Efficacy and safety of vonoprazan-based regimen for Helicobacter pylori eradication therapy in Japanese adolescents: a prospective multicenter study.

BACKGROUND: Vonoprazan (VPZ)-based regimen for Helicobacter pylori (H. pylori) is safe and more efficacious than the proton pump inhibitor-based regimen mainly in adults. This study aimed to evaluate the efficacy and safety of a VPZ-based regimen for H. pylori eradication therapy in adolescents. METHODS: An H. pylori screening and treatment longitudinal project for third-year junior high school students in Saga Prefecture began in 2016. Students who tested positive for both urine and stool tests received a VPZ-based regimen. On the checklist, students were asked for diarrhea, fever, abdominal pain, nausea, vomiting, urticaria, dysgeusia, or bloody stool occurrence during the therapy. RESULTS: The longitudinal project for H. pylori screening and treatment among third-grade students in Saga Prefecture targeted 41,115 students from 2017 to 2021 and 836 as positive. Of the 645 students, 542 (84.0% in per protocol [PP] analysis and 73.6% in intention-to-treat [ITT] analysis) were successful in primary eradication therapy. The secondary eradication therapy was successful in 79 (96.3% in PP analysis and 76.7% in ITT analysis) of 82 students. In the primary eradication therapy, abdominal pain occurred in 164 (27.9%), diarrhea in 217 (36.9%), nausea or vomiting in 7 (1.2%), and urticaria in 13 (2.2%) students. In the secondary eradication therapy, abdominal pain occurred in 12 (19.4%) and diarrhea in 17 (27.4%) students. The eradication therapy of 5 students was interrupted due to adverse events only by primary eradication therapy. CONCLUSIONS: VPZ-based regimen for H. pylori was efficacious and safe for adolescents, as in adults, for both primary and secondary eradication therapies.

Gastrointestinal adverse reactions reduce the success rate of Helicobacter pylori eradication therapy: A multicenter prospective cohort study.

BACKGROUND: The screening and treatment of Helicobacter pylori infection for all junior high students in Saga Prefecture, Japan, were started in 2016. The present study aims to evaluate the influence of adverse reactions on the success of the eradication therapy. METHODS: From 2017 to 2019, 25,006 third-grade junior high school students were tested for urinary anti-H. pylori antibodies. Positive cases were confirmed by H. pylori stool antigen tests. Of the 531 students who were found to be H. pylori-positive, 390 (358 in first-line and 32 in second-line therapy) underwent eradication therapy, and 274 (242 in first-line and 32 in second-line) students actually completed a self-reported form to rate stool consistency (based on the Bristol Stool Scale), the maximum number of bowel movements, and abdominal symptoms during the 7 days of treatment. RESULTS: Among the 274 students, the total of primary and secondary eradication success rates was 87% (95% confidential interval: 82.9-90.1) in intention-to-treat analysis. On days 4, 5, and 6, stool consistency was looser in the primary eradication failure group than in the success group (p < .05). Looser stool consistencies were observed in male students with abdominal pain compared to those who did not experience pain (p < .05). Abdominal pain and diarrhea were detected in 28.5% and 42.7% of the subjects, respectively. The overall incidence of other adverse events was low (n = 8/274, 2.9%), and only two students discontinued treatment because of adverse events. CONCLUSIONS: Softening of the stool was related to the eradication failure in the junior high school students, especially in males with abdominal pain. Adverse effects did not induce discontinuation of the eradication treatment.

Enhanced CCL26 production by IL-4 through IFN-gamma-induced upregulation of type 1 IL-4 receptor in keratinocytes.

A Th2 cytokine, IL-4, induces various chemokines from epidermal keratinocytes which play crucial roles in the pathogenesis of skin disorders such as atopic dermatitis. In contrast, the role of IFN-gamma, a Th1 cytokine, on eosinophilic skin inflammation is unclear. This study investigated the effects of IFN-gamma on IL-4-induced production of eotaxin-3/CCL26, a potent chemoattractant to eosinophils, in normal human epidermal keratinocytes (NHEK). When the cells were stimulated with IL-4 and IFN-gamma simultaneously, IL-4-induced CCL26 production was attenuated. In contrast, prior stimulation with IFN-gamma enhanced IL-4-induced CCL26 production. NHEK constitutively expressed type 1 IL-4 receptor, and expression at the cell surface was upregulated by stimulation with IFN-gamma. This upregulation resulted in an enhanced IL-4-mediated cellular signal. These results indicate that IFN-gamma has opposite effects on IL-4-induced CCL26 production in NHEK depending on the time of exposure. Thus, changes in IL-4R expression by IFN-gamma might modulate eosinophilic skin inflammation.

Squamous cell carcinoma-related antigen in children with acute asthma.

BACKGROUND: Increased serum levels of squamous cell carcinoma-related antigen (SCCA) have been observed in patients with allergic disorders, such as atopic dermatitis and bronchial asthma. T(H)2 cytokines, which are known to be involved in the pathogenesis of allergic disorders, stimulate new synthesis of SCCA in cultured human airway epithelial cells. OBJECTIVE: To investigate whether SCCA levels increase during acute exacerbations of asthma in children and whether the T(H)2 cytokines, interleukin 4 (IL-4) and IL-13, are associated with SCCA levels. METHODS: Serum levels of SCCA, IL-4, and IL-13 were measured by enzyme immunoassay during the acute phase of an asthma exacerbation (on hospital admission) and in the recovery phase (after symptoms had subsided). RESULTS: In the 35 children who participated in this study, serum levels of SCCA were significantly elevated in the acute phase (mean +/- SD, 3.09 +/- 2.03 ng/mL) compared with the recovery phase (mean +/- SD, 1.47 +/- 0.64 ng/mL) of an asthma exacerbation (P < .001). In 12 children, the IL-13 levels were observed to correlate with SCCA levels during the recovery phase (r = 0.68, P = .02) but not during the acute phase of an asthma exacerbation. CONCLUSIONS: Serum SCCA levels increase during the acute phase of an asthma exacerbation. During this phase, the increased synthesis of SCCA is not associated with IL-13 but rather mediated by other undefined stimuli. IL-13 may contribute to the basal production of SCCA in asthmatic children.

Upregulation of interleukin-4 receptor by interferon-gamma: enhanced interleukin-4-induced eotaxin-3 production in airway epithelium.

Airway epithelial cells produce a number of chemokines, including eotaxins. Among the three known eotaxins, T helper (Th) type 2 cytokines have been observed to induce the expression of eotaxin-3 mRNA. This study investigated the effect of interferon (IFN)-gamma, a Th1 cytokine, on Th2 cytokine-induced eotaxin-3 production in a bronchial epithelial cell line, BEAS-2B. BEAS-2B cells produced eotaxin-3 after stimulation with the Th2 cytokines interleukin (IL)-13 and IL-4. When BEAS-2B cells were cultured with varying concentrations of IFN-gamma for 24 h, dose-dependent inhibition of Th2 cytokine-induced eotaxin-3 mRNA expression and protein production was observed. This was associated with downregulation of signal transducer and activator of transcription 6 activation. On the other hand, 2-d pretreatment of BEAS-2B cells with IFN-gamma dose-dependently enhanced Th2 cytokine-induced eotaxin-3 mRNA expression and production. IFN-gamma also increased the mRNA expression and protein production of IL-4 receptor (R) alpha in a time- and dose-dependent manner. In addition, IL-2Rgamma, a component of the type 1 IL-4R, was also upregulated by IFN-gamma. These results indicate that IFN-gamma has opposite effects on Th2 cytokine-induced eotaxin-3 production in BEAS-2B cells, depending on the length of exposure. Because high levels of IFN-gamma are produced during viral infection, airway viral infection may affect allergic airway inflammation in vivo by modulation of eotaxin-3 production.