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Liparis tanakae is a kind of fish in the northwestern Pacific Ocean and sometimes it is used for broth or frozen fish fillets on markets in Korea. A 45-year-old female patient visited Emergency Department because of facial edema, generalized urticaria, dyspnea, and hypotension after eating L. tanakae broth. She recovered after administration of epinephrine. Seven weeks later, she experienced generalized urticaria again after tasting a spoon of L. tanakae broth. In 2 months after recovery, the patient showed positive response to skin prick tests with L. tanakae extract. She also showed positive response to skin prick test with cod which did not induce any symptoms after oral ingestion. The patient was diagnosed as L. tanakae induced anaphylaxis based on the repeated clinical history and skin prick test results. We herein report the first case of L. tanakae induced anaphylaxis.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.

As an essential part of patient safety, pharmacovigilance is of worldwide interest and should expand its scope and focus on new emerging issues. South Korea has been making continuous efforts in the field of pharmacovigilance for the last 3 decades since voluntary adverse drug reaction (ADR) reporting system was first launched in 1988. Korea joined the World Health Organization Program for International Drug Monitoring in 1992, and the activities of Pharmacovigilance Research Network, Korean Society for Pharmacoepidemiology and Risk Management, and Regional Pharmacovigilance Center (RPVC) have contributed to the remarkable progress in the pharmacovigilance area and global status. RPVCs have played pivotal roles in establishment of pharmacovigilance system in Korea by monitoring voluntary ADR reports. RPVCs started with 3 hospitals in 2006 and have now expanded to 27 hospitals nationwide. The Korea Institute of Drug Safety & Risk Management was established in 2012 and in charge of operating the decentralized national pharmacovigilance system. The voluntary report of ADR, which is the basis of current pharmacovigilance system, has various limitations and an active surveillance system can be the overarching alternative. This change in pharmacovigilance paradigm is a global trend and Korea has excellent infrastructure such as broad distribution of electronic medical recording systems and a nationwide single healthcare insurance. As a result, the pharmacovigilance in Korea is now expected to progress to a new active surveillance system from traditional spontaneous reporting system.

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

Background Human rhinoviruses are the major cause of asthma exacerbation in both children and adults. Recently, impaired antiviral interferon (IFN) response in asthmatics has been indicated as a primary reason of the susceptibility to respiratory virus, but the mechanism of defective IFN production is little understood to date. The expression of IFN regulatory factor 7 (IRF7), a transcriptional factor for virus-induced type I IFN production is known to be regulated epigenetically by DNA methylation. Objective We aimed to investigate the expression of IFN-α, IFN-β, and IRF7 in response to rhinovirus infection in the adult asthmatics and evaluate DNA methylation status of IRF7 gene promotor. Methods Twenty symptomatic adult asthmatics and 10 healthy subjects were enrolled and peripheral blood was collected from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and ex vivo stimulated with rhinovirus-16. The mRNA expressions of IFN-α, IFN-β, and IRF7 were analyzed using real time quantitative polymerase chain reaction. Genomic DNA was isolated from untreated PBMCs and the methylation status of IRF7 gene promotor was investigated using bisulfite pyrosequencing. Results The mean age of asthmatics was 45.4 ± 15.7 years and 40% was male, which were not different with those of control group. Asthmatics showed significantly decreased mRNA expressions (relative expression to beta-actin) of IFN-α and IFN-β compared with normal control. The mRNA expression of IRF7 in the asthmatics was also significantly lower than those in the normal control. No significant difference of DNA methylation was observed between asthmatics and controls in all analyzed positions of IRF7 promotor CpG loci. Conclusion The mRNA expression of type I IFN in response to rhinovirus was impaired in the PBMCs of adult asthmatics. The mRNA expression of IRF7, transcriptional factor inducing type I IFN was also reduced, but not caused by altered DNA methylation in the IRF7 gene promotor.

BACKGROUND: Standardized questionnaire is one of key instruments for general population surveys. OBJECTIVE: The present study aimed to develop and validate the Korean version of the European Community Respiratory Health Survey (ECRHS) screening questionnaire for adult asthma surveys. METHODS: The ECRHS screening questionnaire was translated into Korean language according to the international criteria. Study participants were prospectively recruited from six referral hospitals and one health check-up center. Comprehensibility of the translation was tested in a pilot study of 10 patients. The reliability was evaluated by internal consistency and test-retest repeatability. Validity was assess with regard to physician-diagnosed asthma. RESULTS: A total of 100 adult asthma patients and 134 volunteers were recruited. Reliability was examined for 10 items in 100 asthmatics; Cronbach α coefficients were 0.84, and test-retest repeatability was good (Cohen κ coefficient, 0.71-1.00). Validity was assessed for 8 items in 234 participants; in particular, 'recent wheeze' showed a high sensitivity (0.89) for physician-diagnosed asthma. 'Recent asthma attack' and 'current asthma medication' showed high specificity (0.96-0.98). CONCLUSION: The present study demonstrated that the Korean version of the ECRHS screening questionnaire was comprehensible, reliable and valid. We suggest the questionnaire to be utilized in further epidemiological studies for asthma in Korean adult populations.

BACKGROUND Upper respiratory diseases have been linked with lower respiratory diseases. However, the long-term effect of sinusitis on the clinical outcomes of asthma has not been fully evaluated. OBJECTIVE The aim of this study was to investigate the impact of sinusitis on the disease progression of asthma. METHODS Seventy-five asthmatic patients confirmed with the methacholine bronchial provocation test or bronchodilator response were included. The study patients underwent paranasal sinus x-ray upon their asthma evaluation and they visited the hospital at least 3 years or longer. We retrospectively reviewed their medical records and compared data according to the presence of comorbid sinusitis. RESULTS Among the 75 asthmatic subjects, 38 subjects (50.7%) had radiologic evidence of sinusitis. Asthmatics with sinusitis had significantly lower forced expiratory volume in 1 second (FEV1; 79.2% vs. 88.2%) and PC20 values (5.2 mg/mL vs. 8.9 mg/mL) compared to asthmatics without sinusitis at the time of diagnosis. This difference in FEV1 disappeared (82.6% vs. 87.2%) in the 3-year follow-up, although FEV1 was more variable (31.7% vs. 23.5%) and worst FEV1 was also significantly lower in patients with sinusitis compared to those without (70.9% vs. 79.0%). There were no significant differences in the number of hospital visits, acute exacerbations, and scores for the asthma control test. CONCLUSION Although sinusitis was associated with lower baseline lung function and higher hyperreactivity, sinusitis was not related with significant deterioration in lung function over 3 years of follow-up. Asthmatics with sinusitis showed more variability in lung function during the follow-up period. Healthcare utilization was not different except antibiotics use.

Background Theophylline is mainly metabolized by cytochrome P450 (CYP) 1A2 and CYP2E1 which show inter-individual variations. However, the underlying mechanism remains unknown in humans. We investigated the relationship between differences in theophylline clearance and genetic polymorphisms in the CYP1A2 and CYP2E1 gene in 89 Korean asthmatic patients. Methods Polymerase chain reaction (PCR) was performed on the 5'-flanking region of those genes. PCR products were directly sequenced and confirmed using the SNaP shot method. We determined whether the detected SNPs affected gene transcription using electrophoretic mobility shift assay (EMSA). Theophylline clearance (mL/kg/h) was assessed by using a Bayesian approach. Results Genetic polymorphisms were identified at 7 sites in the CYP1A2 gene and at 10 sites in the CYP2E1. Among them, subjects with genotypes (GA+AA) of the -3860G>A polymorphism were found to show higher theophylline clearance than those with genotypes GG (29.11 ± 0.91 mL/kg/h vs. 26.12 ± 0.80 mL/kg/h, p = 0.014). This polymorphic site was revealed to be a protein binding site by conducting EMSA on nuclear hepatocyte extracts. Conclusion In conclusion, increased theophylline clearance was significantly related to the -3860G>A polymorphism, which could be associated with increased CYP1A2 inducibility in Korean non-smoking asthmatics.

Background Recent literature suggests that Staphylococcal enterotoxin specific IgE may be a risk factor for asthma. Objective To investigate the associations between Staphylococcal enterotoxin sensitization and asthma. Methods A systematic review and meta-analysis was performed for relevant case-control or population-based studies, published in the peer-reviewed journals until February 2013. Data were extracted on study designs, subjects, definitions and the prevalence of Staphylococcal enterotoxin sensitization. Results A total of 683 studies were initially identified, of which 7 studies finally met the inclusion criteria (5 case-control and 2 population-based studies). All the included studies reported higher prevalence of the sensitization in asthmatics than in controls, despite clinical and methodological heterogeneity. In a meta-analysis, the pooled odds ratio of the sensitization for asthma was 2.95 (95% confidence intervals 2.28-3.82). Conclusion Staphylococcal enterotoxin sensitization was significantly associated with asthma. The mechanisms of associations warrant further elucidation.

Background Bronchial asthma is usually associated with high sputum eosinophil levels. However, recent reports have suggested the importance of noneosinophilic asthma (NEA) as a distinct phenotype of asthma. Objective The aim of this study was to evaluate clinical significance of sputum eosinophilia and long-term treatment outcomes related to sputum eosinophilia in Korean asthmatics. Methods A total of 201 steroid-naive asthmatics who had undergone induced sputum analysis at baseline were selected from the Cohort for Reality and Evolution of Adult Asthma study population. Clinical evaluation, spirometry, a skin-prick test, a methacholine bronchial provocation test, and sputum eosinophil analysis were performed initially, and patients received the treatment recommended by the Global Initiative for Asthma. Lung function was evaluated every 6 months, and 53 patients completed 24 months of regular follow-up visits. Sputum eosinophilia was defined as a sputum eosinophil count of >3%. Results Of the 201 steroid-naive asthmatics, 97 patients had NEA and 104 had eosinophilic asthma (EA). Only 52% of steroid-naive asthmatic subjects had elevated baseline sputum eosinophil levels. A higher percentage of sputum eosinophils was associated with a lower PC20 (r = -0.193; p = 0.009, Spearman correlation), but not with forced expiratory volume in one second (FEV1) (r = 0.045; p = 0.525). During the 24-month study period, the percentage change of FEV1 was significantly lower in the NEA group than in the EA group at 6, 12, 18, and 24 months (p < 0.05). The NEA group, unlike the EA group, showed no significant improvement in FEV1 at 6, 12, 18, or 24 months (p > 0.05). Conclusion A higher sputum eosinophil percentage was correlated with a higher airway hyperresponsiveness. Compared with EA patients, NEA patients had poor treatment outcomes in the 2-year follow-up of a Korean asthma cohort population.