Exocrine Pancreatic Insufficiency In Acute Recurrent Pancreatitis - Prevalence, Natural History And The Potential Role of Pancreatic Enzyme Replacement Therapy

Introduction: Inflammation of the pancreas (or pancreatitis) is a common but under-studied gastrointestinal condition in South Asian children. The clinical spectrum ranges from mild self-limiting abdominal pain to morbidity from peripancreatic fluid collections, recurrent admission, multi-organ dysfunction as well as long term morbidity and growth faltering from exocrine pancreatic insufficiency (EPI), diabetes mellitus and pancreatic cancer.The risk of malnutrition is especially true for children who may be in an active pubertal growth spurt (with higher nutrient requirements) during the illness, making them vulnerable to specific nutrient deficiency, metabolic bone disease and chronic growth faltering.  An additional aspect that may contribute to nutritional risk in these children is the presence of EPI. EPI is a well-known consequence of chronic pancreatitis in children and adults. However, EPI following acute pancreatitis (AP) is insufficiently acknowledged and there is emerging evidence that it is not uncommon in adults. Two recent reviews of adults with AP at the time of hospitalization, revealed EPI in majority (62%), which reduced to 35% on follow up, with some patients requiring exogenous pancreatic enzyme replacement therapy (PERT) to alleviate symptoms. The time to recovery of EPI has been reported to be variable, ranging from 1 month to many years. The studies referred to above are in reference to an adult population, there are no studies assessing whether EPI exists in the paediatric population with AP. The incidence of childhood AP is not trivial; the worldwide incidence of AP ranges between 3.6-13.2 per 100,000 per year in children <18years old. Objective: To determine the prevalence of EPI in a cohort of children with acute recurrent pancreatitis as measured by the 13C MTG breath test either at diagnosis or in follow upMethodology The day for the experiment will be taken as the second day of starting soft diet in an admitted child with ARP or as mutually decided for an OPD basis child of ARP.  On the day of the experiment, the recruited participant will arrive at 7:00 AM to the Clinical Research Centre in St Johns Medical College after an overnight fast of 8-10 hours. The weight ,height and questionnaires with respect to epidemiology data, socioeconomic status and clinical history will be recorded.Blood sample (10 ml) will be collected in a prelabelled EDTA vial, plasma will be separated after centrifugation and stored in a -80°C freezer. Stool samples will be collected freshly and sent for fecal elastase levels to ensure sample integrity. An initial basal breath sample will be collected in a modified breath bag and transferred into 10 mL glass exetainers.A meal consisting of wheat bread (50 g) and butter (10 g) sandwiches with 300 mg of  13C-MTG will be administered along with 200 ml of water.Breath samples will thereafter be collected in duplicate every 30 mins until 6 hrs. The glass exetainers containing the breath samples will be stored at room temperature until further analysis. At 3rd hr of protocol, carbon dioxide production (VCO2) will be measured for each participant using Indirect Calorimetry (IC). The protocol for IC will be explained prior so that the participant is free from emotional stress and familiar with the apparatus used. VCO2 will be measured by a ventilated hood design, where a transparent and well-ventilated canopy will be placed over the participants head in the supine position. Participants will be allowed to try on the ventilated hood for 5 mins if they wish toAt 4th hr of protocol a light meal consisting of 75 g of a fermented legume and rice preparation (idly) and 25 g of coconut sauce (chutney) will be administered to all participants.The ratio of 13CO2 to 12CO2in the sample will be calculated after comparison with the known ratio of an external 13CO2 standard that is based on the PDB standard for 13C.The atom % excess of 13CO2 for each time point, in breath samples will be used to determine the cumulative percentage dose recovery for 13C-MTG**.**In a subset of case participants, 13C-MTG breath tests will be repeated at 2,4 and 6 months    to assess for spontaneous recovery of EPI with time.