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Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study
Vasundhara Tolia*1,5, Nader N Youssef2,6, Mark A Gilger3, Barry Traxler4 and Marta Illueca4
Abstract Background: Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology. Methods: Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions. Results: Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination. Conclusions: Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children. Trial Registration: D9614C00097; ClinicalTrials.gov identifier NCT00228527. Background Gastroesophageal reflux disease (GERD) increasingly is recognized in young children. A recent retrospective population-based cohort study in Rochester, MN, found that the incidence of GERD in children aged < 5 years was 0.9/1,000 person-years . Data on the prevalence and severity of erosive esophagitis (EE) in young children are limited. The prevalence of endoscopy- and biopsy-proven EE in one study was 29% in 209 patients with GERD aged 18 months to 10 years who had no neurologic abnormalities or congenital esophageal anomalies . A retrospective review of the Pediatric Endoscopy Database SystemClinical Outcomes Research Initiative (PEDS-CORI)
* Correspondence: email@example.com
Wayne State University, Detroit, MI, USA
Full list of author information is available at the end of the article
demonstrated that, of 7,188 children aged ≤ 18 years who underwent endoscopy, 12.4% had EE . Although endoscopy is a valuable tool in the diagnosis of pediatric GERD and EE that provides macroscopic evidence of erosions, histology is important because abnormalities may be present without visible lesions on endoscopy. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines for pediatric GERD recommend esophageal biopsy in conjunction with diagnostic endoscopy . If erosions are identified, histology is not considered mandatory for routine diagnosis of GERD. On histology, esophagitis is diagnosed by the presence of epithelial hyperplasia, intraepithelial inflammation, vascular dilatation in papillae, balloon cells, and ulceration . Dilated intercellular spaces have been described as an
© 2010 Tolia et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
randomized. NJ) or equivalent. similar studies have not been conducted in pediatric populations. Wilmington. bleeding lesions. Parsippany. macroscopic evidence for GERD seen on endoscopy was documented and included hyperemia. and each patient's parent or guardian provided written informed consent with assent from the patient. Children aged 1-11 years with endoscopically confirmed GERD (determined by endoscopy with or without biopsies) were screened and eligible to be enrolled in an international. and nodularity. Patients with allergic or eosinophilic esophagitis. Age-appropriate liquid antacid medication. this study allowed assessment of the usefulness of an adult classification system for EE in the pediatric population. Criteria for establishing and documenting a clinical diagnosis of GERD were consistent with the NASPGHAN guidelines . was allowed as rescue medication. BMC Pediatrics 2010. use in excess of the prescribed amount was reviewed with the parent or guardian at each visit and documented. and pantoprazole . Methods Study design and patients The study design. ulcers. and lansoprazole (1-17 years). Study procedures were conducted in accordance with the ethical principles of the Declaration of Helsinki and its amendments and with the International Conference on Harmonization and Good Clinical Practice guidelines.Tolia et al. Table 1: Los Angeles Classification System for erosive esophagitis LA grade A Description ≥1 Mucosal break ≤5 mm that does not extend between the tops of two mucosal folds ≥1 Mucosal break ≥5 mm long that does not extend between the tops of two mucosal folds ≥1 Mucosal break that is continuous between the tops of two or more mucosal folds but that involves < 75% of the esophageal circumference ≥1 Mucosal break. Although not a planned objective. Institutional Review Boards at each participating center approved the study protocol (AstraZeneca study code D9614C00097.biomedcentral.17]. however. Currently three PPIs are approved by the US Food and Drug Administration for the treatment of EE in children: esomeprazole (1-17 years). Rescue medication use was recorded. the Los Angeles (LA) Classification System. however. DE) 5 or 10 mg (children ≥ 8 kg and < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily for 8 weeks. Novartis Consumer. double-blind (for dose) study evaluating once-daily esomeprazole during 8 weeks of treatment. we describe the healing of EE after esomeprazole treatment in children aged 1-11 years. and Barrett's esophagus were excluded from the study. which involves ≥75% of the esophageal circumference B C D LA: Los Angeles. omeprazole (2-16 years). Acid suppression with a proton pump inhibitor (PPI) is standard treatment for GERD and EE in adults  and increasingly is becoming first-line therapy for children aged 1-17 years . less commonly. In this report. and safety assessments have been described in detail previously . strictures. such as eosinophilic or infectious esophagitis and. As described in the literature . Barrett's esophagus . In addition. Mucosal biopsies also are recommended but not mandatory in current pediatric endoscopy practice to exclude potentially confounding diagnoses.9]. Patients were assigned randomly to esomeprazole (Nexium®. ClinicalTrials. . 10:41 http://www. EE was not required. gastric ulcers. because the literature lacks reports of histologic data from young children with GERD. multicenter.com/1471-2431/10/41 Page 2 of 9 additional morphologic feature of GERD and esophagitis in infancy and childhood . eligibility criteria. MAALOX® (aluminum hydroxide 225 mg/magnesium hydroxide 200 mg per 5 mL. patient characteristics. Valid pediatric indicators of histologic reflux esophagitis were recorded. parallel-group. baseline histology findings are reported here. where applicable. The pharmacokinetic profile of esomeprazole in children aged 1-11 years has been published previously . AstraZeneca LP.11]. The primary safety and clinical outcomes of esomeprazole treatment of GERD from this study have been reported previously . lansoprazole [10. For children aged < 6 years or for those who had difficulty swallowing the capsules. Endoscopic findings were classified using the LA Classification System for EE (Table 1) . when applicable. methodology. capsule contents could be mixed with 1 tablespoon of applesauce. Patients with no visible or definitive lesions underwent a mucosal biopsy during baseline endoscopy for histologic confirmation of reflux esophagitis.gov identifier NCT00228527). before any study-specific procedure was performed. Erosive or histologic GERD was documented. Findings from direct comparative studies in adults show that esomeprazole more effectively heals EE in adults than omeprazole [8. including the presence of intraepithelial eosinophils or neutrophils and increased basal cell layer thickness and papillary height [16. Parents or guardians were instructed to administer rescue medication according to product labeling or as prescribed by the physician.
The ITT population was defined as all patients who had baseline and one or more postbaseline measurements. . The percentage of patients with healed esophageal erosions and the 95% confidence interval for the total were calculated by AstraZeneca (B. and epigastric pain (55%) (Table 2). increased thickness of the basal cell layer (> 20% to 25% of total epithelial thickness) [4. mucosal biopsy specimens were obtained during baseline endoscopy for histologic confirmation of GERD-related esophagitis in patients without visible or definitive lesions . Endoscopy with biopsy was used to document the extent of EE. and from any area with an abnormal appearance. Histologic changes were recorded [24-26] but not required as a research procedure.Tolia et al. and 57 (52. If needed. The LA Classification System was used to grade EE (Table 1) . Safety was assessed by adverse events (AEs) spontaneously reported by the parent or guardian.T. Statistical analysis Outcome analyses of EE healing were conducted on the intention-to-treat (ITT) population dataset. Height.22.). These symptoms were derived from the NASPGHAN guidelines  and included heartburn (burning feeling rising from the stomach or lower part of the chest toward the neck). including the number of intraepithelial eosinophils and neutrophils [4.0 mg/kg. reported in response to an open question from the investigator. GERDrelated symptoms were reported by the parents or guardians on behalf of the patients. and body mass index also were similar across dose groups within each weight stratum (< 20 kg or ≥ 20 kg). France (two sites). no patient underwent endoscopy solely for study enrollment or other research purposes. A total of 109 patients were randomized in the study and included in the ITT population. vomiting (gastric contents are forced up to and out of the mouth). Esomeprazole doses ranged 0. and appropriate histologic confirmation was obtained when indicated [18. Histologic evidence was required for patients who were newly diagnosed with GERD if the patient did not have EE to confirm the presence of esophagitis. and the United States (15 sites).7 years.3%) were aged 6-11 years.g.22]. 10:41 http://www. Biopsy specimens were evaluated at each study site for histologic findings. Accordingly.2-1.5 cm above the Z-line (squamocolumnar junction) based on the investigator's assessment of landmarks. and feeding difficulties (food refusal. Italy (four sites). those listed previously in Methods). and completion of a posttreatment endoscopy. Histologic changes were characterized based on the standards from each pathologist's individual institution. Therefore. the study was designed to randomize ≥ 100 patients to ensure that ≥ 40 patients in each age group would complete the study.19]. and clinical laboratory evaluations. The distribution of patients met the study goal of ≥ 40 evaluable patients in each age group.21. elongated length of papillae (> 50% to 75% of epithelial thickness) [4. and/or poor weight gain). a repeat endoscopy was planned after 8 weeks of esomeprazole treatment to document healing. and increased total epithelial thickness. and specimens were obtained for medical reasons only at the discretion of the investigator. vital signs. Other pediatric endoscopic GERD descriptors of esophagitis as reported in the literature were accepted. An upper gastrointestinal endoscopy was performed during screening at the discretion of the investigator. and rule out certain exclusionary conditions. The most common presenting GERD symptoms at baseline were heartburn (52%). four had eosinophilic esophagitis. acid regurgitation (perception of unpleasant-tasting fluid backing up into the throat and/or mouth). Baseline demographic and nonphysical disease characteristics were similar across all treatment groups (Table 2). Of the 49 patients who failed the screening process. one or more ingested doses of study medication. epigastric pain (perception of discomfort located in the central upper portion of the abdomen). EE was considered healed if no signs of erosion were observed on final endoscopy. Fifty-two patients (47.22]. and 16 were not related to endoscopy (Figure 1). physical examinations. or revealed by observation or change from baseline conditions or values in medical histories. Per routine standards of pediatric medical practice .. approximately 0. lymphocytes per high power field.23]. findings were recorded on the case report form (e. For patients who had EE at baseline. The International Conference on Harmonization guideline E1 recommends randomization of ≥ 100 patients for the safety database of any drug. acid regurgitation (55%).com/1471-2431/10/41 Page 3 of 9 Assessments All procedures including upper endoscopic evaluation were indicated clinically and represented standard practice at the local institution.7%) were aged 1-5 years. 27 had no endoscopic proof of reflux esophagitis.21. Results Patient characteristics The study was conducted between October 2004 and November 2005 at 24 sites within Belgium (three sites). choking with food/drink. difficulty swallowing (difficulty passing anything through the pharynx or esophagus). BMC Pediatrics 2010. Biopsy was optional for patients with endoscopically visible lesions. determine the presence of Helicobacter pylori. weight. Patients who had a previous endoscopic diagnosis of EE within 2 weeks of screening and were candidates for PPI therapy were not required to have an additional endoscopy if a full endoscopic report with photographic documentation was available.biomedcentral. biopsy specimens were recommended to be taken from the distal esophagus. The mean age was 5. two had a normal endoscopy.
Healing of EE did not occur in five patients (11%): two patients in the 20-mg group were rated as improved but not completely healed (i.3%). < 20 kg. 53 (49%) had EE at baseline and 56 (51%) had reflux esophagitis without EE (Table 3). In addition. including those with EE.. 17 (65%) had EE. more importantly. < 20 kg. endoscopy performed outside the study timeframe (n = 1). hyperemia. n = 2. Moreover. The proportion of patients with EE and other reflux esophagitis was distributed evenly across treatment groups. however. Our results demonstrate that the LA Classification System can be used successfully to classify the severity of EE in children. it has not been validated yet for use in pediatric populations. n = 1. Of 109 patients in the ITT population. n = 27 • Presence of eosinophilic esophagitis. which have been adapted previously for pediatric studies [31.. 10-mg/≥ 20 kg group). Other esophageal abnormalities (e.biomedcentral. Dilation of intercellular space was reported in 24% of patients. ≥ 20 kg). 36 (43%) had EE. The majority of children with EE in this study had LA grades A and B (29% and 17%.32]. an extrapolation of the recommended adult esomeprazole doses using an exposureresponse relationship reported previously . n = 2 • Failed for reasons unrelated to endoscopy. this study is the first to prospectively report the use of the LA Classification System  to diagnose and document EE healing in young children. however.com/1471-2431/10/41 Page 4 of 9 Adverse events 158 Patients screened for eligibility • Did not have endoscopic proof of reflux esophagitis. this study did not include a placebo control group but was double blind to dosage. esophageal ulcers.8%. Of 109 patients randomized. of 26 patients enrolled from European sites. nodularity. and three patients in the 10-mg groups exhibited no change from baseline (n = 2. straightforward method to grade EE and document healing in the absence of erosions. . 10:41 http://www. BMC Pediatrics 2010. the use of esomeprazole across a wide dose range (0. n = 4 • Had normal endoscopy. The use of the LA classification system in children may allow for comparison between pediatric and adult data to unify our knowledge of healing of EE. The most commonly reported treatment-related AEs were diarrhea (2. prolapse gastropathy) were present in 55 children (n = 21. the assessment of the clinical outcome of EE was not controlled and was not the primary end point of the study. Hetzel-Dent or Savary-Miller classifications).2-1.e. The lack of a control group is a potential limitation to this study. The LA classification system offered a simple.66 mg/kg. 10-mg/< 20 kg group). n = 3.Tolia et al. revised diagnosis (n = 2). Hiatal hernia was documented in seven children in the < 20-kg group and 12 children in the ≥ 20-kg group. 53 Patients had EE 56 Patients did not have EE Figure 1 Patient disposition. EE: erosive esophagitis. For ethical reasons in a population of children with confirmed GERD.9%. Discussion Based on this study. Investigators reported other gastric and duodenal abnormalities when detected. EE was healed in 40 patients (89%) (Figure 2). Esophageal healing Of 53 patients with EE at baseline. Healing rates were similar across all esomeprazole dose groups. 13 AEs considered by the investigator to be related to esomeprazole treatment occurred in 10 of 108 patients (9. Of 45 patients who had EE at baseline and underwent posttreatment endoscopy. ≥ 20 kg) (Table 3). Furthermore. Other histologic findings were present in the esophagus at baseline (Table 4). and somnolence (1. Patients whose EE was not healed received doses in the range of 0. The results of the present study provide additional evidence to support the safe use and tolerability of PPIs in children with GERD with or without EE . Of 83 patients enrolled from study sites within the United States. and the other had grade D (≥ 20 kg/20-mg group) . the small number of patients in each treatment group precluded a comparison between doses. headache (1.9%. 10-mg/ < 20 kg group).g. All but two patients had LA grades A or B EE (Table 3). n = 34. n = 1. are available [27-34].g.. Several EE classification systems exist in the adult literature (e. respectively). Few studies of PPI treatment of young children with GERD. and the assumption that most children < 12 years weigh 8-60 kg. eight did not undergo final endoscopies or were otherwise excluded from the ITT population because of premature study discontinuation (n = 4). to our knowledge.0 mg/kg) daily for ≤ 8 weeks resulted in significant healing of macroscopic and histologic esophagitis in children aged 1-11 years. 5-mg/< 20 kg group and n = 1. or failure to give reason for not performing endoscopy (n = 1).17-0. n = 16 109 Randomized Safety data were evaluable in 108 of 109 patients randomized and are described in detail elsewhere . The doses used in this study were determined from the results of a pharmacokinetic study of esomeprazole in children aged 1-11 years. ≥ 1 LA grade improvement). 107 had a biopsy. In brief. one patient had grade C (< 20 kg/10-mg group). the clinical benefit of esomeprazole in healing EE was documented.
2) 7 (24. BMC Pediatrics 2010.3) 0.8) 11 (37.5) 7 (30.2) 6 (23. n (%) Mean age.3-0.7) 1 (4. n (%) Symptoms at baseline.2) 8.7 (0.7 (2.3 Girls.0) 7 (43.1 (10-18) 15.7) 5 (17. n (%) White Black Other Mean height (range).9) 19 (73.6 (3.0 (70-109) 12.8) 13 (56.1) 0 134.5 (20-58) 19.4) 3 (9.6) 4 (17.7) 2 (6.4) 13 (50.4) 2 (6.1) 5 (16.5) 13 (44.2-0.0) 6 (20.2) 3 (10.3) 0.4) 13 (56.0) .7) 6 (23. n (%) Heartburn Acid regurgitation Epigastric pain Vomiting Eating difficulties Difficulty swallowing Extraesophageal symptoms at baseline.7) 1 (8. n (%) Hoarseness Coughing Gagging Wheezing/stridor Mean (range) esomeprazole dose.3) 20 (64.7) 4 (17.5) 15 (48.3-1.6-1.3-1. years Age in years.9) 1 (3.8) 0 (0) 0.1) n = 16 4 (25.9) 5 (16.9) 0 90.0) 9 (75.9) 2.0 mg/kg) (n = 29) 11 (37.4) 2 (7. kg Mean body mass index (SD).0) 2 (8.8) 1 (3.7) 6 (20.5) 5 (16.0 mg/kg) (n = 23) 14 (60.7) 6 (19.2) 2 (6.2-0.3) 9 (31.5 Children ≥ 20 kg Esomeprazole 10 mg (0. n (%) 1 2 3 4 5 6 7 8 9 10 11 Race.7) 5 (41.8) 7 (53.3-0.6 mg/kg) (n = 26) 14 (53.5 (108-168) 35.7) 1 (3.1) n = 13 7 (53.8) n = 12 4 (50.4) 3 (13.5) 8 (34.Tolia et al.9) 8. kg/m2 12 (46. cm Mean weight (range).9) 0 Helicobacter pylori-positive.1) 4 (15.8) 5 (21.0) 6 (50.0) 5 (16.8 (8-18) 15. 10:41 http://www.8) 4 (30.0) 19 (61.4 (0.1) 8 (25.com/1471-2431/10/41 Page 5 of 9 Table 2: Demographic and baseline disease characteristics of all patients enrolled (N = 109) Children < 20 kg Characteristic Esomeprazole 5 mg (0.3 (4.4) 0 94.5 (21-60) 18.0) 1 (8.3 (0.2) 1 (3.5) 0.7) 9 (29. mg/kg 15 (57.9 (1.biomedcentral.1) 0 19 (82.1) n = 12 4 (33.1) 6 (20.1) 7 (26.9) 15 (51.3) 26 (83.4) 0 3 (10.6 (0.8) 3 (9.7) 18 (69.2 (80-119) 14.5) 2 (12.7) 1 (4.5) 11 (47.2) 17 (65.8) 2 (12.5 mg/kg) (n = 31) 14 (45.6-1.8) 2.8) 0 25 (86.3) 1 (3.8) 8 (34.4) 134.5 Esomeprazole 20 mg (0.5 (112-159) 34.0) 15 (57.6) 10 (43.1 Esomeprazole 10 mg (0.3) 8 (66.3) 1 (3.
asthma) in GERD. LA: Los Angeles. Additionally.4%) . when available. Determination of the true incidence of these markers in children is an area of future research. Endoscopic findings were required to be documented at study entry to allow for full characterization of the extent of GERD. prominent esophageal folds (n = 11 [10%]). erythema/hyperemia (n = 23 [21%]). the reason for a greater proportion of patients with EE in the European study sites compared with the United States study sites is not clear.4.biomedcentral. Although biopsy specimens were not evaluated by a central reader and therefore were not standardized.0 mg/kg) healed esoph- Children ≥20 kg Esomeprazole 10 mg (0. Large epidemiologic studies in children also are needed to determine the role of extraesophageal symptoms and concomitant conditions (e.35-37]. the histopathologic data obtained contribute to the existing sparse literature in this patient population. Our results suggest that dilation of intercellular space may be a potential histologic diagnostic criterion for EE .Tolia et al. In this pediatric population.0 mg/kg) (n = 23) 11 (48) nosis of other esophageal disorders. The results of the present study parallel the results from those of previous studies of PPIs in adults with EE and provide additional support for the use of esomeprazole treatment for EE in young children.g. including the presence and severity of EE and other gross findings. Furthermore. which have been shown to be a possible predictor of EE in the PEDS-CORI .20]. the clinical course and manifestations of the spectrum of GERD symptoms appear to be similar to those seen in adults. 10:41 http://www. Dilation of intercellular space was reported in 24% of the patients in this study (reporting this information was not mandatory).5 mg/kg) (n = 31) 15 (48) Esomeprazole 20 mg (0. the prevalence of EE (49%) in children aged 1-11 years was higher than that reported previously in children (12.2-0.com/1471-2431/10/41 Page 6 of 9 In the present study. n (%) Children < 20 kg Category Esomeprazole 5 mg (0.2-1. The current study continues to expand on the knowledge and potential management options that are available for young children with GERD and EE. Baseline endoscopic and histologic data showed that 18% of patients had esophageal nodules.0 mg/kg) (n = 29) 16 (55) Total (N = 109) Other reflux esophagitis Erosive esophagitis LA grade A LA grade B LA grade C LA grade D Hiatal hernia Other abnormality* 56 (52) 12 (46) 6 (23) 6 (23) 0 0 4 (15) 11 (42) 12 (52) 6 (26) 5 (22) 1 (4) 0 3 (13) 10 (44) 16 (52) 11 (36) 5 (16) 0 0 8 (26) 16 (52) 13 (45) 9 (31) 3 (10) 0 1 (3) 4 (14) 18 (62) 53 (49) 32 (29) 19 (17) 1 (1) 1 (1) 19 (17) 55 (50) *Abnormalities occurring in ≥4 patients were nodularity (n = 20 [18%]). and adult efficacy data may be extrapolated to this age group [3. aided in excluding the diagTable 3: Endoscopic findings at baseline.6 mg/kg) (n = 26) 14 (54) Esomeprazole 10 mg (0.3-0. The criteria for establishing and documenting endoscopically proven GERD for study entry were consistent with those previously recommended by NASPGHAN [4. BMC Pediatrics 2010. An 8-week treatment duration represents the approximate time needed for healing of EE in adults [8-12]. whereas 49% of patients had endoscopically confirmed EE. . Guidelines for treatment of pediatric GERD recommend a 3-month course of acid suppression treatment for children who have GERD symptoms . histologic assessment. The reasons for such geographic variation need to be studied further. and friability (n = 4 [4%]). we cannot determine accurately the incidence of these potential markers because not every patient was evaluated for these histologic changes in a standardized manner.. Although these potential histologic predictors of EE were identified in patients in this study. such as eosinophilic esophagitis.3-1. Conclusion The findings of this study showed that an 8-week course of esomeprazole treatment (0.6-1. edema (n = 11 [10%]).
NASPGHAN: North American Society for Pediatric Gastroenterology.0 mg/kg) (n = 23) 3 (13) 9 (39) 1 (4) 9 (39) 10 (44) 13 (56) 10 (44) Children ≥20 kg Esomeprazole 10 mg (0. BT made substantial contributions to conception and design and to analysis and interpretation of the data and was involved in drafting the manuscript and revising the manuscript for important intellec- .0 mg/kg) (n = 29) 12 (41) 13 (45) 3 (10) 14 (48) 19 (66) 19 (66) 10 (34) Total (N = 109) Eosinophilic densification Intraepithelial eosinophils† Intraepithelial Intraepithelial lymphocytes† Elongated length of papillae Increased thickness of basal cell layer Increased total epithelial thickness Dilation of intercellular spaces Absent/NR < 25% ≥25% Columnar epithelium Present Not assessable Cardia mucosa Corpus mucosa Diagnosis of microscopic reflux esophagitis *107 Patients had a biopsy. a complementary scoring system is needed to accommodate other pediatric endoscopic findings described in the literature. and NNY have received grant/research support from AstraZeneca.biomedcentral. LA: Los Angeles. EE: erosive esophagitis. PEDS-CORI: Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative. Abbreviations AE: adverse event. Johnson & Johnson. PPI: proton pump inhibitor.6-1. 10:41 http://www.3-1. such as esophageal nodules . Hepatology. Authors' contributions VT made substantial contributions to conception and design. †Per high power field. VT has received research grants from Wyeth. Although the LA Classification System was used successfully to grade EE in this study. NNY made substantial contributions to acquisition of data and analysis and interpretation of data and was involved in revising the manuscript for important intellectual content. NR: not reported.3-0. MAG made substantial contributions to analysis and interpretation of the data and was involved in revising the manuscript for important intellectual content. and MI are employees of AstraZeneca LP. For example.2-0. MAG has served as a speaker and a consultant for TAP and AstraZeneca and has served as a speaker for Nestle. n (%)* Children < 20 kg Category Esomeprazole 5 mg (0. the development of a new pediatric-specific scoring system is suggested.Tolia et al.com/1471-2431/10/41 Page 7 of 9 Table 4: Baseline histologic data of the esophagus. ITT: intention-to-treat. Histologic assessment showed frequent mucosal damage in this population and provides further support for the use of histology to augment endoscopic findings in pediatric patients with GERD. NNY. neutrophils† 27 (25) 40 (37) 15 (14) 53 (49) 61 (56) 62 (57) 41 (38) 21 (81) 3 (12) 2 (8) 21 (91) 2 (9) 0 24 (77) 5 (16) 2 (6) 17 (59) 10 (34) 2 (7) 83 (76) 20 (18) 6 (6) 4 (15) 1 (4) 2 (8) 1 (4) 20 (77) 4 (17) 5 (22) 3 (13) 1 (4) 18 (78) 3 (10) 7 (23) 1 (3) 3 (10) 24 (77) 4 (14) 4 (14) 4 (14) 1 (3) 24 (83) 15 (14) 17 (16) 10 (9) 6 (6) 86 (79) ageal erosions in 89% of children aged 1-11 years who had EE. and Nutrition. Competing interests VT. and GlaxoSmithKline and has served as a speaker for Takeda and SHS Nutritionals.6 mg/kg) (n = 26) 4 (15) 5 (19) 5 (19) 13 (50) 16 (62) 15 (58) 11 (42) Esomeprazole 10 mg (0. MAG. GERD: gastro esophageal reflux disease. BT. and analysis and interpretation of data and was involved in drafting the manuscript and revising the manuscript for important intellectual content. acquisition of data. BMC Pediatrics 2010.5 mg/kg) (n = 31) 8 (26) 13 (42) 6 (19) 17 (55) 16 (52) 15 (48) 10 (32) Esomeprazole 20 mg (0.
Detroit. Brussels. 7:5-16. and published subsequently in Journal of Pediatric Gastroenterology and Nutrition  as an abstract. Boyle JT. Chattanooga. J Pediatr Gastroenterol Nutr 2008. MD. USA . Newtown. The Esomeprazole Study Investigators. and funded by AstraZeneca LP. PA). Dahms BB: Reflux esophagitis: sequelae and differential diagnosis in infants and children including eosinophilic esophagitis. Werlin SL: Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. Klersy C. PhD. NJ. 7. MD. Shub MD: Prevalence of endoscopic findings of erosive esophagitis in children: a population-based study. De Schepper H. PharmD (Scientific Connexions. Patrick Bontems. NY. Morristown. 8. October 19-22. Rindi G: Dilated intercellular spaces: a major morphological feature of esophagitis. PA. MD. eight did not have a final endoscopy. Whipple J. 2. 100:190-200. Rabeneck L: Endoscopic manifestations of gastroesophageal reflux disease in patients between 18 months and 25 years without neurological deficits. MD. 3. Rome. Phoenix. Hershey. Access licensee 10 from: article :41 BioMed http://www. *Of 53 patients with erosive esophagitis at baseline. Frederic Gottrand. Parma. Talley NJ. Ravelli AM. Muhammad Qureshi. Newtown. Wilmington. DE. Medical writing support was provided by Scientific Connexions. Napoli. Am J Gastroenterol 2002. .biomedcentral. & Nutrition (NASPGHAN) Annual Meeting. Am J Gastroenterol 2005. BMC Pediatrics 2010. Villanacci V. respectively. al. MI made substantial contributions to conception and design. tual content. 47:141-146. Rudolph CD. Phyllis Bishop. El-Serag HB. 97:1635-1639. France. IL. MS. 14:1249-1258. Brussels. MD. PhD. Italy. El-Serag HB. Acknowledgements This study was funded by AstraZeneca LP. the terms of the Creative Commons Attribution License (http://creativecommons.biomedcentral. Brooklyn. Schmitt C. MD. MD. Thirumazhisai Gunasekaran. Author Details 1Wayne State University. AZ. USA. DeVault KR. Chitkara DK. Rome. Aliment Pharmacol Ther 2000. and analysis and interpretation of data and was involved in revising the manuscript for important intellectual content. MD. 5. 6. DE. AL. Colletti RB. Ruzzenenti N. Leuven. which permits unrestricted use. USA.com/1471-2431/10/41 distributed Central under Ltd. DE. VT. TN. Gilger M. MD.Tolia et al. the study-site staff members. MD. France. Tobanelli P. Italy. MD. Gregory Kobak. and the following primary investigators: Dean Antonson. References 1. Tsou V. and reproduction in any medium. Dietrich CL. 32(suppl 2):S1-S31. 4. 10:41 http://www. Joelsson B: Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. Italy. Kahrilas PJ. Gianluigi de' Angelis. Hepatology. Norfolk. MD. Jeffrey Bornstein. Orlando. MD. Wilmington. DE. Falk GW.0). 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Nicolas Kalach. The authors thank Daniel Donahue and Libby Pethick (both from AstraZeneca LP) for study leadership and project management. Lisa M. USA Received: 22 January 2010 Accepted: 11 June 2010 Published: 11 June 2010 © This BMC 2010 article is Pediatrics an Tolia Open is et available 2010. Data from this manuscript were presented at the North American Society for Pediatric Gastroenterology. Park Ridge. distribution. 42:510-515. J Pediatr Gastroenterol Nutr 2006. Hamelin B. TX. acquisition of data. and Judy Fallon. David DeVoid. Collins DW. Jackson. Pediatr Dev Pathol 2004. NE. FL . 5Current Address: Providence Hospital. MI. MD. Mary Wiggin (AstraZeneca LP) for editorial assistance. Orlando. Wilmington. the patients and their parents. MI. Bailey NR. Wilmington. 2Atlantic Health. Annamaria Staiano. Italy. Salvatore Cucchiara. and Graciela Wetzler. Richard Colletti. All authors read and approved the final manuscript. Liptak GS. Klumpp. Filippo Torroni. MD. 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