Incidence and Economic Burden of Adverse Drug Reactions in Hospitalization: A Prospective Study in Korea

Background@#Adverse drug reactions (ADRs) are escalating, and their socioeconomic burden is increasing. However, large-scale prospective studies investigating ADRs during hospitalization are rare in Korea. We prospectively investigated the incidence, characteristics, and economic burden of ADRs in hospitalized patients based on electronic medical records (EMRs). @*Methods@#Among patients admitted to three hospitals from October 2016 to October 2017, 5,000 patients were randomly selected and prospectively observed during hospitalization.Research nurses monitored and detected patients who had symptoms, signs, or laboratory findings suspicious for ADRs using an EMR-based detection protocol. Next, allergy and ADR specialists reviewed the medical records to determine the relationship between adverse reactions and drugs. Cases in which a causal relationship was certain, probable/likely, or possible were included in the ADR cases. Clinically meaningful ADR cases or those leading to prolonged hospitalization were defined as significant ADRs. @*Results@#ADRs occurred in 510 (10.2%) patients. The mean length of hospital stay was approximately 5 days longer in patients with ADRs. Opioids accounted for the highest percentage of total ADRs. Significant ADRs were observed in 148 (3.0%) patients. Antibiotics accounted for the highest percentage of significant ADRs. Drug hypersensitivity reactions (DHRs) occurred in 88 (1.8%) patients. Antibiotics accounted for the highest percentage of DHRs. The average medical expenses for one day of hospitalization per patient were highest in significant ADRs, followed by non-significant ADRs, and non-ADRs. @*Conclusion@#ADRs in hospitalized patients are an important clinical issue, resulting in a substantial socioeconomic burden. EMR-based strategy could be a useful tool for ADR monitoring and early detection.

Phenotype of Asthma-COPD Overlap in COPD and Severe Asthma Cohorts

Background@#Asthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. AsthmaCOPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype. @*Methods@#Patients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and postbronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL). @*Results@#The prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) – 9.1%; group B (light smoker with low BEC) – 3.7%; group C (moderate to heavy smoker with high BEC) – 73.8%; and group D (moderate to heavy smoker with low BEC) – 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups. @*Conclusion@#The prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.

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.

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.

Oxidative Stress Modulates the Expression Pattern of Peroxiredoxin-6 in Peripheral Blood Mononuclear Cells of Asthmatic Patients and Bronchial Epithelial Cells

PURPOSE: Reduction-oxidation reaction homeostasis is vital for regulating inflammatory conditions and its dysregulation may affect the pathogenesis of chronic airway inflammatory diseases such as asthma. Peroxiredoxin-6, an important intracellular anti-oxidant molecule, is reported to be highly expressed in the airways and lungs. The aim of this study was to analyze the expression pattern of peroxiredoxin-6 in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients and in bronchial epithelial cells (BECs).METHODS: The expression levels and modifications of peroxiredoxin-6 were evaluated in PBMCs from 22 asthmatic patients. Phosphorylated and acetylated peroxiredoxin-6 in hydrogen peroxide-treated human BECs was detected using immunoprecipitation analysis. The expression level of peroxiredoxin-6 was also investigated in BECs treated with hydrogen peroxide. Cycloheximide and proteasome inhibitors were used to determine whether peroxiredoxin-6 is degraded by proteasomes.RESULTS: Peroxiredoxin-6 expression was significantly reduced in the PBMCs of asthmatic patients compared to control subjects. Distinct modification patterns for peroxiredoxin-6 were observed in the PBMCs of asthmatic patients using 2-dimensional-electrophoresis. The levels of phosphorylated serine and acetylated lysine in peroxiredoxin-6 were significantly increased in the BECs following hydrogen peroxide treatment. The level of peroxiredoxin-6 expression was reduced in hydrogen peroxide-stimulated BECs, presumably due to proteasomes.CONCLUSIONS: The expression of peroxiredoxin-6, which is down-regulated in the immune cells of asthmatic patients and BECs, can be modified by oxidative stress. This phenomenon may have an effect on asthmatic airway inflammation.

Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles

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

Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles

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

Characteristics of Adult Severe Refractory Asthma in Korea Analyzed From the Severe Asthma Registry

PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.

Dilemma of Asthma Treatment in Mild Patients / 결핵

Inhaled corticosteroids (ICSs) have been widely used as a key medication for asthma control. However, ICSs have been known to cause respiratory infections, such as pneumonia and pulmonary tuberculosis. Consequently, a dilemma exists regarding recommendation of persistent lifetime use of ICSs to mild asthma patients. Short-acting β-agonists (SABAs) have also been widely used for symptom relief. However, SABAs have been reported to increase the risk of asthma-related death, though incidences have been very rare. Consequently, a dilemma exists regarding recommendation of a SABA alone without an ICS or a controller to asthma patients even with very mild disease. In the real world, asthma patients tend to intermittently use ICS and more likely to be dependent on SABA since many patients want immediate relief of their symptoms. Consequently, a dilemma exists regarding the underuse of ICSs but the overuse of SABAs. One strategy for solving the presented dilemma would be identification of patients with asthma who require persistent use of asthma controllers. Such patients, who may be referred to as “persistent controller users,” should continuously receive ICSs, even under controlled states of asthma. Another strategy would be a patient-adjusted, symptom-driven, intermittent-to-regular treatment combining low-dose ICS/rapid-onset long-acting β-agonists instead of using a SABA alone or with low-dose ICS for the asthma patients with mild disease. Both of these two strategies could avoid the risky treatment of a SABA alone without an ICS and could reduce the dose of ICS with the maintenance of asthma control.

Bronchial Thermoplasty in Patients with Severe Uncontrolled Asthma: First Korean Cases

Bronchial thermoplasty is a nonpharmacological treatment for severe asthma that delivers thermal energy to the bronchial walls and reduces hypertrophied smooth muscle mass. Previous studies have shown its efficacy and safety, resulting in approval from the Food and Drug Administration in 2010. In Korea, the first bronchial thermoplasty was carried out in 2014; 4 patients have undergone the procedure so far. This case series presents the medical history and treatment outcomes of these 4 patients. All patients presented with uncontrolled asthma despite optimal medical treatment. Bronchial thermoplasty was performed at the right lower lobe, left lower lobe, and both upper lobes in order at 3-week intervals. All procedures were performed under general anesthesia. Two patients had significant decreases in exacerbations and required a lower dose of inhaled corticosteroids after the procedure. One patient had slightly fewer exacerbations but failed to reduce the use of systemic corticosteroids. One patient had no change in symptoms. One limitation of bronchial thermoplasty is the difficulty of predicting clinical responders. However, since more therapeutic options are needed in the management of severe asthma, especially T2-low asthma, discussion with experts about the feasibility and necessity of bronchial thermoplasty will ensure the best possible care.

Serum Levels of Eosinophil-Derived Neurotoxin: A Biomarker for Asthma Severity in Adult Asthmatics

PURPOSE: Eosinophilic inflammation is a key component of severe asthma (SA). However, there has been no reliable serum biomarker for the eosinophilic inflammation of SA. We hypothesized that serum eosinophil-derived neurotoxin (EDN) could predict the eosinophilic inflammation of SA in adult asthmatics. METHODS: Severe asthmatics (n = 235), nonsevere asthmatics (n = 898), and healthy controls (n = 125) were enrolled from Ajou University Hospital, South Korea. The serum levels of EDN and periostin were measured by enzyme-linked immunosorbent assay and compared between severe and nonsevere asthmatics. Their associations with total eosinophil count (TEC) and clinical parameters were evaluated; clinical validation of the K-EDN kit for the measurement of serum EDN was evaluated. RESULTS: Severe asthmatics were older and had longer disease duration with significantly lower levels of forced expiratory volume in 1 second and methacholine PC20 than nonsevere asthmatics. Significant differences were found in TEC or sputum eosinophil count (%) between the groups. The serum levels of EDN and periostin were significantly higher in severe asthmatics than in nonsevere asthmatics and in healthy controls (all P < 0.05). Although significant correlations were found between serum EDN levels measured by the 2 kits (ρ = 0.545, P < 0.0001), higher correlation coefficients between serum EDN levels measured by the K-EDN kit and TEC were higher (ρ = 0.358, P < 0.0001) than those between serum EDN levels measured by the MBL kit and TEC (ρ = 0.319, P < 0.0001) or serum periostin level (ρ = 0.222, P < 0.0001). Multivariate regression analysis demonstrated that serum EDN levels measured by the K-EDN kit predicted the phenotype of SA (P = 0.003), while 2 other biomarkers did not. CONCLUSIONS: The serum EDN level may be a useful biomarker for assessing asthma severity in adult asthmatics.

Dilemma of Asthma Treatment in Mild Patients / 결핵및호흡기질환

Inhaled corticosteroids (ICSs) have been widely used as a key medication for asthma control. However, ICSs have been known to cause respiratory infections, such as pneumonia and pulmonary tuberculosis. Consequently, a dilemma exists regarding recommendation of persistent lifetime use of ICSs to mild asthma patients. Short-acting β-agonists (SABAs) have also been widely used for symptom relief. However, SABAs have been reported to increase the risk of asthma-related death, though incidences have been very rare. Consequently, a dilemma exists regarding recommendation of a SABA alone without an ICS or a controller to asthma patients even with very mild disease. In the real world, asthma patients tend to intermittently use ICS and more likely to be dependent on SABA since many patients want immediate relief of their symptoms. Consequently, a dilemma exists regarding the underuse of ICSs but the overuse of SABAs. One strategy for solving the presented dilemma would be identification of patients with asthma who require persistent use of asthma controllers. Such patients, who may be referred to as “persistent controller users,” should continuously receive ICSs, even under controlled states of asthma. Another strategy would be a patient-adjusted, symptom-driven, intermittent-to-regular treatment combining low-dose ICS/rapid-onset long-acting β-agonists instead of using a SABA alone or with low-dose ICS for the asthma patients with mild disease. Both of these two strategies could avoid the risky treatment of a SABA alone without an ICS and could reduce the dose of ICS with the maintenance of asthma control.

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.

A Delphi approach to the development of standard questionnaire to investigate asthma in Koreans

PURPOSE: Recently, the prevalence and disease burden of asthma have increased. Thus, the need for early diagnosis and appropriate management of asthma is emerging. However, it is difficult to identify the diagnosis, symptoms and the prevalence of asthma due to lack of reliable investigating items. The purpose of this study was to develop a standardized survey format in order to assess the prevalence of asthma in Koreans. METHODS: We investigated surveys and related information that are utilized to assess asthma diagnosis and prevalence by systematic review. After that, Delphi survey was conducted on 44 Korean allergists in order to develop a standardized survey in Korea. The process consisted of 3 serial rounds across 3 age groups. Each subsequent round narrowed investigating items for the decision of standard set about asthma prevalence, current asthma, and asthma aggravation. RESULTS: Lifetime asthma was defined as “ever doctor-diagnosed asthma” in all age groups. Current asthma was defined as “treatment for asthma during the past 12 months” in all age groups, and “doctor-diagnosed asthma during the past 12 months” was added on the ≥5-year-old and adult groups. “Wheezing ever” was defined as “wheezing at any time in the past,” and current wheeze was defined as “wheezing in the last 12 months.” Asthma aggravation was defined as “visits at the emergency department or admission due to asthma attack within the last 12 months” in all age groups. CONCLUSION: We established applicable nationwide definitions of “lifetime asthma,” “current asthma,” and “asthma aggravation” in Koreans by the Delphi survey.

Precision medicine for the best treatment of chronic obstructive airway disease

Bronchial asthma and chronic obstructive pulmonary disease (COPD) are 2 representative diseases of chronic obstructive inflammatory airway diseases, and both show a wide range of heterogeneity in their clinical features. Although one end of typical asthma and the other end of COPD are clearly different, both diseases share lots of similarities in biological aspects and clinical manifestations. Currently, 2 different guidelines exist for asthma and COPD management, respectively, and in many clinical situations it is not easy to manage patients especially who have both features and show refractoriness to available medications. Since the features of the diseases are remarkably diverse in terms of clinical courses, prognosis and responses to therapeutic drugs, there have been vigorous efforts to classify appropriate subtypes in order to improve management of the diseases. However, dichotomous thinking about asthma and COPD precludes precise classification of the diseases in the real world. In this article, thus, chronic obstructive airway disease (COAD) ranging from asthma particularly in adults to COPD is proposed as 1 target subject to analyze precise classification based on exact phenotyping and endotyping of the diseases. In the current article, the reasonable precision medicine approach is also suggested based on treatable traits of COAD to achieve the best treatment for COAD patients.

Perceptions of Severe Asthma and Asthma-COPD Overlap Syndrome Among Specialists: A Questionnaire Survey

PURPOSE: Severe asthma and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) are difficult to control and are often associated with poor clinical outcomes. However, much is not understood regarding the diagnosis and treatment of severe asthma and ACOS. To evaluate the current perceptions of severe asthma and COPD among asthma and COPD specialists, we designed an e-mail and internet-based questionnaire survey. METHODS: Subjects were selected based on clinical specialty from among the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received an e-mail invitation to the survey, 95 subjects, including 58 allergists and 37 pulmonologists, responded and submitted their answers online. RESULTS: The specialists estimated that the percentage of severe cases among total asthma patients in their practice was 13.9%±11.0%. Asthma aggravation by stepping down treatment was the most common subtype, followed by frequent exacerbation, uncontrolled asthma despite higher treatment steps, and serious exacerbation. ACOS was estimated to account for 20.7% of asthma, 38.0% of severe asthma, and 30.1% of COPD cases. A history of smoking, persistently low forced expiratory volume in 1 second (FEV1), and low FEV1 variation were most frequently classified as the major criteria for the diagnosis of ACOS among asthma patients. Among COPD patients, the highly selected major criteria for ACOS were high FEV1 variation, positive bronchodilator response, a personal history of allergies and positive airway hyperresponsiveness. Allergists and pulmonologists showed different assessments and opinions on asthma phenotyping, percentage, and diagnostic criteria for ACOS. CONCLUSIONS: Specialists had diverse perceptions and clinical practices regarding severe asthma and ACOS patients. This heterogeneity must be considered in future studies and strategy development for severe asthma and ACOS.

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.