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Background Laryngeal or vocal cord dysfunction has long been regarded as a mimic of asthma; however, recent evidence indicates that it may be a significant comorbid condition in patients with asthma. Objective We aimed to systematically estimate the prevalence of comorbid laryngeal dysfunction (LD) in adults with asthma and characterize its clinical impact on asthma. Methods Electronic databases were searched for relevant studies published until June 2019. Studies were included if LD was objectively defined by direct visualization of laryngeal movement. Outcomes included the prevalence of LD and its association with clinical asthma indicators, such as severity, control, and quality of life. Random effects meta-analyses were performed to calculate the estimates. Results A total of 21 studies involving 1637 patients were identified. Overall, the pooled prevalence of LD in adults with asthma was 25% (95% CI = 15%-37%; I2 = 96%). Prevalence estimates differed according to the diagnostic test utilized, with the lowest overall prevalence (4% [95% CI = 0%-10%; I2 = 90%]) seen when LD was diagnosed by resting laryngoscopy without external stimuli; however, it was much higher when diagnosed by laryngoscopy studies utilizing an external trigger, such as exercise (38% [95% CI = 24%-53%; I2 = 90%]) or in studies using a computed tomography–based diagnostic protocol (36% [95% CI = 24%-49%; I2 = 78%]). Only 7 studies reported the associations between LD and clinical asthma indicators; inconsistencies between studies limited meaningful conclusions. Conclusion LD may be a common comorbidity in asthma, affecting about 25% of adult patients. Further prospective studies are needed to better characterize its clinical impact and the benefits of detecting and managing LD in patients with asthma.

BACKGROUND: Despite the construction of the metagenome of the asthmatic lung, limitations persist in sampling the bronchial airway. This study analyzed extracellular vesicles (EVs) obtained from exhaled breath condensate (EBC) to compare the distinct characteristics of the microbiome in asthmatics with those in healthy controls and proposed a diagnostic artificial intelligence-based model of asthma. METHODS: We obtained the EBC from 58 healthy controls and 251 patients with asthma. EVs were isolated from the EBC and analyzed. The extracted 16s rDNA was subjected to next generation sequencing. Taxonomic profiling was conducted for all samples at the genus level. A combination of artificial neural network (ANN) and gradient boosting (GBM) was applied to selective EBC biomarkers. RESULTS: The asthma group exhibited significantly higher alpha diversity based on the results of the Chao1, Shannon, and Simpson indices. The bacterial composition of patients with asthma different from that of the controls. At the genus level, Sphingomonas, Akkermansia, Methylophaga, Acidocella, and Marinobacter were significantly more abundant in patients with asthma. The diagnostic model using GBM and ANN demonstrated good performance with respective areas under the curve of 0.832 and 0.769. Firmicutes and Proteobacteria at the phylum level were common important features between the GBM and ANN asthma models. CONCLUSION: We demonstrated a distinct pattern in the microbiome of patients with asthma, indicating the potential role of microbiome-based diagnosis of asthma. To the best of our knowledge, this was the first study to identify the microbiome in asthma using EBC-derived EVs.

Background Hypersensitivity reactions to iodinated contrast media (ICM) is a persistent clinical issue with increased use of computed tomography. With the evidence indicating underlying allergic mechanisms, there have been studies regarding the skin tests using ICM. Objective This study aimed to evaluate the intradermal skin test (IDT) as a tool for preventing recurrent hypersensitivity reactions to ICM in patients with prior reactions to a known culprit agent. Methods Sixty-nine patients who had experienced immediate hypersensitivity reactions to ICM were included in the study. All patients underwent IDT with 7 different ICMs, including the causative ICM. We analyzed clinical data from 38 patients who were reexposed to ICMs, grouped by the IDT results to their original culprit ICM. Results Thirty-eight patients showed positive IDT results to the culprit ICM (CULPRIT+), whereas 31 patients showed negative results (CULPRIT−). Sixteen patients from the CULPRIT+ group and 22 from the CULPRIT− group were subsequently exposed to an ICM. In the CULPRIT+ group, 4 of the 5 patients who were subsequently exposed to an IDT-positive ICM reexperienced hypersensitivity reactions. When patients were exposed to IDT-negative ICM as an alternative, hypersensitivity reactions were not observed. In the CULPRIT− group, IDT-positive ICMs did not provoke hypersensitivity reactions whereas 2 patients using IDT-negative ICMs experienced hypersensitivity reactions. Conclusions When the IDT results are positive for the culprit ICM, additional IDTs with other ICMs are needed to select a safe alternative. If the IDT results are negative against the culprit ICM, further IDTs might not play a role in selecting a safe alternative.

Background Current asthma guidelines recommend stepping down controller treatment when the condition is well-controlled for a certain time. However, the optimal step-down strategy for well-controlled patients receiving a low-dose inhaled corticosteroid (ICS) with a long-acting β2-agonist (LABA) remains unclear. Objective This study was a randomized, open-label, three-arm, parallel pragmatic trial comparing two kinds of step-down approaches for maintaining treatment. Methods Adults with asthma who were aged 18 years or older, and who had been stable with low-dose ICS/LABA for at least 3 months, were enrolled. Subjects (n = 225) were randomly allocated into one of three groups (maintaining low-dose ICS/LABA [G1], discontinuing LABA [G2], and reducing ICS/LABA to once daily [G3]), and were observed for 6 months. The primary end point was a change in Asthma Control Test (ACT) scores between randomization and the final 6-month follow-up. Results The change in ACT was analyzed in the per-protocol population; noninferiority was not demonstrated in either step-down group compared with the maintenance group (95% confidence interval of the difference, G2 vs G1 = –1.40-0.55; G3 vs G1 = –1.19-0.77). Although over 90% of patients were fine, higher rates of treatment failure were observed in step-down groups (G1: 0%; G2: 9.46%; and G3: 9.09%; P = .027). There were no significant differences between step-down approaches in terms of ACT change or treatment failure. Conclusions Both step-down methods were not noninferior to maintenance of treatment. Step-down therapy can be attempted when patients are stable, but appropriate monitoring and supervision are necessary with precautions regarding loss of disease control.

Background Although inhaled corticosteroids (ICSs) are the recommended first-line therapy for asthma, determining whether to continue or discontinue ICS treatment in patients with mild asthma remains challenging for clinicians. Several studies have revealed that patients with mild-persistent asthma maintained a well-controlled state after ICS withdrawal. However, the long-term outcomes of ICS withdrawal have not yet been determined. Objective To determine the possible clinical outcomes of the discontinuation of ICS in patients with well-controlled mild asthma. Methods We investigated the clinical outcomes of discontinuing ICSs in patients with well-controlled mild asthma and compared the time to loss of control (LOC) between patients who stopped ICS treatment (ICS withdrawal group, IWG) and those who continued treatment for 3 years (continuous ICS group, CIG). Results A significant difference in the time to LOC was observed between the IWG and CIG (hazard ratio, 2.56; 95% confidence interval, 1.52-4.33; P Conclusion Our results suggest that the maintenance of ICS treatment may help keep patients’ asthma under control. Furthermore, patients with LOC had significantly higher sputum eosinophil counts in the CIG than those in the non-LOC group. Therefore, continuous ICS use by patients with mild, well-controlled asthma could be associated with good clinical outcomes. Trial Registration ClinicalTrials.gov Identifier: KCT0002234.

Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma.To investigate the association between serum progranulin levels and various clinical features in patients with asthma.Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma.Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P.001) after adjustment for other variables, such as age, sex, smoking status, blood neutrophil count, and current use of systemic corticosteroids.Although the exact mechanism of the anti-inflammatory action of progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma.

Background Although the incidence of anaphylaxis is rapidly increasing, the clinical characteristics and associated factors of a biphasic reaction are unclear. Objective To determine the incidence and clinical characteristics of biphasic reactions in patients with anaphylaxis treated with corticosteroids. Methods A total of 655 patients with anaphylaxis visiting the emergency department of a tertiary teaching hospital from January 2007 through December 2014 were analyzed. Patient characteristics, triggers, symptoms and signs, in-hospital management, and disposition were recorded. A biphasic reaction was defined as the development of anaphylaxis after complete resolution of the initial reaction without further exposure to the offending agent within 7 days. Univariate and multivariate analyses on the predictors of the biphasic reaction were performed. Results Of the 415 patients with anaphylaxis treated with corticosteroids, 9 patients (2.2%) developed a biphasic reaction. The mean age was 48.4 years, and 221 patients (54.4%) were women. The median time from complete resolution of initial clinical symptoms to occurrence of the biphasic reaction was 15 hours (range 1–45). History of drug anaphylaxis (odds ratio 14.3, 95% confidence interval 2.4–85.8) was a contributing factor to the development of the biphasic reaction. Conclusion The incidence of biphasic reactions was 2.2% in patients treated with corticosteroids and those with a history of drug anaphylaxis were at greater risk.

Background No attempt has yet been made to classify asthma phenotypes in the elderly population. It is essential to clearly identify clinical phenotypes to achieve optimal treatment of elderly patients with asthma. Objectives To classify elderly patients with asthma by cluster analysis and developed a way to use the resulting cluster in practice. Methods We applied k-means cluster to 872 elderly patients with asthma (aged ≥65 years) in a prospective, observational, and multicentered cohort. Acute asthma exacerbation data collected during the prospective follow-up of 2 years was used to evaluate clinical trajectories of these clusters. Subsequently, a decision-tree algorithm was developed to facilitate implementation of these classifications. Results Four clusters of elderly patients with asthma were identified: (1) long symptom duration and marked airway obstruction, (2) female dominance and normal lung function, (3) smoking male dominance and reduced lung function, and (4) high body mass index and borderline lung function. Cluster grouping was strongly predictive of time to first acute asthma exacerbation (log-rank P = .01). The developed decision-tree algorithm included 2 variables (percentage of predicted forced expiratory volume in 1 second and smoking pack-years), and its efficiency in proper classification was confirmed in the secondary cohort of elderly patients with asthma. Conclusions We defined 4 elderly asthma phenotypic clusters with distinct probabilities of future acute exacerbation of asthma. Our simplified decision-tree algorithm can be easily administered in practice to better understand elderly asthma and to identify an exacerbation-prone subgroup of elderly patients with asthma.

Background Unbiased cluster analysis has identified several asthma phenotypes. However, these phenotypes did not consistently predict disease prognosis and reflect temporal variability in airway inflammation. Objective We aimed to identify longitudinal trajectories in terms of pulmonary function parameters and investigated whether the trajectories are associated with prognosis. Methods Data were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). Three-year pulmonary function test results were used to apply finite mixture models for group-based trajectory in 486 patients with eligible data set. Results Two main sets of longitudinal trajectories were identified in terms of FEV1% predicted, and FEV1 variability. In the 4 trajectories determined with FEV1% predicted, the pulmonary function showed a consistent course in 4 stratified levels during 3 years of follow-up, which was associated with unexpected hospital visits and the use of steroid bursts due to exacerbation. The variability in pulmonary function showed 3 different patterns, and we found that higher blood and sputum eosinophil levels were associated with the higher variability in pulmonary function and more exacerbations. Conclusions Trajectory analysis is a novel method that provides longitudinal asthma phenotypes and aids in prediction of future risk of exacerbation. Further analysis is needed to validate the usefulness of these trajectories in an independent population.

Background Severe hypersensitivity reactions (HSRs) interfere with the administration of necessary drugs for patients; drug desensitization can be a good alternative strategy. Although rapid drug desensitization (RDD) has been shown to be safe and effective, some patients still experience breakthrough reactions (BTRs) during desensitization. Objective We aimed to estimate clinical outcomes of RDD and to identify risk factors for BTR. Methods From January 2015 to December 2017, retrospective analysis was done in cancer patients with HSRs to chemotherapy and monoclonal antibody who underwent 3-bag, 12-step RDD in Asan Medical Center. Results A total of 58 patients (42 females; mean age, 54.7 ± 11.0) underwent 234 desensitization procedures. The most common underlying malignancy was gynecologic cancer (n = 26, 44.8%), and platinum-based drugs were common target drugs (135 cases of 36 patients). Twenty-six of 58 patients (44.8%) experienced 56 BTRs, whereas 178 cases (76.1%) of total desensitization did not show any reactions. Among them, 12 patients (20.7%) had moderate BTRs requiring systemic steroids, and 3 (5.1%) experienced severe BTRs requiring epinephrine administration. Logistic regression analysis revealed more severe initial HSRs (OR = 17.94, 95% CI = 1.78-181.68, P = .015), drug allergy history (OR = 7.83, 95% CI = 1.48-41.44, P = .035), and frequency of exposure to the chemotherapeutic agents (OR = 1.14, 95% CI = 1.01-1.28, P = .016) increased the risk of moderate to severe BTR. Conclusion The standardized 12-step protocol for RDD was effective and safe for most patients. Severity of initial HSR, history of drug allergy, and previous high exposure to the chemotherapeutic agent showed a positive correlation with BTR above moderate grade. Studies are needed to propose an individualized protocol according to patient-specific risk assessment.

Background Staphylococcus aureus (SA) is a frequent colonizer in humans, and it is known to be associated with chronic allergic diseases including asthma. Recent individual studies suggested that nasal SA colonization may be positively associated with asthma. Objective To examine relationships between nasal SA colonization and asthma prevalence and activity in adults. Methods Electronic databases were searched for studies published until June 2018. Studies that reported nasal SA colonization prevalence and asthma outcome (prevalence and disease activity) in general adult populations or patients with chronic rhinosinusitis (CRS) were included. Random effects meta-analyses were performed to calculate pooled odds ratio (OR) of the relationships. Subgroup analysis was conducted for the presence of nasal polyps within CRS populations. Results A total of 21 cross-sectional studies were identified, and the data from 16 studies using culture methods for SA detection were meta-analyzed (5 general population-based studies and 11 studies of patients with CRS). In studies of general populations, nasal SA colonization had significant relationships with asthma prevalence (OR 1.19; 95% confidence interval [CI] 1.06-1.34; I2 = 1%). In studies of patients with CRS, positive associations were also found but had a considerable heterogeneity (OR 1.87; 95% CI 1.18-2.97; I2 = 72%). However, the results were comparable between CRS with and without nasal polyps. Conclusions This study demonstrated modest but significant relationships between nasal SA colonization and asthma, supporting potential roles of SA in adult patients with asthma. Further longitudinal cohort and intervention studies are warranted to identify host determinants and to clarify causality of the relationships.

A correlation model between tyrosinase inhibitory activities and HPLC chromatograms of Morus alba root bark extracts was calibrated and validated. The correlational approach has been suggested as an alternative technique for quality control and study of natural products. However, this method requires a large number of various samples with similar chemical compositions. In the present study, 42 different extracts were obtained from 6 samples of M. alba root bark under 7 different extraction solvent conditions using an automated pressurized liquid extraction system. HPLC chromatograms and mushroom tyrosinase inhibitory activities of these extract samples were obtained, and the chromatograms were preprocessed with asymmetric least square smoothing and correlation optimized warping algorithms. The partial least squares (PLS) regression model between the preprocessed chromatograms and the bioactivities of samples was created. The full cross validations were performed by changing the selection method of the test sets; plant sample based, extraction method based validation set selections were used for the validation tests. In both validation tests, the PLS models showed excellent performance of prediction. The predictive models showed averagely RMSEP of 9.4309 and R2 values of 0.8717 in the validation test based on plant samples, and RMSEP of 8.1541 and R2 values of 0.8778 in the validation test based on extraction methods. Additionally, an estimation of the bioactive component was made from the regression coefficient, and the result of the estimation was similar to the experimental results of reference papers.

Diarylheptanoids have been the center of the intensive research efforts for Alzheimer's disease and other neurodegenerative diseases. The present study aimed to determine the effect of the standardized extract of B. platyphylla bark and its major diarylheptanoids in scopolamine-induced amnesic mice through cyclic AMP response element-binding protein (CREB) activation. Oral administration of the standardized extract of B. platyphylla bark (100 mg/kg body weight), aceroside VIII (1 mg/kg body weight) and platyphylloside (1 or 2 mg/kg body weight) significantly ameliorated scopolamine-induced amnesia in passive avoidance test. CREB phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the cortex and hippocampus of the scopolamine-treated mice were markedly increased by the treatment of the standardized extract of B. platyphylla bark and platyphylloside. The standardized extract of B. platyphylla bark and its major diarylheptanoids also significantly protected HT22 cells against neurotoxicity induced by glutamate insult. The standardized extract of B. platyphylla bark and platyphylloside may ameliorate memory deficits by activating the CREB–BDNF pathway and prevent a neurodegeneration by inhibiting neuronal cell death.

(−)-Idescarparide, a new spiro compound possessing a tetrahydrobenzodioxole structure from the fruit of Idesia polycarpa Maxim. was identified to be a dimer of (−)-idescarpin by spectroscopic analysis. The absolute configuration of (−)-idescarpin was firstly determined to be of S form by using single-crystal X-ray diffraction. The absolute configuration of (−)-idescarparide was confirmed by comparison with semi-synthetic (−)-idescarparide, achieved via triethylamine-catalyzed dimerization of (−)-idescarpin. (−)-Idescarparide significantly reduced lipid production in 3T3-L1 cells.

The methanolic extract of the bark of Betula platyphylla was found to suppress antigen mediated degranulation of RBL-2H3 cells. Four arylbutanoids ( 1 – 4 ) and eight diarylhepatonoids ( 5 – 12 ) were isolated from the methanolic extract using bioassay-guided fractionation. Among them, compounds 4 and 12 were isolated and assigned for the first time. Compounds 1 , 2 , 3 , 5 , 10 , and 12 showed remarkable inhibitory activity against the degranulation of RBL-2H3 by antigen stimulation in a dose dependent manner at the concentrations ranging from 10 μM to 100 μM.

Background The exact pathogenic role of oxidative stress in the development of allergic airway inflammation is still largely unknown. Objective To investigate a possible link between increased pulmonary oxidative stress and the pivotal features of asthma during the mounting of an allergic inflammatory response. Methods To determine the relationship between oxidative stress and allergic inflammatory responses, we evaluated the sequential kinetics of oxidative stress in the lung, the development of airway inflammation, mucin hypersecretion, and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)–sensitized and challenged mouse with and without antioxidant. Parameters were measured at 9 points for more than 28 days, starting from the first day of OVA challenge with or without antioxidant treatment. The ratio of reduced to oxidized glutathione in the lungs and levels of intracellular reactive oxygen species (ROS) in the bronchial epithelium were serially measured. Bronchoalveolar lavage fluid cells, histopathologic features, and AHR were analyzed at the same time points. Results The reduced to oxidized glutathione ratio was reduced from immediately after OVA challenge to day 1, remained at this level until day 1, and rapidly recovered to the normal level after more than 2 days. Intracellular ROS levels in the bronchial epithelium followed similar kinetics. The inflammatory cells in bronchoalveolar lavage fluid reached a maximum of 3 days and decreased progressively thereafter. Histopathologic examination revealed that substantial airway inflammation persisted through day 28. The proportion of mucin-producing epithelial cells significantly increased after day 1, reached a maximum at day 3, and remained at this level until day 5. The AHR peaked on day 1 and normalized within 5 days. The pretreatment of antioxidant significantly reduced not only the increased ROS levels but also development of other phenotypes of asthma. Conclusion These results indicate that increased oxidative stress in the lung precedes other pivotal phenotypes of allergic airway disease, suggesting a critical role for increased oxidative stress in the induction of allergic airway inflammation.

Background Although asthmatic patients frequently smoke cigarettes, the effect of smoking on asthmatic lungs has not been extensively studied. Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathogenesis of asthma and emphysema. Objective To determine whether the level of airway VEGF might be related to emphysematous lung changes in asthmatic patients with a history of smoking. Methods Pulmonary function tests and volumetric computed tomography (CT) of the lungs were performed in 10 ex-smoking and 15 nonsmoking asthmatic patients. Levels of VEGF were evaluated in the supernatants of induced sputum using an enzyme-linked immunosorbent assay method in these 25 asthmatic patients and in 10 healthy nonsmoking controls. Associations among sputum VEGF levels, emphysema indices on CT, and clinical variables were analyzed. Results Ex-smoking asthmatic patients showed a higher emphysema index on volumetric CT and a decreased mean forced expiratory volume in 1 second to forced vital capacity ratio compared with nonsmoking asthmatic patients. Sputum VEGF levels in asthmatic patients with a history of smoking were significantly lower than those in nonsmoking asthmatic patients but remained higher than those in control subjects. Furthermore, the emphysema index was significantly correlated with sputum VEGF levels in asthmatic patients. Conclusion Lower VEGF levels in the airway might be a surrogate marker for emphysematous changes in the lungs, especially in asthmatic patients with a history of smoking.

A wear resistant Fe–Mn–Cr–Mo–V alloy cladding was deposited on SM45C (equivalent to AISI1045) substrate by automatic submerged arc welding using stoody 105 alloy wire. Microstructure and surface hardness of the cladding were investigated and measured on samples prepared under different welding conditions. The results showed that the retained austenite in the cladding increases with the increased welding current and reduced travel speed. The wear behavior of the clad was studied using ball-on-disk tribometer. Wear mechanism was analyzed based on the analysis of the worn surfaces both the clad and ball by scanning electron microscope (SEM) equipped with an energy dispersive spectrometer (EDS). The scanning electron microscopic examination of the worn surface shows that a layer of oxide film forms on the worn surface. Oxidation wear mechanism controls the wear process. The spalling of the oxide was caused by the repeated rubbing fatigue mechanism.

Background Fractional exhaled nitric oxide (FeNO) is widely used as an inflammatory marker for asthma. However, reference values and influencing factors of FeNO using Niox Mino, which is the only device achieving US FDA approval, are not well described in healthy Asian adults. This study aimed to suggest the reference values and influencing factors of FeNO in healthy Korean adults. Methods Subjects who were over 19 years old and did not have any history of rhinitis, asthma or recent respiratory symptoms were enrolled. FeNO levels were measured using Niox Mino. Age, gender, body mass index (BMI), smoking status and lung function were also measured to analyze factors associated with FeNO levels. Results The mean value of FeNO was 16.14 ± 10.04 ppb. The reference value of FeNO, which was defined as the value of 95% in distribution curve, was same or less than 34 ppb. In a univariate analysis, FeNO levels were not associated with age, BMI and smoking history. However, atopy status (18.2 ± 11.8 for atopy and 15.1 ± 8.5 for nonatopy groups, P = 0.008) and gender (17.8 ± 10.2 for male and 14.8 ± 9.8 for female groups, P < 0.001) were positively associated with FeNO levels. In stratified analysis, the significance of both variables remained unchanged (P < 0.001). Conclusions Our data suggested that the reference value of FeNO in healthy Korean adults seemed to be same or less than 34 ppb. Reference values of FeNO in Korean adults are influenced by gender and atopy status.

Background Liver is the second most commonly involved organ in drug-induced systemic hypersensitivity reactions (DiSH). Although liver function is very important indicator in the course of DiSH, there have been few studies about the characteristics of the liver injury. In present study, we investigated clinical characteristics of DiSH associated with liver injury (liver-DiSH) Methods We retrospectively reviewed medical records of 38 hospitalized patients who developed liver-DiSH (AST or ALT ≥80 IU/L) from January 2008 to February 2011 in a tertiary referral hospital. We analyzed culprit drugs, the type and degree of liver injury, and the effect of systemic corticosteroids. Fisher's exact test and Chi-square test and Mann-Whitney test were used for statistical analysis. Results Thirty-eight patients of liver-DiSH were enrolled, whose clinical phenotypes were Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (n = 9, 24%), drug reaction with eosinophilia and systemic symptoms (DRESS) (n = 23, 60%), maculopapular rash (MP rash) (n = 5, 13%) and acute generalized exanthematous pustulosis (AGEP) (n = 1, 3%). Antibiotics (n = 16/38, 41%) was the most common cause of liver-DiSH. Culprit agents of liver-DiSH were allopurinol (n = 3/9, 33%) in SJS/TEN and antibiotics (n = 13/23, 57%) in DRESS. Mortality tended to be higher in SJS/TEN than in DRESS (22% (2/9) vs 17% (4/23), P = 0.846). Degree of liver injury was statistically more severe in DRESS than in SJS/TEN (mean peak AST [423 IU/L vs 144 IU/L, P = 0.062], mean peak ALT [428 IU/L vs 156 IU/L, P = 0.013], mean peak ALP (alkaline phosphatase) [252 IU/L vs 85 IU/L, P = 0.002], mean total bilirubin [7.7 mg/dL vs 1.3 mg/dL, P = 0.064], and time required for AST/ALT to drop below 80 IU/L [15.8 days vs 4.1 days, P = 0.049]). Seventy-six percents (29/38) of patients were treated with systemic corticosteroid. The use of corticosteroid did not significantly affect both recovery of liver injury and mortality. Conclusions Our results suggest that liver-DiSH has distinguished clinical characteristics according to the disease phenotypes. Further studies are needed to evaluate the role of systemic corticosteroid in liver injury in DiSH.

U E S D A Y 787 Anaphylaxis in the Adult Population: Are We Following Current Treatment Guidelines? Yarden Yanishevsky, MD, Ann Elaine Clarke, MD, MSc, Sebastian La Vieille, MD, Scott Delaney, MD, Reza Alizadehfar, MD, Lawrence Joseph, PhD, Judy Morris, MD, Moshe Ben-Shoshan, MD, MSc; Division of Paediatric Allergy and Clinical Immunology, Department of Paediatrics, McGill University Health Center, Montreal, QC, Canada, Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada, Division of Allergy and Clinical Immunology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada, Food Directorate, Health Canada, Ottawa, ON, Canada, Department of Emergency Medicine, McGill University Health Center, Montreal, QC, Canada, Departments of Epidemiology and Biostatistics, McGill University, Montreal, Canada, Department of Emergency Medicine , Hopital du Sacr e-Coeur, Montreal, QC, Canada. RATIONALE: Curent guidelines (Simons E et el, J Allergy Clin Immunol. 2011:587-93) recommend that all anaphylactic reactions be treated with epinephrine and all cases of non-drug induced anaphylaxis be prescribed an epinephrine auto-injector (EAI). We aimed to assess anaphylaxis rate in an adult emergency department (ED) and determine if management adheres to current guidelines. METHODS: As part of the Cross-Canada Anaphylaxis REgistry (CCARE), charts of all ED visits to the Montreal General Hospital between March and July 2011 were reviewed to identify anaphylaxis cases. Cases were identified based on ICD 10 coding for either anaphylaxis or allergic reaction and only cases fitting the definition of anaphylaxis were included. RESULTS: Among 12,540 ED visits, 41 anaphylaxis cases [0.3 %, (95% CI 0.2%, 0.5%)] were identified. Median age was 35.2 years (IQR 26.5, 50.9) and 31.7% (95% CI 18.6%, 48.2%) were males. Food was responsible for 46.3% (31.0%, 62.4%) of reactions, drugs for 21.9% (11.1%, 38.0%) and venom for 4.9% (0.9%, 17.8%). In 26.83% (14.6%, 43.2%), the trigger was unidentified. Among all cases 53.7% (37.6%, 69.0%) were moderate (difficulty breathing/stridor/wheezing) or severe (hypoxia/cyanosis/circulatory collapse/incontinence/neurological symptoms). Prior to ED arrival, 13.3% (2.3%, 41.6%) of mild and 16.7% (4.4%, 42.3%) of moderate/severe reactions received epinephrine compared to 27.8% (10.7%, 53.6%) and 22.7% (8.7%, 45.8%) after arrival. In 65% (41.0%, 83.7%) of moderate/severe reactions, no epinephrine was given. In nondrug induced anaphylaxis, EAI were prescribed in only 58.06 % (39.3%, 74.9%). CONCLUSIONS: Given the striking underuse of epinephrine in anaphylaxis management, educational programs are required to better implement current guidelines.

Background Cephalosporin is one of the most commonly used beta-lactam antibiotics globally, and also a major offending agent of drug hypersensitivity along with penicillin. Cephalosporin skin test has been widely used in most hospitals in Korea. However, the validity of this test for prediction of immediate hypersensitivity has still not been well studied. Therefore, we conducted this study to determine the predictive validity of cephalosporin skin test prior to administration.