We performed a randomized trial to compare nebulized and viscous topical steroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n=25) received budesonide 1 mg twice daily—either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB)—for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P=.62). Post-treatment counts were 89 and 11 (P=.02). The mucosal medication contact time, measured by scintigraphy, was higher for the OVB group than the NEB group (P<.005) and was inversely correlated with eosinophil count (R= −0.67; P=.001). OVB was more effective than NEB in reducing numbers of esophageal eosinophils in patients with EoE. OVB provided a significantly higher level of esophageal exposure to the therapeutic agent, which correlated with lower eosinophil counts.

Objectives Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy, and determine features that distinguish the two groups. Methods This prospective study conducted at University of North Carolina from 2009–2011 enrolled consecutive adult patients undergoing outpatient upper endoscopy. Subjects had esophageal biopsies to quantify the maximum eosinophil count per high-powered field (eos/hpf; hpf = 0.24mm2). If biopsies revealed ≥15 eos/hpf, subjects were treated with twice daily PPI for 8 weeks and endoscopy was repeated. If ≥15 eos/hpf persisted despite PPI therapy, EoE was diagnosed. If there were <15 eos/hpf, PPI-REE was diagnosed. The proportion of patients in each group was calculated, and patients with EoE and PPI-REE were compared. Results Of the 223 subjects enrolled, 173 had dysphagia and 50 did not. Of those with dysphagia, 66 (38%) had ≥15 eos/hpf. After the PPI trial, 40 (23%) were confirmed to have EoE, and 24 (14%) had PPI-REE. Of those without dysphagia, 2 (4%) had ≥15 eos/hpf and after the PPI trial, 1 (2%) had EoE. Compared with EoE, PPI-REE patients were more likely to be older and male, and less likely to have typical endoscopic findings of EoE. However, none of the individual factors was independently predictive of PPI-REE status on multivariable analysis. Similarly, while some endoscopic findings were differentially distributed between PPI-REE and EoE, none were significantly associated with disease status on multivariable analysis. Conclusions Esophageal eosinophilia is common among patients undergoing EGD for dysphagia. While EoE was seen in nearly a quarter of patients with dysphagia, PPI-REE was almost as common, and accounted for over one-third of those with ≥15 eos/hpf. No clinical or endoscopic features independently distinguished PPI-REE from EoE prior to the PPI trial.

Background Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness in infants is limited. Methods This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute upper respiratory illness (URI) or bronchiolitis during September - May 2004–2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time RT-PCR. Results Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup, and 27% URI. Among infants with bronchiolitis, 76% had RSV, 18% HRV, 10% influenza, 2% coronavirus, 3% HMPV, and 1% PIV. Among infants with croup, 39% had HRV, 28% PIV, 28% RSV, 11% influenza, 6% coronavirus, and none HMPV. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% PIV, and 4% HMPV. Individual viruses exhibited distinct seasonal, demographic, and clinical expression. Conclusions The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.

Background & Aims Distinguishing between eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), and proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is challenging. We assessed whether immunohistochemical analysis of esophageal tissues for major basic protein (MBP), eotaxin3, and tryptase can be used in diagnosis of EoE and to differentiate EoE from PPI-REE. Methods We conducted a prospective study of 196 consecutive adults who underwent outpatient endoscopy at the University of North Carolina from 2009 through 2012. Incident cases of EoE were diagnosed per consensus guidelines. Patients with gastroesophageal reflux disease or dysphagia served as controls. PPI-REE was defined as a symptomatic and histologic response to a PPI. Immunohistochemistry was performed to quantify MBP, eotaxin3, and tryptase. The maximum density of epithelial staining was determined for each assay; levels were compared between EoE and control, and then EoE and PPI-REE groups, and receiver operator characteristic (ROC) curves were constructed. Results Esophageal tissues from patients with EoE (n=50) had a median 951 MBP-positive cells/mm2 whereas those from controls (n=123) had a median 2 MBP-positive cells/mm2 (P<.001). Samples from patients with EoE had a median 155 eotaxin3-positive cells/mm2 and those from controls (n=123) had 18 MBP-positive cells/mm2 (P<.001). Samples from patients with EoE had a median 249 tryptase-positive cells/mm2 and those from controls (n=123) had 11 tryptase-positive cells/mm2 (P<.001). Levels of MBP, eotaxin3, tryptase, and the combination of all 3 identified patients with EoE with area under the ROC curve values of 0.99, 0.94, 0.99, and 1.00. Analyses of only samples with eosinophil counts of 10–100 eos/hpf produced similar results. No marker distinguished EoE from PPI-REE. Esophageal tissues from patients with PPI-REE (n=23) had 987 MBP-positive cells/mm2 (P=.18, compared with controls), 160 eotaxin3-positive cells/mm2 (P=.33), and 243 tryptase-positive cells/mm2 (P=.28). Conclusions Esophageal tissues from patients with EoE have substantially higher levels of MBP, eotaxin3, and tryptase than controls, based in immunohistochemical analysis. Assays for the 3 markers identify patients with EoE 100% accuracy, but cannot distinguish EoE from PPI-REE.

The variability of eosinophilic infiltrates in eosinophilic esophagitis is not well described. This study aimed to determine the distribution of esophageal eosinophilia and the utility of histologic cut-points for eosinophilic esophagitis diagnosis in subjects undergoing endoscopy. We performed a prospective study of adults undergoing outpatient endoscopy. Research protocol esophageal biopsies were obtained from all subjects. Incident cases of eosinophilic esophagitis were diagnosed per consensus guidelines. Biopsies were interpreted following a validated protocol, and maximum eosinophil counts (eosinophils per high-power field; eos/hpf) were determined. Histologic analyses were performed on a per-patient, per-biopsy, and per-hpf basis. There were 213 patients, yielding 923 esophageal biopsies with 4588 hpfs. Overall, 48 patients (23%), 165 biopsy fragments (18%), and 449 hpfs (10%) had ≥ 15 eos/hpf; most subjects had no or low levels of eosinophils. In the eosinophilic esophagitis cases, 119 biopsy fragments (63%) and 332 hpfs (36%) had ≥ 15 eos/hpf. There was a mean 104-fold difference between the lowest and highest hpf eosinophil count for the eosinophilic esophagitis patients; 85% of the biopsies from eosinophilic esophagitis cases also had at least one hpf with < 15 eos/hpf. The cut-point of 15 eos/hpf had a sensitivity of 100% and specificity of 96% for diagnosis of eosinophilic esophagitis. In conclusion, most patients have little to no esophageal eosinophilia. In patients with eosinophilic esophagitis, there was marked variability in the eosinophil counts by biopsy and by hpf within a given biopsy. Additionally, the 15 eos/hpf cut-point was highly sensitive and specific for eosinophilic esophagitis. Multiple esophageal biopsies from different locations should be obtained to optimize eosinophilic esophagitis diagnosis.