Mucosal Eosinophil Count Research Articles

Redefining Histological Cell Counts Using a Standardized Method: The Leuven Intestinal Counting Protocol.

The diagnosis of eosinophilic gastrointestinal diseases is largely based on mucosal eosinophil counts, but thresholds and normal ranges beyond the esophagus are debated, calling for much-needed methodological standardization. We aimed to develop a standardized workflow for duodenal cell quantification and estimate duodenal eosinophil and mast cell numbers in healthy controls. Software-based histological cell quantification using free-sized or fixed-sized regions was developed and applied to digitized hematoxylin and eosin (H&E)-stained slides from 58 individuals (healthy controls [HCs] and patients with functional dyspepsia). Intraclass correlation coefficients (ICCs) compared inter-rater reliability between software-based and microscopic quantification. Reproducibility of the software-based method was validated in an independent cohort of 37 control and functional dyspepsia subjects. Eosinophil identification on H&E staining was compared to immunohistochemistry (IHC). Normal eosinophil (H&E) and mast cell (cKit) ranges were determined in 70 adult HCs. Eosinophil quantification on digitized slides demonstrated excellent (ICC = 0.909) and significantly improved reproducibility over microscopic evaluation (ICC = 0.796, P = 0.0014), validated in an independent cohort (ICC = 0.910). Duodenal eosinophils were more abundant around crypts than in villi ( P < 0.0001), while counts were similar on matched H&E- and IHC-stained slides ( P = 0.55). Mean ± SD (95th percentile) duodenal eosinophils and mast cells in HC were 228.8/mm 2 ± 94.7 (402.8/mm 2 ) and 419.5/mm 2 ± 132.2 (707.6/mm 2 ), respectively. We developed and validated a standardized approach to duodenal histological cell quantification, generalizable to various mucosal cell types. Implementation of software-based quantification identified 400 eosinophils/mm 2 and 700 mast cells/mm 2 as thresholds for abnormal duodenal infiltration.

P266 Predictive tissue-based biomarkers in treatment of Inflammatory Bowel Disease with biologicals and small molecules: a systematic review

Abstract Background The treatment landscape of inflammatory bowel disease (IBD) has changed in the past decade with introduction of new drug classes. For most drugs, only 30% of patients achieve long-term remission. Clinical implementation of predictive biomarkers to support precision medicine is lacking. As the interactions of immune system and microbiome in the colonic mucosa may hold the key to the prediction problem, we performed a systematic review to assess the status of tissue-based biomarkers in the era of biological and small molecule therapies. Methods A literature search was performed in Medline, Embase, the Cochrane Library, Web of science and the ECCO abstract database in July 2023. Papers were considered eligible when reporting on biomarkers, extracted from biopsies obtained during colonoscopy, that had predictive value regarding therapy success of a specific non-TNFα biological or small molecule. Two authors independently assessed eligibility and extracted the data. Results From 10,141 screened records with 155 papers assessed for eligibility, a total of 43 studies were included. The majority was published in the last 5 years (87%). Data on the clinical history of patients and the interval between biopsy and therapy onset was often lacking, in part while 49% of studies were published as conference abstracts. Heterogeneity in therapy success assessment regarding modality (clinical, endoscopic, and/or histologic) and interval (4-58 weeks) was striking. With 28 studies, vedolizumab is the best investigated drug. Of the 16 studies reporting on gene expression, 7 used data from the GEMINI-I/LTS trials. These studies reported a range from a single predictive gene such as TREM1 and OSM to a classifier of 267 differentially expressed genes. Studies looking at the protein level (n=7) focused mostly on target engagement. In 7 studies, biomarker discovery was performed through histological evaluation, mainly looking at mucosal eosinophil counts. One study looking at the microbiome did not find differences between responders and non-responders of vedolizumab. Conclusion Our systematic review shows that tissue-based predictive biomarker discovery in IBD is a young and dynamic field of research. This is reflected by the heterogeneity in how and when therapy success is assessed. Moreover, the various methods to analyze gene expression data yield vastly different results when applied to the same dataset. We therefore propose guideline development to support clinical implementation of predictive biomarkers.

Composite score of physiomechanical esophageal function using functional lumen imaging probe panometry in eosinophilic esophagitis

Background and AimsThe evaluation provided by functional lumen imaging probe (FLIP) Panometry includes esophageal distensibility/compliance (mechanics) of the esophageal body and esophagogastric junction (EGJ) and esophageal motility (secondary peristalsis). We aimed to develop a composite score using these parameters to characterize physiomechanical function in patients with eosinophilic esophagitis (EoE). Methods215 adult patients with EoE that completed FLIP Panometry during sedated endoscopy with esophageal biopsies were included. FLIP metrics of esophageal body Compliance, Contractile response, Distensibility plateau, and maximum EGJ Diameter (C2D2) were scored as 0 for normal, vs 1 or 2 for increasing degree of abnormality. Scores were summed to calculate the composite “C2D2” score. ResultsThe C2D2 score had a significant positive correlation with mucosal eosinophil count (rho=0.241) and total endoscopic (EREFS) score (rho=0.467). Among patients off treatment at baseline evaluation (n=46), future proton pump inhibitor (PPI)-responders (i.e. achieved mucosal eosinophil count <15 per hpf after PPI treatment) had lower C2D2 scores than PPI-non-responders (median (IQR) 2 (1-3) vs 4 (2-6); P=0.003). A regression model (that controlled for age, sex, and baseline eosinophil count) showed a C2D2 score ≤3 had an odds ratio (95% confidence interval) of 14.5 (2.6-85) to predict future PPI-response. However, total EREFS scores (P=0.142) and baseline eosinophil count (P=0.480) did not differ between PPI-responders and PPI-non-responders. ConclusionsThis composite score of FLIP Panometry metrics, the C2D2 score, may facilitate characterizing physiomechanical function in EoE and serve as an objective outcome measure.

A PhysioMechanical Model of Esophageal Function in Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation, but also heterogeneous presentations involving fibrostenotic esophageal remodeling and esophageal dysmotility. We aimed to define and evaluate phenotypes of EoE using functional lumen imaging probe (FLIP) panometry (ie, a PhysioMechanical classification of EoE). Patients with EoE who completed FLIP during endoscopy were included in a cross-sectional study. FLIP studies were analyzed for distensibility plateau and compliance of the esophageal body, maximum esophagogastric junction diameter, and contractile response pattern. These FLIP features were then applied to define PhysioMechanical classifications. A total of 215 patients with EoE (mean [standard deviation] age 38 [12] years; 31% female) were included. Seven PhysioMechanical classifications were identified that differed by various clinical characteristics, including symptom duration (P < .001) and Endoscopic EoE Reference Scores (EREFS) (P < .001). In particular, patients with "nonreactive fibrostenosis" (n= 14), had greater symptom duration (median [interquartile range] 20 [10-30] years) and more frequently had EREFS grade 2 or 3 ring scores (14 of 14 patients) than patients with a "normal" PhysioMechanical classification (symptom duration: 3 [1-8] years; 4 of 50 [8%] had EREFS grade 2 or 3 rings). In addition, among patients off treatment at cross-sectional evaluation (n= 46), there was a difference between PhysioMechanical classifications in future proton pump inhibitor (PPI) response rates (ie, achieving peak mucosal eosinophil count <15 per high-powered field after PPI treatment); P= .009. PPI response ranged from 87% (13 of 15 patients) with "isolated esophagogastric junction outflow obstruction" to 11% (1 of 9 patients) with "spastic-reactive fibrostenosis." Classifying PhysioMechanical esophageal function in EoE based on FLIP panometry features may facilitate defining disease severity and directing management in EoE.

P623 Mucosal eosinophils as markers of post-induction vedolizumab response in paediatric Ulcerative Colitis

Abstract Background Vedolizumab (VDZ) is commonly used as an off-label therapy in children with ulcerative colitis (UC) but no predictive factors of response are available. Vedolizumab binds α4β7 integrin and blocks the migration of T-lymphocytes and other cells, including eosinophils, which are involved in the UC inflammatory process. The aim of our study was to explore the predictive value of pre-therapy mucosal eosinophil count on the response to vedolizumab induction therapy in a paediatric population with UC Methods This is a retrospective, monocentric study, including children with UC treated with VDZ in the Paediatric Gastroenterology Unit of Policlinico Umberto I Hospital – Sapienza University of Rome. Histopathological data were analyzed for eosinophil counts in high power fields (hpf) in the cecum, transverse colon, sigma, and rectum prior to VDZ treatment. Clinical remission and response were evaluated at week 14 based on the PUCAI score. Results Twenty-five UC patients treated with VDZ were enrolled. All patients had failed previous anti-TNF therapy. Median baseline eosinophil count was 21 eo/hpf (5-60) in the cecum, 20 eo/hpf (6-68) in transverse colon, 44 eo/hpf (12-77) in sigma and 31 eo/hpf (9-67) in rectum. Baseline median eosinophil mucosal count in sigma was significantly higher in patients in remission (51[30-82]/ vs. 19[8.5–46] eosinophils/hpf, P&amp;lt;0.05) and clinical response (46[23-79]/ vs. 14[6–45] eosinophils/hpf, P&amp;lt;0.05) at week 14, compared to non-responders. At univariate and multivariate analysis, the number of eosinophils in sigma was confirmed to predict clinical remission [OR=1.0 (95%CI:1.00-1.087), p: 0.03), also independently to concomitant steroid use [OR: 1.06 (95%CI: 1.00-1.122) p: 0.047). The ROC curve identified a risk threshold value for eosinophil count in sigma &amp;gt;23 eosinophils/hpf, with a sensitivity of 85.7% and specificity of 66.7% (Youden’s index 0.83) with an area under the curve (AUC) of 0.778 Conclusion Mucosal eosinophil abundance in sigma may predict remission to vedolizumab induction in paediatric UC. More studies are warranted to confirm these preliminary results and further investigate the role of mucosal eosinophils as a marker of therapeutic response and in the pathogenesis of UC

554 - Establishing normal mucosal eosinophil counts in pediatric gastrointestinal biopsies in Lousiana

554 - Establishing normal mucosal eosinophil counts in pediatric gastrointestinal biopsies in Lousiana

The Relationship between Eosinophil Density in the Colonic Mucosa and Eosinophil Blood Count in Children: A Cross-Sectional Study.

Eosinophils are found in the mucosa of the healthy gastrointestinal tract, but they also often accompany gastrointestinal diseases. We hypothesized that a positive correlation exists between blood eosinophil count and colonic eosinophil mucosal density in children. Electronic health records regarding 181 colonoscopies, performed with biopsy in the years 2019-2022, were screened for information on blood and colonic eosinophil count, age, sex, diagnoses, weight, height, white blood cell (WBC) count, serum C-reactive protein (CRP), and total IgE concentration. The median age (IQR) of the 107 included children (109 colonoscopies) was 12.4 years (8.1-15.5); 32 presented with blood eosinophilia (29.3%). The median eosinophil density/high-power field in the colonic mucosa was 22.5 (9-31). We found a weak correlation between colonic mucosal eosinophil density and blood eosinophil count (r = 0.295, 95% CI 0.108-0.462, p = 0.0018). This association was more pronounced in patients with elevated CRP (r = 0.529, 95% CI 0.167-0.766, p = 0.0054) and older than 12.4 years (r = 0.448, 95% CI 0.197-0.644, p = 0.00068). Peripheral blood eosinophilia might hint at increased mucosal colonic eosinophil density, especially in older children and in the presence of systemic inflammation. However, it seems unlikely that blood and colonic eosinophilia are strongly linked in younger children. Studies in adults are warranted.

Mucosal Eosinophil Abundance in Non-Inflamed Colonic Tissue Is Associated with Response to Vedolizumab Induction Therapy in Inflammatory Bowel Disease.

Vedolizumab is used as a treatment for patients with inflammatory bowel disease (IBD), but induction therapy leads to clinical response and remission in approximately 55% and 30% of patients with IBD, respectively. In this study, we aimed to explore the predictive value of mucosal eosinophils and serum eotaxin-1 regarding response to vedolizumab induction therapy. Eighty-four (84) patients with IBD (37 Crohn’s disease [CD], 47 ulcerative colitis [UC]) were included. For 24 patients with IBD, histopathology was assessed for eosinophil counts in non-inflamed colonic tissue prior to vedolizumab treatment. For 64 patients with IBD, serum eotaxin-1 levels were quantified prior to (baseline) and during vedolizumab treatment. Serum samples of 100 patients with IBD (34 CD, 66 UC) from the GEMINI 1 and 2 trials were used for external validation. Baseline mucosal eosinophil numbers in non-inflamed colonic tissue were significantly higher in responders to vedolizumab induction therapy when compared to primary non-responders (69 [34–138] vs. 24 [18–28] eosinophils/high-power field, respectively, p < 0.01). Baseline serum eotaxin-1 levels in the discovery cohort were significantly elevated in responders, compared to primary non-responders (0.33 [0.23–0.44] vs. 0.20 [0.16–0.29] ng/mL, p < 0.01). Prediction models based on mucosal eosinophil counts and serum eotaxin-1 showed an area under the curve (AUC) of 0.90 and 0.79, respectively. However, the predictive capacity of baseline serum eotaxin-1 levels could not be validated in the GEMINI cohort. Mucosal eosinophil abundance in non-inflamed colonic tissue was associated with response to vedolizumab induction therapy in patients with IBD. Future studies are warranted to further validate the potential value of mucosal eosinophils and serum eotaxin-1 as biomarkers for response to vedolizumab therapy.

P577 Mucosal eosinophil abundance in non-inflamed colonic tissue predict response to vedolizumab induction therapy in inflammatory bowel disease

Abstract Background Vedolizumab has shown efficacy, safety and tolerability as treatment for patients with inflammatory bowel disease (IBD). However, vedolizumab induction therapy only shows clinical response and remission in roughly 55% and 30% of IBD patients, respectively. Vedolizumab binds and blocks migration of T-lymphocytes and eosinophils. In this study, we aimed to explore the predictive value of mucosal eosinophils and serum eotaxin-1, an eosinophil chemoattractant, regarding response to vedolizumab induction therapy. Methods 84 IBD patients treated within the University Medical Center Groningen (UMCG) (37 Crohn’s disease [CD], 47 ulcerative colitis [UC]) were included. In a subset of 24 IBD patients (9 CD, 15 UC) histopathological data were analyzed for eosinophil counts in high power fields (hpf) in non-inflamed colon ascendens tissue prior to vedolizumab treatment. In another subset of 64 IBD patients, (28 CD, 36 UC) baseline serum eotaxin-1 was quantified prior to vedolizumab treatment. Clinical response or remission was defined as a decrease of the Harvey Bradshaw Index (HBI) for CD or Simple Clinical Colitis Activity Index (SCCAI) for UC together with physician’s global assessment (PGA). Serum eotaxin-1 was externally assessed as a biomarker for response to vedolizumab induction therapy in 100 IBD patients derived from the GEMINI 1 &amp; 2 trials. Results Baseline eosinophil mucosal count was significantly higher in vedolizumab induction therapy responders, compared to primary non responders (69[34–138] vs. 24[18–28] eosinophils/hpf respectively, P&amp;lt;0.01). Baseline serum eotaxin-1 levels in the UMCG cohort were significantly elevated in therapy responders, compared to primary non-responders (0.33 vs. 0.20 ng/mL, P&amp;lt;0.01). The final prediction model based on mucosal eosinophil count showed an area under the curve (AUC) of 0.90 and serum eotaxin-1 an adjusted AUC of 0.79 The optimal with balanced cut-off value for eosinophil count was &amp;gt; 30 eosinophils/hpf with a sensitivity of 90.9% and specificity of 92.3% (Youden’s index 0.83). Results derived from the GEMINI I &amp; II cohorts did not show any associations between eotaxin-1 levels and therapy response. Conclusion Mucosal eosinophil abundance in non-inflamed colon ascendens biopsies can predict vedolizumab induction therapy response in IBD patients. More studies are warranted to confirm these preliminary results and further investigate the additional value of eotaxin-1 regarding predicting vedolizumab therapy response.

The Effect of Platanus orientalis L. Distillate on Mouse Model of Allergic Rhinitis

Platanus orientalis L. has been used in traditional Persian medicine to treat allergic rhinitis. In this study, the therapeutic effects of P. orientalis L. distillate on allergic rhinitis mouse model were assessed. Furthermore, chemical components of P. orientalis L. were analyzed, using gas chromatography–mass spectrometry. Allergic rhinitis was induced in ninety mice using ovalbumin, and they were divided into six groups (group 1: negative control, experienced no treatment; group 2: positive control, received loratadine; groups 3, 4 and 5: received different amounts of P. orientalis L. distillate, orally and group 6: received intranasal P. orientalis L. distillate). Clinical signs, serum level of interleukin 4 and eosinophil counts of nasal mucosa were determined. α-eudesmol and β-eudesmol were found as the major components of the distillate. Clinical signs improved significantly in the groups that had received P. orientalis L. distillate in comparison with the control group. Also, pathological findings were in favor of decrement in the nasal mucosal eosinophil counts. The serum level of interleukin 4 was not in the detectable ranges in any of the groups. Improving effects of P. orientalis L. distillate were observed in allergic rhinitis mouse models.

Use of mucosal eosinophil count as a guide in the management of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a local inflammatory process driven by eosinophils. Mucosal eosinophil count (MEC) has previously been demonstrated to be a reliable indicator of disease severity. We aim to evaluate use of MEC in guiding medical management of CRS after functional endoscopic sinus surgery (FESS). We retrospectively reviewed patients with CRS who underwent FESS from 2004 to 2017. Tissue MEC per high-power field (HPF) was determined by pathologic examination. MECs were compared by polyp status, postoperative medication requirements, and revision surgery. Patients received normal saline (NS) nasal irrigations with additional treatment as needed for disease control: 1-drug therapy (1-DT) intranasal steroid spray (ISS), 2-drug therapy (2-DT) ISS plus budesonide nasal irrigations (BNI) or leukotriene receptor antagonist (LRA), or 3-drug therapy (3-DT) ISS plus BNI and LRA. Correlations between MEC and 22-item Sino-Nasal Outcome Test (SNOT-22), preoperative computed tomography (CT), and nasal endoscopy scores were evaluated. A total of 156 patients were included. Fifty-seven were managed with 1-DT, 35 with 2-DT, and 62 with 3-DT. Across all patients, mean postoperative 6-month and 1-year SNOT-22 (18.1 ± 17.0, 18.1 ± 20.2, respectively) and nasal endoscopy (3.6 ± 3.8, 3.6 ± 4.1, respectively) scores were significantly lower than preoperative scores (37.4 ± 22.8, 6.5 ± 4, respectively). With increasing MEC, odds of requiring 2-DT (odds ratio [OR] = 1.1, p = 0.0002), 3-DT (OR = 1.12, p < 0.0001), and revision surgery (OR = 1.11, p < 0.0001) were significantly increased. Preoperative endoscopy (ρ = 0.44, p < 0.0001) and CT scores (ρ = 0.51, p < 0.0001) and postoperative 6-month (ρ = 0.55, p < 0.0001) and 1-year (ρ = 0.4, p < 0.0001) endoscopy scores demonstrated good correlation with MEC. MEC correlates with objective clinical disease severity and may guide aggressiveness of management for the individual patient.

One-Hour Esophageal String Test: A Nonendoscopic Minimally Invasive Test That Accurately Detects Disease Activity in Eosinophilic Esophagitis.

OBJECTIVES:Eosinophilic esophagitis (EoE), a chronic food allergic disease, lacks sensitive and specific peripheral biomarkers. We hypothesized that levels of EoE-related biomarkers captured using a 1-hour minimally invasive Esophageal String Test (EST) would correlate with mucosal eosinophil counts and tissue concentrations of these same biomarkers. We aimed to determine whether a 1-hour EST accurately distinguishes active from inactive EoE or a normal esophagus.METHODS:In a prospective, multisite study, children and adults (ages 7–55 years) undergoing a clinically indicated esophagogastroduodenoscopy performed an EST with an esophageal dwell time of 1 hour. Subjects were divided into 3 groups: active EoE, inactive EoE, and normal esophageal mucosa. Eosinophil-associated protein levels were compared between EST effluents and esophageal biopsy extracts. Statistical modeling was performed to select biomarkers that best correlated with and predicted eosinophilic inflammation.RESULTS:One hundred thirty-four subjects (74 children, 60 adults) with active EoE (n = 62), inactive EoE (n = 37), and patient controls with a normal esophagus (n = 35) completed the study. EST-captured eosinophil-associated biomarkers correlated significantly with peak eosinophils/high-power field, endoscopic visual scoring, and the same proteins extracted from mucosal biopsies. Statistical modeling, using combined eotaxin-3 and major basic protein-1 concentrations, led to the development of EoE scores that distinguished subjects with active EoE from inactive EoE or normal esophagi. Eighty-seven percent of children, 95% of parents, and 92% of adults preferred the EST over endoscopy if it provided similar information.DISCUSSION:The 1-hour EST accurately distinguishes active from inactive EoE in children and adults and may facilitate monitoring of disease activity in a safe and minimally invasive fashion.

Eotaxin-3 as a Plasma Biomarker for Mucosal Eosinophil Infiltration in Chronic Rhinosinusitis.

Objective: Chronic rhinosinusitis with nasal polyps exhibits marked eosinophilic infiltration and its mucosal eosinophilia is associated with more severe symptoms. The Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis found that patients with nasal polyps required multiple surgeries when there were higher infiltrating eosinophils in the mucosa. In order to identify plasma biomarkers for local eosinophil infiltration in rhinosinusitis for surgery, we examined the levels of molecules in the plasma of patients and compared the number of infiltrating eosinophils in the nasal mucosa.Materials and Methods: Mucosal tissues from 97 patients with chronic rhinosinusitis (CRS) were obtained from the nasal polyps during surgery. Tissues were immediately fixed and sections were stained with hematoxylin-eosin. The number of eosinophils in the mucosa was counted at HPF (x 400). Blood samples were obtained and the plasma was stored at −80°C. We measured the plasma cytokine and chemokine levels using multiple assay systems according to the manufacturers' protocols. The tissues were divided into high- and low-eosinophil mucosal infiltration group for recurrence after endoscopic sinus surgery (ESS). We also observed chemokine secretion from nasal fibroblasts.Results: The plasma level of eotaxin-3/ CC chemokine ligand 26 (CCL26) was significantly higher in the high-eosinophil mucosal infiltration group (p < 0.005). The number of infiltrating eosinophils in the mucosa was significantly higher in the group with the higher eotaxin-3 level (p < 0.001), but there was no significant difference in the blood eosinophil numbers among two groups. A significant positive correlation was found between the mucosal eosinophil count and the plasma levels of eotaxin-3 (p < 0.005). The levels of interleukin 33 (IL-33) (p < 0.001) and thymic stromal-derived lymphopoietin (TSLP) (p < 0.005) were significantly higher in the high-level eotaxin-3 group. IL-13 strongly induced the secretion of eotaxin-3 from human nasal fibroblasts (p < 0.05).Conclusion: This is the first report suggesting eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration. Furthermore, the level of eotaxin-3 was found to be closely related to IL-33 and TSLP levels which indicate respiratory diseases.

The 1-Hour Esophageal String Test: A Non-Endoscopic Minimally Invasive Test to Accurately Detect Disease Activity in Eosinophilic Esophagitis

OBJECTIVES: Eosinophilic esophagitis (EoE), a chronic food allergic disease, lacks sensitive and specific peripheral biomarkers. We hypothesized that levels of EoE-related biomarkers captured using a 1-hour minimally invasive Esophageal String Test (EST) would correlate with mucosal eosinophil counts and tissue concentrations of these same biomarkers. We aimed to determine whether a 1-hour EST accurately distinguishes active from inactive EoE or a normal esophagus. METHODS: In a prospective, multisite study, children and adults (ages 7–55 years) undergoing a clinically indicated esophagogastroduodenoscopy performed an EST with an esophageal dwell time of 1 hour. Subjects were divided into 3 groups: active EoE, inactive EoE, and normal esophageal mucosa. Eosinophil-associated protein levels were compared between EST effluents and esophageal biopsy extracts. Statistical modeling was performed to select biomarkers that best correlated with and predicted eosinophilic inflammation. RESULTS: One hundred thirty-four subjects (74 children, 60 adults) with active EoE (n 5 62), inactive EoE (n 5 37), and patient controls with a normal esophagus (n 5 35) completed the study. EST-captured eosinophil-associated biomarkers correlated significantly with peak eosinophils/high-power field, endoscopic visual scoring, and the same proteins extracted from mucosal biopsies. Statistical modeling, using combined eotaxin-3 and major basic protein-1 concentrations, led to the development of EoE scores that distinguished subjects with active EoE from inactive EoE or normal esophagi. Eightyseven percent of children, 95% of parents, and 92% of adults preferred the EST over endoscopy if it provided similar information. DISCUSSION: The 1-hour EST accurately distinguishes active from inactive EoE in children and adults and may facilitate monitoring of disease activity in a safe and minimally invasive fashion.

Effect of a 4-Food Elimination Diet and Omeprazole in Children with Eosinophilic Esophagitis – A Randomized, Controlled Trial

The present trial assessed whether a 4-food elimination diet (4-FED), in combination with proton pump inhibitor (PPI) treatment, is superior to PPI monotherapy in children with eosinophilic esophagitis (EoE). After a baseline gastroscopy, patients with histologically proven EoE (≥15 eosinophils per high power field; HPF) were randomized to omeprazole 1mg/kg twice daily (max. dose 20mg b.i.d.) plus a 4-FED (cow’s milk, soy, egg, wheat) vs omeprazole monotherapy. A second gastroscopy was performed after 8-12 weeks. Complete mucosal remission was defined as eosinophils <5/HPF, and partial remission as <10/HPF on repeat biopsy. Of 64 patients (median age 9.1 yrs) with EoE, 32 were randomized to PPI+4-FED, and 32 to PPI only. There was a higher rate of non-completers in the diet group (5/32 vs 1/32; NS). At baseline, median eosinophil counts were similar between groups (PPI 44.5 [IQR 24-82] vs PPI+4-FED 37 [IQR 21.5-57]; p=0.24). At 8-12 weeks, participants in the PPI+4-FED group had lower median mucosal eosinophil counts, compared to the PPI group (2.5 [IQR 0.5-19] vs 12 [IQR 0-37]; p=0.11). Eosinophil counts were significantly different only in the lower esophagus (PPI+4-FED 2 [IQR 0-18] vs PPI 24 [IQR 5-43]; p=0.003). On per-protocol analysis, at least partial remission (<10 eosinophils/HPF) was significantly more likely for PPI+4-FED vs PPI (88% vs 45%; p=0.002), with borderline significance on intention-to-treat analysis (PPI+4-FED 69% vs PPI 44%; p=0.054). This is the first randomized clinical trial demonstrating that a 4-FED combined with PPI is significantly more effective than PPI monotherapy in children with EoE.

Elevated Tryptase in EoE Is an Independent Phenomenon Associated with Extra-Esophageal Symptoms.

Eosinophilic esophagitis (EoE) is a chronic disease characterized histologically by > 15 eosinophilsper high-power field (eos/hpf). Esophageal mucosal mast cells have been implicated in EoE pathogenesis. The association of atopy with EoE has been established but has not been correlated with levels of serum tryptase. The lack of concurrent atopy in some patients suggests the possibility that atopy may either be the related subtype of EoE or may be a sign of comorbidities. No study has looked at whether patients present with different phenotypes/comorbid disease when they have evidence of elevated serum tryptase. We hypothesized that these patients differ with respect to presentation and comorbidities with more refractory GI disease. To examine whether elevations of serum tryptase associate with different, more severe clinical presentations in EoE patients which may be explained via mast cell activation. Retrospective chart review identified 72 patients with EoE with results for serum tryptase between 2015 and 2016. Patients were classified as TryptaseHI (tryptase > 10.9µg/l) and TryptaseLO (< 10.9µg/l). Clinical characteristics and treatment response were compared using univariate analysis and multivariate regression between the groups. Out of 72 patients, 12 were tested as TryptaseHI (16.7%, 95% CI 8.1-25.3%). TryptaseHI was associated frequently with asthma (P = 0.0003), urticaria (P = 0.002), arthralgia (P = 0.005), sinusitis (P = 0.03), nausea/vomiting (P = 0.046), and eosinophilic gastrointestinal disease (P = 0.001). Asthma and arthralgia were found to be significantly associated with TryptaseHI (P = 0.0013, P = 0.0098, respectively). Mucosal eosinophil counts and tryptase levels were not correlated (R2 0.095, P = 0.77). Tryptase did not resolve with resolution of esophageal eosinophilia. We found that EoE patients with elevated tryptase levels more commonly presented with asthma, urticaria, arthralgia, nausea/vomiting, sinusitis, and more distal eosinophilia. This indicates that atopy in EoE patients warrants further exploration. The lack of correlation between histologic remission and reduction of serum tryptase levels post-treatment suggests that mast cell activation may be an independent, yet associated disease. More study into this unique association is warranted.

JESREC score and mucosal eosinophilia can predict endotypes of chronic rhinosinusitis with nasal polyps

ObjectiveRecently, JESREC score and mucosal eosinophil count have been used to diagnose eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, it remains unknown whether the subtypes of CRS diagnosed by these criteria have different endotypes. In the present study, we investigated whether JESREC score and mucosal eosinophil count were appropriate for classification of CRS subgroups into endotypes. MethodsA cross-sectional study involving 71 consecutive patients with CRS with nasal polyps (CRSwNP) and 13 control patients was performed. Nasal polyp tissues from CRSwNP patients and uncinate process tissues from control patients were collected for analysis of inflammatory cells by immunohistochemistry and measurement of cytokines and chemokines by ELISA and quantitative real-time PCR. We compared the differences between subtypes according to JESREC score and mucosal eosinophil count and investigated the subgroups with different endotypes by cluster analysis and principal component analysis. ResultsIn the 71 CRSwNP patients, 9 patients had JESREC score <11 and mucosal eosinophil count <70/HPF (Group A), 20 patients had JESREC score ≥11 and mucosal eosinophil count <70/HPF (Group C), and 42 patients had JESREC score ≥11 and mucosal eosinophil count ≥70/high-power field (HPF) (Group D). Semiquantitative analysis of inflammatory cells showed that eosinophils, neutrophils, macrophages, mast cells, and basophils differed significantly between the subgroups. At the mRNA level, CLC, IL5, IL13, CCL11, CCL24, CCL26, POSTN, CSF3, and IL8 showed significant differences. At the protein level, eotaxin-2/CCL24, eotaxin-3/CCL26, and G-CSF had significant differences. Cluster analysis using gene expression levels in 55 CRS patients and 11 control patients revealed that the patients could be classified into five clusters. Cluster 1 (n=27) contained all patients with Group D. Cluster 2 (n=11) comprised all control patients. Cluster 3 (n=4) included mixed subtypes: one with Group A and three with Group D. Cluster 4 (n=7) and Cluster 5 (n=17) contained all patients with Groups A and C, respectively. Furthermore, the principal component analysis revealed that the subtypes had different characteristics. ConclusionCRS subtypes based on JESREC score and mucosal eosinophil count showed different inflammatory patterns, and unsupervised statistical analyses supported the classification that can predict endotypes. From these results, we concluded that the classification based on JESREC score and mucosal eosinophil count was useful for predicting CRS endotypes.

Comparison of mucosal impedance measurements throughout the esophagus and mucosal eosinophil counts in endoscopic biopsy specimens in eosinophilic esophagitis

Assessing eosinophilic esophagitis (EoE) activity from limited esophageal mucosal biopsy samples has been questioned. Here our aim was to compare mucosal impedance (MI) throughout the esophagus and eosinophil counts in endoscopic biopsy samples in EoE. We compared 20-site MI using a balloon catheter in the esophagus and eosinophils per high-power field (eos/HPF) in esophageal mucosal biopsy samples. Data are summarized as median (interquartile range) comparing control subjects and EoE using Mann-Whitney rank sum test and between endoscopic reference score and MI (minimal and average) using rank Spearman correlation. Ten adult control patients (ages 38-70) and 23 EoE patients (ages 21-80, 18 active) were studied. The mean (range) pan-esophageal MI in control subjects was significantly higher (6435 ohms [4546-7301]) compared with EoE patients (2004 ohms [1437-2546], P< .001). In control patients 172 of 180 (95.6%) individual impedance measurements (18 per patient) were normal when compared with 126 of 432 (29.2%) measurements in EoE. No EoE patient had uniformly normal MI. MI varied widely, with 19 of 23 patients having values above and below 2300 ohms (normal) regardless of EoE activity. Correlation of maximim eos/HPF with minimum and average MI per patient was r= -.243, P= .072 and r= -.358, P= .086, respectively. Of 5 patients with inactive EoE, 3 had >50% abnormal MI segments. Correlation coefficients of the endoscopic reference score with minimum and average MI were r= -.154, P= .47 and r= -.27, P=.20, respectively. The procedure was<5 minutes without adverse events. MI is lower in the esophagus of EoE patients compared with control subjects with poor correlation between peak esophageal eosinophil counts, EoE activity, and MI. Segmental esophageal MI provides a unique marker of esophageal dysfunction in EoE. (Clinical trial registration number: NCT02995395.).

Could Eosinophilia predict clinical severity in nasal polyps?

BackgroundAlthough nasal polyps are one of the most frequent diseases, their etiopathogenesis remains unclear.Since eosinophils are the main inflammatory cells in the substantial proportion of nasal polyp tissues, they are considered potentially responsible for the etiopathogenesis and prognosis of the disease. Aim of this study was to investigate the relation between mucosal and peripheral eosinophilia and their relation with disease severity in nasal polyps.MethodsThe study included 53 patients with nasal polyps who underwent endoscopic sinus surgery. Preoperative Lund-MacKay computed tomography (CT) scores and the Lund-Kennedy endoscopic scores of the patients were recorded. Nasal polyp tissues were stained with hematoxylin and eosin, eosinophil counts were performed using high-power field (HPF, 400×) under the light microscope, and the patients were grouped as those with high mucosal eosinophil count and those with low mucosal eosinophil count.ResultsThe mean Lund-MacKay CT score and the mean Lund-Kennedy endoscopic score were higher in the patients with high mucosal eosinophil count than in those with low mucosal eosinophil count. Likewise, the mean Lund-MacKay CT score and the mean Lund-Kennedy endoscopic scores were significantly higher in the patients with high peripheral eosinophil count than in those with low peripheral eosinophil count (p < 0.05 for both). Moreover, the mean peripheral eosinophil count was significantly higher in the patients with high mucosal eosinophil count than in those with low mucosal eosinophil count (p < 0.05).ConclusionMucosal and peripheral eosinophilia can be used as a marker to predict disease severity in nasal polyps.

Could eosinophilia predict clinical severity in nasal polyps?

Background: Although nasal polyps are one of the most frequent diseases, their etiopathogenesis remains unclear. Since eosinophils are the main inflammatory cells in the substantial proportion of nasal polyp tissues, they are considered potentially responsible for the etiopathogenesis and prognosis of the disease. Aim of this study was to investigate the relation between mucosal and peripheral eosinophilia and their relation with disease severity in nasal polyps.&#x0D; Methods: The study included 53 patients with nasal polyps who underwent endoscopic sinus surgery. Preoperative Lund-MacKay computed tomography (CT) scores and the Lund-Kennedy endoscopic scores of the patients were recorded. Nasal polyp tissues were stained with hematoxylin and eosin, eosinophil counts were performed using high-power field (HPF, 400×) under the light microscope, and the patients were grouped as those with high mucosal eosinophil count and those with low mucosal eosinophil count.&#x0D; Results: The mean Lund-MacKay CT score and the mean Lund-Kennedy endoscopic score were higher in the patients with high mucosal eosinophil count than in those with low mucosal eosinophil count. Likewise, the mean Lund-MacKay CT score and the mean Lund-Kennedy endoscopic scores were significantly higher in the patients with high peripheral eosinophil count than in those with low peripheral eosinophil count (p &lt; 0.05 for both). Moreover, the mean peripheral eosinophil count was significantly higher in the patients with high mucosal eosinophil count than in those with low mucosal eosinophil count (p &lt; 0.05).&#x0D; Conclusion: Mucosal and peripheral eosinophilia can be used as a marker to predict disease severity in nasal polyps.