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.

Risk of Coronavirus Disease 2019 Occurrence, Severe Presentation, and Mortality in Patients with Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to analyze whether patients with lung cancer have a higher susceptibility of coronavirus disease 2019 (COVID-19), severe presentation, and higher mortality than those without lung cancer. @*Materials and Methods@#A nationwide cohort of confirmed COVID-19 (n=8,070) between January 1, 2020, and May 30, 2020, and a 1:15 age-, sex-, and residence-matched cohort (n=121,050) were constructed. A nested case-control study was performed to compare the proportion of patients with lung cancer between the COVID-19 cohort and the matched cohort. @*Results@#The proportion of patients with lung cancer was significantly higher in the COVID-19 cohort (0.5% [37/8,070]) than in the matched cohort (0.3% [325/121,050]) (p=0.002). The adjusted odds ratio [OR] of having lung cancer was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR, 1.51; 95% confidence interval [CI], 1.05 to 2.10). Among patients in the COVID-19 cohort, compared to patients without lung cancer, those with lung cancer were more likely to have severe COVID-19 (54.1% vs. 13.2%, p < 0.001), including mortality (18.9% vs. 2.8%, p < 0.001). The adjusted OR for the occurrence of severe COVID-19 in patients with lung cancer relative to those without lung cancer was 2.24 (95% CI, 1.08 to 4.74). @*Conclusion@#The risk of COVID-19 occurrence and severe presentation, including mortality, may be higher in patients with lung cancer than in those without lung cancer.

A Novel Hypothesis and Characterization to Isolate Microvascular Endothelial Cells Simultaneously with AdiposeDerived Stem Cells from the Human Adipose-Derived Stromal Vascular Fraction

BACKGROUND@#Angiogenesis and vasculogenesis are essential processes for successful tissue regeneration in tissue engineering and regenerative medicine. The adipose-derived stromal vascular fraction (SVF) is not only a source of adipose stem cells (ASC) but also a suitable source of microvascular endothelial cells because it is a rich capillary network. So, we propose a new hypothesis for isolating adipose-derived human microvascular endothelial cells (HMVEC-A) from the SVF and developed a dual isolation system that isolates two cell types from one tissue.METHOD: To isolate HMVEC-A, we analyzed the supernatant discarded when ASC is isolated from the adipose-derived SVF. Based on this analysis, we assumed that the SVF adherent to the bottom of the culture plate was divided into two fractions: the stromal fraction as the ASC-rich fraction, and the vascular fraction (VF) as the endothelial cells-rich fraction floating in the culture supernatant. VF isolation was optimized and the efficiency was compared, and the endothelial cells characteristics of HMVEC-A were confirmed by flow cytometric analysis, immunocytochemistry (ICC), a DiI-acetylated low-density lipoprotein (DiI-Ac-LDL) uptake, and in vitro tube formation assay. @*RESULTS@#Consistent with the hypothesis, we found a large population of HMVEC-A in the VF and isolated these HMVEC-A by our isolation method. Additionally, this method had higher yields and shorter doubling times than other endothelial cells isolation methods and showed typical morphological and phenotypic characteristics of endothelial cells. @*CONCLUSION@#Cells obtained by the method according to our hypothesis can be applied as a useful source for studies such as tissue-to-tissue networks, angiogenesis and tissue regeneration, patient-specific cell therapy, and organoid chips.

Risk of Coronavirus Disease 2019 Occurrence, Severe Presentation, and Mortality in Patients with Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to analyze whether patients with lung cancer have a higher susceptibility of coronavirus disease 2019 (COVID-19), severe presentation, and higher mortality than those without lung cancer. @*Materials and Methods@#A nationwide cohort of confirmed COVID-19 (n=8,070) between January 1, 2020, and May 30, 2020, and a 1:15 age-, sex-, and residence-matched cohort (n=121,050) were constructed. A nested case-control study was performed to compare the proportion of patients with lung cancer between the COVID-19 cohort and the matched cohort. @*Results@#The proportion of patients with lung cancer was significantly higher in the COVID-19 cohort (0.5% [37/8,070]) than in the matched cohort (0.3% [325/121,050]) (p=0.002). The adjusted odds ratio [OR] of having lung cancer was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR, 1.51; 95% confidence interval [CI], 1.05 to 2.10). Among patients in the COVID-19 cohort, compared to patients without lung cancer, those with lung cancer were more likely to have severe COVID-19 (54.1% vs. 13.2%, p < 0.001), including mortality (18.9% vs. 2.8%, p < 0.001). The adjusted OR for the occurrence of severe COVID-19 in patients with lung cancer relative to those without lung cancer was 2.24 (95% CI, 1.08 to 4.74). @*Conclusion@#The risk of COVID-19 occurrence and severe presentation, including mortality, may be higher in patients with lung cancer than in those without lung cancer.

A Novel Hypothesis and Characterization to Isolate Microvascular Endothelial Cells Simultaneously with AdiposeDerived Stem Cells from the Human Adipose-Derived Stromal Vascular Fraction

BACKGROUND@#Angiogenesis and vasculogenesis are essential processes for successful tissue regeneration in tissue engineering and regenerative medicine. The adipose-derived stromal vascular fraction (SVF) is not only a source of adipose stem cells (ASC) but also a suitable source of microvascular endothelial cells because it is a rich capillary network. So, we propose a new hypothesis for isolating adipose-derived human microvascular endothelial cells (HMVEC-A) from the SVF and developed a dual isolation system that isolates two cell types from one tissue.METHOD: To isolate HMVEC-A, we analyzed the supernatant discarded when ASC is isolated from the adipose-derived SVF. Based on this analysis, we assumed that the SVF adherent to the bottom of the culture plate was divided into two fractions: the stromal fraction as the ASC-rich fraction, and the vascular fraction (VF) as the endothelial cells-rich fraction floating in the culture supernatant. VF isolation was optimized and the efficiency was compared, and the endothelial cells characteristics of HMVEC-A were confirmed by flow cytometric analysis, immunocytochemistry (ICC), a DiI-acetylated low-density lipoprotein (DiI-Ac-LDL) uptake, and in vitro tube formation assay. @*RESULTS@#Consistent with the hypothesis, we found a large population of HMVEC-A in the VF and isolated these HMVEC-A by our isolation method. Additionally, this method had higher yields and shorter doubling times than other endothelial cells isolation methods and showed typical morphological and phenotypic characteristics of endothelial cells. @*CONCLUSION@#Cells obtained by the method according to our hypothesis can be applied as a useful source for studies such as tissue-to-tissue networks, angiogenesis and tissue regeneration, patient-specific cell therapy, and organoid chips.

Cluster Analysis of Inhalant Allergens in South Korea: A Computational Model of Allergic Sensitization

Objectives@#. Sensitization to specific inhalant allergens is a major risk factor for the development of atopic diseases, which impose a major socioeconomic burden and significantly diminish quality of life. However, patterns of inhalant allergic sensitization have yet to be precisely described. Therefore, to enhance the understanding of aeroallergens, we performed a cluster analysis of inhalant allergic sensitization using a computational model. @*Methods@#. Skin prick data were collected from 7,504 individuals. A positive skin prick response was defined as an allergen-to-histamine wheal ratio ≥1. To identify the clustering of inhalant allergic sensitization, we performed computational analysis using the four-parameter unified-Richards model. @*Results@#. Hierarchical cluster analysis grouped inhalant allergens into three clusters based on the Davies-Bouldin index (0.528): cluster 1 (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cluster 2 (mugwort, cockroach, oak, birch, cat, and dog), and cluster 3 (Alternaria tenus, ragweed, Candida albicans, Kentucky grass, and meadow grass). Computational modeling revealed that each allergen cluster had a different trajectory over the lifespan. Cluster 1 showed a high level (>50%) of sensitization at an early age (before 19 years), followed by a sharp decrease in sensitization. Cluster 2 showed a moderate level (10%–20%) of sensitization before 29 years of age, followed by a steady decrease in sensitization. However, cluster 3 revealed a low level (<10%) of sensitization at all ages. @*Conclusion@#. Computational modeling suggests that allergic sensitization consists of three clusters with distinct patterns at different ages. The results of this study will be helpful to allergists in managing patients with atopic diseases.

Active Pharmacovigilance of Drug-Induced Liver Injury Using Electronic Health Records

No abstract available.

Impact of Grilling Meat or Fish at Home on Peak Expiratory Flow Rate in Adults With Asthma

Grilling, a common cooking method worldwide, can produce more toxic gases than other cooking methods. However, the impact of frequently grilling meat or fish at home on airflow limitation in adult asthma has not been well elucidated. We performed a prospective cohort study of 91 adult patients with asthma enrolled from 2 university hospitals. Of the patients, 39 (42.9%) grilled meat or fish at least once a week and 52 (57.1%) less than once a week. Patients who grilled at least once a week tended to have lower peak expiratory flow rate (PEFR) than those who grilled less than once a week (median, 345.5 L/min; 95% confidence interval [CI], 291.8–423.2 L/min vs. median, 375.1 L/min; 95% CI, 319.7–485.7 L/min; P = 0.059). Among patients with severe asthma who received step 4–5 treatment, PEFR was significantly lower in patients who grilled at least once a week compared with those who grilled less than once a week (median, 297.8 L/min; 95% CI, 211.3–357.7 L/min vs. median, 396.1 L/min; 95% CI, 355.0–489.6 L/min; P < 0.001). Our results suggest that the frequency of grilling meat or fish at home may affect PEFR in asthmatic patients, especially those with severe asthma who needed a high level of asthma treatment.

Validation of the Korean Version of the Bronchiectasis Health Questionnaire / 결핵및호흡기질환

Background@#The Bronchiectasis Health Questionnaire (BHQ) is a simple and repeatable, self-reporting health status questionnaire for bronchiectasis. We have translated the original version of the BHQ into Korean using a standardized methodology. The purpose of this study was to assess the validity of the Korean version of the BHQ (K-BHQ) with Korean patients. @*Methods@#Stable state patients with bronchiectasis from two academic hospitals were enrolled in this study. The validity was assessed by investigating the relationship between the K-BHQ scores and the Korean version of the Chronic Obstructive Pulmonary Disease Assessment Test (K-CAT) scores. We also investigated the relationship between the K-BHQ scores and other variables of the modified Medical Research Council’s (mMRC) dyspnea scale, lung function, and exacerbations. @*Results@#A total of 126 patients with bronchiectasis were enrolled. The mean age was 64.3 (standard deviation [SD], 9.7). Women comprised 53.2% of the patients. The mean forced expiratory volume in one second (FEV1) was 60% of the predicted value (SD, 18.9%); the mean K-CAT score was 17.6 (SD, 9.1). The K-BHQ scores correlated strongly with the K-CAT scores (r=–0.656, p<0.001). There was significant correlation between the K-BHQ scores and the mMRC dyspnea scale (ρ=–0.409, p<0.001), FEV1 (r=0.406, p<0.001), and number of exacerbations requiring hospitalization (ρ=–0.303, p=0.001). @*Conclusion@#The K-BHQ is valid for assessing the health-related quality of life or health status of Korean bronchiectasis patients.

Impact of Grilling Meat or Fish at Home on Peak Expiratory Flow Rate in Adults With Asthma

Grilling, a common cooking method worldwide, can produce more toxic gases than other cooking methods. However, the impact of frequently grilling meat or fish at home on airflow limitation in adult asthma has not been well elucidated. We performed a prospective cohort study of 91 adult patients with asthma enrolled from 2 university hospitals. Of the patients, 39 (42.9%) grilled meat or fish at least once a week and 52 (57.1%) less than once a week. Patients who grilled at least once a week tended to have lower peak expiratory flow rate (PEFR) than those who grilled less than once a week (median, 345.5 L/min; 95% confidence interval [CI], 291.8–423.2 L/min vs. median, 375.1 L/min; 95% CI, 319.7–485.7 L/min; P = 0.059). Among patients with severe asthma who received step 4–5 treatment, PEFR was significantly lower in patients who grilled at least once a week compared with those who grilled less than once a week (median, 297.8 L/min; 95% CI, 211.3–357.7 L/min vs. median, 396.1 L/min; 95% CI, 355.0–489.6 L/min; P < 0.001). Our results suggest that the frequency of grilling meat or fish at home may affect PEFR in asthmatic patients, especially those with severe asthma who needed a high level of asthma treatment.

Neuroprotective effects of Suhexiang Wan on the in vitro and in vivo models of Parkinson's disease.

OBJECTIVE: To examine the role of KSOP1009 (a modified formulation of Suhexiang Wan essential oil) in an animal model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection. METHODS: Cell toxicity, apoptosis, and reactive oxygen species (ROS) levels were analyzed in the human neuroblastoma cell line SH-SY5Y. After that, changes in animal behavior and tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) of MPTP-injected mice were examined. Three different doses of KSOP1009 (30, 100, and 300 mg/kg, n = 8 for each group) were administered daily for 7 d before MPTP injection and 14 d after MPTP injection, totaling 21 d. RESULTS: MPP+, the active metabolite of MPTP, decreased the viability of SH-SY5Y cells, whereas KSOP1009 alleviated MPP+-induced cytotoxicity. KSOP1009 (10 and 50 mg/mL) reduced MPP+-induced ROS generation compared with the control group. Treatment with 1 mM MPP+ increased the percentage of depolarized/live cells, whereas KSOP1009 intake at a dose of 10 mg/mL decreased the percentage of these cells. The mean latency to fall in the rotarod test was reduced in mice treated with MPTP compared with the control group. However, mice receiving three different doses of KSOP1009 performed better than MPTP-treated animals. MPTP-treated mice were more hesitant and took longer to traverse the balance beam than the control animals. In contrast, KSOP1009-treated mice performed significantly better than MPTP- treated mice. Furthermore, the KSOP1009-treated groups had a significantly higher number of TH-positive neurons in the lesioned SN and significantly higher expression of TH in the striatum than the MPTP-treated group. MPTP treatment strongly induced Jun-N-terminal kinase (JNK) activation, whereas KSOP1009 suppressed MPTP-induced JNK activation. In addition, KSOP1009 intake reversed the decrease in the phosphorylation levels of cAMP-response element-binding protein in the brain of MPTP-treated mice. KSOP1009 also restored the decrease in dopaminergic neurons and dopamine levels in the brain of MPTP-treated mice. CONCLUSION: KSOP1009 protected mice against MPTP-induced toxicity by decreasing ROS formation and restoring mitochondrial function.

Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

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.

MBP-FGF2-Immobilized Matrix Maintains Self-Renewal and Myogenic Differentiation Potential of Skeletal Muscle Stem Cells

The robust capacity of skeletal muscle stem cells (SkMSCs, or satellite cells) to regenerate into new muscles in vivo has offered promising therapeutic options for the treatment of degenerative muscle diseases. However, the practical use of SkMSCs to treat muscle diseases is limited, owing to their inability to expand in vitro under defined cultivation conditions without loss of engraftment efficiency. To develop an optimal cultivation condition for SkMSCs, we investigated the behavior of SkMSCs on synthetic maltose-binding protein (MBP)-fibroblast growth factor 2 (FGF2)-immobilized matrix in vitro. We found that the chemically well-defined, xeno-free MBP-FGF2-immobilized matrix effectively supports SkMSC growth without reducing their differentiation potential in vitro. Our data highlights the possible application of the MBP-FGF2 matrix for SkMSC expansion in vitro.

Risk of Pneumonia Associated With the Use of Inhaled Corticosteroids in Asthma

No abstract available.

Cough-Related Laryngeal Sensations and Triggers in Adults With Chronic Cough: Symptom Profile and Impact

PURPOSE: Recent evidence suggests that cough hypersensitivity may be a common feature of chronic cough in adults. However, the clinical relevance remains unclear. This study evaluated the cough-related symptom profile and the clinical relevance and impact of cough hypersensitivity in adults with chronic cough. METHODS: This cross-sectional multi-center study compared cough-related laryngeal sensations and cough triggers in patients with unexplained chronic cough following investigations and in unselected patients newly referred for chronic cough. A structured questionnaire was used to assess abnormal laryngeal sensations and cough triggers. Patients with unexplained cough were also evaluated using the Leicester Cough Questionnaire (LCQ) and a cough visual analogue scale (VAS), and these scores were assessed for correlations with the number of triggers and laryngeal sensations. RESULTS: This study recruited 478 patients, including 62 with unexplained chronic cough and 416 with chronic cough. Most participants reported abnormal laryngeal sensations and cough triggers. Laryngeal sensations (4.4 ± 1.5 vs. 3.9 ± 1.9; P = 0.049) and cough triggers (6.9 ± 2.6 vs. 5.0 ± 2.8; P < 0.001) were more frequent in patients with unexplained chronic cough than in those with chronic cough. The number of triggers and laryngeal sensations score significantly correlated with LCQ (r = −0.51, P < 0.001) and cough VAS score (r = 0.53, P < 0.001) in patients with unexplained chronic cough. CONCLUSIONS: Cough hypersensitivity may be a common feature in adult patients with chronic cough, especially those with unexplained chronic cough. Cough-related health status and cough severity were inversely associated with the number of triggers and laryngeal sensations, suggesting potential relevance of assessing cough hypersensitivity in chronic cough patients.

Multifaceted interventions to reduce acute exacerbations in elderly asthmatics

BACKGROUND: Although many risk factors are known to be associated with poor asthma outcomes in the elderly, the literature on the effect of risk factor control on asthma outcomes in the elderly is very sparse. OBJECTIVE: To evaluate the role of multifaceted interventions in reducing acute exacerbations in elderly asthmatics. METHODS: A total of 100 subjects were randomly selected from our prospective cohort of elderly asthmatics aged 65 years or older and were provided multifaceted intervention for 1 year. Our multifaceted interventions included repeated education on asthma and inhaler technique for patients and their caregivers, provision of an action plan to cope with acute exacerbations, short message service to prevent follow-up losses, and oral replacement of magnesium. The primary outcome was an acute asthma exacerbation rate compared to the previous year. RESULTS: Ninety-two subjects completed this study, although only 58 subjects continued to take magnesium. Compared to the previous year, the acute asthma exacerbation rate showed a significant reduction from 67% to 50% (p = 0001) and significant improvement was observed in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) (p = 0.04, p = 0.036 for each). Interestingly, a subgroup analysis revealed that predicted value of FEV1 increased significantly in subjects who continued to take magnesium from 79.6% to 87.1% (p = 0.008). CONCLUSION: To reduce acute exacerbations in elderly asthmatics, a multifaceted approach in increase medical awareness, proficiency and adherence to inhaler, assistance of caregivers and correction of micronutrients deficiency is likely to be effective. In addition, a continuous oral replacement of magnesium may increase FEV1 in elderly asthmatics.

The KAAACI Standardization Committee Report on the procedure and application of the bronchial provocation tests

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.

Real-Life Clinical Use of Symbicort® Maintenance and Reliever Therapy for Asthmatic Patients in Korea

The aim of this study was to examine the daily practice patterns of Symbicort® Maintenance and Reliever Therapy (SMART) in Korean asthmatic patients and to analyze clinical signs related to overuse. This study used an observational, multicenter, noninterventional, prospective, uncontrolled design for examining asthmatic patients prescribed SMART to assess the frequency and pattern of Symbicort® usage as a maintenance and reliever medication. The characteristics of patients showing signs of overuse (frequency of inhalation: 8 or more times per day) were also analyzed. Among the 1,518 patients analyzed, 1,292 (85.1%) completed the trial. The number of mean inhalations per day was 2.14±1.15; the number of patients who had at least 1 as needed usage (PRN) inhalation per day was 843 (55.5%); the mean frequency of PRN use was 0.25±0.67 inhalations per day. The number of patients who overused for at least 1 day was 260 (17.1%). In particular, young patients, patients with limited physical activity, and patients with nocturnal symptoms demonstrated high frequency of overuse. The frequency of overuse during SMART was not high in Korean asthmatic patients and the asthma status of follow-up outpatients improved overall. However, there is a need for careful education targeted toward younger patients, patients with limited physical activity, and patients with nocturnal symptoms owing to their tendency to frequently overuse.

The Fas Signaling Pathway Is a Common Genetic Risk Factor for Severe Cutaneous Drug Adverse Reactions Across Diverse Drugs

PURPOSE: Human leukocyte antigen (HLA) has been recognized as the most important genetic risk factor for severe cutaneous adverse drug reactions (SCARs) caused by certain drugs. However, cumulated observations suggest the presence of genetic risk factors for SCARs other than drug-specific HLA. We aimed to identify a common genetic risk factor of SCARs across multiple drugs. METHODS: We performed 2 independent genome-wide association studies (GWASs). A total of 68 and 38 subjects with a diagnosis of SCAR were enrolled in each GWAS. Their allele frequencies were compared to those of healthy subjects in Korea. RESULTS: No single nucleotide polymorphism (SNP) with genome-wide significance was found in either GWAS. We next selected and annotated the 200 top-ranked SNPs from each GWAS. These 2 sets of annotated genes were then entered into the web interface of ConsensusPathDB for a pathway-level analysis. The Fas signaling pathway was significantly over-represented in each gene set from the 2 GWASs. CONCLUSIONS: Our observations suggest that the Fas signaling pathway may be a common genetic risk factor for SCARs across multiple drugs.