Less common etiologies of exocrine pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases (diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin (CCK); celiac or inflammatory bowel disease (IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery (asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy (PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI (66%-92%). EPI occurs in patients with type 1 (26%-57%) or type 2 diabetes (20%-36%) and is typically mild to moderate; by definition, all patients with type 3c (pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease (4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD (14%-74%) and up to 100% of gastrointestinal surgery patients (47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.

Pancreatic enzyme replacement therapy dosing and nutritional outcomes in children with cystic fibrosis.

OBJECTIVES: To utilize the Cystic Fibrosis Foundation Patient Registry to evaluate whether pancreatic enzyme dose is associated with better nutritional status as measured by average body mass index (BMI) percentile. STUDY DESIGN: A retrospective analysis of the Cystic Fibrosis Foundation Patient Registry from 2005-2008 was performed. The final analysis included 42 561 patient visits from 14 482 patients 2-20 years of age taking pancreatic enzyme replacement therapy from 179 programs. Cystic fibrosis care programs were assigned to quartiles based on adjusted mean patient BMI percentiles. Differences in median lipase dose between programs in the highest and lowest BMI quartiles were examined using a mixed effects model that adjusted for individual patient BMI, age, race, ethnicity, forced expiratory volume in 1 second percent, acid-blocker use, presence of Pseudomonas aeruginosa, nutritional supplement use, growth hormone use, and diagnosis of cystic fibrosis-related diabetes. RESULTS: A significant difference in median enzyme dose existed between the highest and lowest BMI quartiles. Multivariable analysis demonstrated the effect persisted after adjustment for covariates. Highest quartile programs had a median enzyme dose of 1755 lipase units/kg/meal compared with 1628 lipase units/kg/meal for lowest quartile programs. CONCLUSION: Patients attending US cystic fibrosis programs achieving highest nutritional outcomes, measured by mean BMI percentile, have higher enzyme dosing than those attending programs at lower performance levels. Further randomized clinical trials are necessary to determine the role of enzyme dose in improving nutritional outcomes.

Successful use of plasmapheresis for granulomatosis with polyangiitis presenting as diffuse alveolar hemorrhage.

Diffuse alveolar hemorrhage (DAH) is uncommon in pediatric patients and is a rare presenting sign of granulomatosis with polyangiitis (GPA). We present the case a 14-year-old girl who presented with respiratory failure secondary to DAH as the initial presenting sign of GPA. Her clinical course improved after initiation of plasmapheresis therapy and she is now in clinical remission.

Sleep related expiratory obstructive apnea in children.

STUDY OBJECTIVES: We describe the respiratory, cardiac, and sleep-related characteristics of two types of sleep-related respiratory pauses in children that can fulfill current criteria of pathological apnea, but often seem to be benign: prolonged expiratory apnea (PEA) and post-sigh central apnea (PSCA). METHODS: All outpatient comprehensive overnight polysomnography completed on children without significant underlying medical conditions completed during an 18-month period were retrospectively reviewed for the presence of augmented breaths followed by a respiratory pause. Events were identified as a PEA or PSCA based on characteristic features. Physiologic parameters associated with the respiratory events were recorded and compared. RESULTS: Fifty-seven (29 PEA and 28 PEA) events were identified in 17 patients (8.5 ± 3.5 years old). Median durations of PEA and PSCA were not significantly different. For both PEA and PSCA, average heart rate (HR) during the augmented breath before the respiratory pause differed from lowest instantaneous HR during the first half of the pause. When compared to each other, the lowest instantaneous HR recorded in the first half of PEA was lower than that for PSCA (63.9 [59.41-68.3] vs 66.75 [61.7-80.75]) beats per min, p = 0.03. No PEA or PSCA event was associated with an oxygen desaturation more than 3% from baseline. CONCLUSION: PEA and PSCA have stereotypic HR changes and resemble pathologic apneas but appear to be benign. Clinical significance of PEA and PSCA is yet to be determined. Consistent recognition of the events is required, given their frequency of occurrence and potential for misclassification.

Successful prolonged use of recombinant human insulin-like growth factor-1 in a child with cystic fibrosis.

Growth failure is a common and complicated process in children with cystic fibrosis (CF). Growth hormone, which is becoming a more commonly used agent in such patients, has demonstrated beneficial effects aside from increased growth velocity. Recently, insulin-like growth factor-1 has gained significant attention in the understanding of growth failure in children with CF. We report the successful prolonged use of recombinant human insulin-like growth factor-1 in an adolescent boy with CF, who demonstrated significant clinical benefits from the therapy.