Background Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE)-mediated food allergy that affects infants. It is characterized by massive and repetitive vomiting, lethargy, pallor, and watery diarrhea. Although FPIES can mimic acute gastrointestinal diseases, for which ultrasonography is useful, few studies on ultrasonographic findings in non-IgE-mediated food allergic disorders are available. We investigated the ultrasonographic features of patients with FPIES. Methods Patients who underwent an oral food challenge (OFC) test or were diagnosed with acute FPIES were enrolled. We divided the patients into the FPIES and non-FPIES groups. Ultrasonography was performed before and 6h after the OFC test. Patients in the FPIES group underwent ultrasonography 24 h after the OFC tests. We evaluated intestinal findings, including peristaltic movement, fluid accumulation, and wall thickness of the gastrointestinal tract. Results Fourteen patients in the FPIES group and 11 in the non-FPIES group were enrolled. Ultrasonography performed 6h after the OFC test showed that the number of patients with small intestinal fluid accumulation and hyperperistalsis was significantly higher in the FPIES group than in the non-FPIES group. In the FPIES group, jejunal wall thickness significantly increased 6h after the OFC test. Small bowel intussusception occurred in three patients with FPIES. Conclusions Small-intestinal wall thickening, fluid accumulation, and abnormal peristalsis on ultrasonography suggest its utility in diagnosing FPIES. In cases of small intestinal intussusception, FPIES should be considered in the differential diagnosis.

Background: Severe asthma exacerbation is an important comorbidity of the 2009 HIN1 pandemic [A(H1N1)pdm09] in asthmatic patients. However, the mechanisms underlying severe asthma exacerbation remain unknown. In this study, airway hyperresponsiveness (AHR) was measured in paediatric asthma patients infected with A(H1N1)pdm09. We also evaluated AHR in asthmatic mice with A(H1N1)pdm09 infection and those with seasonal influenza for comparison. Methods: AHRs in asthmatic children were defined as the provocative acetylcholine concentration causing a 20% reduction in FEV1.0 (PC20). To investigate the pathophysiology using animal models, BALB/c mice aged 6-8 weeks were sensitized and challenged with ovalbumin. Either mouse-adapted A(H1N1)pdm09, seasonal H1N1 virus (1×105 pfu/20 μL), or mock treatment as a control was administered intranasally. At 3, 7, and 10 days after infection, each group of mice was evaluated for AHR by methacholine challenge using an animal ventilator, flexiVent®. Lung samples were resected and observed using light microscopy to assess the degree of airway inflammation. Results: AHRs in the children with bronchial asthma were temporarily increased, and alleviated by 3 months after discharge. AHR was significantly enhanced in A(H1N1)pdm09-infected asthmatic mice compared to that in seasonal H1N1-infected mice (p<0.001), peaking at 7 days post-infection and then becoming similar to control levels by 10 days post-infection. Histopathological examination of lung tissues showed more intense infiltration of inflammatory cells and severe tissue destruction in A(H1N1)pdm09-infected mice at 7 days post-infection than at 10 days post-infection. Conclusions: Our results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE cell-mediated food allergy characterized by repetitive vomiting and other gastrointestinal symptoms. Although little is known about FPIES pathophysiology, some cytokines have been reported to be involved. Since one of the main symptoms is vomiting, which is common to other diseases, it is difficult to distinguish acute FPIES from other conditions such as infectious enterocolitis. Thus, specific biomarkers are required for differential diagnosis. We aimed to identify potential biomarkers distinguishing acute FPIES from infectious enterocolitis and IgE-mediated anaphylaxis, which also cause vomiting. Methods: Seven patients with acute FPIES, nine with IgE-mediated anaphylaxis, and six with infectious enterocolitis were enrolled. The serum concentrations of interleukins (IL)-2, -4, -6, -8, -10, interferon-γ, and tumor necrosis factor-α were measured and compared among the three groups of patients. The serum concentrations of IL-2 and IL-10 were also compared between the symptomatic and asymptomatic stages. Alterations in serum cytokine levels were evaluated in acute FPIES during an oral food challenge test. Results: Serum IL-2 and IL-10 levels were significantly higher in acute FPIES patients than in patients with infectious enterocolitis and IgE-mediated anaphylaxis, whereas no significant differences were detectable in the serum levels of the other cytokines. The IL-2 and IL-10 elevation was only observed in the symptomatic stage of acute FPIES. Conclusion: The elevation in serum levels of IL-2 and IL-10 was specifically observed in symptomatic acute FPIES cases, suggesting that the measurement of IL-2 and IL-10 could be employed for differential diagnosis.

Background: Severe asthma exacerbation is an important comorbidity of the 2009 HIN1 pandemic [A(H1N1)pdm09] in asthmatic patients. However, the mechanisms underlying severe asthma exacerbation remain unknown. Using a mouse model of asthma, we evaluated airway hyperresponsiveness (AHR) in mice with A(H1N1)pdm09 infection and those with seasonal influenza for comparison. We also measured AHR in paediatric participants infected with A(H1N1)pdm09. Methods: BALB/c mice aged 6-8 weeks were sensitized and challenged with ovalbumin. Either mouse-adapted A(H1N1)pdm09, seasonal H1N1 virus (1×105 pfu/20 μL), or mock treatment as a control was administered intranasally. At 3, 7, and 10 days after infection, each group of mice was evaluated for AHR by methacholine challenge using an animal ventilator, flexiVent®. Lung samples were resected and observed using light microscopy to assess the degree of airway inflammation. AHRs in paediatric participants were defined as the provocative acetylcholine concentration causing a 20% reduction in FEV1.0 (PC20). Results: Airway resistance was significantly enhanced in A(H1N1)pdm09-infected asthmatic mice compared to that in seasonal H1N1-infected mice (p<0.001), peaking at 7 days post-infection and then becoming similar to control levels by 10 days post-infection. Histopathological examination of lung tissues showed more intense infiltration of inflammatory cells and severe tissue destruction in A(H1N1)pdm09-infected mice at 7 days post-infection than at 10 days post-infection. AHRs in the paediatric participants were temporarily increased, and alleviated by 3 months after discharge. Conclusions: Our results suggest that enhanced AHR could contribute to severe exacerbation in human asthmatic patients with A(H1N1)pdm09 infection.