Factors associated with eosinophilic esophagitis in an urban, tertiary care pediatric aerodigestive population undergoing triple endoscopy.

BACKGROUND: Children with aerodigestive dysfunction often undergo triple endoscopy (flexible bronchoscopy, rigid direct laryngoscopy and bronchoscopy, and esophagogastroduodenoscopy) for diagnostic evaluation as well as screening prior to airway reconstruction. Prevalence and risk factors for eosinophilic esophagitis (EoE) in this population are poorly understood. METHODS: A retrospective chart review was performed for pediatric patients, aged 0-21 years, who received a triple endoscopy with biopsy from January 1, 2015, to December 31, 2019, at the Children's Hospital at Montefiore (CHAM). Bivariate and multivariable analyses were used to compare the baseline characteristics between patients with and without EoE to assess for potential predictors of EoE. RESULTS: Of the 119 cases included in the analysis, 16.0 % (19) received a histopathologic diagnosis of EoE following triple endoscopy. Patients with EoE were more likely to have a family history of eczema (p = 0.02) and a dairy-free diet (p = 0.02). Age, sex, history of environmental allergies, and recency of initiating oral diet were not significantly associated with increased odds of an EoE diagnosis. CONCLUSIONS: A family history of eczema and a diet lacking allergenic foods, such as milk, may be associated with an increased risk of a future diagnosis of EoE in patients with aerodigestive dysfunction. Larger, multi-institutional studies are needed to identify early predictors of EoE.

High glucose induces podocyte apoptosis by stimulating TRPC6 via elevation of reactive oxygen species.

Podocyte number is significantly reduced in diabetic patients and animal models, but the mechanism remains unclear. In the present study, we found that high glucose induced apoptosis in control podocytes which express transient receptor potential canonical 6 (TRPC6) channels, but not in TRPC6 knockdown podocytes in which TRPC6 was knocked down by TRPC6 silencing short hairpin RNA (shRNA). This effect was reproduced by treatment of podocytes with the reactive oxygen species (ROS), hydrogen peroxide (H2O2). Single-channel data from cell-attached, patch-clamp experiments showed that both high glucose and H2O2 activated the TRPC6 channel in control podocytes, but not in TRPC6 knockdown podocytes. Confocal microscopy showed that high glucose elevated ROS in podocytes and that H2O2 reduced the membrane potential of podocytes and elevated intracellular Ca(2+) via activation of TRPC6. Since intracellular Ca(2+) overload induces apoptosis, H2O2-induced apoptosis may result from TRPC6-mediated elevation of intracellular Ca(2+). These data together suggest that high glucose induces apoptosis in podocytes by stimulating TRPC6 via elevation of ROS.