J_pediatr_gastroenterol_nutr_2025_Almazan_EndoFLIP_distensibility

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Received: 4 July 2024 | Accepted: 11 December 2024
DOI: 10.1002/jpn3.70013
OR I G I NA L ART I C L E
G a s t r o e n t e r o l o g y
EndoFLIP distensibility index correlates with histologic
findings in children with eosinophilic esophagitis
Erik Almazan1 | Tom Z. Liang2 | Brenna Hohl3 | Brett J. Hoskins4 |
Jacqueline E. Birkness‐Gartman5 | Kenneth Ng6
1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
2Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
3Department of Pediatrics, Children's National Hospital, Washington, District of Columbia, USA
4Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children at IU
Health, Indianapolis, Indiana, USA
5Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
6Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Correspondence
Kenneth Ng, Division of Pediatric
Gastroenterology, Hepatology, and Nutrition,
Johns Hopkins Children's Center,
550 N Broadway, Suite 1003, Baltimore,
MD 21205, USA.
Email: kng13@jhmi.edu
Jacqueline E. Birkness‐Gartman, Department
of Pathology, Johns Hopkins Hospital, 1800
Orleans St, Sheikh Zayed Tower – M2101B,
Baltimore, MD 21231, USA.
Email: jbirkne1@jhmi.edu
Funding information
This publication was made possible by the
Johns Hopkins Institute for Clinical and
Translational Research (ICTR) which is funded
in part by Grant Number UL1 TR003098 from
the National Center for Advancing
Translational Sciences (NCATS), a component
of the National Institutes of Health (NIH), and
NIH Roadmap for Medical Research. Its
contents are solely the responsibility of the
authors and do not necessarily represent the
official view of the Johns Hopkins ICTR,
NCATS, or NIH.
Abstract
Background and Aims: The Eosinophilic Esophagitis Histology Scoring System
(EoEHSS) is useful for diagnosing and characterizing eosinophilic esophagitis
(EoE). A limitation of the EoEHSS is that lamina propria fibrosis scores are
infrequently determined due to challenges in sampling lamina propria. Low dis-
tensibility index (DI) measured by endoluminal functional lumen imaging probe
(EndoFLIP) is associated with fibrostenotic severity in pediatric patients with EoE.
We investigated the correlation between DI and the EoEHSS to understand
whether EndoFLIP could be a useful complementary tool for evaluating EoE‐
associated remodeling in children.
Methods: We reviewed the medical records of patientsthe EoEHSS is that
components of the model, namely BZH and DIS, do
not evaluate eosinophil inflammation, but effectively
distinguish between treated and untreated patients,
indicating that disease severity in EoE encompasses
features beyond eosinophilia.6 One limitation of the
EoEHSS is the low intraobserver and interobserver
reproducibility for components of the score, including
LPF grade and stage scores.8 There are also fre-
quent challenges in obtaining sufficient and appro-
priate quality lamina propria samples from biopsies
for analysis.6,9–14 Characterizing LPF, nevertheless,
is important as it is prevalent in children with EoE and
is associated with dysphagia.15
1.3 | EoE and the endoluminal
functional lumen imaging probe
(EndoFLIP)
LPF is associated with decreased esophageal dis-
tensibility in children, suggesting that distensibility
may be a useful proxy for fibrosis and esophageal
remodeling.12 This idea is supported by data showing
that esophageal distensibility negatively correlates
with eosinophil‐associated proteins, which are
themselves associated with biochemical markers of
the epithelial–mesenchymal transition (EMT) that
occurs during esophageal remodeling.16 Distensibil-
ity measurements, furthermore, may allow for the
identification of early remodeling, even in the
absence of eosinophilia or endoscopic findings. In
children and adults, decreased esophageal distensi-
bility can be a marker for early fibrostenotic changes
independent of eosinophil count.17,18 Decreases in
esophageal diameter and cross‐sectional area,
resulting in lower distensibility, have also been re-
ported to occur independently of endoscopic findings,
such as furrowing, rings, or white plaques.19 These
early changes are important, not only for diagnostic
purposes, but also because of their prognostic value
for characterizing EoE severity as they are associ-
ated with food impaction and the need for esopha-
geal dilation.18,20 EndoFLIP is a diagnostic tool that
utilizes impedance technology to measure key lumi-
nal parameters and characteristics in real time during
endoscopy. EndoFLIP may greatly complement the
EoEHSS and provide data on early esophageal re-
modeling in EoE disease progression. We sought to
compare the EndoFLIP and histology findings in
pediatric patients who underwent an esophagogas-
troduodenoscopy (EGD) with biopsy.
2 | METHODS
2.1 | Study design
Electronic medical records were reviewed to identify all
patients under 21 years of age who underwent an EGD
with biopsy and EndoFLIP between October 2017 and
July 2023 at the Johns Hopkins Children's Center, a
tertiary‐care, academic center.
2.2 | Ethics statement
The study was approved by the Johns Hopkins Uni-
versity Institutional Review Board.
2.3 | EndoFLIP procedure and
parameters
EGD with biopsy and EndoFLIP were performed by
one pediatric gastroenterologist (KN). All patients
were sedated under general anesthesia and mana-
ged by a pediatric anesthesiologist. EGDs were
performed using an Olympus gastroscope (model
GIF‐H180 or GIF‐H190). An 8 cm EndoFLIP catheter
was selected for patients under 42 in. in height, and
a 16 cm catheter was used for those at least 42 in.
tall. Preprocedural calibration of the FLIP computer
was performed by the nurse or technician according
to the manufacturer's guidelines. During each En-
doFLIP procedure, the deflated EndoFLIP catheter
was advanced to the lower esophageal sphincter
(LES) under direct visualization via the gastroscope.
A sodium chloride‐based solution provided by the
manufacturer was used to inflate the balloon cath-
eter to 15 mL, and the catheter was centered at the
LES. At the discretion of the endoscopist, the cath-
eter was inflated to the 20, 30, 40, 50, and/or 60 mL
settings. EndoFLIP luminal parameters, including
diameter (cm), cross‐sectional area (mm2), compli-
ance (cm2/cm H2O), distensibility index (DI; mm2/
mmHg), and pressure (mmHg) were recorded by the
operating room staff at each setting used during the
procedure.
2.4 | Electronic medical record review
Demographic, clinical, procedural, and pathology
data were extracted from the electronic medical
record. Procedural data included EndoFLIP param-
eter values after inflation to 20, 30, 40, 50, and/or
60 mL. Pathology data included the biopsy site and
the original diagnosis rendered in the pathology
report.
ALMAZAN ET AL. | 3
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2.5 | EoEHSS
Biopsies from the distal esophagus were examined
by two pathologists with subspecialty expertise in
gastrointestinal pathology (JBG and TL). Histologic
diagnoses were categorized as normal/reactive,
reflux esophagitis, or EoE (Figure S1). For each
biopsy, the PEC was quantified based on the
number of eosinophils seen in an HPF (400×
magnification). EI, EA, SL, SEA, DEC, DIS, BZH,
and LPF were subsequently evaluated and individ-
ually scored using a 4‐point scale for grade
(severity) and stage (extent) according to the
EoEHSS developed by Collins et al.6 Following the
EoEHSS, overall scores for grade and stage was
calculated for each sample after taking the sum of
the respective EI, EA, SL, SEA, DEC, DIS, BZH, and
LPF scores and dividing the sum by the maximum
possible score.6
2.6 | Statistical analysis
Median, minimum, and maximum values were re-
ported for continuous variables, and percentages
were reported for categorical variables. Demo-
graphics, histologic scores, and EndoFLIP parame-
ters were compared between histologic cohorts using
the Kruskal–Wallis test for continuous variables
and Fisher's exact test for categorical variables.
Spearman's rank correlation coefficient analyses
were performed to compare EndoFLIP parameter
values with the overall and component scores of the
EoEHSS. The EndoFLIP parameter values at the
30 mL inflation setting were the only values used for
comparative analyses as the 30 mL setting was the
most used setting for patients in our cohort.
All analyses were conducted using the Statistical
Package for the Social Sciences (SPSS version
29.0). p valuesL
ibrary for rules of use; O
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3.2 | EndoFLIP parameter comparison
The 30mL inflation setting at the LES was used for
comparison of the three groups (Table 2). At this
inflation setting, the median DI was lowest in the EoE
group (2.1 mm2/mmHg) compared to the reflux
group (3.3 mm2/mmHg) and normal/reactive group
(2.9 mm2/mmHg) (p = 0.03). Of note, a narrower range
of distensibility values was observed in the EoE group
(1.2–4.4mm2/mmHg) compared to the normal/reactive
group (0.7–11.7mm2/mmHg) and the reflux group
(0.6–9.1mm2/mmHg). No differences were observed
for diameter, cross‐sectional area, compliance, or
pressure across groups (all p > 0.05). There was no
significant difference in distensibility based on sex,
race, ethnicity, or age (all p > 0.05).
3.3 | EoEHSS validation
A comparison of EoEHSS scores across the histologic
groups was made to validate the score for assessing
EoE in our patient population (Table S1). The overall
grade and stage scores were higher in the EoE group
compared to the reflux and normal/reactive groups
(pinflammation stage −0.21 (−0.37 to −0.02) 0.02
Eosinophil abscesses grade −0.20 (−0.37 to −0.02) 0.03
Eosinophil abscesses stage −0.20 (−0.37 to −0.02) 0.03
Surface layering grade −0.23 (−0.40 to −0.05) 0.01
Surface layering stage −0.23 (−0.40 to −0.05) 0.01
Surface epithelial alteration grade −0.17 (−0.34 to 0.02) 0.07
Surface epithelial alteration stage −0.17 (−0.34 to 0.02) 0.07
Dyskeratotic epithelial cells grade −0.07 (−0.25 to 0.12) 0.46
Dyskeratotic epithelial cells stage −0.07 (−0.25 to 0.12) 0.45
Dilated intercellular spaces grade −0.23 (−0.40 to −0.05) 0.01
Dilated intercellular spaces stage −0.23 (−0.40 to −0.05) 0.01
Basal zone hyperplasia grade −0.27 (−0.43 to −0.09)findings in pediatric
patients with eosinophilic esophagitis. J Pediatr. 2022;98(1):
26‐32. doi:10.1016/j.jped.2021.03.004
9. Collins MH. Histopathology of eosinophilic esophagitis. Dig Dis.
2014;32(1‐2):68‐73. doi:10.1159/000357012
10. Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic eso-
phagitis in children and adults: a systematic review and con-
sensus recommendations for diagnosis and treatment.
Gastroenterology. 2007;133(4):1342‐1363. doi:10.1053/j.
gastro.2007.08.017
11. Parfitt JR, Gregor JC, Suskin NG, Jawa HA, Driman DK.
Eosinophilic esophagitis in adults: distinguishing features
from gastroesophageal reflux disease: a study of 41 patients.
Mod Pathol. 2006;19(1):90‐96. doi:10.1038/modpathol.
3800498
12. Menard‐Katcher C, Benitez AJ, Pan Z, et al. Influence of age
and eosinophilic esophagitis on esophageal distensibility in a
pediatric cohort. Am J Gastroenterol. 2017;112(9):1466‐1473.
doi:10.1038/ajg.2017.131
13. Hiremath G, Correa H, Acra S, Dellon ES. Correlation of en-
doscopic signs and mucosal alterations in children with
eosinophilic esophagitis. Gastrointest Endosc. 2020;91(4):
785‐794.e1. doi:10.1016/j.gie.2019.11.031
14. Hiremath G, Sun L, Correa H, et al. Development and validation
of web‐based tool to predict lamina propria fibrosis in eosino-
philic esophagitis. Am J Gastroenterol. 2021;117(2):272‐279.
doi:10.14309/ajg.0000000000001587
15. Chehade M, Sampson HA, Morotti RA, Magid MS. Esophageal
subepithelial fibrosis in children with eosinophilic esophagitis.
J Pediatr Gastroenterol Nutr. 2007;45(3):319‐328. doi:10.1097/
MPG.0b013e31806ab384
16. Muir AB, Ackerman SJ, Pan Z, et al. Esophageal remodeling in
eosinophilic esophagitis: relationships to luminal captured bio-
markers of inflammation and periostin. J Allergy Clin Immunol.
2022;150(3):649‐656.e5. doi:10.1016/j.jaci.2022.03.022
17. Kwiatek MA, Hirano I, Kahrilas PJ, Rothe J, Luger D,
Pandolfino JE. Mechanical properties of the esophagus in eo-
sinophilic esophagitis. Gastroenterology. 2011;140(1):82‐90.
doi:10.1053/j.gastro.2010.09.037
18. Hoffmann NV, Keeley K, Wechsler JB. Esophageal distensibility
defines fibrostenotic severity in pediatric eosinophilic esopha-
gitis. Clin Gastroenterol Hepatol. 2023;21:1188‐1197.e4.
doi:10.1016/j.cgh.2022.08.044
19. Lee J, Huprich J, Kujath C, et al. Esophageal diameter is
decreased in some patients with eosinophilic esophagitis and
might increase with topical corticosteroid therapy. Clin
Gastroenterol Hepatol. 2012;10(5):481‐486. doi:10.1016/j.cgh.
2011.12.042
20. Nicodème F, Hirano I, Chen J, et al. Esophageal distensibility
as a measure of disease severity in patients with eosinophilic
esophagitis. Clin Gastroenterol Hepatol. 2013;11(9):
1101‐1107.e1. doi:10.1016/j.cgh.2013.03.020
21. Carlson DA, Kahrilas PJ, Lin Z, et al. Evaluation of esophageal
motility utilizing the functional lumen imaging probe. Am
J Gastroenterol. 2016;111(12):1726‐1735. doi:10.1038/ajg.
2016.454
22. Carlson DA, Kou W, Lin Z, et al. Normal values of esophageal
distensibility and distension‐induced contractility measured by
functional luminal imaging probe panometry. Clin Gastroenterol
Hepatol. 2019;17(4):674‐681.e1. doi:10.1016/j.cgh.2018.07.042
23. Hoskins B, Almazan E, Mogul D, Ng K. Endoluminal
functional lumen imaging probe is safe in children under
five years old. J Pediatr Gastroenterol Nutr. 2022;74(6):
e148‐e152. doi:10.1097/mpg.0000000000003430
24. Muir AB, Wang JX, Nakagawa H. Epithelial‐stromal crosstalk
and fibrosis in eosinophilic esophagitis. J Gastroenterol.
2019;54(1):10‐18. doi:10.1007/s00535-018-1498-3
25. Aceves SS, Newbury RO, Dohil R, Bastian JF, Broide DH.
Esophageal remodeling in pediatric eosinophilic esophagitis.
J Allergy Clin Immunol. 2007;119(1):206‐212. doi:10.1016/j.jaci.
2006.10.016
26. Hiremath G, Choksi YA, Acra S, Correa H, Dellon ES. Factors
associated with adequate lamina propria sampling and presence
of lamina propria fibrosis in children with eosinophilic esophagitis.
Clin Gastroenterol Hepatol. 2021;19(9):1814‐1823.e1. doi:10.
1016/j.cgh.2020.07.035
SUPPORTING INFORMATION
Additional supporting information can be found online
in the Supporting Information section at the end of this
article.
How to cite this article: Almazan E, Liang TZ,
Hohl B, Hoskins BJ, Birkness‐Gartman JE, Ng K.
EndoFLIP distensibility index correlates with
histologic findings in children with eosinophilic
esophagitis. J Pediatr Gastroenterol Nutr.
2025;1‐8. doi:10.1002/jpn3.70013
8 | ALMAZAN ET AL.
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iley O
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ibrary on [15/04/2025]. See the T
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s and C
onditions (https://onlinelibrary.w
iley.com
/term
s-and-conditions) on W
iley O
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ibrary for rules of use; O
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icense
https://doi.org/10.14740/gr1423
https://doi.org/10.1016/j.jped.2021.03.004
https://doi.org/10.1159/000357012
https://doi.org/10.1053/j.gastro.2007.08.017
https://doi.org/10.1053/j.gastro.2007.08.017
https://doi.org/10.1038/modpathol.3800498
https://doi.org/10.1038/modpathol.3800498
https://doi.org/10.1038/ajg.2017.131
https://doi.org/10.1016/j.gie.2019.11.031
https://doi.org/10.14309/ajg.0000000000001587
https://doi.org/10.1097/MPG.0b013e31806ab384
https://doi.org/10.1097/MPG.0b013e31806ab384
https://doi.org/10.1016/j.jaci.2022.03.022
https://doi.org/10.1053/j.gastro.2010.09.037
https://doi.org/10.1016/j.cgh.2022.08.044
https://doi.org/10.1016/j.cgh.2011.12.042
https://doi.org/10.1016/j.cgh.2011.12.042
https://doi.org/10.1016/j.cgh.2013.03.020
https://doi.org/10.1038/ajg.2016.454
https://doi.org/10.1038/ajg.2016.454
https://doi.org/10.1016/j.cgh.2018.07.042
https://doi.org/10.1097/mpg.0000000000003430
https://doi.org/10.1007/s00535-018-1498-3
https://doi.org/10.1016/j.jaci.2006.10.016
https://doi.org/10.1016/j.jaci.2006.10.016
https://doi.org/10.1016/j.cgh.2020.07.035
https://doi.org/10.1016/j.cgh.2020.07.035
https://doi.org/10.1002/jpn3.70013
	EndoFLIP distensibility index correlates with histologic findings in children with eosinophilic esophagitis
	1 INTRODUCTION
	1.1 Eosinophilic esophagitis (EoE) in the pediatric setting
	1.2 EoE and the eosinophilic esophagitis histology scoring system (EoEHSS)
	1.3 EoE and the endoluminal functional lumen imaging probe (EndoFLIP)
	2 METHODS
	2.1 Study design
	2.2 Ethics statement
	2.3 EndoFLIP procedure and parameters
	2.4 Electronic medical record review
	2.5 EoEHSS
	2.6 Statistical analysis
	3 RESULTS
	3.1 Patient characteristics
	3.2 EndoFLIP parameter comparison
	3.3 EoEHSS validation
	3.4 Comparison of EoEHSS and EndoFLIP distensibility data
	4 DISCUSSION
	5 CONCLUSION
	ACKNOWLEDGMENTS
	CONFLICT OF INTEREST STATEMENT
	ORCID
	REFERENCES
	SUPPORTING INFORMATION