Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles

Purpose@#Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. @*Methods@#We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. @*Results@#Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. @*Conclusions@#The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles

Purpose@#Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. @*Methods@#We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. @*Results@#Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. @*Conclusions@#The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Lactobacillus plantarum-derived Extracellular Vesicles Protect Atopic Dermatitis Induced by Staphylococcus aureus-derived Extracellular Vesicles

PURPOSE: The microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV composition METHODS: Twenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively. RESULTS: The proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level. CONCLUSIONS: We suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation.

Importance of indoor dust biological ultrafine particles in the pathogenesis of chronic inflammatory lung diseases

The role of infectious agents in the etiology of inflammatory diseases once believed to be non-infectious is increasingly being recognized. Many bacterial components in the indoor dust can evoke inflammatory lung diseases. Bacteria secrete nanometer-sized vesicles into the extracellular milieu, so-called extracellular vesicles (EV). which are pathophysiologically related to inflammatory diseases. Microbiota compositions in the indoor dust revealed the presence of both Gram-negative and Gram-positive bacteria. Escherichia coli is a model organism of Gram-negative Enterobacteriaceae. The repeated inhalation of E. coli-derived EVs caused neutrophilic inflammation and emphysema in a dose-dependent manner. The emphysema induced by E. coli-derived EVs was partially eliminated by the absence of Interferon-gamma or interleukin-17, suggesting that Th1 and/or Th17 cell responses are important in the emphysema development. Meanwhile, the repeated inhalation of Staphylococcus aureus-derived EVs did not induce emphysema, although they induced neutrophilic inflammation in the lung. In terms of microbial EV compositions in the indoor dust, genera Pseudomonas, Acinetobacter, Enterobacter, and Staphylococcus were dominant. As for the clinical significance of sensitization to EVs in the indoor dust, EV sensitization was closely associated with asthma, chronic obstructive pulmonary disorder (COPD), and lung cancer. These data indicate that biological ultrafine particles in the indoor dust, which are mainly composed of microbial EVs, are important in the pathogenesis of chronic lung diseases associated with neutrophilic inflammation. Taken together, microbial EVs in the indoor dust are an important diagnostic and therapeutic target for the control of chronic lung diseases, such as asthma, COPD, and lung cancer.

Influence of the Adjuvants and Genetic Background on the Asthma Model Using Recombinant Der f 2 in Mice

Der f 2 is the group 2 major allergen of a house dust mite (Dermatophagoides farinae) and its function has been recently suggested. To determine the optimal condition of sensitization to recombinant Der f 2 (rDer f 2) in murine model of asthma, we compared the effectiveness with different adjuvants in BALB/c and C57BL/6 mice. Mice from both strains sensitized with rDer f 2 by intraperitoneal injection or subcutaneous injection on days 1 and 14. The dosage was 20 microg. Freund's adjuvants with pertussis toxin (FP) or alum alone were used as adjuvants. On days 28, 29, and 30, mice were challenged intranasally with 0.1% rDer f 2. We evaluated airway hyperresponsivenss, eosinophil proportion in lung lavage, airway inflammation, and serum allergen specific antibody responses. Naive mice were used as controls. Airway hyperresponsiveness was increased in C57BL/6 with FP, and BALB/c with alum (PC200: 13.5+/-6.3, 13.2+/-6.7 vs. >50 mg/ml, p<0.05). The eosinophil proportion was increased in all groups; C57BL/6 with FP, BALB/c with FP, C57BL/6 with alum, BALB/c with alum (24.8+/-3.6, 20.3+/-10.3, 11.0+/-6.9, 5.7+/-2.8, vs. 0.0+/-0.0%, p<0.05). The serum allergen specific IgE levels were increased in C57BL/6 with FP or alum (OD: 0.8+/-1.4, 1.1+/-0.8, vs. 0.0+/-0.0). C57BL/6 mice were better responders to rDer f 2 and as for adjuvants, Freund's adjuvant with pertussis toxin was better.

Murine subcutaneous immunotherapy models with beneficial immunological and physiological effects

BACKGROUND: Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far. OBJECTIVE: We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule. METHODS: To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times. RESULTS: Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR. CONCLUSION: This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.

Clinical Features of Patients with Anaphylaxis at a Single Hospital / 소아알레르기및호흡기학회지

PURPOSE: The studies concerning the clinical features of patients with anaphylaxis, who meet the newly established diagnostic criteria, are reported in Korea, but comparative studies regarding the clinical features of children and adult patients with anaphylaxis are lacking. The purpose of this study is to compare the clinical features of the children and adults with anaphylaxis, who meet the new diagnostic criteria at a single hospital. METHODS: We reviewed the medical records of patients who were diagnosed with anaphylaxis, anaphylactic shock, urticaria, and angioedema, including inpatients, outpatients and emergency room visited patients, at the National Medical Center from July, 2005 to August, 2011. The clinical characteristics of children and adults, who met the new diagnostic criteria for anaphylaxis, were analyzed. RESULTS: We identified 91 patients with anaphylaxis. Sixteen were children and 75 were adults. The sex ratio (male:female) and the mean age were 1:1.7 and 9.6 years among children, respectively, and 1:2.3 and 42.3 years, respectively, among adults. The most common cause of anaphylaxis based on clinical history was foods in 15 children (93.7%) and 35 adults (46.7%). Twelve children (75%) and 36 adults (48%) were rediagnosed with anaphylaxis. Patients with cardiovascular symptoms and severe severity were 1 (6.3%) and 1 (6.3%), respectively, among children, and 28 (37.3%) and 23 (30.3%), respectively, among adults. CONCLUSION: We rediagnosed some cases of anaphylaxis, using the new diagnostic criteria and most of the cases were diagnosed initially as urticaria or angioedema. The adults had more severe and more cardiovascular symptoms than children. In the future, a nationwide, multiinstitutional research will be necessary for the prevalence and the clinical features of anaphylaxis by the new diagnostic criteria in Korea.

Differences in airway inflammation according to atopic status in patients with chronic rhinitis

BACKGROUND: Chronic rhinitis is a heterogeneous group of diseases that cause nasal inflammation. And the nose may be a window into the lung in the concept of "one airway one disease." OBJECTIVE: This study was conducted to evaluate differences between the different forms of chronic rhinitis in terms of lower airway inflammation. METHODS: Patients that attended the allergy clinic and presented with moderate/severe persistent rhinitis symptoms for more than 1 year were enrolled. The patients with chronic rhinitis were classified into two groups (house dust mites [HDM]-sensitive allergic rhinitis [AR] or non-allergic rhinitis [NAR]) according to the presence of atopy, and additionally according to nasal polyposis and airway hyperresponsiveness, respectively. Medical records were reviewed and the mRNA expression levels of IL-5, IFN-γ, TGF-β1, IL-17A, and IL-25 were evaluated in induced sputum samples in each group. RESULTS: Induced sputum samples of 53 patients were evaluated. Patients with NAR were significantly older than patients with HDM-sensitive AR (p < 0.05). Nasal polyposis was more prevalent in NAR patients than in HDM-sensitive AR patients (10.2% vs. 62.5%, p < 0.001). The expression levels of IL-17A mRNA were higher in NAR patients, regardless of the presence of airway hyperresponsiveness (p = 0.005). CONCLUSION: These results suggest that patients with different forms of chronic rhinitis could have different inflammatory environments in their lower airway and NAR patients might have bronchial inflammation related to the elevated levels of IL-17A compared to HDM-sensitive AR patients.

Two Cases of H2-Receptor Antagonist Hypersensitivity and Cross-Reactivity

H2-receptor antagonists, such as cimetidine, ranitidine and famotidine, are some of the most commonly prescribed medications for gastric acid-related disorders. These compounds are generally well-tolerated and anaphylactic reactions to them are rare. Here, we report two cases of H2-receptor antagonist-induced anaphylactic reactions: the first presented with sudden dyspnea, sneezing, urticaria, and swelling of the eyelids after ranitidine intake. The second presented with sudden severe urticaria, facial swelling, chest discomfort, dizziness, and hypotension. Possible cross-reactivity with other H2-receptor antagonists was assessed by oral challenge and skin tests. To date, only a few reports addressing cross-reactivity among H2-receptor antagonists have been published. We review the literature and summarize the data available on drug cross-reactivity in H2-receptor antagonist hypersensitivity.

The Financial Burden of Asthma: A Nationwide Comprehensive Survey Conducted in the Republic of Korea

PURPOSE: Asthma-related morbidity and mortality are increasing, and the financial burden imposed by this condition will substantially increase. Nevertheless, little information is available regarding the nature and magnitude of the burden due to asthma at the national level. This study was conducted to characterize the financial burden imposed by asthma in the Republic of Korea at the national level. METHODS: The overall prevalence of asthma and the costs of related medical services were determined using data from the National Health Insurance Corporation, which is responsible for the National Health Insurance scheme. Indirect costs, including expenditures on complementary and alternative medicines, and the economic impact of an impaired quality of life (intangible costs) were estimated by surveying 660 asthmatics, and these estimates were transformed to the national level using the prevalence of asthma. RESULTS: The prevalence of asthma and total costs related to the disease in 2004 were 4.19% and $2.04 billion, respectively. Direct costs and indirect costs contributed equally to total costs (46.9% and 53.1%, respectively). However, when intangible costs were included, total costs rose to $4.11 billion, which was equivalent to 0.44% of the national gross domestic product in 2004. CONCLUSIONS: The results provide evidence that asthma is a major health cost factor in the Republic of Korea and that intangible costs associated with asthma are significant cost drivers.

A Case of Chlorpheniramine Maleate-Induced Hypersensitivity With Aspirin Intolerance

Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines.

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1beta, IL-6 and TNF-alpha, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.

Customized Asthma Control Test with Reflection on Sociocultural Differences

We evaluated the utility and feasibility of customizing Asthma Control Test (ACT) items to generate a Korean Asthma Control Test (KACT) specific for Korean patients. We surveyed 392 asthma patients with 19 items, selected to reflect the Korean sociocultural context. Guideline ratings were integrated with the evaluations of specialists (i.e., using both guide base rating together with specialist's rating), and items with the greatest discriminating validity were identified. Stepwise regression methods were used to select items. KACT scale scores showed significant differences between the asthma control ratings generated by integrating ratings (r=0.77, P<0.001), by specialist's evaluations (r=0.54, P<0.001), or by FEV1 percent predicted (r=0.39, P<0.001). Specialist's and guideline ratings detected 56% and 48.6% of patients with well-controlled asthma, respectively. However, the integrated ratings indicated that only 34.3% of the patients in the test sample were well controlled. The overall agreement between KACT and the integrated rating ranged from 45% to 78%, depending on the cut-off points used. It is possible to formulate a valid, useful country-specific diagnostic tool for the assessment of asthma patients based on the original ACT that reflect differences in sociocultural context.

Past, Present, and Future of Allergy in Korea

Korean allergology has made great progress in keeping pace with global scientific advances in spite of a short history. Outstanding academic and scientific researches have been performed in a variety of allergy fields in Korea. Epidemiologic studies revealed increasing prevalence of asthma and allergic diseases and considerable morbidity and mortality in Korea. Novel inhalant allergens such as citrus red mite and two-spotted spider mite as causes of asthma and allergic rhinitis have been discovered and reported in Korea. Bidirectional translational researches have been performed and are underway to elucidate the pathogenesis of asthma and allergy, mechanisms of airway inflammation and remodeling, and new therapeutic modalities for asthma and allergic diseases. Experimental asthma models of different phenotypes according to exposed levels of lipopolysaccharide or double-stranded RNA suggested the crucial role of the innate immunity in the development of allergic airway inflammation and a new insight for asthma pathogenesis, in which both Th1 and Th2 inflammation are involved. In the field of genetic researches, numerous genetic associations with asthma and asthma-related phenotypes, such as atopy, IgE production, and airway hyperresponsiveness, have been demonstrated in Korean population. The Easy Asthma Management (EAM) program, a computer-assisted asthma management program, is anticipated to facilitate the achievement of more successful clinical outcomes by filling the gaps between guidelines and actual practices. The Integration of these multi-disciplinary allergy research resources and translation of scientific achievements to the bedside and society will lead to better allergy and asthma control in Korea.

A Case of Churg-Strauss Syndrome with Endomyocardial Fibrosis / 대한류마티스학회지

Cardiac involvement is an important cause of mortality in patients with Churg-Strauss syndrome. The typical cardiac presentation of Churg-Strauss syndrome includes pericarditis, myocarditis, and cardiomyopathy. Endomyocardial fibrosis has rarely been described in patients with Churg-Strauss syndrome. We experienced a patient with Churg-Strauss syndrome who exhibited exertional dyspnea and endomyocardial fibrosis visualized as delayed enhancement on cardiac magnetic resonance imaging (MRI). After glucocorticoid treatment, the patient's symptom resolved, and the eosinophil count decreased to normal. Nine months later, the delayed-enhanced lesion on the cardiac MRI nearly disappeared. Here, we report a case of endomyocardial fibrosis in a patient with Churg-Strauss syndrome with a literature review.

Physicians' Preferences for Asthma Guidelines Implementation

PURPOSE: Patient care based on asthma guidelines is cost-effective and leads to improved treatment outcomes. However, ineffective implementation strategies interfere with the use of these recommendations in clinical practice. This study investigated physicians' preferences for asthma guidelines, including content, supporting evidence, learning strategies, format, and placement in the clinical workplace. METHODS: We obtained information through a questionnaire survey. The questionnaire was distributed to physicians attending continuing medical education courses and sent to other physicians by airmail, e-mail, and facsimile. RESULTS: A total of 183 physicians responded (male to female ratio, 2.3:1; mean age, 40.4+/-9.9 years); 89.9% of respondents were internists or pediatricians, and 51.7% were primary care physicians. Physicians preferred information that described asthma medications, classified the disease according to severity and level of control, and provided methods of evaluation/treatment/monitoring and management of acute exacerbation. The most effective strategies for encouraging the use of the guidelines were through continuing medical education and discussions with colleagues. Physicians required supporting evidence in the form of randomized controlled trials and expert consensus. They preferred that the guidelines be presented as algorithms or flow charts/flow diagrams on plastic sheets, pocket cards, or in electronic medical records. CONCLUSIONS: This study identified the items of the asthma guidelines preferred by physicians in Korea. Asthma guidelines with physicians' preferences would encourage their implementation in clinical practice.

A Case of Recurrent Toxocariasis Presenting With Urticaria

Human toxocariasis is the most prevalent helminthiasis in Korea and other industrialized countries. The clinical features of toxocariasis are diverse, according to the involved organ. Typically, Toxocara spp. infection is easily treated with 400 mg albendazole twice a day for 5 days. However, we experienced a case of recurrent toxocariasis that was refractory to this standard therapy and presented with urticaria, an uncommon symptom in toxocariasis. A 35-year-old male visited our emergency room because of abdominal pain. He had recently consumed raw cow liver (3 weeks prior to presentation). Laboratory analyses revealed eosinophilia (1,612 cells/microliter) and increased total IgE (3,060 IU/mL). Chest X-ray showed multiple lung nodules in both lungs, and computed tomography revealed multiple ground-glass opacities in both lungs and multiple tiny liver abscesses. Liver biopsy revealed an eosinophilic abscess. Enzyme-linked immunosorbent assay findings for Toxocara antigens were positive (optical density, 2.140), leading to a diagnosis of toxocariasis. We initiated a 5-day treatment with albendazole and prednisolone; however, 6 days after completing the treatment, the patient again experienced urticaria and severe itching that could not be controlled by antihistamines or hydrocortisone cream. A second bout of eosinophilia suggested recurring toxocariasis, for which we prescribed a second round of albendazole. Despite an initial improvement in his symptoms, the patient returned after 6 weeks complaining of abdominal pain for 6 hours, which was reminiscent of his first attack; he also exhibited eosinophilia. Accordingly, albendazole was administered once more for an additional 3 weeks, and his symptoms resolved.

Association between genetic variations of the transforming growth factor beta receptor type III and asthma in a Korean population

Transforming growth factor-beta (TGF-beta) and its receptors have been suggested to play key roles in the pathogenesis of asthma. The aim of this study was to evaluate the effects of genetic variations in the TGF-beta receptor type III (TGFBR3) on asthma and on its related phenotypes in the general population. A cohort of 2,118 subjects aged from 10 to 18 years responded to a questionnaire concerning asthma symptoms and risk factors. Methacholine airway hyperresponsiveness (AHR), skin test responses to common aeroallergens, and serum total IgE levels were evaluated in the cohort. A total of 19 SNPs for TGFBR3 were found using direct re-sequencing in 24 healthy adults. Of these, informative SNPs [+44T>C (S15F) and +2753G>A at 3'UTR] were selected and scored using the high throughput single base extension method. Atopy was identified in subjects with 44T>C allele [P = 0.04, OR (95% CI) = 0.79 (0.62-0.99)] and in subjects with Ht1 (CG) more frequently than in subjects with other haplotypes [P = 0.04, OR (95% CI) = 1.27 (1.01-1.59)]. The A allele in 2753G>A was more common in subjects with non-atopic asthma [OR (95% CI) = 1.76 (1.01-3.05)]. A significant association was found between non-atopic asthma and 44T_2753A [OR (95% CI) = 2.16 (1.22-3.82)]. Genetic variations in TGFBR3 appear to be associated with a genetic predisposition to development of asthma and to phenotypes of asthma. Also, the minor allele 2753G and the haplotype TA in the TGFBR3 gene were associated with a pathogenesis of non-atopic asthma.

The Current Practice of Skin Testing for Antibiotics in Korean Hospitals

BACKGROUND/AIMS: Antibiotic skin testing is a useful procedure for identifying patients with IgE-mediated hypersensitivity to antibiotics. The procedures, however, have not been standardized, and the testing is performed with diverse protocols in Korean hospitals wards. Thus, we examined the current practice of antibiotic skin testing in Korea. METHODS: We sent questionnaires to 12 allergists working in secondary or tertiary referral hospitals and collected them by e-mail or fax. The questionnaire included items such as the types and concentrations of the tested antibiotics, the methods of antibiotic skin testing, and the interpretation of the results. RESULTS: All hospitals responded to the questionnaire. The antibiotic skin testing protocols were variable, inconsistent, and differed with regard to the type and concentrations of antibiotics, the volume injected, and the interpretation of the results. Moreover, the protocols differed from the commonly recommended procedures in the medical literature. CONCLUSIONS: Standardized guidelines for antibiotic skin testing are needed for the safe and effective use of antibiotics in Korea.

The Effect of CpG-Oligodeoxynucleotides with Different Backbone Structures and 3' Hexameric Deoxyriboguanosine Run Conjugation on the Treatment of Asthma in Mice

CpG-Oligodeoxynucleotide (ODN) has two backbones. Phosphorothioate backbone (PS) shows a strong immunostimulating effect while phosphodiester (PE) shows little in vivo. 3' hexameric deoxyriboguanosine-run (3' dG6-run) conjugation to PE CpG-ODN has been reported to enhance immunostimulation and to protect against asthma when injected at the time of sensitization in mice. We evaluated the treatment effects of PE and PS CpG-ODN with or without 3' dG6-run on asthma in presensitized mice. BALB/c mice sensitized with ovalbumin and alum were challenged with 1% ovalbumin on three days. CpG-ODNs (100 microgram) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG6: CpG-ODN with 3' dG6-run, PE*-CpG-dG6: PE-CpG-dG6 with two PS backbones at the 5' terminus). PE-CpG showed no treatment effect. PE-CpG-dG6 only increased ovalbumin-specific IgG2a. PE*-CpG-dG6 increased ovalbumin-specific IgG2a but also reduced BAL fluid eosinophils and airway hyperresponsiveness. PS-CpG increased ovalbumin-specific IgG2a, reduced airway inflammation and airway hyperresponsiveness. PS-CpG-dG6 was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3' dG6-run but also the modification of two PS linkages at 5' terminus to inhibit features of asthma. PS-CpG was strong enough to inhibit asthma but PS-CpG-dG6 was less effective.