Yuma Fukutomi

Rhinoconjunctival sensitization to hydrolyzed wheat protein in facial soap can induce wheat-dependent exercise-induced anaphylaxis

Background Wheat protein is responsible for various kinds of allergic disease. Wheat-dependent exercise-induced anaphylaxis (WDEIA) is one of the most important clinical phenotypes of adult wheat allergy. Relatively homogenous clinical and immunological presentations of this phenotype have already been described. More recently, some studies have shown that sensitization to hydrolyzed wheat protein (HWP) in cosmetics can induce allergy to HWP-containing food as well as contact allergy to HWP-containing cosmetics.

Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxis

Background Anaphylaxis is a life‐threatening syndrome resulting from the sudden release of mast cell‐ and basophil‐derived mediators into the circulation. However, pathological evidence of the association between inflammatory mediators and human anaphylaxis is insufficient.

Profile of eicosanoid generation in aspirin-intolerant asthma and anaphylaxis assessed by new biomarkers

BACKGROUND It has recently demonstrated that a free radical-mediated pathway generates prostaglandins (PGs) and the corresponding prostaglandin enantiomers (ent-PGs). Aspirin-intolerant asthma and anaphylaxis accompany PGD(2) overproduction, possibly associated with mast cell activation via the COX pathway. However, free radical-mediated PG generation in the pathophysiology of these diseases, which can be demonstrated by measuring urinary ent-PGF(2)alpha, has not been reported. OBJECTIVES To evaluate the characteristic profile of eicosanoid generation via the COX and/or free radical-mediated pathway underlying aspirin-intolerant asthma and anaphylaxis. METHODS A comparative group analysis consisted of asthma (n = 17) and anaphylaxis (n = 8, none with aspirin-induced anaphylaxis) cases. Urinary eicosanoid concentrations were quantified as follows: 2,3-dinor-9alpha,11beta-PGF(2) by gas chromatography-mass spectrometry; leukotriene E(4), 9alpha,11beta-PGF(2), and PGs by enzyme immunoassay. RESULTS 2,3-Dinor-9alpha,11beta-PGF(2) is a more predominant PGD(2) metabolite in urine than 9alpha,11beta-PGF(2). At baseline, the aspirin-intolerant asthma group (n = 10) had significantly higher leukotriene E(4) and lower PGE(2) concentrations in urine than the aspirin-tolerant asthma group. During the reaction, the urinary concentrations of leukotriene E(4) and PGD(2) metabolites correlatively increased, but with markedly different patterns of the mediator release, in the aspirin-intolerant asthma group and the anaphylaxis group, respectively. The urinary PGD(2) metabolites and primary PGs were significantly decreased in the aspirin-tolerant asthma group. Urinary ent-PGF(2)alpha concentrations were significantly increased in the anaphylaxis group but not the aspirin-intolerant asthma group. CONCLUSIONS When assessed by urinary 2,3-dinor-9alpha,11beta-PGF(2), PGD(2) overproduction during aspirin-intolerant bronchoconstriction was clearly identified, regardless of COX inhibition. It is evident that free radical-mediated PG generation is involved in the pathophysiology of anaphylaxis.

A functional polymorphism in IL-18 is associated with severity of bronchial asthma.

RATIONALE IL-18 is a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses. Recent murine and human genetic studies have shown its role in the pathogenesis of asthma. OBJECTIVES We conducted an association study in a Japanese population to discover variants of IL-18 that might have an effect on asthma susceptibility and/or progression and conducted functional analyses of the related variants. METHODS The IL-18 gene locus was resequenced in 48 human chromosomes. Asthma severity was determined according to the 2002 Global Initiative for Asthma Guidelines. Association and haplotype analyses were performed using 1,172 subjects. MEASUREMENTS AND MAIN RESULTS Although no polymorphisms differed significantly in frequency between the control and adult asthma groups, rs5744247 C>G was significantly associated with the severity of adult asthma (steps 1, 2 vs. steps 3, 4; P = 0.0034). We also found a positive association with a haplotype (P = 0.0026). By in vitro functional analyses, the rs5744247 variant was found to increase enhancer-reporter activity of the IL-18 gene in bronchial epithelial cells. Expression levels of IL-18 in response to LPS stimulation in monocytes were significantly greater in subjects homozygous for the susceptibility G allele at rs5744247 C>G. Furthermore, we found a significant correlation between the serum IL-18 level and the genotype of rs5744247 (P = 0.031). CONCLUSIONS Although the association results need to be replicated by other studies, IL-18 variants are significantly associated with asthma severity, and the rs5744247 variant reflects higher transcriptional activity and higher expression of IL-18 in LPS-stimulated monocytes and a higher serum IL-18 level.

Rhinoconjunctival sensitization to hydrolyzed wheat protein in facial soap and induce wheat-dependant exercise-induced anaphylaxis

Background Wheat protein is responsible for various kinds of allergic disease. Wheat-dependent exercise-induced anaphylaxis (WDEIA) is one of the most important clinical phenotypes of adult wheat allergy. Relatively homogenous clinical and immunological presentations of this phenotype have already been described. More recently, some studies have shown that sensitization to hydrolyzed wheat protein (HWP) in cosmetics can induce allergy to HWP-containing food as well as contact allergy to HWP-containing cosmetics. Case reports We experienced treating five Japanese women with WDEIA with atypical presentation. They presented exercise-induced anaphylaxis after ingestion of normal wheat products, but also had episodes of skin and/or rhinoconjunctival contact allergy to hydrolyzed wheat protein (HWP)-containing facial soap. Furthermore, case histories and serological analyses of these patients indicated that the development of their WDEIA was induced by primary sensitization to HWP in the facial soap they used and accompanying sensitization to natural wheat protein. Methods and results All of the patients had started to use the same facial soap product containing HWP 1 to 3 years prior to the onset of WDEIA. At first, they used the facial soap without any problem. When they continued to use the soap, they started to experience itchiness and urticaria of the eyelids or face after using the soap. Their symptoms of allergy to facial soap resembled prodromal symptoms that develop following the combination of wheat ingestion and exercise. A significantly higher IgE reactivity to HWP than to natural wheat protein was observed in these patients. Inhibition analyses of their sera showed that IgE reactivity to HWP was not inhibited by natural wheat extracts, whereas those to natural wheat extracts were fully inhibited by HWP, indicating that the primary sensitizer of these patients is HWP. Discussion

Nationwide Cross-Sectional Population-Based Study on the Prevalences of Asthma and Asthma Symptoms among Japanese Adults

Background: Asthma is a common respiratory disease worldwide. However, few reports are available on the prevalences of asthma and asthma symptoms among Asian subjects. Methods: To determine the prevalences of asthma and asthma symptoms among Japanese subjects, we performed a nationwide cross-sectional, population-based study on Japanese adults aged 20–79 years. Ten areas spread throughout the country were randomly selected. Door-to-door or postal surveys were performed using a translated version of the European Community Respiratory Health Survey questionnaire. Results: The survey was completed by 23,483 participants. The overall response rate was 70.6%. The prevalences of wheeze and current asthma among all participants aged 20–79 years were 10.1% (95% CI: 9.7–10.5%) and 4.2% (95% CI: 4.0–4.5%), respectively. The prevalences among young adults aged 20–44 years were 9.3% (95% CI: 8.7–9.9%) and 5.3% (95% CI: 4.8–5.8%), respectively. The prevalence of current asthma was highest in females aged 30–39 years in comparison with the other gender and age groups. Conclusions: This nationwide study determined the prevalences of asthma and asthma symptoms among Japanese adults. The results provide fundamental information on the respiratory health of Japanese adults.

Sensitization to fungal allergens: Resolved and unresolved issues.

Exposure and sensitization to fungal allergens can promote the development and worsening of allergic diseases. Although numerous species of fungi have been associated with allergic diseases in the literature, the significance of fungi from the genera Alternaria, Cladosporium, Penicillium, Aspergillus, and Malassezia has been well documented. However, it should be emphasized that the contribution of different fungal allergens to allergic diseases is not identical, but species-specific. Alternaria and Cladosporium species are considered to be important outdoor allergens, and sensitization and exposure to species of these genera is related to the development of asthma and rhinitis, as well as epidemics of asthma exacerbation, including life-threatening asthma exacerbation. In contrast, xerophilic species of Penicillium and Aspergillus, excluding Aspergillus fumigatus, are implicated in allergic diseases as indoor allergens. A. fumigatus has a high capacity to colonize the bronchial tract of asthmatic patients, causing severe persistent asthma and low lung function, and sometimes leading to allergic bronchopulmonary aspergillosis. Malassezia are common commensals of healthy skin, although they are also associated with atopic dermatitis, especially on the head and neck, but not with respiratory allergies. Despite its importance in the management of allergic diseases, precise recognition of species-specific IgE sensitization to fungal allergens is often challenging because the majority of fungal extracts exhibit broad cross-reactivity with taxonomically unrelated fungi. Recent progress in gene technology has contributed to the identification of specific and cross-reactive allergen components from different fungal sources. However, data demonstrating the clinical relevance of IgE reactivity to these allergen components are still insufficient.

The prevalence of rhinitis and its association with smoking and obesity in a nationwide survey of Japanese adults

Rhinitis is a common disease, and its prevalence is increasing worldwide. Several studies have provided evidence of a strong association between asthma and rhinitis. Although smoking and obesity have been extensively analyzed as risk factors of asthma, associations with rhinitis are less clear.

Epidemiological link between wheat allergy and exposure to hydrolyzed wheat protein in facial soap

Recent studies have highlighted the importance of extra‐intestinal routes of sensitization to food‐related allergens as the cause of epidemics of food allergy. Instances of Japanese women developing food allergy to wheat after exposure to hydrolyzed wheat protein (HWP) present in facial soap have been reported. However, the epidemiologic impact of these ingredients as a cause of food allergy has not been well studied.

Time Trend in the Prevalence of Adult Asthma in Japan: Findings from Population-Based Surveys in Fujieda City in 1985,1999, and 2006

BACKGROUND The burden of asthma is recognized as an important public health problem worldwide. In most countries, the prevalence of asthma has been reported to increase in the last few decades. However, more recent epidemiological studies have shown that the prevalence of asthma has been flat or even decreasing after the 1990 s in some developed countries. The recent time trend in the prevalence of adult asthma in Japan is unknown. METHODS Population-based surveys were conducted three times in the same region, in 1985, 1999, and 2006, at Fujieda City, Shizuoka, Japan, and the results were reported previously. We compared the results of these surveys to reveal the time trend in the prevalence of adult asthma. Although the questionnaires used in these surveys were not exactly the same, the time trend was assessed by comparing the responses to relevant questions between questionnaires. RESULTS The prevalences of wheeze following a common cold and dyspneal feeling at night increased significantly from 1985 to 1999 (4.2% to 7.6%, and 3.2% to 5.3%, respectively). The prevalences of lifetime asthma and current asthma also significantly increased from 1999 to 2006 (5.1% to 6.7%, and 1.5% to 3.4%, respectively). CONCLUSIONS The prevalences of asthma among adults in Fujieda City consistently increased from 1985 to 2006. There was no evidence that the prevalences were in plateau or decreasing. These findings suggest that more efforts are required to stop the increase in the burden of this disease in Japan.BACKGROUND The burden of asthma is recognized as an important public health problem worldwide. In most countries, the prevalence of asthma has been reported to increase in the last few decades. However, more recent epidemiological studies have shown that the prevalence of asthma has been flat or even decreasing after the 1990s in some developed countries. The recent time trend in the prevalence of adult asthma in Japan is unknown. METHODS Population-based surveys were conducted three times in the same region, in 1985, 1999, and 2006, at Fujieda City, Shizuoka, Japan, and the results were reported previously. We compared the results of these surveys to reveal the time trend in the prevalence of adult asthma. Although the questionnaires used in these surveys were not exactly the same, the time trend was assessed by comparing the responses to relevant questions between questionnaires. RESULTS The prevalences of wheeze following a common cold and dyspneal feeling at night increased significantly from 1985 to 1999 (4.2% to 7.6%, and 3.2% to 5.3%, respectively). The prevalences of lifetime asthma and current asthma also significantly increased from 1999 to 2006 (5.1% to 6.7%, and 1.5% to 3.4%, respectively). CONCLUSIONS The prevalences of asthma among adults in Fujieda City consistently increased from 1985 to 2006. There was no evidence that the prevalences were in plateau or decreasing. These findings suggest that more efforts are required to stop the increase in the burden of this disease in Japan.