Rapid advances in microarray technologies and the related computational analyses have led to a paradigm shift in biological investigation. The number of studies using the microarray technology is logarithmically increasing. Thus, this technology is becoming a standard laboratory technique. Here, we introduce some successful microarray studies in relation to allergic diseases, and discuss why these authors succeeded, and discuss the strategy for microarray studies from data generation to data analysis.

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Recent genomic studies have revealed many kinds of genetic polymorphisms. Some genetic polymorphisms have a correlation with allergic phenotypes, however there is only a statistical association without a precise molecular mechanism being demonstrated. Analysis of the molecular mechanisms from a proteomic perspective should contribute to a better understanding of diseases and indicate possible therapeutic approaches. Recent advances in identification and characterization of many immunological molecules have led to a shift to profiling research, clinical proteomics, of already known factors. However, analysis of such biomarkers in allergies requires methodological improvements because allergic reactions can be greatly influenced by subtle changes of factors. These subtle changes cannot be detected by conventional techniques such as 2D-PAGE, and the grammar behind the system is not well recognized by conventional proteomics. Examples of innovative methods useful for proteomic approaches to allergies are discussed here; especially high throughput screening and structural methods for allergy targeting.

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Allergy is a common immune disorder characterized by raised IgE levels, which leads to clinical disorders such as asthma, rhinitis and eczema. Our understanding of the pathogenesis of allergic disease is largely dependent on our current understanding of the related pathophysiology and the available technology. Recent advances in molecular biology techniques have allowed a rapid and accurate identification of polymorphisms in various genes that may be important for determining the susceptibility to allergic disorders. In this review, we present some developments in genetic studies of allergic disease with particular focus on asthma and atopy in the Japanese population.

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Recently, several clinical trials have been published to discuss the possibility of probiotic supplementation, especially some products of lactic acid bacteria such as Lactobacillus and Bifidobacterium strains, in prevention and treatment of allergic disorders. However, the results of some investigations were inconsistent with each other. The contradictory effect of probiotics among different individuals might suggest differences in genetic or environmental factors, or both. It is conceivably beneficial to use inbred mice as experimental models to explore whether the effect of probiotics on limiting allergy is under the influence of genetic factors. In this review, firstly, we summarized recent publications regarding the effects of lysed Enterococcus faecalis FK-23 (LFK), which is a preparation of a probiotic lactic acid bacterium strain, on suppressing allergic responses in BALB/c mice. And then, we presented our latest data focused on the effects of LFK on suppressing active cutaneous anaphylaxis and local accumulation of eosinophils in four inbred mouse models by using the BALB/c, C57BL/6, C3H/HeN and C3H/HeJ strains. The finding of our experimental study suggests that the effect of LFK on combating allergic inflammatory reactions might be affect by individuals' hereditary background.

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Background: Thymus and activation-regulated chemokine (TARC/CCL17) is a highly specific ligand for CCR4. TARC may contribute to the recruitment, activation, and development of Th2 polarized cells that express CCR4. These characteristics have led investigators to hypothesize that TARC is involved in the development of Th2 responses. Suplatast tosilate ((±)-[2-[4-(3-ethoxy-2-hydroxy-propoxy) phenylcarbamoyl] ethyl] dimethylsulfonium p-toluenesulfonate) is an anti-allergic agent that selectively suppresses the synthesis of Th2 cytokines. We examined the effect of suplatast tosilate on TARC production and CCR-4 expression in vitro. Furthermore, we attempted to clarify whether TARC production was suppressed after clinical administration of suplatast tosilate.
Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with allergic rhinitis who tested positive to house dust. PBMCs were stimulated with mite antigen. TARC mRNA was detected by real time PCR. The amount of TARC was estimated using an ELISA kit. PBMCs expressing CCR-4 were sorted by flow cytometry. The plasma level of TARC was examined in patients with chronic allergic rhinitis before and after treatment with suplatast tosilate for 4 weeks.
Results: Suplatast tosilate significantly reduced TARC production by PBMCs. TARC mRNA was also suppressed in a concentration dependent manner. However, suplatast tosilate did not inhibit the expression of CCR-4 on PBMCs. The plasma level of TARC was significantly decreased in patients administered suplatast tosilate.
Conclusions: Suplatast tosilate suppressed TARC production by PBMCs and decreased the plasma level of TARC in patients with chronic allergic rhinitis.

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Background: Inhaled corticosteroids (ICSs) have become widely used in asthma management during pregnancy since the publication of the NIH report Management of Asthma during Pregnancy in 1993. In the current study, the usefulness and safety of ICSs in the treatment of pregnant women with asthma were investigated.
Methods: Of 11,358 women who delivered in our hospital between January 1987 and December 2003, 592 women had asthma. Their midwifery records, delivery records, and clinical charts retained in the outpatient clinic of the internal medicine department were reviewed to identify treatments provided, pregnancy/delivery course, and possible perinatal abnormalities. On the basis of these data, the usefulness and safety of ICSs were retrospectively investigated.
Results: The percentage of pregnant women with asthma receiving asthma treatment was 17.5% from 1987 to 1989, 32.7% from 1990 to 1994, 43.8% from 1995 to 1999, and 40.7% from 2000 to 2003. Among those treated, the proportion treated with ICSs showed an increase (0% from 1987 to 1989, 10.0% from 1990 to 1994, 55.3% from 1995 to 1999, and 83.3% from 2000 to 2003). Intrapartum asthma attacks occurred in 1.38% of the asthma patients from 1995 to 1999, while there was no such occurrence in 2000 or later. In the untreated patients, the incidence of perinatal abnormalities remained unchanged with the guideline publication (31.6% before and 31.3% after). In contrast, the incidence of perinatal abnormalities in the treated patients decreased from 59.6% to 26.2% with the guideline publication. The incidence of perinatal abnormality among the treated was compared between the ICS therapy and non-ICS therapy groups. No difference was observed between the two groups from 1987 to 1994, but from 1995 to 2003, the total incidence of perinatal abnormalities was significantly higher in the non-ICS group.
Conclusions: ICSs can be considered to be safe and useful for the prevention of asthma attacks during pregnancy and for decreasing perinatal abnormalities.

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Background: The importance of peanut allergy has not been well recognized in Japanese society. IgE antibody to peanut can be, however, detected in patients without clinical peanut allergy.
Methods: Clinical characteristics of 14 patients (aged 1—8 years) with peanut allergy were evaluated. IgE antibodies to peanut from patients with and without clinical peanut allergy were compared with those to soybean and other nuts. To examine the role of cross-reactive carbohydrate determinant (CCD) on the clinically false positive detection of peanut IgE, horseradish peroxidase (HRP) and bromelain specific IgE were measured by Uni CAP IgE kit. Inhibition of peanut IgE by HRP was also examined.
Results: The patients repeatedly experienced potentially life-threatening symptoms, including anaphylaxis. Sera from patients with peanut allergy had negative or relatively low IgE antibodies to other nuts. However, clinically false positive peanut IgE showed significant correlation-coefficients with soybean, almond, chestnut, pistachio, macadamia and cashew (r = 0.61—1.00). Anti-HRP and anti-bromelain IgE antibodies were detected in the clinically false positive sera, but not in the sera from patients with peanut allergy. Two out of four clinically false positive peanut IgE antibodies were significantly inhibited by HRP.
Conclusions: Social education about the features of peanut allergy is needed in Japan. Anti-CCD IgE antibody was suggested to be one of the mechanisms contributing to the false positive detection of peanut IgE. Detection of anti-HRP or anti-bromelain IgE can be a useful tool to recognize the presence of anti-CCD antibodies.

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Background: The development of an inexpensive point-of-care testing system for antigen-specific IgE is greatly needed. We, therefore, tried to develop a quantitative enzyme immunochromatography assay system for antigen-specific IgE in fresh whole blood.
Methods: Whole blood sample was mixed with a reagent containing detergent to lyse red blood cells, and the mixture was applied to an immunochromatography strip. The lysate was observed to migrate in the strip and was washed away by the substrate buffer. When the sample contained the specific IgE, the antigen-specific IgE line was clearly observed on the strip macroscopically.
Results: Results were obtained 20 minutes after the application of hemolysed blood sample to immunochromatography, and these results showed positive correlation with those obtained by the AlaSTAT system, which is one of the popular assay kits for specific IgE. The results were not affected significantly by the hematocrit value of the blood sample, by the kind of anticoagulant in the blood collection tube, or by the concentration of the total IgE, provided it was lower than 20000 IU/ml.
Conclusions: These results indicate that our system is applicable for point-of-care testing for antigen-specific IgE.

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Background: The importance of smoking in bronchial asthma has been thoroughly investigated. Although a high smoking rate has been recognized in Japan, there have been few studies of the relationship between active smoking and bronchial asthma, and little analysis of the gender difference in this relationship. The aims of this study were to examine the contribution of active smoking to asthma and to clarify any gender difference.
Methods: For 8 weeks from September through October 2000, a smoking questionnaire survey was performed on adult patients with bronchial asthma, and their attending physicians, in Niigata Prefecture, Japan. The questionnaire surveyed asthma control, asthma-related emergencies and satisfaction in daily life. The attending physicians were questioned about patient profiles and medications. Patients were classified into three groups: non-smokers (NS), ex-smokers (ES) and current smokers (CS). For examination of gender differences, the CS group was compared with the NS group, due to variable duration of smoking and of cessation of smoking in the ES group.
Results: Complete data were received from 2947 cases. Of the male patients, 340 (23.0%) were in the CS group, 325 (22.0%) were in the NS group and 812 were in the ES group. Of the female patients, 109 (7.4%) were in the CS group, 1132 (77.4%) were in the NS group, and 229 (7.4%) were in the ES group. The male CS group had more severe asthma-related symptoms in the morning and at night, more sputum and cough in the morning, and more severe sleep disturbance than the male NS group. In the female patients, these differences were not detected. A logistic and multiple regression analysis confirmed these significant differences between male and female asthma patients.
Conclusions: The gender differences in the susceptibility of asthma to smoking suggests the need for gender-specific strategies for smoking cessation, although further investigation is required.

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Background: Fluticasone propionate (FP) Diskus^® is generally regarded as an easy to use and efficacious inhaled device. This study clinically evaluated whether its easy handling and inhalation process were affected by the aging factor or not, compared with those of the FP Diskhaler^® and Beclomethasone dipropionate (BDP).
Methods: Twenty-four elderly patients with stable moderate asthma (12 aged 65—74 years and 12 aged 75 years or older) who were accustomed to using the Diskhaler^® were evaluated by measuring the required time for finishing one-time inhalation with the device, compared with 7 patients aged less than 65. Ten elderly patients (5 aged 65—74 years, and 5 aged 75 years or older), who used the BDP, were also similarly evaluated and compared with 8 patients aged less than 65. All subjects then switched to use with the Diskus^® and the required time for finishing one-time inhalation was measured soon after and 2 weeks after the change. The patients' usage impressions were also questioned.
Results: The mean required times (seconds) were significantly different between patients aged 75 years or older, and with patients less than 65 years of age; 45.8 ± 8.1 vs. 31.8 ± 12.3 (p = 0.046) in the BDP group, and 56.8 ± 25.3 vs. 33.3 ± 18.5 (p = 0.047) in the Diskhaler^®, respectively. Soon after changing to the Diskus^®, those times became insignificant in both groups. After 2 weeks, the required time for using the Diskus^® was significantly shortened in all age groups. 50.0% patients in the BDP group and 79.2% in the Diskhaler^® group finally chose the Diskus^®.
Conclusions: The FP Diskus^® inhalation was not affected by the aging factor and all patients could quickly get accustomed to using it, suggesting its clinical efficacy for older patients.

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Background: We recently demonstrated that the vitamin A derivative etretinate was clinically effective in the treatment of skin disorders in patients with systemic sclerosis (SSc). The aim of the present study is to investigate whether the oral treatment with etretinate improves sclerosis in bleomycin (BLM)-induced sclerotic skin mice.
Methods: BLM-induced sclerotic skin mice were treated orally with 10 mg/kg etretinate for 1 to 28 days. One control group received only the vehicle, 50 μl peanut oil, while another group received no agents. BLM-treated skin was removed and dermal thickness was measured histologically. Histopathological observation and TUNEL assay were also studied. Messenger RNA (mRNA) ratios for procollagen α 1 (I) chain to β actin from etretinate-treated and control mice were quantified at 1, 6, 14, and 28 days post-treatment, using quantitative RT-PCRs.
Results: There was a significant decrease in mean dermal thickness (P < 0.05) and changes in collagen bundles in the etretinate-treated mice group for a 28-day period compared to control groups. TUNEL assay showed that the density of TUNEL-positive cells in the dermis of etretinate-treated mice for a 14-day period was significantly increased (P < 0.05). The ratio of procollagen α 1 (I) chain to β actin mRNA from etretinate-treated mice for a 1-day period decreased significantly compared to that of the control mice, but the ratio from etretinate-treated mice for a 14-day period increased significantly (P < 0.05).
Conclusions: Etretinate improved BLM-induced scleroderma. These results suggest that etretinate can be applied to the treatment of SSc skin disorders.

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Background: Nasal obstruction is considered the most serious problem for patients with allergic rhinitis. We have previously established a model of nasal obstruction in guinea pigs. In the present study, we tried to establish an allergic model of nasal obstruction using Brown Norway (BN) rats to evaluate the effects of phosphodiesterase (PDE) 4 inhibitors in this model.
Methods: The volume of the nasal cavity was measured with an acoustic rhinometer. Decrease in the volume of the nasal cavity was taken as nasal obstruction. BN rats were actively sensitized with ovalbumin conjugated with aluminium hydroxide. Intranasal antigen instillation induced biphasic nasal obstruction in sensitized BN rats.
Results: Early and late phase responses (EPR and LPR) were observed peaking at 0.5 and 6 hours after the antigen challenge, respectively. Chlorpheniramine did not inhibit EPR or LPR at 10 mg/kg, although the dose was sufficient for the compound to exert its anti-histamine activity. Prednisolone inhibited both responses at 30 mg/kg. Rolipram and CDP-840, PDE4 inhibitors, inhibited both responses at 100 mg/kg. KF19514, a PDE1/4 dual inhibitor, inhibited EPR at 0.1 mg/kg or more and inhibited LPR at 10 mg/kg.
Conclusions: The present study provides a simple model of allergic biphasic nasal obstruction in BN rats, and also suggests that the PDE4 inhibitor may alleviate nasal obstruction in patients with allergic rhinitis.

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Background: In the 1960s when air pollution levels were high in Kanagawa prefecture as same as in other Japanese metropolises, the prevalence of asthma increased distinctly. Air pollution has been reduced rapidly from the 1970s, but asthma morbidity has not decreased and therefore air pollution has not been considered as an essential factor in asthma development. However, air pollution may be considered as a risk factor for infantile asthma. To clarify the influence of air pollution on infantile asthma development, we compared the background of adult asthmatics who were born in 1960s and in 1970s.
Methods: We studied 10,823 adult asthma patients who underwent examination at Sagamihara hospital from 1972 to 1995. We investigated the ratio of young onset (equal to or less than 19 years old, 3264 cases) asthma in adult asthma year by year. In order to ascertain the influence of air pollution on airway hypersensitivity, we compared the asthmatics born in 1960s (born in 1963—1970) when air pollution was severe with those born in 1970s (born in 1971—1978) when air pollution levels were reduced.
Results: Childhood onset (less than 15 years old) asthma held a constant ratio in adult asthma from 1972 to 1980. However, infancy onset (0—4 years old) asthma increased in 1980, peaked in 1988, and then decreased. From a viewpoint of the birth year, young onset asthma has increased since 1945. In particular, the ratio of infancy onset (0—4) asthma had become distinctly higher than the other onset groups since 1960, peaking in 1970 and then decreasing. The fluctuation of infancy onset asthma coincided with the indices of air pollution in Japan.
Lung function tests in the three groups (group I; born in 1955—62, group II; born in 1963—70, group III; born in 1971—78) did not have a difference among each other. However, we were able to find a difference in threshold of non-specific airway hypersensitivity. The airway hypersensitivity of the infancy onset asthmatics born in 1960s was much more enhanced than that of the asthmatics born in 1970s.
Conclusions: The dramatic increase of infancy onset asthmatic born after 1960 coincided with the increases in levels of air pollution. The infancy onset adult asthmatics born in 1960s were more hypersensitive to non-specific bronchial stimuli than those born in 1970s. This strongly suggested that the air pollution of 1960s might have accelerated the development of infancy onset asthma and aggravated non-specific bronchial hyperreactivity.

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Background: Specific immunotherapy for bronchial asthma has been documented to be efficacious in several studies; however, it is not known whether this efficacy is sustained for several years after cessation of immunotherapy. The aim of this study is to determine the efficacy of house dust mite immunotherapy over a 15-year period.
Methods: This study is an open, parallel, comparative trial in which 31 patients were administered immunotherapy for 5 years and then followed-up for a further 10 years. Their global symptom scores and FEV1 values were compared with another group of 38 patients who refused immunotherapy.
Results: The use of immunotherapy resulted in a statistically significant improvement in both global symptom scores and FEV1 in patients receiving immunotherapy when compared with those in the control group who did not receive immunotherapy. This improvement was sustained for at least 10 years after cessation of immunotherapy.
Conclusions: The benefits of house dust mite immunotherapy are significant and sustained, a decade after its discontinuation.

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Background: The interleukin-12B gene (IL-12B) encodes the p40 chain of interleukin-12 (IL-12), which promotes cell-mediated Th1 responses and the production of interferon-gamma (IFN-γ) that downregulates IgE production. Chromosome 5q31-q33 near the IL-12B locus is significantly linked to asthma, as determined by a genome-wide search in the Japanese population.
Methods: We sequenced exons 1-8 including parts of the introns and promoter region of IL-12B in asthmatic patients and healthy controls. We examined plasma IL-12 concentrations, IL-12 production by Derf1-stimulated peripheral blood mononuclear cells (PBMCs) and the IL-12B transcriptional activity.
Results: IL-12B promoter polymorphism existed as ^-2703CTCTAA/GC and ^-2403T/C alleles, which were linked to each other. Homozygosity for haplotype 1 (^-2703CTCTAA /^-2403T) was associated with asthma susceptibility in Japanese children (P < 0.001). Both plasma IL-12 concentrations and IL-12 production by Derf1-stimulated PBMCs in the subjects with homozygotes for haplotype 1 were lower than those with homozygotes for haplotype 2 (^-2703GC /^-2403C) (P < 0.001). The transcriptional activity of the construct with haplotype 1 was lower than that of the construct with haplotype 2, and the IL-12B transcriptional activity was influenced by the ^-2403T/C allele rather than by the ^-2703CTCTAA/GC allele.
Conclusions: Homozygosity for haplotype 1, which is associated with reduced IL-12B transcriptional activity and reduced IL-12 production, is a predisposing factor for asthma susceptibility in Japanese children.

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Background: Asthma can have a negative impact on the productivity of paid and unpaid individuals. In this study, we aimed to investigate the impact of salmeterol, which, in recent years, has become available for the treatment of asthma in Japan, on the productivity of patients with asthma.
Methods: Relevant data were extracted from the medical records of 54 patients aged ≥15 years with moderate or severe asthma. Loss of productivity was estimated via the human capital approach in the year before and the year after introduction of salmeterol.
Results: Lost productivity was significantly reduced (p < 0.001) after salmeterol's introduction compared to the period before its introduction in both paid labors and unpaid ones. Reduced loss of productivity avoided loss of approximately 800,000 yen in the paid ones and 61.3 days in unpaid ones. It was estimated that loss of about 105.4 billion yen in the paid group and 64.5 billion yen in the unpaid group could be avoided if this result was expanded to the wider society. In paid labors, productivity loss was avoided when symptoms were absent during the day, irrespective of the presence or absence of symptoms during the night, whereas, in the unpaid group, the loss was avoided when symptoms were absent during the day or night.
Conclusions: It was considered that improvement of clinical symptoms, which occurred in association with the introduction of salmeterol, resulted in avoidance of losses in productivity that had previously occurred in patients with asthma.

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Background: Hazelnut has been reported to be one of the most important food allergens.
We set out to study whether exposure to hazelnut allergen by occupational contact increases hazel pollen and hazelnut sensitivity and causes workplace-related allergic symptoms in hazelnut processing factory workers.
Methods: The study group consisted of 308 employees working in a hazelnut processing factory and 138 subjects with similar age ranges formed the control group. All subjects were asked to fill in a questionnaire about allergic symptoms and then underwent skin prick tests with 9 allergens (Betula verrucosa, Corylus avellana, Quercus robur, D. farinae, D. pteronyssinus, Mould mix, hazelnut, peanut and walnut).
Results: There were no workplace-related symptoms in the study group. No significant difference was found in the rate of allergic and respiratory symptoms between the study and control groups. The skin prick tests showed that birch (Betula verrucosa) and hazel (Corylus avellana) pollen sensitivities were higher in the study group than in the control group (p < 0.01 and p = 0.021, respectively). All the other skin prick test results were similar among the two groups.
Conclusions: This study showed that occupational exposure to hazelnut caused skin sensitivity to hazel and birch pollen, but this was not associated with an enhanced risk for allergic diseases.

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Background: : An asthma-specific questionnaire, the Asthma Health Questionnaire (AHQ) was developed for Japanese asthmatic patients. A self-administered 37-item version (AHQ-37) consisting of 36 disease-specific items and a Face Scale was designed for socially active patients.
Methods: : Exploratory factor analysis, test-retest reliability, internal consistency, concurrent validity and longitudinal validity were evaluated. A total of 326 asthma patients (202 men; range of age from 18 to 65 years) answered the AHQ-37 twice.
Results: : Each item of the AHQ-37 was well accepted by the patients with answering rates of 95 to 100%. Six subscales (Asthmatic Symptoms, Emotion, Daily Activity, Factors which Worsened Symptoms, Social Activity and Economics) were extracted by factor analysis. Psychometric testing showed high feasibility, good repeatability and good internal consistency. The Face Scale moderately correlated with all subscales except for Economics, indicating that the Face Scale alone could measure global quality of life (QOL) functioning of asthmatic patients. Concurrent validity with peak-flow values was insufficient (Spearman's correlation coefficient = 0.05—0.27), showing that the peak flow alone could not estimate QOL. In longitudinal validity, however, changes in peak-flow values had an impact on the Asthmatic Symptoms, Daily Activity and Factors which Worsened Symptoms (P = 0.000—0.419), indicating that changes in peak-flow were important to asthmatic patients' QOL.
Conclusions: : The QOL of asthmatic patients must be evaluated by asthma-specific questionnaires, such as the AHQ-37.

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Background: Epstein Barr virus (EBV) has been suspected of being involved in the development of atopy. There are several studies suggesting a positive as well as negative association between EBV infection and atopic diseases. Here, we carried out a large-scale, systematic investigation to address the issue of the possible association between EBV infection and atopic diseases.
Methods: Anti-EBV-viral capsid antigen (VCA) antibody titer, anti-EBV nuclear antigen (EBNA) antibody titer, atypical lymphocyte (AtLy) count and EBV-DNA copy number in 10⁶ WBC were examined as evidence for EBV infection, and characteristic parameters of atopic disease such as total serum immunoglobulin E (IgE) level, highest antigen-specific IgE antibody titer (h-RAST) and peripheral blood eosinophil (Eos) count were measured and compared among atopic subjects and non-atopic controls, and correlations between parameters of atopy and EBV infection were subjected to statistical analysis.
Results: Anti-EBV, in particular anti-EBNA antibody titer and AtLy count in peripheral blood were markedly higher in patients with bronchial asthma (BA) and/or atopic dermatitis (AD) than in non-atopic controls, especially in early childhood. No similar findings were obtained for antibodies to cytomegalovirus (CMV). EBV-DNA copy numbers in WBC were elevated in atopic subjects. Correlations between EBV-DNA copy number and other parameters of EBV infection (anti-EBV antibody titer and AtLy count) but those with cytomegalovirus (CMV) infection and markers of atopic disease (IgE, h-RAST level, and Eos count) were demonstrated. It was found that anti-EBNA seronegative atopics have higher copy numbers of EBV DNA in WBC and more elevated levels of IgE and h-RAST than anti-EBNA seropositive atopics. Anti-EBV VCA antibody titer in individuals aged 15 years and younger and anti-EBNA antibody titer among Japanese were suggested to have declined considerably in the past 15 years.
Conclusions: The present study suggests that EBV infection in early childhood could precipitate atopic diseases.

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Background: We report a rare case of acute eosinophilic pneumonia (AEP) associated with heated rubber fume exposure.
Methods: A 31-year-old Ethiopian man, working at a rubber plant, was admitted to our hospital because of refractory dyspnea and fever. Computed tomography of the chest showed bilateral interstitial shadows and pleural effusion. We suspected AEP and performed fiberoptic bronchoscopy.
Results: The eosinophil fraction was elevated at 59% in the bronchoalveolar lavage fluid (BALF). From the history of inhalation of heated rubber at the working place and hypereosinophilic counts in the BALF, he was given a diagnosis of AEP associated with heated rubber fume exposure. His symptoms and chest radiographic findings were drastically improved by corticosteroid therapy.
Conclusions: Heated rubber fume can be a causative substance for AEP. In similar situations, physicians should consider AEP and order various examinations for confirmation.

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A Case of Food-dependent Exercise- induced Anaphylaxis after Grapefruit Ingestion

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