Allergen-specific immunotherapy represents the only causative approach towards allergy treatment. Conventional immunotherapy reduces symptoms and medication requirements in allergic rhinitis and asthma but its use is limited by the risk of adverse effects and the inconvenience of the prolonged course of therapy. However, immunotherapy seems to have the potential to alter the natural course of allergic diseases by preventing onset of new sensitization and progression from rhinitis to asthma. Novel approaches to immunotherapy currently being explored include the use of new adjuvants, such as immunostimulatory DNA sequences, and the use of allergen-derived peptides, or modified recombinant allergen, with the aim to reduce IgE-mediated side effects during immunotherapy and to foster certain advantageous immunogenicity. This article reviews the development of immunotherapy, our current understanding of its mechanisms of action and its future prospects.

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Studies of the natural history of asthma have demonstrated that 30-50% of children with asthma experience remission, and that approximately 30% of them relapse later. Factors contributing to persistence or relapse of asthma are following; delayed use of inhaled steroid, airway remodeling, allergic states, genetic factors, and environments. The most promising strategy for inducing remission and keeping their remission states longer could be a multi-interventional approach focusing on these factors. However, there have been few evidences in this context. Further prospective long-term studies will be needed.

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Asthma is characterised by chronic airway inflammation that is likely to be evident even in children. Current asthma treatment recommendations, as stated in many guidelines, therefore suggest early intervention with inhaled corticosteroids. We performed retrospective research to determine whether inhaled fluticasone propionate (FP) exerts any long-term effects on growth in young children with persistent asthma. Subjects comprised 64 patients aged 18-68 months. Long-term treatment was started with FP as a virgin inhaled corticosteroid, lasting for at least 6 months (mean dosage, 109.5μg/day). A significant reduction in clinical symptoms was achieved after FP treatment. No significant growth suppression was found among subjects in comparison with the standard growth curve for Japanese children. In conclusion, even in children younger than 6-years-old, FP significantly improves asthmatic symptoms without causing significant growth suppression. However, the growth of each child treated with FP should still be monitored.

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The prognoses that had been made for asthmatic children admitted to our hospital with asthmatic attack from 1980 through 1984 were followed up by survey conducted in 2001. The subjects of our investigation were 239 patients, of whom 101 (42.2%) respondent to our survey instrument, a questionnaire. The survey revealed a remission rate of 50.5%, among the respondents. A relation between the severity of the patients' asthma attacks at the first visit to our hospital and the remission rates was also revealed: The result shows that the remission rate for the mild cases was 90.5%; the moderate cases, 48.3%; the severe cases,18.2%. The correlation between our prognosis and patients' personal factors (sex, age at the first asthma attack, severity of asthma attack at the first hospital visit, type of allergy, and IgE-value, and frequency of hospitalization) was investigated by the Logistic Regression Analysis. The result shows that severity of asthma attack at the first hospital visit was most strongly correlated. Considering the results of this study and that 43.7% of the patients were not given treatments when attacks were absent, we conclude that clearer explanations to the patients and their parents are needed not only about treatments of asthma attacks but also about the patients' asthma as well as the importance of long-term preventive control.

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A questionnaire on the prognosis of bronchial asthma was sent in 2002 to 136 patients who had a first visit in department of Allergy, Kanagawa Children's Medical Center between 1982 and 1984. The average age of the first visit was 6.9±3.8 years. The average age at the questionnaire was 25.7±3.9 years. 2 year-remission was 54.1% (56.8% males, 48.9% females). There were significant differences in blood eosinophil, serum total IgE, a severity at the initial visit, airway responsiveness (acetylcholine threhsould) in male, and V₅₀ in female between remission group and non-remission group. The prognosis was significantly poorer among asthmatics with pharmacotherapy of inhaled beclomethasone dipropionate, inhaled sodium cromoglycate, or theophylline, because these drugs predominantly are used by severer patients. Relapses after 2 year-remission was 16.7%, and 21.4% of these entered further remission. Smoking ratio was 33.6%, but not associated with remission.

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Food allergy is a common allergic manifestation in early childhood. Since 2001, when we surveyed kindergartens regarding their food elimination policies for food allergic children, food allergy has become more publicized. Therefore, we resurveyed in 2006. A questionnaire was sent to all 439 kindergartens in Toyama Prefecture, and 229 valid answers (52.2%) were received. Food elimination had been undertaken in 86.9% of the kindergartens for 1.97% of the children, and both values were higher than those in 2001 (70.5 and 1.24%, respectively). Regarding elimination regimen, the percentage of the kindergartens requested a written form was increased from 13.5% to 58.3%, during five-year period. We also found elevated number of the kindergartens where they prepared for accidental intake of offending foods (from 22.7 to 79.9%). However, caregivers in 73.4% of the kindergartens had never heard about an injectable adrenaline device. Although their policies are clearly improved, there still appears to be a need for a food allergy guideline specified to kindergarten.

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We examined the validity of evaluating asthmatic symptoms in children under 2 years of age using a questionnaire designed for 3-year-old children. We requested the guardians (mostly mothers) of 64 children under the age of 2 years who were seen by pediatricians to complete the questionnaire. The responses were compared to the pediatrician's diagnosis based on the ''Japanese Pediatric Guideline for the Treatment and Management of Asthma 2005''. For most of the children diagnosed as having infantile asthma by their pediatrician, the guardians reported a history of wheezing. In about half of the children who were not diagnosed as having asthma, a history of wheezing was also reported by their guardians. A history of three or more episodes of dyspnea was reported by guardians in 14.3% of children diagnosed as having infantile asthma, and in none of the other children. A history of two or more episodes of dyspnea was reported in 17.9% of children diagnosed as having infantile asthma and in 2.8% not diagnosed as having infantile asthma. If a child who experienced dyspnea three times or more was defined as having ''asthma'', then the sensitivity and the specificity for the diagnosis made by a pediatrician were 14.3% and 100%, respectively. When a child with two or more episodes of dyspnea was defined as having ''asthma'', the sensitivity improved to 17.9%, and the specificity was still sufficiently high (97.2%). These findings suggest that, in children under the age of 2 years, a history of two or more episodes of dyspnea is a distinctive symptom of asthma.

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The causes of childhood asthma death were analyzed on 194 patients from 0 to 34 years of age, who had died from 1988 to 2005 and were reported to the committee until October in 2006. Subjects analyzed were divided into two groups by year to study the annual change in asthma death; the former group who died between 1988 and 1997 and the latter group between 1998 and 2005.
The number of annual asthma death has tended to be decreased since 1998.
Sex ratio (Male to female) was 97 to 62 (1.6 : 1) in the former group and 22 to 13 (1.7 : 1) in the latter group. The grades of asthma severity during one year before asthma death were severe 44%, moderately severe 30%, mild 26% in the former group and severe 45%, moderately severe 25%, mild 30% in the latter group respectively showing no differences between the groups.
Number of deaths in the hospital where they had usually visited were 72% in 0 to6, 54% in 7 to 12 and 39% in older than 13 years of age showing that the older asthmatics became, the more the number of asthma deaths in the places other than the hospital increased. Tere were some cases of astma death where school was concerned. The main contributory factors to asthma death were unexpected rapid exacerbation 71% that was most important and the second was delay in visiting the hospital 65%. The medication in the last one year indicated increases in inhaled corticosteroids from 20% in the former group to 33% in the latter group and also a novel beta-agonist patch was recognized. Concerning asthma death by month of the year, the data shows a tendency that the number of asthma deaths increased in October, November, December, January, June and August, by contrast, decreased in February, March, April, May, July and September. Related to asthma deaths by time of the day, the data shows that the number of the asthma deaths increased between two and three, three and four, seven and eight, and fifteen and sixteen, however there was no special focus-time of the day in asthma deaths.

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