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Occupational asthma (OA) can improve after cessation of exposure; however, some patients suffer from persistence or aggravation of their asthmatic symptoms. Here we report a case of a new sensitization to house dust mites during the follow-up period in a 37-year-old female patient with OA induced by cefteram pivoxil powder (cefteram powder). She was previously diagnosed with OA caused by inhalation of cefteram powder. Consequently, she left her job and had been well for 9 subsequent years. She began to experience aggravation of her rhinitis and asthmatic symptoms again several months prior to presentation. Her skin-prick test results had converted to strongly positive responses to two types of house dust mites. The serum levels of eosinophil cationic protein (ECP) and the total and specific immunoglobulin (Ig)E levels against the two types of house dust mites were elevated. An inhalation challenge test with Dermatophagoides farinae was performed, and significant bronchoconstriction (21.1% reduction in the forced expiratory volume in the first second) with asthma symptoms was observed at 10 minutes. To our knowledge, this is the first case demonstrating a new sensitization to house dust mites in a patient with OA caused by cefteram powder. Regular monitoring, including skin-prick tests and measurement of specific serum IgE/ECP levels, may help to screen potential cases.

Purpose: Although the mechanism of virus-induced, aspirin-exacerbated respiratory disease (AERD) is not known fully, direct activation of viral components through Toll-like receptor 3 (TLR3) has been suggested. TLR3 recognizes double-stranded RNA (dsRNA), and activates nuclear factor-κB and increases interferon-γ, which signals other cells to induce airway inflammation in asthma. Considering the association of TLR3 in viral infections and AERD, we investigated whether promoter and non-synonymous variants of TLR3 were associated with AERD., Methods: The three study groups, 203 with AERD, 254 with aspirin-tolerant asthma (ATA), and 274 normal healthy controls (NC) were recruited from Ajou University Hospital, Korea. Two polymorphisms, -299698G>T and 293391G>A [Leu412Phe], were genotyped using primer extension methods., Results: Genetic associations were examined between two genetic polymorphisms of TLR3 (-299698G>T and 293391G>A [Leu412Phe]) in the three study groups. AERD patients that carried the GG genotype of 293391G>A showed a significantly lower frequency compared with ATA in both co-dominant (P=0.025) and dominant models (P=0.036). Similarly, in the minor allele frequency, the A allele was significantly higher (P=0.023) in AERD compared with ATA for this polymorphism. AERD patients who carried HT2 [GA] showed a significantly higher frequency than other haplotypes in co-dominant (P=0.02) and recessive (P=0.026) models., Conclusions: Our findings suggest that the -299698G>T and 293391G>A [Leu412Phe] polymorphisms of the TLR3 gene are associated with the AERD phenotype.

Background: The thromboxane A2 receptor (TBXA2R) is a potent broncho- and vaso-constrictor and is associated with leukotriene synthesis. Polymorphisms in the TBXA2R gene have been linked to atopy, asthma, and atopic dermatitis. This study evaluated the association between genetic TBXA2R variants and the development of acetyl salicylic acid (ASA)-intolerant acute urticaria (AIAU)., Methods: AIAU patients (n=167), ASA-intolerant chronic urticaria (AICU) patients (n=149), and healthy controls (NC) (n=265) were included. All patients were enrolled at Ajou University Hospital in Suwon, Korea. Two TBXA2R polymorphisms (-4684T>C and 795T>C) were genotyped by primer extension using a SNAPshot ddNTP primer extension kit. Luciferase activity was measured using a dual-luciferase reporter assay kit. An electrophoretic mobility shift assay (EMSA) was performed using a nuclear extract from a human mast cell line (HMC-1)., Results: Genetic association data demonstrated that compared with NC subjects, AIAU patients had a significantly higher frequency of the homozygous TT genotype of TBXA2R-4684T>C (P=0.005, P(corr) =0.03). No differences were identified between the AICU and the NC groups. Luciferase activity, reflecting promoter activity, was significantly lower with the TBXA2R-4684T-containing construct than with the -4684C-containing construct (P<0.001); the activity decreased further upon co-transfection with ETS-like gene transcription factor-1 (ELK-1) (P=0.012). EMSA revealed that the -4684T allele produced a specific shifted band, with a greater affinity than that produced by the -4684C allele., Conclusion and Clinical Relevance: These results suggest that the TBXA2R-4684T allele may be associated with lower TBXA2R expression, which may contribute to the development of the AIAU phenotype., (© 2010 Blackwell Publishing Ltd.)

Background: To improve understanding of aspirin hypersensitivity, this study focused on adenosine as a noncyclooxygenase target molecule of aspirin. Adenosine may affect the release of histamine from cutaneous mast cells through a mechanism mediated by the adenosine A3 receptor., Objectives: To investigate the genetic contribution of adenosine A3 receptor gene (ADORA3) polymorphisms in the pathogenesis of aspirin-induced urticaria (AIU) in a case-control association study in a Korean population., Methods: A case-control association study was performed in 385 patients with AIU and 213 normal controls from a Korean population. The functional variability of genetic polymorphisms in the ADORA3 gene was analysed in in vitro studies that included a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA), and ex vivo studies that included real-time polymerase chain reaction for mRNA expression in peripheral blood mononuclear cells and a histamine release assay., Results: A significant association of ADORA3 promoter polymorphism at -1050G/T was found with the phenotype of AIU. Patients with AIU showed higher frequency of the haplotype, ht1 (T(-1050) C(-564) ), compared with normal healthy controls. Moreover, ht1 (TC) was found to be a high-transcript haplotype by the luciferase activity assay, and a -564C allele-specific DNA binding protein was found by EMSA. Increased basophil histamine release was noted in subjects who had the high-transcript haplotype, ht1 (TC)., Conclusion: These results suggest that the high-transcript haplotype, ht1 (TC), of the ADORA3 gene may contribute to the development of cutaneous hyper-reactivity to aspirin, leading to the clinical presentation of AIU., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

Purpose: A genetic polymorphism of the beta 2-adrenergic receptor is a major factor associated with the asthmatic phenotype. The association of this polymorphism with toluene diisocyanate (TDI)-induced asthma has not been investigated. We examined 103 TDI-induced asthma patients (TDI-OA), 60 asymptomatic exposed controls (AEC), and 263 unexposed healthy controls (NC) in order to identify beta 2-adrenergic receptor gene (ADRB2) polymorphisms and the possible association with TDI-induced asthma., Methods: Single nucleotide polymorphisms (SNPs) of ADRB2 were genotyped by direct sequencing. Serum-specific IgE and IgG levels were measured using an enzyme-linked immunosorbent assay. Phenotypes and clinical patient parameters were compared., Results: SNPs were identified (-47 T>C, -20 T>C, Arg16Gly A>G, Gln27Glu C>G, Leu134Leu G>A, Arg175Arg C>A) during ADRB2 screening (from -231 to 793 bp). No significant differences in allelic and genotypic frequencies were noted for any of the six ADRB2 SNPs. The Arg16Gly A>G, Leu134Leu G>A, and Arg175Arg C>A SNPs and haplotype 1 [TTACGC] were significantly associated with specific IgE antibodies to the TDI-human serum albumin (HSA) conjugate in TDI-exposed subjects (P<0.05). Exposed workers with the ADRB2 ht1/ht1 homozygote had a significantly higher TDI-HSA conjugate-specific IgE sensitization rate than did those with the null ht1 haplotype (odds ratio, 15.40; 95% confidence interval, 1.81-131.06)., Conclusions: ADRB2 polymorphisms may affect IgE-specific sensitization to TDI-HSA conjugate in TDI-exposed workers.

Purpose of Review: The purpose of this article is to review the recent findings of studies reporting on the genetic and ethnic factors associated with hypersensitivity reactions to common drugs such as acetyl salicylic acid/NSAIDs, antibiotics, antituberculus medications, and other drugs including carbamazepine (CBZ), abacarvir, and allopurinol that can cause severe hypersensitivity reactions., Recent Findings: Aspirin hypersensitivity has recently been associated with a variety of genetic polymorphisms associated with leukotriene overproduction, eosinophil infiltration, and histamine-related genes. Recently, beta-lactam antibiotic hypersensitivity has been reported to be associated with interleukin (IL)-4 and IL-13 receptors in Italian, Chinese, and French populations. Moreover, a significant association of CYP2E1 in the Chinese, NAT2 in Koreans and glutathione S-transferase genotypes in Caucasians has been reported with antituberculus drug-induced hepatitis. The association of the HLA-B*1502 allele with CBZ-induced Stevens-Johnson syndrome in Asian population has also recently been observed., Summary: Aspirin hypersensitivity has been associated with various genetic polymorphisms. Human leukocyte antigen (HLA)-related markers and a variety of genetic polymorphisms of leukotriene-related genes, eosinophil-related genes, and genes associated with immune function have been described according to ethnicity. The genetic mechanisms of antibiotic hypersensitivity have been reported in Italian, French, and Chinese populations in addition to antibiotics-induced cutaneous reactions in the Korean population. Most prior genetic studies on antituberculus drug-induced hepatitis have focused on a few drug-metabolizing enzymes such as cytochrome P450 and N-acetyltransferase 2. HLA-related markers associated with CBZ, lamotrigine, and abacavir-induced severe hypersensitivity reactions have been described.

Beef allergies are relatively rare, especially in adults. However, clinical manifestations can vary from urticaria, angioedema, anaphylaxis to gastrointestinal symptoms. Currently available tests, such as skin testing or in vitro determination of beef-specific immunoglobulin E (IgE), do not provide an accurate diagnosis of beef allergy. The recent development of the basophil activation test (BAT) presents a new opportunity for the diagnosis of food allergies. Here, we report a 37-year-old woman with a history of recurrent generalised urticaria, nausea, vomiting and hypotension after ingestion of beef, suggesting a beef allergy. Although the skin prick test and serum specific IgE to beef, pork and milk allergens showed negative results using commercial kits, the BAT showed significant upregulation of CD203c in a dose-dependent manner compared to both non-atopic and atopic controls. To our knowledge, this is the first case study of beef allergy consisting of a non-IgE-mediated reaction. The detection of food allergies using direct basophil activation is suggested to complement conventional diagnostic tests.

Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases.

Diisocyanate is a leading cause of occupational asthma (OA). Diisocyanate-induced OA is an inflammatory disease of the airways that is associated with airway remodelling. Although the pathogenic mechanisms are unclear, oxidative stress may be related to the pathogenesis of diisocyanate-induced OA. In our previous report, we observed that the expression of ferritin light chain (FTL) was decreased in both of bronchoalveolar lavage fluid and serum of patients with diphenyl-methane diisocyanate (MDI)-induced OA compared to those of asymptomatic exposed controls and unexposed healthy controls. In this study of toluene diisocyanate (TDI)-OA, we found identical findings with increased transferrin and decreased ferritin levels in the serum of patients with TDI-OA. To elucidate whether diisocyanate suppresses FTL synthesis directly, we tested the effect of TDI on the FTL synthesis in A549 cells, a human airway epithelial cell line. We found that haem oxygenase-1 as well as FTL was suppressed by treatment with TDI in dose- and time-dependent manners. We also found that the synthesis of other anti-oxidant proteins such as thioredoxin-1, glutathione peroxidase, peroxiredoxin 1 and catalase were suppressed by TDI. Furthermore, TDI suppressed nuclear translocation of Nrf2 through suppressing the phosphorylation of mitogen-activated protein kinases (MAPKs); extracellular-regulated kinase 1/2 (ERK1/2); p38; and c-Jun N-terminal kinase (JNK). Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, 15-deoxy-Delta(12,14)-PGJ2 and rosiglitazone rescued the effect of TDI on HO-1/FTL expression. Collectively, our findings suggest that TDI suppressed HO-1/FTL expression through the MAPK-Nrf2 signalling pathway, which may be involved in the pathogenesis of TDI-induced OA. Therefore, elucidating these observations further should help to develop the therapeutic strategies of diisocyanate-induced OA.

Introduction: Aspirin hypersensitivity represents two distinct clinical syndromes, such as aspirin exacerbated respiratory disease (AERD) and aspirin-intolerant chronic urticaria/angioedema (AICU) which have different clinical phenotypes resulting from different genetic backgrounds in a Korean population. Persistent eosinophilic inflammation in airway is a characteristic feature of AERD and chemokine CC motif receptor 3 (CCR3) plays an important role in eosinophilic infiltration into the asthmatic airway., Objectives: The main objective of this study is to investigate the association between CCR3 gene polymorphisms and aspirin hypersensitivity, including AERD and AICU., Methods: CCR3 mRNA expression was measured after an aspirin provocation test by real-time PCR. In total, 330 patients with aspirin hypersensitivity (191 AERD and 139 AICU) and 217 normal healthy controls (NC) were genotyped for two CCR3 promoter polymorphisms (-520T/G and -174C/T), and the functional effects of the polymorphisms were analyzed applying a luciferase reporter assay and an electrophoretic mobility shift assay., Results: CCR3 mRNA expression was significantly increased after aspirin provocation in AERD patients (P=0.002) but not in AICU patients. An in vitro functional study showed that the reporter construct having a -520G allele exhibited significantly higher promoter activity compared with the construct having a -520T allele in human myeloid (U937), lymphoid (Jurkat), and mast (HMC-1) cell lines (P<0.001). We found -520G and -174T specific bands on EMSA., Conclusion: This result suggests that the CCR3 genetic polymorphisms may contribute to the development of the AERD phenotype and may be used as a genetic marker for differentiating between the two major aspirin hypersensitivity phenotypes.

Purpose: Aspirin-intolerant asthma (AIA) is characterized by moderate to severe asthma that is aggravated by aspirin or other non-steroidal anti-inflammatory drugs. Affected patients frequently have chronic rhinosinusitis and nasal polyposis due to persistent upper and lower airway inflammation with marked eosinophilia. IL-13 plays a crucial role in the development of allergic asthma by inducing airway eosinophilia and hyper-reactivity and it has been correlated with an increased eosinophil count., Methods: Two promoter polymorphisms of the IL-13 gene (-1510 A>C and -1055C>T) and one coding nonsynonymus Arg110Gln (110G>A) polymorphism were genotyped using primer extension methods in 162 patients with AIA, 301 patients with aspirin-tolerant asthma (ATA), and 430 normal healthy controls (NC)., Results: There was no significant difference in the genotype, allele, and haplotype frequencies of the three polymorphisms among the three groups. AIA patients with the AA genotype -1510A>C (P=0.012) and CC genotype -1055C>T (P<0.001) had a significantly higher frequency of rhinosinusitis, as compared to those with the minor alleles of these two single nucleotide polymorphisms. AIA patients with the GG genotype had a higher peripheral eosinophil count (P=0.025) and a higher serum eotaxin-1 level (P=0.044), as compared to patients with the AA genotype IL-13 Arg110Gln (110G>A)., Conclusions: These findings suggest that the IL-13 polymorphisms at -1510A>C and 1055C>T are associated with the development of rhinosinusitis in AIA patients. IL-13 Arg110Gln may be associated with an increased eosinophil count and eotaxin-1 level and could increase eosinophilic inflammation in the upper and lower airways of patients with AIA.

Rice is the major staple food in a large part of the world, especially in Asia. Hypersensitivity reactions to rice are rare. Moreover, cases of occupational allergies induced by inhalation of rice powder are uncommon. We report a 31-year-old male with work-related rhinitis and conjunctivitis symptoms caused by occupational exposure to rice powder in the grain industry. He showed positive responses to rice extracts on a skin prick test, and a high level of serum specific IgE to rice was detected by ELISA. Occupational rhinitis was confirmed by a nasal provocation test with rice extracts. An IgE ELISA inhibition test showed cross-creativity between rice and various grass pollen extracts. These findings suggest that the inhalation of rice powder can induce IgE-mediated occupational rhino-conjunctivitis, which may be derived from cross-reactivity to major grass pollens.

Introduction: CRTH2 is expressed on the surface of eosinophils and has been shown to mediate PGD2-induced eosinophil migration in vitro. Eosinophilic infiltration in the upper and lower airways is the key feature of asthma. Considering the fact that eosinophil infiltration is prominent in the upper and lower airways of aspirin exacerbated respiratory disease (AERD) compared to aspirin-tolerant asthma (ATA) patients, we hypothesized that activation of eosinophils via dysregulation of the CRTH2 gene may play an important role and be an important marker for AERD., Methods: The three study groups - 107 with AERD, 115 with ATA and 133 normal healthy controls (NC) - were recruited from Ajou University Hospital, South Korea. Two polymorphisms of the CRTH2 gene at -466T>C and -129C>A were genotyped using primer extension methods., Results: AERD patients had significantly higher serum eotaxin-2 levels than did those with ATA (P = 0.034). A significant difference in the genotype frequencies of CRTH2 -466T>C was detected between AERD and ATA patients (P < 0.05). The serum eotaxin-2 level was significantly higher in AERD patients carrying the TT genotype of CRTH2 -466T>C than those with the CT and CC (P < 0.05). In vitro functional study demonstrated that the -466T allele had lower luciferase activity (P < 0.001) and lower mRNA expression with higher production of eotaxin-2 (P = 0.003) in human lung epithelial cells. EMSA showed that CRTH2 -466T produced a specific band with a higher affinity than CRTH2 -466C had., Conclusion: The CRTH2 -466T>C polymorphism increases serum and cellular eotaxin-2 production through lowered CRTH2 expression, leading to eosinophilic infiltration in AERD patients.

Background: Allergic rhinitis (AR) is a very common disease and a risk factor for allergic asthma. The discovery of new biomarkers for the early detection of AR would improve the clinical outcomes and reduce socio-economic burden. We sought to identify a novel serologic marker for detection of AR using a proteomic approach., Methods: To identify the proteins involved in AR, comparative proteomics was applied using nasal lavage fluids (NLFs) taken before and after a nasal provocation test (NPT) with Dermatophagoides pteronyssinus (Dpt) in a subject with AR sensitized to Dpt. The clinical relevance of the identified proteins was evaluated by ELISA using NLFs and sera from the three study groups: Dpt-sensitive AR; asymptomatic Dpt-sensitive controls; and non-atopic healthy controls. The sensitivities and specificities of the candidate proteins for predicting AR were determined using receiver operating characteristic (ROC) curves., Results: In proteomic analysis, lactoferrin expression was up-regulated after NPT. The validation study using ELISA showed a significantly lower serum lactoferrin level in the AR group than those of the other two groups (P<0.05, respectively). To discriminate between subjects with or without AR, the optimal serum cut-off level of lactoferrin was set at <307 ng/mL using the ROC curve. The sensitivity and specificity for predicting AR were 81.4% and 58%. When combined with serum Dpt-specific IgE level, the sensitivity and specificity for predicting AR were 76.7% and 79.2%., Conclusion: These results suggest that the serum lactoferrin level is associated with the phenotype of Dpt-sensitive AR, and in combination with the serum Dpt-specific IgE level, may be a potential serologic marker for early detection of AR.

Background: It has been reported that pancreatic extracts may induce IgE-mediated respiratory allergy in medical personnel. The aim of the study was to identify genetic factors associated with IgE sensitization to digestive powders containing pancreatic extract., Methods: This case-control study was performed on 153 subjects routinely exposed to digestive powder and on 123 nonexposed controls working in Ajou University Hospital. Skin prick testing was performed using 4 commonly used digestive powders and α-amylase. Serum specific IgE levels were measured by ELISA. Three single nucleotide polymorphisms, ADRB2 46A>G, IL10 -1082A>G and IL4 -589T>C, were genotyped using the single base extension method., Results: The positive rate of serum specific IgE to digestive powder was significantly higher in the 41 (26.8%) exposed personnel with work-related respiratory symptoms than in controls (24.4 vs. 5.4%, p = 0.012). Thirty-nine (25.5%) of the 153 exposed personnel were found to have an allergy to digestive powder, as determined by a positive skin prick test and/or a high serum specific IgE level to digestive powder. The ADRB2 46A>G and IL10 -1082A>G polymorphisms were found to be significantly associated with the development of an allergy to digestive powder in exposed medical personnel by multiple logistic regression analysis after controlling for age, atopy and job type (pharmacist or nurse; p = 0.035 and p = 0.027, respectively)., Conclusion: These results suggest that the genetic polymorphisms ADRB2 46A>G and IL10 -1082A>G are genetic factors that increase IgE sensitization to pancreatic extracts in medical personnel occupationally exposed to digestive powders., (Copyright © 2010 S. Karger AG, Basel.)

Anti-tuberculosis drugs frequently result in cutaneous adverse reactions, including pruritus, maculopapular exanthems, and urticaria. However, anti-tuberculosis drug-associated cutaneous leukocytoclastic vasculitis (CLV) has been rarely reported. We describe a case of CLV induced by rifampin and pyrazinamide. A 38-year-old male had been diagnosed with pulmonary tuberculosis two months ago and then he started standard anti-tuberculosis therapy with isoniazid, rifampin, ethambutol, and pyrazinamide. Purpuric lesions developed in the extremities after 1.5 months of anti-tuberculosis medication; the lesions progressively spread over the entire body. Histopathology of the purpuric skin lesion was consistent with leukocytoclastic vasculitis. The skin lesion improved after cessation of anti-tuberculosis medications and treatment with oral corticosteroids and antihistamines. Anti-tuberculosis drugs were rechallenged one at a time over 3 days. Purpura recurred on the right forearm and forehead after taking 300 mg of rifampin. The skin lesion disappeared after taking oral prednisolone. Finally, 1,500 mg of pyrazinamide was readministrated, and then purpuric lesions recurred on both forearms. This report describes a case of leukocytoclastic vasculitis secondary to rifampin and pyrazinamide therapy.

Background and Objective: Inhaled corticosteroids (ICS) are widely used as maintenance regimens for asthma patients. However, response to ICS shows marked inter-individual variability. Genetic factors have been shown to be potential predictors of responsiveness to ICS. We aimed to evaluate those pharmacogenetic effects on asthma control in further detail., Methods: Fifty-three mild-to-moderate asthmatics were genotyped for four genetic polymorphisms of four genes: beta2-adrenergic receptor (ADRB2), adenylate cyclase 9 (ADCY9), neurokinin receptor 2 (NK2R) and T-box 21 (TBX21). The principal clinical outcome was the achievement of asthma control, as assessed using the Global Initiative for Asthma (GINA) guidelines. During treatment with ICS, the forced expiratory volume in 1 second (FEV(1)), maximal mid-expiratory flow (MMEF) and peak expiratory flow rate (PEFR) were monitored every 4 weeks and twice daily., Results: Forty-eight of the 53 patients with asthma were in a controlled or partly controlled state after 12 weeks of treatment with ICS, whereas five asthmatics were in an uncontrolled state even after active treatment. Of the four genetic polymorphisms examined, NK2R G231E G>A and TBX21 H33Q C>G were significantly associated with asthma control status (P = 0.041 and P = 0.006). The subjects with wild-type alleles at each polymorphism showed a significant association with the well-controlled or partly controlled state, as compared to those with mutant alleles. At 5-12 weeks after ICS treatment, the NK2R G231E G>A was associated with therapeutic response to ICS, as reflected by improvement in predicted FEV(1)%., Conclusion: Our results suggest that NK2R G231E G>A and TBX21 H33Q C>G are genetic predictors of response to ICS, at least with respect to asthma control status and changes in FEV(1)%, in Korean patients with asthma. Further prospective validation of those associations is necessary.

Background: This study was conducted to evaluate whether tissue transglutaminase (tTG) may be involved in airway inflammation of toluene diisocyanate-induced occupational asthma (TDI-OA)., Methods: We enrolled 93 patients with TDI-OA, 177 asymptomatic exposed subjects, 43 patients with allergic asthma, and 70 unexposed normal controls. The prevalence of serum immunoglobulin G (IgG) to tTG in the TDI-OA group (20.2%) was significantly higher than that in the three other groups (P < 0.001)., Results: TDI-OA patients with serum IgG to tTG had significantly lower methacholine PC(20) values (P < 0.02) and significantly higher prevalence of specific immunoglobulin E to vapor type TDI-human serum albumin conjugate (P < 0.01; r(2) = 0.411, P < 0.05). TDI exposure could increase tTG activity via reactive oxygen species (ROS) production, which was found to cross-link with cytokeratin 19 on immunoblot analysis., Conclusion: Therefore, TDI exposure may activate tTG via ROS-mediated mechanism in the airway epithelium leading to persistent airway inflammation in TDI-OA patients.

Aspirin-intolerant chronic urticaria (AICU) is a common condition among the chronic urticaria population, but the genetic mechanism is not yet understood. In this study, the genotypes and haplotypes of three interleukin (IL)-13 polymorphisms, -1510 A>C, -1055C>T, and Arg110Gln (110G>A), as well as their respective clinical phenotypes were examined to determine whether genetic variants of IL-13 play a role in AICU. Single-nucleotide polymorphism (SNP) genotyping was used to compare IL-13 genotype and allele frequencies among 135 patients with AICU, 146 with aspirin-tolerant chronic urticaria (ATCU), and 430 normal controls (NC). Relationships among the AICU phenotype, atopy, and total IgE level were also investigated. The results failed to show a significant difference in the allele or genotype frequencies between the AICU group and either the ATCU or NC group (P>0.05, respectively). Haplotype analysis confirmed that there was no significant difference among the three study groups (P>0.05), nor was there a significant difference in atopy or total IgE level according to the three genetic polymorphisms (P>0.05, respectively). Our data lead to the conclusion that there is no evidence supporting genetic polymorphisms in IL-13 as a genetic risk factor for the development of AICU.

Hyaluronidase is a goat testicular protein that hydrolyzes hyaluronic acid, a structural component of the intercellular matrix. It is commonly used as a spreading factor to improve the diffusion of drugs, including local anesthetics and chemotherapeutics. We experienced a 55-yr-old female with generalized urticaria that developed within 1 hr after the epidural injection of hyaluronidase. She had a history of allergic rhinitis, and had suffered from post-herpetic neuralgia and a herniated disc for several years. To relieve her pain, she had been given epidural injections consisting of mepivacaine hydrochloride, triamcinolone acetonide, and morphine sulfate biweekly for one year. Hyaluronidase had been administered several times with these drugs before this episode of generalized urticaria. Skin prick testing showed a positive response to 1,500 IU/mL of hyaluronidase extract, as compared to histamine. The patient's serum hyaluronidase-specific IgE level, determined using an enzyme-linked immunosorbent assay (ELISA), was markedly elevated, as compared to unexposed healthy controls. An IgE immunoblot analysis using hyaluronidase extract and the patient's serum showed IgE binding components at 31 and 21 kDa, whereas no corresponding IgE binding component was found in healthy controls. An ELISA inhibition test showed significant, dose-dependent inhibition with the serial addition of hyaluronidase extract. This is the first case of an IgE-medicated allergic reaction to goat (Naemorhedus goral raddenus) hyaluronidase, demonstrated by skin testing and a specific IgE and immunoblot assay.

Background: It has been known that interleukin (IL)-10 promoter polymorphisms at -1082A/G, -819T/C and -592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-beta. The goal of this study was to investigate a gene-gene interaction between IL-10 and TGF-beta1 polymorphisms in Korean asthmatics with aspirin hypersensitivity., Methods: Single-nucleotide polymorphism genotyping of IL-10 and TGF-beta1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay., Results: Among the patients with asthma, polymorphism at -1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, P(c) = 0.021). Moreover, a synergistic effect between the TGF-beta1-509C/T and IL-10-1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-beta1-509C/T and AG or GG genotype of IL-10-1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504-11.235). In an in vitro functional assay, the -1082G reporter plasmid exhibited significantly greater promoter activity when compared with the -1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the -1082G allele., Conclusion: Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-beta1.

Background: IgG autoantibodies to airway epithelial cell proteins have been detected in patients with nonallergic asthma., Objective and Methods: To evaluate the functional significance of these autoantibodies, we examined the presence of IgG antibody-induced cytotoxicity against airway epithelial cells (A549) by the microcytotoxicity assay using IgG antibodies purified from patients with nonallergic asthma., Results: IgG antibody-induced cytotoxicity (expressed as percent cell lysis) was significantly increased in nine patients with nonallergic asthma (mean +/- standard deviation; 30.6 +/- 7.3%) as compared with eight healthy controls (13.9 +/- 5.1%) and nine patients with allergic asthma (20.3 +/- 10.4%; p < 0.05). In addition, IgG antibody-induced cytotoxicity was significantly inhibited when IgG antibodies from patients with nonallergic asthma were pre-incubated with recombinant human airway epithelial cell autoantigens (cytokeratin 18 or alpha-enolase proteins; p < 0.05)., Conclusion: These results suggest a possible involvement of IgG autoantibody-induced cytotoxicity against airway epithelial cells in the pathogenesis of nonallergic asthma.

Background: Increased vessel number and permeability are important features of the nasal mucosa in allergic rhinitis (AR), and are mediated in part by the cytokine vascular endothelial growth factor (VEGF). Eosinophils are the major effector cells in the nasal secretions of patients with AR during the responses to allergen challenges. To evaluate the involvement of VEGF in nasal allergic inflammation, we monitored the levels of VEGF, eosinophil cationic protein (ECP), and specific antibodies in the nasal lavage fluids (NLFs) of patients with AR in response to Dermatophagoides pteronyssinus (Dpt)., Methods: Sixty-three subjects with sensitization to Dpt were enrolled: 29 patients with AR (group I) who showed positive responses in a nasal provocation test (NPT) with Dpt; and 34 asymptomatic controls (group II) who showed sensitization to Dpt but negative NPT results. NLF samples were collected at baseline, 10, 30, and 60 min, and at 3, 6, and 24 h during the NPT. The ECP levels in the NLF samples were measured using the ImmunoCAP system. VEGF and Dpt-specific IgE, IgA, and IgG in the NLF samples were detected by ELISA., Results: The eosinophil counts and ECP levels in the samples were significantly increased in group I, but not in group II, during the early and late responses. Although the baseline VEGF level was not significantly different between groups I and II, increased VEGF production was noted in group I after the NPT, especially during the early response. The level of Dpt-specific IgA was significantly increased in group I during the NPT. A relationship was found between the levels of VEGF and ECP or Dpt-specific IgA in the NLF samples collected at 10 min and at 3-6 h (P<0.05, respectively)., Conclusion: Nasal VEGF secretion in response to allergen exposure may augment eosinophilic inflammation in the nasal mucosa of patients with AR.

Purpose: Combination treatment of inhaled corticosteroid (ICS) plus long-acting beta2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the beta2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA., Materials and Methods: 43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 microg/day) plus terbutaline (5 microg prn). as needed. During the 24-week active treatment period, they received budesonide 160 microg and formoterol 4.5 microg b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology., Results: During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV(1)) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients., Conclusion: Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy.

In asthmatic airways, adenosine is a potent bronchoconstrictor with either pro- or anti-inflammatory effects depending on receptor interactions. While aspirin has been suggested to mediate adenosine action, the roles of adenosine and its receptors in aspirin-intolerant asthma (AIA) are not well-defined. Therefore, we evaluated associations between genetic polymorphisms of adenosine deaminase and the four adenosine receptors (A(1), A(2A), A(2B), and A(3)) with the AIA phenotype. The genes for adenosine deaminase (ADA) and the four adenosine receptors (ADORA1, ADORA2A, ADORA2B, and ADORA3) were screened by direct sequencing, and 13 single nucleotide polymorphisms (SNPs) were selected among 23 polymorphisms. Using multivariate logistic regression analysis, we compared the frequencies of SNP genotypes and haplotypes among 136 patients with AIA, 181 patients with aspirin-tolerant asthma (ATA), and 183 normal individuals. We found significant differences between normal and patients with AIA in the ADORA1 SNP genotype frequencies for 1405C>T (P=0.001) and A102A (P=0.013). No other significant associations were detected for the other SNPs. In the haplotype analysis, ht[C-T-G] (P=0.003) and ht[A-C-G] (P=0.032) in ADORA1 and ht[A-T] in ADORA2 (P=0.013) were significantly associated with AIA. Genetic polymorphisms of adenosine receptors A(1) and A(2A) were associated with AIA, suggesting that adenosine might play a crucial role in the development of AIA through interactions with the A(1) and A(2A) receptors.

Introduction: Chronic urticaria (CU), defined as the recurring incidence of wheals with or without angioedema for more than 6 weeks, is a common disorder associated with mast cell activation, degranulation, and histamine release. Considering the association between the CRTH2 gene and mast cells, we investigated the association of this gene polymorphism with the CU phenotype and antihistamine drug requirement in patients with CU., Materials & Methods: Two groups consisting of 384 patients with CU and 231 patients as normal controls (NCs) were enrolled from the Department of Allergy and Rheumatology, Ajou University Hospital, Suwon, Korea. Two polymorphisms of the CRTH2 gene, -466T>C and -129C>A were genotyped using primer extension methods., Results: No significant differences were detected in the genotype and allele frequencies of the two CRTH2 polymorphisms between the CU and NC groups, and no significant associations were observed with clinical parameters, such as atopy status, serum total IgE, prevalence of autoantibodies and duration of CU. However, CU patients with homozygous TT genotypes had significantly higher dose requirements of antihistamines to control the CU symptoms (164.56 +/- 115.62 vs 137.38 +/- 90.15 loratadine equivalents, mg/week) than those with the CT and CC genotypes (p = 0.025). The luciferase activity was significantly enhanced in the construct containing CRTH2 466C compared with the -466T-containing construct (p < 0.001). Co-transfection experiments with GATA-3 (300 ng) and the -466T and -466C CRTH2 alleles revealed that the CRTH2 -466T allele produced a greater increase in induction of luciferase activity than the -466C allele (p < 0.001)., Conclusion: The CRTH2 -466T>C gene polymorphism may not affect on the phenotype of CU, but contributes to the required dose of antihistamines in patients with CU.

Background: Histamine plays an important role in allergic inflammation. Histamine levels are regulated by histamine N-methyltransferase (HNMT)., Objective: To investigate the functional variability of HNMT gene in relation to genetic polymorphisms in patients with aspirin intolerant chronic urticaria (AICU)., Methods: Two single-nucleotide polymorphisms of the HNMT gene (314C>T, 939A>G) were genotyped in chronic urticaria patients. The functional variability of 3'-untranslated region polymorphism (3'-UTR) was assessed using the pEGFP-HNMT 3'-UTR reporter construct to examine mRNA stability and fluorescence-tagged protein expression. The HNMT enzymatic activities related to the 939A>G polymorphism were examined both in the human mast cells (HMC-1) transfected with the pHNMT CDS-3'-UTR construct and in the patients' red blood cells (RBCs). Histamine release from the basophils of AICU patients was examined., Results: The 939A>G polymorphism was significantly associated with the AICU phenotype, while no association was found with the 314C>T polymorphism. An in vitro functional study using HMC-1 cells demonstrated that the 939A allele gave lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele. The in vivo functional study demonstrated that the AICU patients with the 939A allele had lower HNMT activity in RBC lysates and higher histamine release from their basophils., Conclusion: The HNMT 939A>G polymorphism lowers HNMT enzymatic activity by decreasing HNMT mRNA stability, which leads to an increase in the histamine level and contributes to the development of AICU.

Background: Chronic urticaria/angioedema is a common phenotype in patients with aspirin sensitivity; however, its genetic mechanism is not understood. Transforming growth factor (TGF)beta1 is a key regulatory cytokine involved in allergic inflammation., Objective: We examined the association of a TGFbeta1 genetic polymorphism with aspirin-intolerant chronic urticaria (AICU) and aspirin-tolerant chronic urticaria (ATCU) in a Korean population., Methods: A promoter polymorphism in the TGFbeta1 gene, TGFbeta1 -509C>T, was analysed in 112 AICU patients, 153 ATCU patients and 457 normal controls (NC), and the frequency was compared among the groups. Serum TGFbeta1 levels were measured by ELISA., Results: The minor allele frequency of the -509C>T polymorphism was significantly higher in patients with AICU compared with the other two groups (P < 0.02 for AICU vs. NC; P < 0.05 for AICU vs. ATCU). Among the AICU patients, those with the T allele tended to have lower serum TGFbeta1 levels., Conclusion: These findings suggest that the -509C>T polymorphism in the TGFbeta1 promoter may contribute to the development of the AICU phenotype.

Food-dependent exercise-induced anaphylaxis is a unique form of food allergy. Recent studies indicate that gliadin is a major allergen in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). We evaluated the value of serum gliadin-specific IgE in the diagnosis of WDEIA, as well as the characteristics and digestibilities of the IgE-binding components of gliadin. We analyzed 32 adult subjects sensitized to wheat; 26 were asymptomatic sensitizers and 6 had WDEIA. Wheat flour and gliadin-specific IgE levels were measured, and corresponding receiver operator characteristics (ROC) curves were determined. Patients with WDEIA had higher levels of gliadin-specific IgE than patients without WDEIA (p = 0.003). The area under the ROC curve for gliadin-specific IgE was 0.872, which suggested this assay could be used as a supplementary test for the diagnosis of WDEIA. IgE immunoblot analyses of reactions to wheat and gliadin extracts were compared both with and without simulated gastric fluid (SGF) and intestinal fluid incubation (SIF). All six WDEIA patients had high IgE binding signals to 50 kDa of gliadin extract on IgE immunoblots. This binding was suppressed by SGF, although minimal inhibition was noted with SIF incubation.

It has been well established that bacterial superantigens lead to the induction and aggravation of chronic inflammatory skin diseases. We investigated the clinical significance of serum specific immunoglobulin E (lgE) to the staphylococcal superantigens staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin (TSST)-1 in patients with chronic urticaria (CU), focusing on the differences in these prevalences between aspirin-intolerant CU (AICU) and aspirin-tolerant CU (ATCU) patients. Aspirin sensitivity was confirmed by oral aspirin provocation test. There were 66 patients AICU and 117 patients ATCU in the study. Serum IgE antibodies specific for SEA, SEB, and TSST-1 were measured by the ImmunoCAP test and the patients were compared with 93 normal controls (NC). The prevalences of serum specific IgE to staphylococcal superantigens were significantly higher in CU than in NC patients (IgE to SEA, 13.7% vs. 5.4%; IgE to SEB, 12.0% vs. 4.3%; IgE to TSST-1, 18.0% vs. 6.5%; p<0.05, respectively). The patients with specific IgE to SEA, SEB, and TSST-1 had higher serum total IgE levels and higher rates of atopy. Significant associations were noted between the prevalence of specific IgE to SEA and SEB and the HLA DQB1*0609 and DRB1*1302 alleles in the AICU group. We confirmed that a sub-population of patients with CU possesses serum IgE antibodies to SEA, SEB, and TSST- 1. Particularly, the IgE immune response to TSST-1 is associated with aspirin sensitivity in CU patients.

Background: Although methylene diphenyl diisocyanate (MDI) may induce occupational asthma in the workplace, the pathogenic mechanisms are unclear., Objectives: By using bronchoalveolar lavage fluid, we sought to identify proteins that were differentially expressed between subjects with MDI-induced occupational asthma (MDI-OA) and asymptomatic exposed controls (AECs)., Methods: To find proteins that were differentially expressed between the MDI-OA and AEC groups, 2-dimensional electrophoresis was performed by using bronchoalveolar lavage fluid obtained from subjects after MDI-specific inhalation challenge. The selected protein spots were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The clinical relevance of the differentially expressed spots was compared by ELISA using sera from the MDI-OA/eosinophilic bronchitis, AEC, and unexposed healthy control groups. Receiver operating characteristic curves were then plotted, and the sensitivity and specificity were determined., Results: Twenty-three protein spots were identified that distinguished the subjects with MDI-OA from those in the AEC group. Among them, ferritin expression was downregulated whereas transferrin expression was upregulated in subjects with MDI-OA compared with AEC; these results were validated by ELISA using sera from the MDI-OA/EB and AEC groups. To identify subjects with MDI-OA, the optimal serum cutoff levels were 69.84 ng/mL for ferritin and 2.48 microg/mL for transferrin. When these 2 parameters were combined, the sensitivity was 71.43% and the specificity was 85.71%., Conclusion: Serum ferritin and transferrin levels are associated with the phenotype of MDI-OA.

Introduction: Although methylene diphenyl diisocyanate (MDI) is widely used in industries, there have been few studies of the pathogenic mechanisms of MDI-induced occupational asthma (MDI-OA)., Methods: We performed immunohistochemical analyses, measured inflammatory mediators and cytokines, and quantified histamine release (HR) from peripheral basophils in MDI-OA patients. Thirteen MDI-exposed workers (five MDI-OA, two MDI-induced esoinophilic bronchitis, and six asymptomatic exposed controls, AEC) were enrolled., Results and Discussion: Immunochemical analyses indicated significantly increased anti-eosinophilic cationic protein-stained cells in MDI-OA patients as compared with controls (P < 0.05). Sputum eosinophil cationic protein levels were increased after MDI-specific inhalation challenge test in MDI-OA/EB patients (P < 0.02). Sputum eosinophil counts were highly correlated with IL-8 and MMP-9 levels (P < 0.05 and P < 0.01, respectively). Basophil HR was significantly increased in MDI-OA patients after stimulations with anti-IgG4 and MDI-human serum albumin conjugates (both P < 0.05). Eosinophil activation is a major feature of airway inflammation in MDI-OA patients. Increased HR by MDI may contribute to the pathogenic mechanisms of MDI-OA.

Background and Objective: The high-affinity IgE receptor comprises a tetramer of the ligand-binding alpha chain, a signal-augmenting beta chain, and a signal-transducing gamma chain dimer on mast cells. We hypothesized that the three subsets of the FCER1 gene may play a role in the development of the aspirin-intolerant asthma (AIA) phenotype and analyzed these genetic polymorphisms in association with clinical parameters in AIA patients., Subjects and Methods: Six polymorphisms of FCER1 (FCERIA-344C>T, FCER1A-95T>C, MS4A2-109T>C, MS4A2 E237G, FCER1G-237A>G, FCER1G-54G>T) were genotyped in 126 AIA patients compared to 177 patients with aspirin-tolerant asthma (ATA) and 222 normal health controls (NC)., Results: A significant difference in the genotype frequencies of FCER1G-237A>G was detected between AIA and ATA patients (p<0.05) both in co-dominant and recessive analysis models, whereas no significant relationships were identified between the frequencies of the other five single-nucleotide polymorphisms and AIA, ATA, and NC subjects. In addition, AIA patients carrying the homozygous AA genotype of FCER1G-237A>G exhibited significantly higher total serum IgE levels than did those with the GG/AG genotype (p=0.012). AIA patients expressing the CT/TT genotype at FCERIA-344C>T showed a higher prevalence of serum IgE specific to Staphylococcal enterotoxin A than did those with the CC genotype (p=0.008)., Conclusion: The FCER1G-237A>G and FCERIA-344C>T polymorphisms may contribute to the development of AIA in a Korean population.

The pathogenic mechanism of acetyl salicylic acid (ASA)-induced urticaria (AIU) is not fully understood. We compared the levels of neutrophil activation and related cytokines in patients with ASA-intolerant acute urticaria (AIAU) and ASA-intolerant chronic urticaria (AICU). A total of 51 patients with AIAU, 88 patients with AICU, and 102 normal controls (NC) were enrolled in this study. The serum levels of myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-18 were compared among the three groups. The serum levels of MPO were highest in the AIAU group, followed by the AICU and NC groups, and the serum levels of IL-18 were significantly higher in the AIAU and AICU groups than in NC group. Within the AIU groups, significant correlations were noted between the levels of MPO and IL-8, and IL-8 and IL-18. In conclusion, neutrophil activation, which was associated with the levels of IL-8 and IL-18 in the AIAU group, may be involved in the pathogenic mechanism of AIU. A role for IL-18 in the pathogenesis of AIU is also suggested.

Chronic urticaria (CU) associated with aspirin sensitivity, termed aspirin-intolerant CU (AICU), is a common condition in the general population. The genetic mechanism of AICU still is not fully understood. We investigated genetic polymorphisms of FcepsilonR1beta and FcepsilonR1gamma in patients with CU including AICU and aspirin-tolerant CU (ATCU) by analyzing the genotypes and haplotypes of four subsets of FcepsilonR1 genes in association with various clinical parameters. Four polymorphisms of FcepsilonR1 (FcepsilonR1beta -109T>C, FcepsilonR1beta E237G, FcepsilonR1gamma -237A>G, and FcepsilonR1gamma -54G>T) were genotyped in 119 AICU patients and compared with 154 patients with ATCU and 224 normal healthy controls (NCs). No significant differences were observed with respect to the allele and genotype frequencies of all four FcepsilonR1 single-nucleotide polymorphisms (SNPs; p > 0.05) in CU including AICU and ATCU patients. However, two SNPs at FcepsilonR1beta E237G and FcepsilonR1gamma -237A>G were associated with atopy in AICU patients but not in ATCU. AICU patients with the AG/GG genotype of FcepsilonR1beta E237G and FcepsilonR1gamma -237G allele had a significantly higher frequency of atopy than those with the AA genotype (p = 0.02 and p = 0.040), respectively. The release of histamine from basophils induced by anti-IgE antibodies was significantly higher in AICU patients than in NCs and was increased in atopic patients compared with nonatopic patients (p = 0.006 and p = 0.007, respectively). The FcepsilonR1beta E237G and FcepsilonR1gamma -237T>G polymorphisms may be associated with the rate of atopy, which in turn could increase the release of histamine from basophils and may lead to the development of the AICU phenotype.

Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of alpha-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.

Background: Although baker's asthma (BA) is a common occupational asthma, there have been few reports on this disease in Korean subjects., Objectives: We evaluated the prevalence of serum-specific IgE, IgG1, and IgG4 antibodies in relation to work-related respiratory symptoms in a single industrial bakery., Methods: Three hundred and ninety-two bakery workers were administered and taken a questionnaire regarding respiratory symptoms. For symptomatic workers, the methacholine bronchial challenge test and specific bronchoprovocation tests with wheat extracts were carried out. Skin prick tests were performed and serum-specific IgE, IgG1, and IgG4 antibodies to wheat flour were detected. The IgE- and IgG4-binding components were identified by immunoblotting., Results: Sixty-seven workers (17.1%) complained of work-related upper and lower respiratory symptoms. The prevalence of BA based on positive bronchoprovocation test results was 1.5%. The sensitization rate to wheat flour was 5.9% by skin prick test and 6.5% by ELISA, and was closely associated with the presence of atopy and work-related lower respiratory symptoms (P<0.001 for both). IgE immunoblotting revealed six major IgE-binding components (27, 31, 36, 43, 54, and 72 kDa). The presence of wheat-specific IgG1 and IgG4 antibodies was found to be significantly associated with exposure intensity (P<0.05 for both)., Conclusions: The overall prevalence of wheat sensitization in a Korean bakery was 5.9%. We confirmed that an IgE-mediated response is the major pathogenic mechanism for the induction of work-related symptoms in wheat-exposed workers. Wheat-specific IgG antibodies may represent current or previous exposure to wheat dust.

Background: Although methylene diphenyl diisocyanate (MDI) is widely used in many industries, there have been few immunological studies of MDI-induced occupational asthma., Objectives: We investigated the effects of MDI exposure on the clinical and immunologic condition of workers in a single car upholstery factory., Methods: Fifty-eight MDI-exposed workers were studied. Work-related lower-respiratory symptoms (WRRS) were identified using a questionnaire. Serum-specific IgE and IgG antibodies to MDI-human serum albumin conjugate were detected by ELISA. Atopy was evaluated using a skin prick test. MDI-induced occupational asthma was confirmed in the symptomatic workers with a positive result on an MDI-specific inhalation test., Results: Thirteen (22.4%) of the subjects complained of WRRS. MDI-induced occupational asthma was confirmed in five (8.6%) of the workers, and occupational eosinophilic bronchitis was confirmed in two (3.5%). The prevalence of specific IgG antibodies (20.7%) was higher than that of specific IgE antibodies (8.6%). The prevalence of MDI-induced occupational asthma/eosinophilic bronchitis was strongly associated with the presence of both WRRS and serum-specific IgG antibodies to an MDI-human serum albumin conjugate (P<0.01, <0.05, respectively)., Conclusion: These findings suggest that MDI could be a causative agent of occupational asthma among MDI-exposed workers. The prevalence of MDI-induced occupational asthma was 8.6%, and MDI-induced eosinophilic bronchitis was confirmed in two workers. The presence of work-related lower-respiratory symptoms and serum-specific IgG antibodies to an MDI-human serum albumin conjugate may be used to predict MDI-induced occupational asthma/eosinophilic bronchitis in MDI-exposed workers.

The mechanisms of eosinophil activation in perennial allergic rhinitis (AR) are not fully understood but may be mediated by a series of inflammatory mediators, including locally produced specific antibodies. The aim of this study was to evaluate the role of locally produced allergen-specific antibodies in the nasal lavage fluid during the recruitment of inflammatory cells in AR. Thirteen patients with AR and a positive nasal provocation test (NPT) with Dermatophagoides pteronyssinus and 10 asymptomatic subjects, sensitized to D. pteronyssinus but who had a negative NPT were enrolled. Nasal lavage fluids were collected before and at 10, 30, and 60 minutes and 3, 6, and 24 hours after the NPT. Inflammatory cells were counted, and eosinophil cationic protein (ECP) and specific immunoglobulin E (IgE), IgG, and IgA antibodies were measured by enzyme-linked immunosorbent assay. After NPT, six subjects showed early responses and seven subjects showed dual responses. The eosinophil count and ECP level in lavage fluid were significantly increased after NPT in patients with positive NPTs, and these values were significantly higher than in the negative group. The specific IgA level in lavage fluid was increased after NPT in the positive group, and significant differences were noted for both the early and the late positive responses. Significant correlations were found between specific IgA and ECP levels in lavage fluid during early and late responses. Eosinophil recruitment occurred during both early and late responses after allergen exposure in perennial AR. Locally produced allergen-specific IgA (but not IgE or IgG) may be involved in eosinophil activation in both early and late responses.