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Currently, the prevention of recurrent immediate hypersensitivity reactions (HSRs) to contrast media (CM) requests premedication and changing the culprit contrast agent. However, strategies for the prevention of immediate HSRs to gadolinium-based magnetic resonance contrast agents (GBCAs) have not yet been established. This study aimed to evaluate the effectiveness of changing the contrast agent and single-dose premedication for HSR recurrence prevention in patients with a history of mild immediate HSR to GBCA.The outcomes of patients with mild immediate HSR to GBCA who subsequently underwent enhanced magnetic resonance imaging between October 2012 and July 2017 were analyzed. The institutional CM monitoring system was retrospectively reviewed, and data on the application of premedication and choice of CM were obtained. Gadolinium-based magnetic resonance contrast agents were classified into 3 classes according to their molecular structure (macrocyclic ionic, macrocyclic nonionic, and linear ionic). Intravenous chlorpheniramine 4 mg, 30 minutes before the GBCA administration, or intravenous methylprednisolone sodium succinate 40 mg plus chlorpheniramine 4 mg, 1 hour before the GBCA administration, was administrated as premedication regimen. Recurrence rates of immediate HSR were compared according to prevention strategies.A total of 185 patients with a history of mild immediate HSR to GBCA were re-exposed to GBCA 397 times during the study period. The overall recurrence rate was 19.6% (78/397). Changing the culprit GBCA significantly reduced the recurrence rate, compared with reusing the culprit GBCA (6.9%, 9/130 and 25.8%, 69/267; P0.001). The recurrence rate was lowest when the GBCA was changed to a different molecular structure class from the culprit agent, followed by changing to CM with the same molecular structure and reusing the culprit GBCA (6.2%, 7/113 vs 11.8%, 2/17 vs 25.8%, 69/267; P0.001 with χ test for trend). Single-dose premedication demonstrated no significant prophylactic effect on recurrence (20.4%, 17/98 vs 17.3%, 61/299 with and without premedication, respectively; P = 0.509). Premedication in addition to changing CM also showed no additional prophylactic effect (7.2%, 7/97 and 6.1%, 2/33, respectively; P = 0.821).Changing the CM from the culprit agent could reduce the chance of HSR recurrence in patients with prior mild immediate HSR to GBCA, especially when the CM was changed to one of a different molecular structure class. However, single-dose premedication administration did not show significant HSR recurrence rate difference.

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.

Background Intraoperative anaphylaxis to neuromuscular blocking agents (NMBAs) is a rare event that is unpredictable and potentially life threatening. Most of the previous reports on such intraoperative anaphylaxis used market share surveys or self-reported data to estimate the incidence. Objective To determine the incidences of intraoperative anaphylaxis to NMBAs using electronic medical records. Design A retrospective observational study. Setting Two tertiary hospitals in South Korea. Patients This study involved patients exposed to NMBAs during anaesthesia between 1 January 2005 and 31 May 2014. Nineteen episodes were deemed to be intraoperative anaphylaxis to NMBAs. Main outcome measures We calculated the incidences of intraoperative anaphylaxis to NMBAs. Exposure to the agents was determined from intraoperative records maintained in an electronic medical recording system. An anaphylactic reaction was determined from both clinical signs and the results of skin tests. Results Over 9 years, 729 429 patients were exposed to NMBA, the most frequently used being rocuronium [425 047 (58.3%)] and vecuronium [274 801 (37.7%)]. The overall incidence of intraoperative anaphylaxis was 2.6 per 100 000 (19 cases), and was higher with rocuronium (16 cases, 3.8 per 100 000) than with vecuronium (two cases, 0.7 cases per 100 000), P = 0.014. Comparing the first 3 years with the last 6 years, the incidence of intraoperative rocuronium anaphylaxis appeared to increase 1.4-fold (P = 0.006). Conclusion Among commonly used NMBAs, rocuronium appears to have the highest incidence of anaphylaxis. Our findings suggest that future prospective investigation for NMBA-induced anaphylaxis should use internationally agreed skin test protocols.

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.

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 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.

The incidence trend of anaphylaxis in Asia is not well investigated. The aim of this study is to estimate the entire population-based incidence of anaphylaxis in Korea using a nationwide administrative database. Data over a 7-year period (2008–2014) was obtained from the Korean National Health Insurance (NHI) claims database which covers 97.9% of the entire Korean population. Using diagnosis codes from the International Classification of Diseases-10 for anaphylaxis (T78.0, T78.2, T80.5, and T88.6), we identified the annual number of patients who had visited any hospital with a primary diagnosis of anaphylaxis. Incidence rates were calculated using the population distribution data of all NHI beneficiaries. The incidence of anaphylaxis in Korea was 32.19 episodes per 100,000 person-years in 2014, which nearly doubled from 2008 (16.02 episodes per 100,000 person-years). The incidence of anaphylaxis increased continuously throughout these years regardless of gender and age groups (P for trend < 0.001). Female was significantly less predisposed than male (adjusted odds ratio [OR], 0.69; 95% confident interval [CI], 0.66–0.72; P