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as "normal") or celiac disease.

METHODS METHODS

Five gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner's glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value.

RESULTS RESULTS

Biopsies from the duodenal bulb showed higher intramucosal Brunner's gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner's glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan.

CONCLUSIONS CONCLUSIONS

This scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED.

Identifiants

DOI: 10.1016/j.ajcnut.2024.02.028 PMID: 39300660

pubmed: 39300660

pii: S0002-9165(24)00271-5

doi: 10.1016/j.ajcnut.2024.02.028

pii:

doi:

Types de publication

Journal Article Comparative Study

Langues

eng

Sous-ensembles de citation

Pagination

S15-S30

Investigateurs

Kumail Ahmed (K)

Sheraz Ahmed (S)

Md Ashraful Alam (MA)

S M Khodeza Nahar Begum (SMKN)

Ellen Besa (E)

Kanta Chandwe (K)

Miyoba Chipunza (M)

Subhasish Das (S)

Lee A Denson (LA)

Shah Mohammad Fahim (SM)

Md Amran Gazi (MA)

Md Mehedi Hasan (MM)

Aneeta Hotwani (A)

Junaid Iqbal (J)

Najeeha Talat Iqbal (NT)

Sadaf Jakhro (S)

Furqan Kabir (F)

Sarah Lawrence (S)

Barbara J Mann (BJ)

Ramendra Nath Mazumder (RN)

Waheeda Memon (W)

Brooks Morgan (B)

Victor Mudenda (V)

Chola Mulenga (C)

Monica Mweetwa (M)

Abdul Khalique Qureshi (AK)

Masudur Rahman (M)

Najeeb Rahman (N)

Kamran Sadiq (K)

Shafiqul Alam Sarker (SA)

Fayaz Umrani (F)

Kanekwa Zyambo (K)