Inhaled corticosteroid (ICS) therapy plays a pivotal role in the long-term treatment of childhood asthma. The reduction of asthma symptoms and the improvement of quality of life (QOL) of the patients and their guardians are expected when ICS therapy in conformity with the guideline (JPGL2005) becomes familiar in primary care. The efficacy and safety of ICS therapy depends on the application of proper medication and on the continuous patient education.

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In recent year, the number of patients with Japanese cedar pollinosis has been increasing because infantile and elderly patients are elevating. Whereas, various investigations and researches are performed for pollinosis as a subject of public concern.
The clinical guideline for allergic rhinitis was created due to elucidation of the mechanism of pollinosis and selection of drugs was defined. Furthermore, more safety and effective treatments are investigated and exploited. The Japanese government build panel for pollinosis. They develop specialized Japanese cedars that are diminished pollen and also convert Japanese cedar to needle-leaved trees. And some functional diets that inhibit allergic reaction are now investigated. The author believes that the Japanese cedar pollinosis will be overcome in the future.

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The role of antigen-specific T cells in the allergic reactions to hen's egg or in the induction of tolerance hasn't been fully investigated. This time, we performed transcriptome analysis of allergen specific T cells from hen's egg allergic patients to clarify these issues and to identify biomarkers of hen's egg allergy. By using microarray technology, allergen-stimulated T cells from hen's egg-allergic children were analyzed to identify genes that are specifically up-regulated in these cells. In microarray analyses of allergen-stimulated T cells, 43 genes were up-regulated in hen's egg-allergic children but not in non-hen's egg-allergic children. Among the up-regulated 43 genes, cytokine inducible SH2-containing protein (CISH) in patients was significantly higher than controls (p<0.01) in real-time PCR confirmation. CISH may function as a diagnostic bio-maker for hen's egg allergy.

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[in Japanese]

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It is known that airway mucus contributes widely to mucociliary defense system at airway for protecting from pathogens and environmental toxins. However, in chronic airway diseases, such as bronchial asthma, inflammatory and immune mediators cause hypersecretion of airway mucus and hyperplasia of mucus-secreting cells. Thus, the hypersecretion exaggerates the disease. We have produced a murine model of asthma in which both IAR and LAR were observed after antigen provocation. In this model, we compared the mucus area in the airway lumen during IAR and LAR. Our results suggested that airway hypersecretion may be involved as a component of airway obstruction during LAR, and this is unlikely during IAR. DSCG reduced excessive airway mucus during LAR. Our study showed that the control of airway hypersecretion would be useful for preventing and treating bronchial asthma, especially in infants.

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The exacerbation of asthma during viral infections is mainly explained by neutrophils infiltrating into airways. However, enhanced functions of eosinophils are also observed. The aim of this study was to reveal the mechanism of how eosinophils are activated during and after viral infection of the airways. Eotaxin-3 is a chemokine that shows potent chemoattractant activity toward eosinophils. Airway epithelial cells produced eotaxin-3 after stimulation with the Th2 cytokine interleukin (IL) -4. When the cells were cultured with Th1 cytokine interferon (IFN) -γ and IL-4 simultaneously, IFN-γ inhibited the production of IL-4-induced eotaxin3. On the other hand, pretreatment of the cells with IFN-γ dose-dependently enhanced IL-4-induced eotaxin-3 production. IFN-γ also increased expression of IL-4 receptors in a time- and a dose-dependent manner. AS a model of viral infedction, a synthetic double-strand RNA, poly inosinic-cytidynic acid ( Poly (IC)), was transfected to the airway epithelial cells. Also poly (IC) transfecion increased expression of IL-4R, and pretreatment of the cells with poly (IC) enhanced IL-4-induced eotaxin-3. These results suggest that viral airway infection may enhance IL-4-induced eotaxin-3 production through upregulation of the IL-4R in airway epithelial cells. Thus, mediators that exist in the airway might modulate production of chemokines by affecting the expression of several molecules such as cytokine receptors of airway epithelial cells.

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Anti-inflammatory effects of erythromycin have drawn notice to its clinical application for chronic respiratory inflammatory diseases. Since dendritic cells have been shown to play pivotal roles in antigen sensitization and exacerbation of allergic inflammation, we examined the effects of erythromycin on the function of dendritic cells activated with pathogen-derived stimuli and helper T cell activation. As a results, erythromycin selectively inhibited expressions of costimulatory molecules and cytokine production by dendritic cells stimulated with poly (I:C) and LPS, but not with peptidoglycan. Erythromycin suppressed IFN regulatory factor-3 activation and IFN-β production induced by poly(I:C) and LPS, and suppressed poly (I:C)-mediated differentiation of naïve T cells into Th1 effector cells. Moreover, erythromycin suppressed IL-17 production by memory T cells that were activated by PGN-stimulated dendritic cells. These results collectively suggest that erythromycin presents anti-inflammatory effects depending on the nature of pathogen-derived stimuli, and thereby modulates allergic inflammation.

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Back ground: Mucosal changes associated with food-sensitive intestinal inflammation have been identified in several animal model mice. The histological examination will provide an important clue for clarifying the mechanism of food hypersensitivity. However it is unknown where the severest inflammation occurs.
Method: To identify the severest inflammation site, we focused on the histological changes in Nc⁄Jic mice sensitized with ovalbumin (OVA). We sensitized Nc⁄Jic mice (n=7) with low doses of OVA both orally and peritoneally, and then sacrificed 3 hours after a high oral dose of OVA challenge. The control group (n=7) was primed with saline in the same manner. The severity of mucosal inflammation, the villous edema occurrence, and the number of intramucosal mast cells of the OVA group were compared with those of the control group in the entire small intestine, 3 parts and 30 parts divided equally.
Results: The severity of inflammation and the villous edema occurrence of the OVA group were significantly higher than those of the control group in the pyloric and central parts, and many of the significantly higher segments were found in the pyloric part. The number of mast cells was significantly lower in the pyloric part of the OVA group than that of the control group.
Conclusion: Food hypersensitivity mucosal inflammation is the severest in the pyloric part.

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Background
To assess wheezing at the end of expiration in infants, the author tested auscultatory techniques in children using toys.
Study methods
Breath sounds were obtained with a sonograph while children were playing with a pinwheel, a blow-up ball (ball), or an elephant blow-up thread (elephant), and analyzed. Physicians who volunteered to assess these toys returned 77 questionnaires.
Results
Sonograms showed a low inspiratory-expiratory ratio and the greatest dispersion when the pinwheel was used, the highest inspiratory-expiratory ratio and large dispersion when the ball was used, and a lower inspiratory-expiratory ratio than that obtained with the ball and the smallest dispersion when the elephant was used. Questionnaires showed that physicians rated the elephant most highly for auscultation of breath sounds and wheezing. Physicians pointed out that the ball was difficult to handle and involved the risk of accidental ingestion.
Discussion
The present study showed that children repeated forced respiration regularly to the end of expiration while playing with the elephant. Questionnaires have also revealed that the elephant was rated highly as an aid to auscultation. This toy is expected to allow easy confirmation of resolution of wheezing at the end of expiration and more reliable asthma management in infants.

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Objective: We examined sputum cytology repeatedly for one intractable asthmatic patient and compared the results with clinical conditions to determine whether sputum cytology work as a tool for monitoring airway inflammation.
Methods: The case was 4-year-old girl with severe persistent asthma. She has been hospitalized 10 times for asthma exacerbation and twice for pneumonia in the last one year. We obtained spontaneous sputum in exacerbation phases, and induced sputum in stable phases for differential cell counts.
Results: Four or five days after sputum eosinophils increased to 50 to 60%, she was admitted to hospital for acute exacerbation. Systemic steroid therapy for acute exacerbation decreased sputum eosinophils to 5-10%. In acute phase of pneumonia, sputum neutrophils occupied 90% and eosinophils almost disappeared. Sputum eosinophils were usually more than 10%, but when she stayed at mother's home island for one month in summer vacation, asthma symptom disappeared, and eosinophils decreased to 4% without using systemic steroids.
Conclusions: Sputum cytology can be a useful tool for monitoring bronchial inflammation.

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Patients with asthma are generally instructed to keep an asthma diary and measure their daily peak flow, so that they can grasp their disease condition and manage asthma symptoms by themselves. However, the data from an asthma diary is not too reliable because patients often miss entries in the diary and make entries all at once not everyday, furthermore the time of measuring peak flow is often varied. In recent years, electronic diary and peak flow meter have begun to be used in the West to raise the reliability of the data obtained in clinical studies. We performed a feasibility study involving Japanese children with bronchial asthma (age 5 to 15) to investigate the acceptability of an electronic diary and electronic peak flow meter. As a result, compliance regarding entries in the electronic diary on awakening and at bedtime was good (>94.0%). Most of the patients reported high convenience of their use, although some of them pointed out the need for further improvement in training and support systems. The results suggest the usefulness of an electronic diary and an electronic peak flow meter in clinical studies and research of pediatric asthma.

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We assessed the efficacy, safety and convenience of salmeterol (SLM)/fluticasone propionate (FP) combination (SFC) in children with asthma. Subjects were children aged 5 to 14 years. Efficacy population consisted of 48 patients, 32 male and 16 female patients who had mild persistent asthma (11 patients) or moderate persistent asthma (37 patients). The mean age was 8.4 years. Each subject received the two treatments SFC 25/50μg (one inhalation twice daily by pMDI) and SLM 25μg plus FP 50μg (each one inhalation twice daily by DPI) in a two-way crossover. Both treatments showed statistically significant improvements in morning PEF and the improvements were not statistically different. In the assessment of convenience, SFC was rated higher compared with SLM+FP, suggesting high adherence to SFC in clinical settings.

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