Soluble ACE2 and TMPRSS2 Levels in the Serum of Asthmatic Patients

Background@#Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics. @*Methods@#Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed. @*Results@#The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2. @*Conclusion@#The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.

Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma

Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma

Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Therapeutic Effects of Mesenchymal Stem Cells on a Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Model

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are the most severe cutaneous drug hypersensitivity reactions, which are unpredictable adverse drug reactions. SJS/TEN is associated with significant mortality and morbidity; however, effective treatment is difficult. Mesenchymal stem cells (MSCs) are well-known for their anti-inflammatory and tissue regeneration properties. The purpose of the present study was to verify whether MSCs could be applied for the treatment of SJS/TEN. We developed an SJS/TEN mouse model using peripheral blood mononuclear cells from a lamotrigine-induced SJS patient. MSCs were injected into the model to verify the treatment effect. In SJS model mice treated with MSCs, ocular damage rarely occurred, and apoptosis rate was significantly lower. We demonstrated a therapeutic effect of MSCs on SJS/TEN, with these cells presenting a potential novel therapy for the management of this disorder.

Evaluation of Drug-Induced Liver Injury Developed During Hospitalization Using Electronic Health Record (EHR)-Based Algorithm

PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm.METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI.RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13–0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction.CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.

High Prevalence of Asthma in Elderly Women: Findings From a Korean National Health Database and Adult Asthma Cohort

PURPOSE: The prevalence and burden of asthma is increasing worldwide. In this study, we analyzed 3 different Korean national health survey datasets to determine the general features of adult asthma in Korea and to obtain basic information that would support future strategies for better management of adult asthma. METHODS: The surveys used in this study included the Korea National Health and Nutrition Examination Survey (KNHANES), Korea Community Health Survey (KCHS) and National Health Insurance Service-National Sample Cohort (NHIS-NSC). We investigated annual asthma prevalence, evaluating the rate and risk factors of asthma exacerbation by age and sex, and clinical data of 1,832 patients with asthma who were registered in the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) were analyzed to elucidate risk factors for asthma exacerbation. We also analyzed another asthma cohort and added it as replication data. RESULTS: In the KNHANES database, annual asthma prevalence rates varied from 1.2% to 3.1%. In the KCHS database, overall prevalence increased, with significant regional differences (1.6%–2.1%). The NHIS-NSC indicated a gradual increase in annual asthma prevalence from 4.5% to 6.2%. Interestingly, all 3 surveys indicated the highest prevalence of asthma among elderly women. In addition, elderly women with asthma had a significantly higher risk of asthma exacerbation (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.19–2.93; P=0.006). Approximately 11% of patients were classified as having severe asthma. An asthma cohort analysis identified female sex, low baseline pulmonary function, longer treatment duration, high variability in pulmonary function and significant changes in Asthma Control Test scores as risk factors for asthma exacerbation. CONCLUSIONS: The prevalence of asthma in Korea is consistently high among elderly and female populations. These results should lay the foundation for strategies for effective asthma prevention and management; elderly female patients with asthma should receive particular attention.

The virtual asthma guideline e-learning program: learning effectiveness and user satisfaction

BACKGROUND/AIMS: Effective educational tools are important for increasing adherence to asthma guidelines and clinical improvement of asthma patients. We developed a computer-based interactive education program for asthma guideline named the Virtual Learning Center for Asthma Management (VLCAM). We evaluated the usefulness of program in terms of its effects on user awareness of asthma guideline and level of satisfaction. METHODS: Physicians-in-training at tertiary hospitals in Korea were enrolled in a cross-sectional questionnaire survey. The e-learning program on asthma guideline was conducted over a 2-week period. We investigated changes in the awareness of asthma guideline using 35-item self-administered questionnaire aiming at assessing physicians' knowledge, attitude, and practice. Satisfaction with the program was scored on 4-point Likert scales. RESULTS: A total of 158 physicians-in-training at six tertiary hospitals completed the survey. Compared with baseline, the overall awareness obtained from the scores of knowledge, attitude, and practice was improved significantly. Participants were satisfied with the VLCAM program in the following aspects: helpfulness, convenience, motivation, effectiveness, physicians' confidence, improvement of asthma management, and willingness to recommend. All items in user satisfaction questionnaires received high scores over 3 points. Moreover, the problem-based learning with a virtual patient received the highest user satisfaction among all parts of the program. CONCLUSIONS: Our computer-based e-learning program is useful for improving awareness of asthma management. It could improve adherence to asthma guidelines and enhance the quality of asthma care.

The transition of sputum inflammatory cell profiles is variable in stable asthma patients

BACKGROUND: The sputum inflammatory cell profile is an important indicator for classifying asthma phenotypes. OBJECTIVE: To investigate if sputum inflammatory cell profile remains stable and there are different characteristics between groups that show different profile over time in stable asthmatic patients. METHODS: A total of 149 asthmatic patients, who were clinically stable at the time of sputum examination and had undergone sputum analysis twice, were subjected to a detailed review. Eosinophilic inflammation was diagnosed when the proportion of the sputum eosinophils was >3%. We divided the patients into 4 groups according to the transition patterns of their sputum profiles: group 1, persistent eosinophilia; group 2, eosinophilic to noneosinophilic; group 3, noneosinophilic to eosinophilic; and group 4, persistent noneosinophilia. The results of the pulmonary function tests and other clinical parameters were compared between these 4 groups. RESULTS: Thirty-four of the initially eosinophilic asthmatic patients (39.5%; 34 of 86 patients) demonstrated noneosinophilic airway inflammation at their second sputum examination, and 24 of the initially noneosinophilic patients (38.1%; 24 of 63 patients) demonstrated eosinophilic airway inflammation at follow-up. Various clinical parameters, except the blood eosinophil count, demonstrated no significant differences between the eosinophilic and noneosinophilic asthmatic patients or among the 4 groups. CONCLUSION: A substantial proportion of asthmatic patients who demonstrate a certain sputum inflammatory cell profile at the initial examination demonstrated profile transition in clinically stable settings over time. The clinical significance of using induced sputum analysis to phenotype stable asthmatic patients requires further evaluation.

Palonosetron-Induced Anaphylaxis During General Anesthesia: A Case Report

Palonosetron is a 5-hydroxytryptamine-3 (5-HT-3) receptor antagonist used for preventing postoperative nausea and vomiting. Compared with ondansetron and granisetron, it is a better drug because of prolonged action and minimal side effects. Some adverse effects of palonosetron have been reported. In this report, we describe a 37-year-old male who developed severe hypersensitivity reactions to palonosetron during surgery for kidney donation. His medical history was unremarkable, except for inguinal hernia with herniorrhaphy 8 years ago. The surgery was uneventful until 2 hours 20 minutes. After palonosetron injection, his blood pressure dropped to 80/50 mm Hg, and facial edema, rash, conjunctival swelling, and wheezing developed. The patient was resuscitated by administration of ephedrine, hydrocortisone, and peniramine. Following the surgery, the patient was monitored for 3 days, and there were no subsequent anaphylactic reactions or other complications. The skin test on postoperative day 54 was positive for hypersensitivity to palonosetron. Although palonosetron is known for its safety, other hypersensitivity events have been reported. Ondansetron is another widely used 5-HT-3 antagonist, which has been reported to cause anaphylaxis. Therefore, clinicians should be aware of the possibility of patients experiencing severe adverse reactions to palonosetron.

hMSCs suppress neutrophil-dominant airway inflammation in a murine model of asthma

Although chronic eosinophilic inflammation is a common feature in patients with asthma, some patients have neutrophil-dominant inflammation, which is known to be associated with severe asthma.Human mesenchymal stem cells (hMSCs) have shown promise in treating various refractory immunological diseases. Thus, hMSCs may represent an alternative therapeutic option for asthma patients with neutrophil-dominant inflammation, in whom current treatments are ineffective. BALB/c mice exposed to ovalbumin and polyinosinic:polycytidylic acid (Poly I:C) to induce neutrophilic airway inflammation were systemically treated with hMSCs to examine whether the hMSCs can modulate neutrophilic airway inflammation. In addition, cytokine production was evaluated in co-cultures of hMSCs with either anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asthmatic patients or cells of the human bronchial epithelial cell line BEAS-2B to assess the response to hMSC treatment. The total number of immune cells in bronchoalveolar lavage fluid (BALF) showed a dramatic decrease in hMSC-treated asthmatic mice, and, in particular, neutrophilic infiltration was significantly attenuated. This phenomenon was accompanied by reduced CXCL15 production in the BALF. BEAS-2B cells co-cultured with hMSCs showed reduced secretion of IL-8. Moreover, decreased secretion of IL-4, IL-13 and IFN-γ was observed when human PBMCs were cultured with hMSCs, whereas IL-10 production was greatly enhanced. Our data imply that hMSCs may have a role in reducing neutrophilic airway inflammation by downregulating neutrophil chemokine production and modulating T-cell responses.

Rapid-onset of severe tigecycline-induced coagulopathy in drug reaction with eosinophilia and systemic symptom syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome-also known as drug-induced hypersensitivity syndrome-is an uncommon disease entity that manifests as fever, skin rash, blood cell abnormalities, lymphadenopathy, and often coagulopathy. Tigecycline is an antibiotic that is selectively used to treat complicated intra-abdominal and soft-tissue infections. Recently, a few cases of tigecycline-induced coagulopathy have been reported. Herein, we report a case of tigecycline-induced coagulopathy in a patient with DRESS syndrome. Both prothrombin time and activated partial thromboplastin time were abruptly exceeded beyond 180 seconds on day 6 of tigecycline treatment and normalized after discontinuation of tigecycline.

Immediate-type hypersensitivity response to systemic hydrocortisone sodium succinate

Immediate-type hypersensitivity responses to systemic corticosteroids are rare despite their widespread use. It is still controversial whether the responses rarely occur or are underdiagnosed in clinical settings. Many cases probably remain underdiagnosed because the symptoms often mimic symptoms of underlying diseases. This case report describes a 73-year-old man who had immediate hypersensitivity reactions after intravenous administration of hydrocortisone, which was primarily intended to prevent hypersensitivity reactions to contrast media. Whole body rash with pruritus developed shortly after the steroid injection. Since the patient already experienced rash and itching sense after contrast media and antihistamine injection, we conducted skin testing to figure out which drug triggered the hypersensitivity reactions. Intradermal skin tests revealed a positive response to hydrocortisone sodium succinate, which suggested his hypersensitivity reactions were developed by hydrocortisone. Being a common therapy for allergic reaction, corticosteroids themselves are rarely suspected of causing hypersensitivity reactions. Considering there is no typical symptom or standard diagnostic test, awareness of corticosteroid hypersensitivity reactions is of importance to make the diagnosis.

Factors Affecting Recovery Time of Pulmonary Function in Hospitalized Patients With Acute Asthma Exacerbations

PURPOSE: Prolonged recovery time of pulmonary function after an asthma exacerbation is a significant burden on asthmatics, and management of these patients needs to be improved. The aim of this study was to evaluate factors associated with a longer recovery time of pulmonary function among asthmatic patients hospitalized due to a severe asthma exacerbation. METHODS: We retrospectively reviewed the medical records of 89 patients who were admitted for the management of acute asthma exacerbations. The recovery time of pulmonary function was defined as the time from the date each patient initially received treatment for asthma exacerbations to the date the patient reached his or her previous best FEV1% value. We investigated the influence of various clinical and laboratory factors on the recovery time. RESULTS: The median recovery time of the patients was 1.7 weeks. Multiple linear regression analysis revealed that using regular inhaled corticosteroids (ICS) before an acute exacerbation of asthma and concurrent with viral infection at admission were associated with the prolonged recovery time of pulmonary function. CONCLUSIONS: The prolonged recovery time of pulmonary function after a severe asthma exacerbation was not shown to be directly associated with poor adherence to ICS. Therefore the results indicate that an unknown subtype of asthma may be associated with the prolonged recovery of pulmonary function time after an acute exacerbation of asthma despite regular ICS use. Further prospective studies to investigate factors affecting the recovery time of pulmonary function after an asthma exacerbation are warranted.

Transient global amnesia associated with toxocariasis and secondary hypereosinophilia

Toxocariasis is an important cause of secondary hypereosinophilia in Korea. Here, we describe a rare case of toxocariasis presenting as transient global amnesia due to secondary hypereosinophilia. A 44-year-old male visited the Emergency Department (ED) for transient global amnesia. He ate raw cow liver and omasum 2 weeks before the ED visit. The initial peripheral blood eosinophil count was 15,250/µL and serologic test for serum specific IgG antibodies to Toxocara canis larval antigen was positive. Radiologic studies revealed multiple small embolic infarctions of brainwithout cardioembolic sources or vascular abnormalities. He was treated with systemic corticosteroid, and neither neurologic deficit nor motor deficit was left. In our current case, the patient have a history of frequently eating raw cow liver and omasum, and his total IgE level was extremely high (>5,000 IU/mL). Thus, the patient was diagnosed as having toxocariasis and secondary hypereosinophilia. Toxocariasis should be considered in the differential diagnosis in patients with eosinophilia and atypical neurologic symptoms, such as transient amnesia.

S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress

Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2-nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-β (TGF-β)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-β-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma.

Heart transplantation in a patient with eosinophilic granulomatosis with polyangiitis known as Churg-Strauss syndrome

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a rare systemic necrotizing vasculitis affecting small- to medium-sized vessels. EGPA is associated with severe asthma and eosinophilia. The most frequently involved organs are skin and peripheral nerves; however, EGPA may involve other organs, such as the gastrointestinal tract, kidney, and heart. Antineutrophil cytoplasm antibodies (ANCAs)-related abnormal immune reactions are known to be associated with EGPA, but only 30%-40% of patients have a positive marker of ANCA. ANCA-negative patients are at higher risk of cardiac involvement than ANCA-positive patients. Cardiac involvement is one of the leading causes of mortality and could be resistant to conventional treatment. Early treatment with steroid plus cyclophosphamide is important because it could give chances of restoration of cardiac function. For patients undergoing heart transplantation, we should consider the severity of cardiac disease and the presence of systemic diseases, including vasculitis. Here, we report a case of a 25-year-old EGPA patient with cardiac involvement who eventually received heart transplantation for progressive heart failure, although treated with systemic corticosteroid with cyclophosphamide. EGPA patients undergoing heart transplantion are rarely reported worldwide, and this is the first case report in Korea.

Clinical Factors Affecting Discrepant Correlation Between Asthma Control Test Score and Pulmonary Function

The Asthma Control Test (ACT) score is widely used in asthma clinics, particularly with the recent emphasis on achievement and maintenance of optimal asthma control. However, this self-assessment score does not always correspond with lung function parameters, leading to uncertainty about each patient's control status; therefore, we investigated the clinical characteristics that are associated with discrepant correlation between the ACT score and pulmonary function. The 252 adult asthmatic subjects were divided into 5 groups according to their changes in FEV1% predicted values and ACT scores between 2 consecutive visits three months apart. The data were retrospectively reviewed and several clinical variables were compared. Elderly, non-eosinophilic, non-atopic asthma patients were more likely to show paradoxical changes of pulmonary function and ACT score. Female patients were prone to report exaggerated changes of ACT score compared with baseline lung function and changes in FEV1 levels. This group was using more medications for rhinosinusitis. Male patients seemed less sensitive to changes in lung function. From these findings, we conclude that when assessing asthma control status, physicians should carefully consider patient age, gender, atopy status, blood eosinophil levels, and comorbidities along with their ACT scores and pulmonary function test results.

Pholcodine consumption and immunoglobulin E-sensitization in atopics from Australia, Korea, and Japan

BACKGROUND: Accumulating data indicates that pholcodine (PHO)-consuming countries have higher sero-prevalences of immunoglobulin E (IgE)-antibodies to PHO and suxamethonium (SUX) and increased frequencies of IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBAs) than nonconsuming. Withdrawing PHO-containing cough syrups resulted in a significant decrease of cases with anaphylaxis in Scandinavia. Nevertheless, the European Medicines Agency in 2011 advised to continue the unrestricted use throughout the European Union. OBJECTIVE: To extend studies on PHO consumption and prevalence of IgE-sensitization to morphine (MOR), PHO, and SUX to countries representing high (Australia), and low (Korea and Japan), consumers, respectively. METHODS: IgE-antibodies to SUX, MOR, and PHO in atopic subjects were determined by immunoassay and compared with official figures for PHO consumption and reported anaphylaxis to NMBA. RESULTS: The prevalences of IgE-antibodies to PHO, MOR, and SUX were 10%, 8.6%, and 4.3%, respectively, in Australia. The corresponding figures for Japan were 0.8%, 0.8%, and 1.5%, and for Korea 1.0% to PHO and 0.5% to MOR and SUX. Of the SUX-positive sera, 100% were positive to PHO or MOR in Australia and 0% in Japan and Korea. CONCLUSION: The study supports previous findings; exposure to PHO may induce IgE-antibodies to the substituted ammonium ion epitope of NMBAs, thus increasing risk of NMBA-induced anaphylaxis considerably. However, other, still unknown factors occasionally might induce IgE-antibodies to SUX.

Rapid onset of Stevens-Johnson syndrome and toxic epidermal necrolysis after ingestion of acetaminophen

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but life-threatening, severe cutaneous adverse reactions most frequently caused by exposure to drugs. Several reports have associated the use of acetaminophen with the risk of SJS or TEN. A typical interval from the beginning of drug therapy to the onset of an adverse reaction is 1-3 weeks. A 43-year-old woman and a 60-year-old man developed skin lesions within 3 days after administration of acetaminophen for a 3-day period. Rapid identification of the symptoms of SJS and TEN caused by ingestion of acetaminophen enabled prompt withdrawal of the culprit drug. After administration of intravenous immunoglobulin G, both patients recovered fully and were discharged. These two cases of rapidly developed SJS/TEN after ingestion of acetaminophen highlight the possibility that these complications can develop within only a few days following ingestion of over-the-counter medications such as acetaminophen.

Reference Ranges and Determinant Factors for Exhaled Nitric Oxide in a Healthy Korean Elderly Population

PURPOSE: Exhaled nitric oxide (NO) is a useful non-invasive biomarker for asthma diagnosis; however, the literature suggests that exhaled NO levels may be affected by demographic factors. The present analysis investigated determinant factors that present exhaled NO reference levels for Korean elderly adults. METHODS: For reference levels, we analyzed the baseline data of healthy adult participants in the Ansung cohort. The fraction of exhaled NO (FeNO) was measured by NIOX MINO(R). The characterization of the subjects was performed through structured questionnaires, spirometry, and methacholine challenge tests. To validate the diagnostic utility of the determined reference levels, asthma patients were recruited from medical institutions for FeNO measurement. RESULTS: A total of 570 healthy subjects were analyzed (mean age, 59.9+/-12.3; male, 37.0%) for reference levels. FeNO levels significantly correlated with weight, height, body mass index, atopy, or forced expiratory volume in 1 second % predicted by simple linear regression analysis. Multiple linear regression analysis identified gender as an independent determinant for FeNO levels; subsequently, the reference values for FeNO were 18.2+/-10.6 ppb (5th to 95th percentile, 6.0 to 37.4 ppb) for males and 12.1+/-6.9 ppb (5th to 95th percentile, 2.5 to 27.0 ppb) for females. The diagnostic utility of FeNO reference levels was validated by receiver operating curve analysis (area under curve, 0.900 for males and 0.885 for females) for diagnosing asthma. The optimal cutoff values for the prediction of asthma were 30.5 ppb for males and 20.5 ppb for females. CONCLUSIONS: The current analysis presented reference ranges and the diagnostic utility of FeNO levels for asthma in Korean elderly adults.