Project Summary. This study investigates whether genetic variation in CYP2C19 contributes to proton pump inhibitor-associated infections and chronic illness exacerbations in children. Study aims include: 1) To compare rates of infection in healthy and obese children, and children with chronic illnesses of asthma and inflammatory bowel disease before and during treatment with proton pump inhibitors; 2) To determine the effect of proton pump inhibitor medications on rates of disease exacerbations among children with chronic illnesses of asthma and inflammatory bowel disease before and during treatment with proton pump inhibitors; and 3) Among children with existing DNA specimens, we will genotype a subsample for CYP2C19 metabolizer status and compare the rates of infection and disease exacerbations between poor vs. normal metabolizer phenotypes.

Study Design. This study will use a retrospective cohort design across PEDSnet participating institutions to identify otherwise healthy children as well as children with obesity, asthma and inflammatory bowel disease who have been prescribed PPI medications in the outpatient setting.

Engagement. We will actively engage the existing PEDsnet stakeholders across all sites: site specific representatives from quality and safety, disease specific experts in obesity, asthma and inflammatory bowel disease, North American Society of Pediatric Gastroenterology, Hepatology and Nutrition, the American Lung Association, the Childhood Asthma Leadership Coalition, the Chronic and Colitis Foundation (CCFA), the Delaware-CTR, the Value Institute at Christiana Healthcare, and parent/child representatives. The stakeholders will provide input into the clinical question, design, interpretation and dissemination of study results primarily by the established PEDsnet infrastructure and also planned conference calls and in-person meetings.

Data Elements. Basic query of study inclusion criteria among healthy children, obese children and children with asthma, and inflammatory bowel disease. Descriptive statistics of incident PPI medication prescriptions, infectious outcomes and disease exacerbations as described. In addition, among a subsample of subjects from the basic query, to identify children with biobanked DNA or biobanked specimens from which DNA can be extracted (blood, saliva or tissue collected from an endoscopy or colonoscopy for clinical purposes). This preliminary data is necessary for a more developed biostatistical plan and sample size calculations.