Reiji Kojima's research while affiliated with National Research Institute for Child Health and Development, Tokyo and other places

Although there is an increasing number of eosinophilic gastrointestinal disorders (EGID) cases including eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), being reported globally, no systematic reviews have been conducted to elucidate the racial differences in these disorders. We aimed to show the racial differences, especially among Caucasians and Asians, in the risk of EoE and EGE. We conducted a systematic review using PubMed in September 2012. All case reports and case series on EGID that involved human subjects and described race or ethnicity, as well as pathological findings, were included. For the comparison of reported cases between Caucasians and Asians, a chi-squared test was used. Among the 687 studies found in PubMed, 121 studies fulfilled the eligibility criteria. In total, 2621 patients were reviewed. Among Caucasian EGID patients, 94% had EoE; while among Asian EGID patients, 72% had EGE (p < 0.001). Among EoE, Asians were significantly less likely to have dysphagia and heartburn, but more likely to have vomit and abdominal pain, compared to Caucasians (p < 0.001). Further, among EGE, Asians were significantly more likely to have eosinophil-infiltrated colon than Caucasians (OR: 3.22, 95% confidence interval [CI]: 1.60-7.04), but were less likely to have eosinophil-infiltrated stomach (OR: 0.29, 95% CI: 0.17-0.49). We found that EoE occurs more frequently in Caucasian EGID patients than Asian EGID patients, while the reverse is true for EGE. Also, racial disparities in symptoms and eosinophil-infiltrated tissues were observed. Our findings suggest further genetic and environmental studies to elucidate the etiology of EGID. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Silica crystals (silica), which are the main mineral component of volcanic ash and desert dust, can activate the caspase-1-activating inflammasome in phagocytic cells to secrete IL-1β. Although inhalation of silica-containing dust is known to exacerbate chronic respiratory diseases, probably through inflammasome activation, its direct effects on bronchial epithelial cells remain unclear. Here, we show that silica and double-stranded RNA (dsRNA) synergistically induced caspase-9-dependent apoptosis, but not inflammasome activation, of bronchial epithelial cells. Intranasal administration of silica and dsRNA to mice synergistically enhanced neutrophil infiltration in the airway, without IL-1β release in the bronchoalveolar lavage fluid. Histopathological analysis revealed that silica or dsRNA alone induced slight airway inflammation, whereas combined administration significantly enhanced both airway inflammation and epithelial damage. These novel findings suggest that inhalation of silica-containing dust may cause inflammasome-independent airway inflammation, possibly by damaging the epithelial barrier, especially at the time of viral infection. These responses may also be involved in acute lung injury caused by inhaled silica-containing dust.

Galectin-9 (Gal-9), a lectin having a β-galactoside-binding domain, can induce apoptosis of Th1 cells by binding to TIM-3. In addition, Gal-9 inhibits IgE/Ag-mediated degranulation of mast cell/basophilic cell lines by binding to IgE, thus blocking IgE/Ag complex formation. However, the role of Gal-9 in mast cell function in the absence of IgE is not fully understood. Here, we found that recombinant Gal-9 directly induced phosphorylation of Erk1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express FcεRI. Gal-9 induced apoptosis and inhibited PMA/ionomycin-mediated degranulation of HMC-1 cells. On the other hand, Gal-9 induced cytokine and/or chemokine production by HMC-1 cells, dependent on activation of ERK1/2 but not p38 MAPK. In addition, the lectin activity of Gal-9 was required for Gal-9-mediated cytokine secretion by HMC-1 cells. These observations suggest that Gal-9 has dual properties as both a regulator and an activator of mast cells.

  Topical corticosteroids (TCS) are first-line therapeutic agents for atopic dermatitis (AD). Some patients express irrational fear and anxiety about using TCS, which leads to poor outcomes for AD. Although it is important to understand the factors underlying steroid phobia so that its effects can be minimized, few studies have addressed this subject. Here, we used a questionnaire to investigate predictive factors for steroid phobia in the caregivers (usually mothers) of children with AD. We studied 436 children with AD (mean age 47.6 mos, range 2-236 mos) who newly visited our AD outpatient unit. The caregivers were asked to complete a medical history questionnaire regarding AD. Steroid phobia was analyzed for correlations with other patient and caregiver variables. Overall, 38.3% of the caregivers were reluctant to use TCS on their children's skin. Patient characteristics female sex (odds ratio [OR] = 1.85 vs male; p = 0.005), child's paternal history of AD (OR = 1.94; p = 0.03), and frequent changing of clinics (OR = 1.25; p = 0.03) were predictive factors for steroid phobia. AD severity did not correlate with steroid phobia. Our findings suggest that greater attention to the patient's sex and clinical background of patients with AD is important to the success of AD therapy, regardless of AD severity.

  Poor responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis under stress may be one explanation for stress-induced exacerbation of atopic dermatitis (AD) symptoms. In previous studies, children and adults with AD showed attenuated salivary cortisol responses to psychosocial stress, suggesting hyporesponsiveness of the HPA axis, but few studies have been conducted in young children, who are vulnerable to systemic side effects of topical corticosteroid (TCS) therapy. We evaluated whether salivary cortisol responses to the stress of venipuncture in young children with AD were related to the severity of AD or performance of TCS therapy. We studied 38 young children with AD (median age 16.5 mos, range 3-66 mos) being treated at our outpatient unit. Patients were divided into three groups according to the scoring of atopic dermatitis index: mild (n = 12), moderate (n = 14), and severe (n = 12). To evaluate the responsiveness of the HPA axis to stress, salivary cortisol was determined before and after venipuncture. Salivary cortisol responsiveness to stress correlated negatively with severity of AD (p = 0.048) but not with previous use of TCS (p = 0.43) in young children with AD. Our findings suggest that the disease activity of AD, rather than TCS use, is responsible for HPA axis dysfunction in children with AD.