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Objective: In functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia., Methods: This study was conducted utilizing an existing biorepository. Patients had plasma samples obtained at the time of endoscopy. All had undergone endoscopy for dyspepsia and reported early satiety. Two groups were identified including those with peak duodenal mucosal eosinophil densities above 30/high power field (N = 28) and those below 30 (N = 16). The fasting plasma samples were analyzed by liquid chromatography/high-resolution mass spectrometry. Significant differences between groups were determined., Results: The eosinophilia group demonstrated significant elevations in several gamma-glutamyl amino acids. The eosinophilia group had elevations of metabolites associated with oxidative stress including glutathione metabolites (cysteinlyglycine and cys-gly oxidized), and metabolites related to nitric oxide synthesis (arginine, citrulline, ornithine, and dimethylarginine). Eosinophilia was also associated with alterations in lipid metabolism including several long-chain acylcarnitine conjugated fatty acids. Carnitine levels were lower in the eosinophilia group. Lastly, vanillymandelate, a derivative of norepinephrine and epinephrine was elevated in the eosinophilia group., Conclusions: In patients with dyspepsia and early satiety, duodenal mucosal eosinophilia is associated with metabolites levels which are consistent with increased oxidative stress and alterations in lipid metabolism. Eosinophilia was also associated with lower carnitine levels. These alterations may contribute to pathophysiology and represent therapeutic targets., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: We prospectively studied children with portal hypertension (PHT) for portal hypertensive duodenopathy (PHTD) and small bowel intestinal permeability (SIP) with the objectives of defining histopathological parameters for PHTD and to find out whether any association existed among structural changes, SIP, and nutritional status., Method: SIP was assessed by using lactulose and mannitol sugar probes in 31 children with PHT (cirrhosis n = 15 and extrahepatic portal venous obstruction n = 16) and 15 healthy children as controls. Morphometric assessment from duodenal biopsies was done in children with PHT. SIP and morphometric parameters were correlated with nutritional status and dietary intake., Results: Among children with PHT, 48% had PHTD defined as presence of villous atrophy (villous to crypt ratio < 2.5:1), dilated capillaries (capillary diameter > 16.8 μm, capillary area > 151 μm, capillary perimeter > 56 μm), and thickened muscularis mucosae (>22.2 μm). Lactulose excretion alone was increased in children with PHT as compared with healthy children (median %: 0.03, 0.02, and 0.01 for cirrhosis, extrahepatic portal venous obstruction, and controls, respectively [P < 0.01]) signifying increased paracellular permeability in PHT. Children with PHT had significantly lower z scores for height, weight, and triceps skin-fold thickness (<-2SD), whereas no differences were found in dietary intake between patients and controls. Increased SIP, nutritional compromise, and PHTD in our patients had no correlation., Conclusions: PHT is often associated with duodenopathy. SIP does occur as a result of increased paracellular permeability. Factors of increased SIP, undernutrition, and PHTD do not have correlation in childhood PHT.

Background: Montelukast, a competitive cysteinyl leucotriene-1 receptor antagonist, reduces airway eosinophilia in asthmatics. We evaluated the effect of this drug in children with eosinophilic duodenitis, defined histologically as duodenal mucosa with peak eosinophil count of more than 10 eosinophils/hpf., Methods: Forty children and adolescents (6-18 yr) with dyspepsia and duodenal eosinophilia were enrolled in a double blind, randomized, placebo-controlled, cross-over study of monteleukast therapy. Subjects were randomized to receive either 10 mg montelukast or an identical placebo once daily and were evaluated on day 14 for symptomatic and biochemical responses. Subjects were also randomized to one of two blood sampling schemes to evaluate montelukast pharmacokinetics., Results: Using a post treatment global pain assessment, a positive clinical response was observed in 62.1% of patients receiving montelukast compared with 32.4% on placebo (p < 0.02). Pain assessment score deteriorated in 45% of montelukast responders (5/11) after cross-over to placebo and improved in 62% (8/13) of placebo non-responders on cross-over to montelukast. In patients with peak duodenal eosinophil counts between 20-29/hpf (n=19), a positive pain assessment response was observed in 84% of patients receiving montelukast compared to 42% receiving placebo (p < 0.01). Response rate did not differ by age, gender or histologic findings at baseline. Pharmacokinetic analysis yielded parameter estimates for absorption rate constant (Ka), apparent volume of distribution (Vd/F) and elimination rate constant (Kel) of 0.42 h, 0.19 L/kg and 0.26 h, respectively. The relative extent of systemic drug exposure was comparable to that observed in previous pediatric investigations with similar weight-adjusted montelukast doses. Neither dose nor calculated drug exposure were associated with the level of post treatment pain assessment or the change in biochemical markers., Conclusions: These data suggest a beneficial role for montelukast in the treatment of pediatric patients with dyspepsia associated with duodenal eosinophilia.