Behavioral functioning and treatment adherence in pediatric eosinophilic gastrointestinal disorders.

OBJECTIVE: To examine behavioral predictors of treatment adherence in patients with eosinophilic gastrointestinal disorders (EGID). METHODS: Participants were 96 patients 2.5-18 yr of age with eosinophilic esophagitis or eosinophilic gastroenteritis and their caregivers (mother, father). We assessed maternal and paternal report of child/adolescent internalizing symptoms (e.g., anxiety, depression) and externalizing symptoms (e.g., aggression, anger) using the Behavior assessment system for children, 2nd edition (BASC-2). A multi-informant adherence assessment approach and an 80% cut point were used to classify patients as adherent or non-adherent. RESULTS: Sociodemographic predictors did not distinguish between adherent and non-adherent patients. Maternal report of internalizing symptoms significantly correlated with non-adherence (p < 0.001). Post hoc probing revealed a significant contribution of depression, with depressed patients being more likely (OR = 7.27; p < 0.05) to be non-adherent than non-depressed patients. Paternal report of internalizing and externalizing symptoms was not associated with non-adherence. CONCLUSIONS: Maternal report of patient internalizing behavioral symptoms, particularly depression, is significantly associated with non-adherence in patients with EGID. These symptoms are potential risk factors and should be considered when assessing and treating non-adherence. Clinical care of patients with EGID should include routine screening for depression.

Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis.

We have previously proposed that the pathogenesis of eosinophilic esophagitis (EE) is mediated by an IL-13-driven epithelial cell response associated with marked gene dysregulation including eotaxin-3 overproduction. In this study, we compared epithelial responses between healthy patients and those with EE, aiming to uncover molecular explanations for EE pathogenesis. Esophageal epithelial cells could be maintained for up to five passages, with 67% and 62% of cell lines reaching confluence in healthy controls and EE cases, respectively. Both sets of epithelial cells avidly responded to IL-13 at similar levels as assessed by eotaxin-3 production. Acidic pH increased cellular release of eotaxin-3 (4.6 +/- 1.98 ng/ml versus 12.46 +/- 2.90 ng/ml at pH 7.4 and 4, respectively; p < 0.05). Numerous epidermal differentiation complex (EDC) genes, such as filaggrin and SPRR3, were downregulated both in IL-13-stimulated esophageal epithelial cells and in EE biopsies specimens compared with healthy controls. Whereas the filaggrin loss of function mutation 2282del4 was overrepresented in EE compared with control individuals (6.1% versus 1.3% respectively; p = 0.0172), the decreased filaggrin expression was uniformly seen in all EE cases in vivo. Indeed, expression of the EDC genes filaggrin and involucrin was strongly decreased directly by IL-13. These results establish that the epithelial response in EE involves a cooperative interaction between IL-13 and expression of EDC genes.

Treatment adherence in pediatric eosinophilic gastrointestinal disorders.

OBJECTIVE: Examine treatment adherence rates in pediatric eosinophilic gastrointestinal disorders (EGID). METHODS: Participants were children aged 2.5-18 years with eosinophilic esophagitis or eosinophilic gastroenteritis (EGE) and their caregivers. A multimethod, multi-informant assessment including parent report and electronic monitoring was utilized, with a 90% cut point for nonadherence. RESULTS: Medication nonadherence prevalence was 30%. Adherence frequency was 91% ± 14% (0-100%) per parent report and 100% ± 69% (0-194%) per electronic monitors. Tube-feeding adherence was 99% ± 3%. Food allergen exposures were less than 1 per 2 weeks, with 33% nonadherence prevalence. Patients with EGE and toddlers with both conditions demonstrated poorer medication adherence (p's < .05). Caregivers reported higher number of missed medication doses than food exposures (p < .05). CONCLUSIONS: The prevalence and range of nonadherence demonstrates that subsets of these patients are nonadherent. Adherence to treatment in EGID is complex and multifaceted, with nonadherence varying across treatments.

A striking local esophageal cytokine expression profile in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EE) is an emerging worldwide disease that mimics gastroesophageal reflux disease. OBJECTIVE: Early studies have suggested that esophageal eosinophilia occurs in association with T(H)2 allergic responses, yet the local and systemic expression of relevant cytokines has not been well characterized. METHODS: A human inflammatory cytokine and receptor PCR array containing 84 genes followed by PCR validation and multiplex arrays were used to quantify cytokine mRNA in esophageal biopsies and blood samples. RESULTS: Esophageal transcripts of numerous chemokines (eg, chemokine [C-C motif] ligand [CCL] 1, CCL1, CCL23, CCL26 [eotaxin-3], chemokine [C-X-C motif] ligand [CXCL] 1, and CXCL2), cytokines (eg, IL13 and ATP-binding cassette, subfamily F, member 1), and cytokine receptors (eg, IL5 receptor, alpha) were induced at least 4-fold in individuals with EE. Analysis of esophageal biopsies (n = 288) revealed that eotaxin-3 mRNA level alone had 89% sensitivity for distinguishing individuals with and without EE. The presence of allergy was associated with significantly increased esophageal expression of IL4 and IL5 mRNA in patients with active EE. We identified 8 cytokines (IL-4, IL-13, IL-5, IL-6, IL-12p70, CD40 ligand, IL-1α, and IL-17) whose blood levels retrospectively distinguished 12 patients without EE from 13 patients with EE with 100% specificity and 100% sensitivity. When applied to a blind, prospectively recruited group of 36 patients, the cytokine panel scoring system had a 79% positive predictive value, 68% negative predictive value, 61% sensitivity, and 83% specificity for identifying EE. CONCLUSION: Evidence is presented that IL13 and IL5 associate with eosinophil and eotaxin-3 levels, indicating the key role of adaptive T(H)2 immunity in regulating eotaxin-3-driven esophageal eosinophilia in the absence of a consistent systemic change in cytokines.

Implementation of a novel on-ward computer-assisted surveillance system for device-associated infections in an intensive care unit.

For the presented study a computer-based surveillance system for detecting nosocomial infections (NI) with direct data input from attending on-ward physicians was implemented. During a 12-month period surveillance of ventilator-associated pneumonia (VAP) and catheter-associated bloodstream infections (BSI) was performed prospectively by on-ward physicians guided by infection control specialists on an 11-bed medical intensive care unit in a German university hospital. In 603 patients 3282 patient days were assessed. Completeness of data entry during the routine phase was 94% for ventilator days and 88% for central venous catheter days. The concordance of infection detection by automated evaluation and evaluation based clinical considerations was fairly good and was quantified by kappa measures of 0.49 for VAP and 0.57 for BSI. Detected infection rates ranged within the German national reference data. Personnel costs for on-ward physicians and infection control personnel were 1.01 Euro per device day in the routine phase. Time expenditure of less than 3 min per device day, rendered in about equal parts by physicians and infection control personnel, was lower than in studies relying on on-ward assessment by infection control personnel.

Psychological Functioning of Children and Adolescents With Eosinophil-Associated Gastrointestinal Disorders.

This study examined health-related quality of life and adjustment among children with eosinophil- associated gastrointestinal disorders (EGID) compared with an age-matched sample without acute or chronic illness. Participants were youth ages 2 to 18 years. Children and caregivers completed measures of psychological symptoms and health-related quality of life (HRQOL). Significant group differences were found for child report of depressive, as well as anxiety symptoms. Significant group differences were also found for caregiver report of psychological symptoms and social skills. Finally, based on parent and youth report, HRQOL and greater school absenteeism were associated with EGID diagnosis.