Executive summary: Japanese pediatric guideline for the treatment and management of asthma (JPGL) 2020.

This article covers the salient and updated themes of the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2020 published by the Japanese Society of Pediatric Allergy and Clinical Immunology. In the 2020 guidelines, five new clinical questions (CQs) have been added to address the 12 CQs regarding the treatment of childhood asthma. "Infant and preschool asthma" is diagnosed when young children (<6 years of age) have three or more episodes of clear expiratory wheezing, which continue for more than 24 h, and symptom improvement can be observed after beta-2 agonist inhalation. In children without clear improvement, diagnostic therapeutic trial for the duration of 1 month with controller treatment can be used. Since long-term management is initiated, the treatment level is adjusted based on the current control status and the management of risk factors, with the provision for holistic care. This underscores the smooth transition of pediatric patients into adult services. There are several differences between the JPGL and the guidelines of other countries. Further evidence is obtained as the utility of the newly proposed management plans should be evaluated in the Japanese population.

'Benifuuki' green tea containing o-methylated catechin reduces symptoms of Japanese cedar pollinosis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP). METHODS: The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season. RESULTS: Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group. CONCLUSIONS: 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.

'Benifuuki' Green Tea Containing O-Methylated Catechin Reduces Symptoms of Japanese Cedar Pollinosis: A Randomized, Double- Blind, Placebo-Controlled Trial.

BACKGROUND: Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP). METHODS: The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700 ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season. RESULTS: Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group. CONCLUSIONS: 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.

The use of complementary and alternative medicine by pediatric food-allergic patients in Japan.

BACKGROUND: In developed countries, increasing food allergy prevalence and concern regarding food allergies have been reported. Although the use of complementary and alternative medicine (CAM) for the treatment of allergic diseases has increased in some Western countries, the actual proportion and patterns of CAM use for pediatric food allergies in Japan are still unknown. METHODS: Fourteen allergy centers in Japan participated in the study using a questionnaire survey regarding the use of CAM by pediatric patients. A diagnosis of food allergy was made at each hospital by pediatric allergists. RESULTS: Surveys were completed by parents/guardians, and data were collected for a total of 962 pediatric food-allergic patients. Overall, 8.4% of the participants used CAM to treat a food allergy. The major CAM therapies used were herbal teas (22.2%), including several Japanese herbal teas, Chinese herbal medicine (18.5%) and lactic acid bacteria (16%). Among the participants using CAM to treat food allergy, 13.6% thought that the CAM being used was very effective, while 11.1% of participants thought that CAM caused some type of side effect. CONCLUSIONS: Our study is the first large-scale national survey regarding the use of CAM in pediatric patients with food allergies in Japan. Unlike in the USA, which has a higher rate of CAM use (17%), approximately 8.4% of food-allergic patients used CAM in Japan. Interestingly, the major types of CAM used in Japan differed from those used in the USA. Cultural differences and food customs may affect the use of CAM.

The efficacy of early treatment of seasonal allergic rhinitis with benifuuki green tea containing O-methylated catechin before pollen exposure: an open randomized study.

BACKGROUND: We previously reported that 'benifuuki' green tea containing O-methylated catechin significantly relieved the symptoms of perennial or seasonal rhinitis compared with a placebo green tea that did not contain O-methylated catechin in randomized double-blind clinical trials. In this study we assessed the effects of 'benifuuki' green tea on clinical symptoms of seasonal allergic rhinitis. METHODS: An open-label, single-dose, randomized, parallel-group study was performed on 38 subjects with Japanese cedar pollinosis. The subjects were randomly assigned to long-term (December 27, 2006-April 8, 2007, 1.5 months before pollen exposure) or short-term (February 15, 2007: after cedar pollen dispersal--April 8, 2007) drinking of a 'benifuuki' tea drink containing 34 mg O-methylated catechin per day. Each subject recorded their daily symptom scores in a diary. The primary efficacy variable was the mean weekly nasal symptom medication score during the study period. RESULTS: The nasal symptom medication score in the long-term intake group was significantly lower than that of the short-term intake group at the peak of pollen dispersal. The symptom scores for throat pain, nose-blowing, tears, and hindrance to activities of daily living were significantly better in the long-term group than the short-term group. In particular, the differences in the symptom scores for throat pain and nose-blowing between the 2 groups were marked. CONCLUSIONS: We conclude that drinking 'benifuuki' tea for 1.5 months prior to the cedar pollen season is effective in reducing symptom scores for Japanese cedar pollinosis.

Antigen-induced expression of CD203c on basophils predicts IgE-mediated wheat allergy.

BACKGROUND: For in vitro diagnosis of wheat allergy, specific IgE to wheat is known to be a poor predictive marker. Oral food challenge, the gold standard for the diagnosis, is accompanied by a risk of severe induced reactions. Reliable in vitro tests are needed to be developed for safe indication for oral challenge. OBJECTIVE: We examined the utility of a basophil activation marker, CD203c, for the diagnosis of IgE-mediated wheat allergy. METHODS: Fifty-eight children with suspected wheat allergy with positive CAP-FEIA to wheat were enrolled. On 70 occasions, the clinical distinction between patients with wheat allergy (WA) and patients tolerant to wheat (TW) was made by means of an oral food challenge test or recent history of immediate allergic reactions or tolerance after ingestion of wheat. Twelve replicate evaluations were performed in 9 patients over more than a 6-month interval. Thirty two patients on 43 occasions were diagnosed with WA and 27 were confirmed to be TW. One patient had both diagnoses 18 months apart. Peripheral blood was incubated with fractionated wheat extracts, purified native omega-5 gliadin (nOG5) and recombinant omega-5 gliadin (rOG5). Expression of CD203c on basophils was then analyzed by flow cytometry using a commercial kit. RESULTS: All wheat proteins induced concentration-dependent enhancement of CD203c expression in WA, but did not in TW. The analysis of receiver operating characteristics (ROC) showed that nOG5-induced CD203c(high)% values provided the best power for discriminating between WA and TW, with a sensitivity of 85.0% and specificity of 77.0% at the cut-off level of 14.4%. AUC for CD203c with nOG5 were significantly higher than that for conventional CAP-FEIA, 0.89 and 0.73, respectively (p < 0.01). CONCLUSIONS: Measurement of nOG-induced enhancement of CD203c on basophils is useful for the diagnosis of immediate wheat allergy in children.

Allergen-induced basophil CD203c expression as a biomarker for rush immunotherapy in patients with Japanese cedar pollinosis.

BACKGROUND: Rush immunotherapy (RIT) can confer rapid clinical benefit on patients with allergic rhinitis or asthma. However, biomarkers representing mechanisms for the efficacy of RIT are still to be established. CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcepsilonRIalpha receptor and may serve as a useful marker. OBJECTIVE: We sought to investigate the changes in allergen-induced CD203c expression in patients with Japanese cedar pollen (JCP) pollinosis who received RIT. METHODS: Nine patients treated with RIT were enrolled in the study. Whole blood was incubated with various concentrations of JCP extract. CD203c expression on basophils was quantitated by means of flow cytometry. JCP-specific IgG4 levels in sera were measured with ELISA. Basophil histamine release, CAP-RAST to JCP (JCP-IgE) and total IgE were also examined. The biomarkers listed above were evaluated before and sequentially after RIT. Symptom and quality of life scores were obtained during pre- and posttreatment pollen seasons. RESULTS: All patients showed significant improvement in symptom and quality of life scores after RIT. Serum JCP-specific IgG4 titers were significantly elevated at 1 month and remained at high levels 12 months after the treatment. Stimulation with JCP extract induced enhancement of basophil CD203c expression in a concentration-dependent manner except for 2 subjects in whom no increase in CD203c by an anti-IgE antibody was observed (nonresponders). Significant reductions in the responses were observed in 4 subjects after RIT (reduction in CD203c expression, RCE) whereas no changes were seen in 3 subjects (non-RCE). RCE subjects were older than non-RCE counterparts, with mean ages of 20 and 12 years, respectively. No significant changes in JCP-specific IgE and total IgE levels were seen before and after RIT. CONCLUSION: Allergen-induced CD203c expression in basophils may represent, at least in part, the cellular mechanism for the therapeutic responses to RIT for JCP pollinosis. However, further larger-scale studies to confirm the utility of the test are necessary.

Blocking antibody is generated in allergic rhinitis patients during specific immunotherapy using standardized Japanese cedar pollen extract.

BACKGROUND: Japanese cedar pollen is by far the most important cause of allergic rhinitis in Japan. In this study, we assessed the induction of blocking antibody during specific immunotherapy (SIT) using a recently standardized allergen extract from Japanese cedar pollen. METHODS: Basophils from nonallergic subjects were passively sensitized with serum samples prepared from pollinosis patients before and after SIT; all patients showed good clinical efficacy. The cells were then stimulated with the standardized allergen, and histamine release was measured. In most experiments, the basophil stimulation buffer contained 1% serum. RESULTS: Pollinosis patients' sera obtained both before and after SIT showed essentially similar sensitizing capacity for basophils. Basophil degranulation in response to a relatively low concentration of pollen extract was effectively suppressed by addition of post-SIT serum samples, indicating the presence of blocking antibody. The blocking antibody was IgG, and its potency varied widely among the donor patients. CONCLUSIONS: The standardized allergen extract from Japanese cedar pollen is useful not only for clinical application in SIT, but also for testing for induction of blocking antibody during SIT.

[Prevalence of sensitization of Japanese cedar pollen in children from infancy to adolescence].

BACKGROUND: In Japan, morbidity of Japanese cedar pollinosis has dramatically increased, especially in children. However, little is known about the prevalence of pollinosis and sensitization to Japanese cedar pollen (JCP) in young children. OBJECTIVE: The aim of this study is to investigate the prevalence of sensitization to JCP in allergic and non-allergic children from infancy to adolescence. METHODS: Two hundred forty three children with allergic diseases (age 8 months-16 years, mean 5 years) and 137 children without allergic diseases (age 1 month-15 years, mean 4 years) were recruited. Their specific IgE to JCP, house dust mite, orchard grass pollen, egg white, and milk were measured with the CAP-RAST system. A questionnaire was filled out by their parents. RESULTS: The percentage of positive (> or = 2) CAP-RAST to JCP was 47.1% in children with allergic diseases and 19.9% in children without allergic diseases. In children with allergic diseases, the ratio had risen rapidly from 3 to 5 years old. In children without allergic diseases, the ratio of JCP sensitization has gradually increased from the infancy to adolescence. The youngest child who had been sensitized to JCP was 23-month-old boy with atopic dermatitis. The proportion of children who were born from January to march was significantly higher in JCP sensitized group than JCP non-sensitized group. The ratio of house dust mite and orchard grass pollen sensitization was higher in JCP sensitized group than those in JCP non-sensitized group. CONCLUSION: Large number of children acquire sensitization to JCP in their preschool age. We need to develop the way how to protect JCP sensitization in the early stage of life.