Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease.

BACKGROUND: We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers. METHODS: Clinical response was assessed by Pediatric Crohn's Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls. RESULTS: Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls. CONCLUSIONS: Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.

Aerodigestive Approach to Chronic Cough in Children.

PURPOSE OF REVIEW: Chronic cough is the most common presenting complaint in a pediatric aerodigestive clinic. The etiology of chronic cough is varied and often includes more than one organ system. This review aims to summarize the current literature for a multidisciplinary approach when evaluating a child with chronic cough. RECENT FINDINGS: There is very little medical literature focused on a multidisciplinary approach to chronic cough. In the limited data available, multidisciplinary clinics have been shown to be more cost-efficient for the families of children with complex medical problems, and also increase the likelihood of successfully obtaining a diagnosis. SUMMARY: There is no consensus in the literature on how to work-up a child with chronic cough presenting to an aerodigestive clinic. Current studies from these clinics have shown improved outcomes related to cost-effectiveness and identifying definitive diagnoses. Future studies evaluating clinical outcomes are necessary to help delineate the utility of testing routinely performed, and to demonstrate the impact of interventions from each specialty on quality of life and specific functional outcome measures.