Thymic stromal lymphopoietin (TSLP) triggers dendritic cell–mediated T helper (Th) 2 inflammatory responses. A single-nucleotide polymorphism (SNP), rs3806933, in the promoter region of the TSLP gene creates a binding site for the transcription factor activating protein (AP)–1. The variant enhances AP-1 binding to the regulatory element, and increases the promoter–reporter activity of TSLP in response to polyinosinic-polycytidylic acid (poly[I:C]) stimulation in normal human bronchial epithelium (NHBE). We investigated whether polymorphisms including the SNP rs3806933 could affect the susceptibility to and clinical phenotypes of bronchial asthma. We selected three representative (i.e., Tag) SNPs and conducted association studies of the TSLP gene, using two independent populations (639 patients with childhood atopic asthma and 838 control subjects, and 641 patients with adult asthma and 376 control subjects, respectively). We further examined the effects of corticosteroids and a long-acting β2-agonist (salmeterol) on the expression levels of the TSLP gene in response to poly(I:C) in NHBE. We found that the promoter polymorphisms rs3806933 and rs2289276 were significantly associated with disease susceptibility in both childhood atopic and adult asthma. The functional SNP rs3806933 was associated with asthma (meta-analysis, P = 0.000056; odds ratio, 1.29; 95% confidence interval, 1.14–1.47). A genotype of rs2289278 was correlated with pulmonary function. Moreover, the induction of TSLP mRNA and protein expression induced by poly(I:C) in NHBE was synergistically impaired by a corticosteroid and salmeterol. TSLP variants are significantly associated with bronchial asthma and pulmonary function. Thus, TSLP may serve as a therapeutic target molecule for combination therapy.

Background

The food labeling system for food allergens was introduced from April 2002 in Japan. To confirm the effectiveness of the system, we regularly conduct a nationwide food allergy survey every 3 years.

Methods

The survey was conducted in cooperation with over 1000 volunteer allergists in Japan at 2001, 2002, 2005 and 2008. We sent questionnaire to contributing doctors every 3 months based on the past survey system, and contributing doctors were asked to report immediate type food allergy cases seen by those doctors. In this survey, immediate type food allergy was defined as the patients who had developed symptoms due to food allergic reaction within 60 minutes after intake of offending food. The details of questionnaire consisted of age, sex, cause of food allergy, symptoms, CAP system, and type of onset.

Results

A total of 8581 immediate type food allergy cases were reported by the doctors. The most common offending foods were hen's egg (39.0%), milk products (18.0%), wheat (9.4%), fruit (5.3%), crustacean (4.6%), peanuts (3.7%), fish egg, buckwheat and fish (3.6%). The most common clinical symptom was observed on skin (89.7%) followed by respiratory system (29.6%). Interestingly, the causes of food allergy were completely different from infancy (egg, milk, and wheat) to adulthood (wheat, crustacean and fruits). Anaphylactic shock was observed in 10.9% of the total reported cases. The cases of anaphylactic shock were due to hen's egg (27.1%), milk products (21.4%) and wheat (18.1%). Eleven percentages of patients had been hospitalized.

Conclusions

We revealed the current condition of the immediate type food allergy cases seen in Japan recent decade. Based on these data, countermeasures against food allergy are ongoing in collaboration with the Ministry of Health, Labour, and Welfare in Japan in order to improve quality of life of patients.

Background

The aim of this study is to clarify the cross section of pediatric food allergy patients. We investigated the profiles of food allergy (FA) patients seen in our department.

Methods

The number of food allergy patients seen in our department from January to December in 2010 was a total of 1,822 (male: 1207, female: 615, mean age: 5.8 ± 3.8 year). We collected and analyzed the clinical information of these patients from our medical record. We obtained information on the age of FA onset & FA diagnosis, clinical types of FA at the onset, causative food allergens, other allergic complications, and application of oral immunotherapy (OIT).

Results

The average age of FA onset was 8 months, and that of diagnosis was 1 year old, respectively. The most common clinical types of FA at the time of onset were infantile atopic dermatitis (AD) type with food allergy (66.4%) followed by immediate type (30.8%). Food allergens avoided by the patients were the total number of 4,203 items (2.1 items as average). The most common eliminated food was hen's egg (1,245 cases; 29.6%), followed by cow's milk (786 cases; 18.7%), peanut (449 cases; 10.7%), and wheat (407 cases; 9.7%). Food-dependent exercise-induced anaphylaxis (FDEIA) was the total of 18 cases, and the most common causative food for FDEIA was wheat (10 cases) followed by peach (4 cases). One hundred and seventy five cases (9.6%) were currently receiving OIT. Main causative foods under OIT were hen's egg (63 cases), cow's milk (80 cases), and wheat (30 cases). The average starting age of OIT was 7.1 years old. Regarding complications of allergic diseases other than FA, 1119 (61.4%) had atopic dermatitis, and 541 (29.7%) bronchial asthma.

Conclusions

We were able to clarify the cross section of food allergy patients in our department and to obtain the basic data to follow continuous transition of these patients.

Background

The food labeling system for food allergens was introduced from April 2002 in Japan. To confirm the effectiveness of the system, we regularly conduct a nationwide food allergy survey every 3 years.

Methods

The survey was conducted in cooperation with over 1000 volunteer doctors in Japan at 2001+2002, 2005 and 2008. We have sent questionnaires to contributing doctors every 3 months based on the previous survey system, and contributing doctors were asked to report immediate type food allergy cases seen by those doctors. In this survey, immediate type food allergy was defined as the patients who had developed symptoms due to food allergic reaction within 60 minutes after intake of causative foods. The details of questionnaire consisted of age, sex, cause of food allergy, symptoms, antigen-specific IgE, and type of onset.

Results

A total of 8581 immediate type food allergy cases were reported by the doctors in these surveys. The most common causative foods were hen's egg (39.0%), milk products (18.0%), wheat products (9.4%), fruits (5.3%), crustacean (4.6%), peanuts (3.7%), fish egg, buckwheat and fish (3.6%). The most common clinical symptom was observed on skin (89.7%) followed by respiratory system (29.6%). Interestingly, the causes of food allergy were completely different from infancy (egg, milk, and wheat) to adulthood (wheat, crustacean and fruits). Anaphylactic shock was observed in 10.9% of the total reported cases. The cases of anaphylactic shock were due to hen's egg (27.1%), milk products (21.4%) and wheat (18.1%). Eleven percentages of patients had been hospitalized.

Conclusions

We could clarify the detail of the immediate type food allergy cases seen in Japan for a recent decade. Based on these data, countermeasures against food allergy have been conducted in collaboration with the Ministry of Health, Labour, and Welfare in Japan in order to improve quality of life of patients with food allergy.

Background

Efficacy and safety of slow oral immunotherapy (SOIT) is not yet clear, especially regarding tolerance acquisition.

Methods

We recruited 32 cow's milk (CM) allergy confirmed by oral food challenge (OFC). Twenty-five subjects were enrolled as SOIT group, and remaining 7 were as control. The inclusion criteria were as follows; (1) CM allergy without anaphylaxis confirmed by OFC just before the trial, and (2) children >4 years. In SOIT group, they were asked to take small amount of CM at home after the OFC. The initial dose was about 1/4 of the threshold eliciting positive objective symptoms, and it was built up to 200 mL CM depends on the symptoms (build up phase). After reaching 200 mL, they were asked to take 200 mL CM daily until the asymptomatic duration lasting for more than 3m (maintenance phase). The subjects, who completed maintenance phase, underwent OFC to confirm the tolerance acquisition after the cessation of CM ingestion for 2w (confirm-OFC). In control group, they had eliminated CM completely and underwent the confirm-OFC after 9.8 ± 2.9 m (mean ± SD). We investigated the endpoints (adverse reactions, medical treatments, results of confirm-OFC, and laboratory findings), prospectively.

Results

In SOIT group (n = 25) and control group (n = 7), the average age was 6.6y and 4.7y, respectively. The average threshold was 52 mL and 17 mL, and the CM specific IgE was 17.6 Ua/mL/9.9 Ua/mL, respectively. The average period of build up and maintenance phases in SOIT group was 80d (n = 25) and 98d (n = 15), respectively. The frequency of adverse reactions in all of build up (1973d) and maintenance phases (2924d) were 13.5% (mild symptoms)/2.3% (moderate symptoms) and 1.7% (mild)/0.3% (moderate), respectively. No patient had administered adrenaline during SOIT. Fifteen subjects in SOIT and 7 in control underwent the confirm-OFC. In SOIT, 8 subjects (53.3%) passed the confirm-OFC, whereas 2 (28.6%) passed in control. There was no statistically significant difference regarding tolerance acquisition between these 2 groups (P = 0.277).

Conclusions

This study suggests that SOIT for about 1/2 year induces desensitization effectively for CM allergy without severe adverse reactions. Further and longer study would be required to prove accelerated tolerance acquisition by SOIT.

Background

Food allergy (FA) is prevalent among children however natural history of FA is not fully clarified.

Methods

We sought to investigate the natural course of childhood FA. To follow up the transition of same patients, we collected clinical records of patients with 3 years’ interval from 2008 to 2010. Four hundred ninety-one patients (male 321 and female 170) were recruited to this study.

Results

The onset of FA was at the age of 5 months ± 1 year 3 month (mean ± SD). The clinical type at the onset was with infantile atopic eczema (84.1%), and followed by immediate reactions without eczema (14.9%). The initial diagnosis age was 10 months ± 1 year 4 months, and the first visit to our department was 1 year 11 month ± 2 years 5 months. Current age of the patients was 7 years 5 months ± 2 years 11 months, and 444 patients (90.4%) had experienced immediate reactions. The number of eliminated foods decreased from 2.4 ± 1.5 items/patient (n = 1191) to 1.9 ± 1.6 items/patient (n = 926) in 3 years. The ratio of stopping elimination of major allergens was 35.9% (121/337 patients) for hen's egg, 25.6% (52/203 patients) for cow's milk and 47.8% (44/92 patients) for wheat. Fourteen patients (2.9%) had developed new food allergies, and 2 of them had experienced anaphylaxis by tree nuts. Newly diagnosed allergens were only 0.1 ± 0.3 items/patient (n = 32), and nuts (n = 6) and peanut (n = 5) were the most frequent. Seventy-nine patients (16.1%) had developed complete remission of FA in 3 years, and 21.5% of them (17 patients) had never developed immediate reactions.

Conclusions

Most of pediatric FA started during infancy with atopic eczema, and developing tolerance is expected with aging. In some patients, persistent FA is troublesome for school age children.

Background

Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown.

Objective

To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.

Methods

We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1st stage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2nd stage), 541 independent patients, and 744 controls (3rd stage).

Results

SNPs located in the 5' region of PEX19 (rs2820421) were significantly associated with P < 0.05 through the 1st to the 3rd stage analyses; however, the P values did not reach statistically significant levels (combined, P = 3.8 × 10-5; statistically significant levels with Bonferroni correction, P = 6.57 × 10-7). SNPs on HPCAL1 (rs3771140) and on IL18R1 (rs3213733) were associated with asthma in the 1st and 2nd stage analyses, but the associations were not observed in the 3rd stage analysis.

Conclusion

No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.