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Background: Anaphylaxis after the ingestion of foods contaminated with mites has recently been recognized. Case series and case reports thus far have shown that mite-contaminated wheat flour is the major cause of oral mite anaphylaxis. However, we have found 8 cases of oral mite anaphylaxis which were caused by mite-contaminated okonomiyaki-mix, a savory Japanese style pancake mix, in our hospital., Methods: In addition to our 8 cases, the databases of MEDLINE and ICHUSHI were systematically searched for patients with oral mite anaphylaxis in Japan., Results: Thirty-six patients including our 8 cases with oral mite anaphylaxis were identified. Thirty-four out of 36 cases (94%) ingested okonomiyaki or takoyaki, prepared at home using okonomiyaki-mix or takoyaki-mix which was previously opened and stored for months at ambient temperature. Microscopic examination of culprit mixes of 16 cases including our 1 case revealed contamination of mites such as Dermatophagoides farina (Der f) (5 cases), Tyrophagus putrescentiae (Tyr p) (4 cases), and Dermatophagoides pteronyssinus (Der p) (3 cases). The specific IgE to each mite is generally upregulated in these patients. Especially, the titers of specific IgE to Der p and Der f were more than class 2 in all cases., Conclusions: Mite-contaminated flavored flour is the major cause of oral mite anaphylaxis in Japan.

Background: Treatment guidelines recommend the use of inhaled corticosteroids (ICS) as first-line therapy for all stages of persistent asthma. However, it is unknown whether ICS dose reduction in adult asthmatics is compatible with maintaining asthma control. Moreover, there are no predictors of efficacy in maintaining asthma control upon ICS reduction., Methods: We recruited 90 adult patients with moderate or severe asthma but no clinical symptoms of asthma for at least 6 months. All patients reduced their ICS doses by half but continued taking other asthma-related medications. As a primary outcome, we measured asthma exacerbations during the 12 months following ICS reduction. We also further monitored patients from the above study who had maintained total asthma control for 12 months after ICS reduction and who had continued on their reduced doses of ICS or had further reduced, or stopped, their ICS., Results: Forty of ninety patients (44.4%) experienced exacerbations after ICS reduction (time to first exacerbation: 6.4 ± 3.6 months). Multivariate logistic regression modeling revealed a rank order of predictors of success in ICS reduction while retaining asthma control: acetylcholine (ACh) PC(20) (p < 0.01); length of time with no clinical symptoms before ICS reduction (p < 0.01); FeNO (p = 0.028); and forced expiratory volume in 1 s (FEV(1); % predicted) (p = 0.03). Finally thirty-nine of 50 patients maintained total asthma control for at least 2 years after the initial ICS reduction., Conclusions: In asthma patients with normalized AChPC(20) of 20mg/mL or 10mg/mL and no clinical symptoms for at least 12 or 24 months it may be possible to successfully reduce ICS without increasing exacerbations for long time.

Statins are lipid-lowering agents with pleiotropic effects. We investigated the apoptotic effects of fluvastatin on peripheral CD4+ T cells from healthy subjects. Fluvastatin induced apoptosis in resting CD4+ T cells but not in CD4+ T cells strongly activated with a high concentration of PMA plus ionomycin (PMA/I) analyzed with annexin V and propidium iodide staining. However, CD4+ T cells activated with a low concentration of PMA/I or with anti-CD3 antibodies were apoptotic after treatment with fluvastatin. Activities of caspases-8, -9, and -3 were increased in resting CD4+ T cells treated with fluvastatin (10 microM). In strongly activated CD4+ T cells, fluvastatin inhibited the activation of caspase-8 induced by PMA/I and increased caspase-9 activity. The caspase-3 activity did not differ between untreated and fluvastatin-treated strongly activated CD4+ T cells. Treatment with fluvastatin (10 microM) enhanced cytochrome c release and increased the Bax/Bcl-2 ratio in both resting and strongly activated CD4+ T cells. Although the in vitro concentration of fluvastatin used in this study is higher than in vivo, other factors may sensitize apoptotic cell death of CD4+ T cells in vivo. In conclusion, fluvastatin induces apoptosis in resting T cells but not in strongly activated T cells, a difference that might be due to the interaction between caspase-8 and caspase-9.

Study Objectives: Tumor necrosis factor (TNF)-alpha is involved in the pathogenesis of atherosclerosis. In the present study, we examined TNF-alpha production by monocytes, serum levels of TNF-alpha, and the effects of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS)., Design: Prospective observational study., Setting: University hospital., Subjects: Twenty-four patients with OSAS, 15 obese control subjects, and 12 healthy subjects., Measurements and Results: After polysomnography, venous blood was collected at 5 am. Spontaneous production of TNF-alpha by monocytes for 24 h and serum levels of TNF-alpha were investigated. In addition, patients with moderate-to-severe OSAS were treated with nCPAP for 1 month, and spontaneous production of TNF-alpha by monocytes and serum levels of TNF-alpha were also measured. Spontaneous production of TNF-alpha by monocytes was significantly higher in patients with moderate-to-severe OSAS than in patients with mild OSAS (p < 0.0001), obese control subjects (p < 0.0001), or healthy subjects (p < 0.0001). Serum levels of TNF-alpha were also significantly higher in patients with moderate-to-severe OSAS than in patients with mild OSAS (p < 0.03), obese control subjects (p < 0.0005), or healthy subjects (p < 0.0001). Duration of hypoxia during total sleep time was independently associated with spontaneous production of TNF-alpha by monocytes in patients with OSAS and healthy and obese control subjects. nCPAP significantly decreased spontaneous production of TNF-alpha by monocytes (p < 0.03) and serum levels of TNF-alpha (p < 0.05) in patients with moderate-to-severe OSAS., Conclusions: Spontaneous production of TNF-alpha by monocytes and serum levels of TNF-alpha are elevated in patients with moderate-to-severe OSAS but are decreased by nCPAP.

Interleukin (IL)-12 production and IL-12 receptor (IL-12R) beta2 chain expression were investigated in patients with allergic asthma successfully treated with rush immunotherapy (RIT) and control patients with mild allergic asthma. Peripheral blood mononuclear cells (PBMCs) were stimulated with Dermatophagoides farinae (Der f), and production of cytokines was measured. Furthermore, the effects of cytokines on IL-12R beta2 chain expression on CD4(+) T cells were investigated. Production by PBMCs of IL-12 and IFN-gamma was significantly higher and production of IL-4 was significantly lower after stimulation with Der f allergen in RIT-treated patients than in control patients. Significant increases in the expression of IL-12R beta2 chain before and after stimulation of CD4(+) T cells with IL-12 or IFN-gamma were observed in RIT-treated patients compared with that in control patients. Allergen RIT increases IL-12 production and IL-12R beta2 chain expression and thus may convert cytokine production from Th2 to Th1 or Th0 type in allergic asthma.

Objective: Leukotrienes (LTs) are involved in airway eosinophilic inflammation in patients with asthma. We examined the effects of a cysteinyl LT 1-receptor antagonist, montelukast, on sputum eosinophil levels, and the correlation between sputum eosinophils and bronchodilatation in patients with asthma., Design: Double-blind, randomized, crossover study., Setting: University hospital and private hospital., Patients: Twenty-nine patients with mild-to-moderate asthma., Interventions: Montelukast, 10 mg, and placebo tablet, once daily, each for 4 weeks., Measurements: Sputum eosinophils analyzed using hypertonic saline solution-induced sputum and airway hyperresponsiveness to histamine were evaluated before and after treatment. In addition, morning and evening peak expiratory flow (PEF), asthma symptoms, and peripheral blood eosinophil levels were assessed., Results: The percentage of eosinophils in sputum decreased from 24.6 +/- 12.3% at baseline to 15.1 +/- 11.8% after montelukast treatment, for a change of - 9.5 +/- 12.7% (n = 20). During placebo administration, the percentage of eosinophils fell from 21.3 +/- 12.1% to 21.0 +/- 11.5%, resulting in a decrease of - 0.3 +/- 10.8% (n = 20). There was a statistically significant difference in the change in sputum eosinophil levels between these two periods (p < 0.005). The number of peripheral blood eosinophils also significantly decreased after montelukast treatment (314.1 +/- 237.6/mL) compared with placebo (413.1 +/- 232.1/mL; p < 0.005, n = 21). Although morning and evening PEF values were significantly improved from baseline after montelukast treatment (p < 0.01, n = 20), asthma symptoms and airway responsiveness to histamine were not significantly altered. Furthermore, there was no significant correlation between the decrease in sputum eosinophils and the increase in PEF., Conclusion: These results suggest that montelukast has anti-inflammatory effects on the airway in patients with asthma, and that its bronchodilatory effect is not solely dependent on a decrease in airway eosinophilia.