HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity.

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.

Skin Test-Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study.

BACKGROUND: Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. OBJECTIVE: We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. METHODS: We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. RESULTS: A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003). CONCLUSIONS: Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.

Clinical outcomes of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe for peripheral lung lesions - A prospective pilot study.

OBJECTIVES: Transbronchial cryobiopsy (TBCB) is a novel technique for the diagnosis of peripheral lung lesions (PLLs). We aim to evaluate the clinical outcomes of TBCB using a new 1.1-mm diameter cryoprobe for the diagnosis of PLLs. MATERIALS AND METHODS: We performed a prospective observational pilot study on the diagnosis of PLLs (diameter ≤30 mm) by TBCB, using a 1.1-mm diameter cryoprobe with radial endobronchial ultrasound (RP-EBUS), virtual bronchoscopic navigation and fluoroscopy from December 2021 to July 2022. Primary outcome was the pathological diagnostic yield of TBCB, and secondary outcome was adverse event. RESULTS: A total of 50 patients were enrolled (mean lesion size, 21 mm). TBCB was performed in 49 patients up to three times except for the one with "invisible" finding on RP-EBUS. The overall diagnostic yield of TBCB was 90% (45/50). There was no difference in the diagnostic yield between size (20 mm vs. 20-30 mm; 88% [22/25] vs. 92% [23/25]; P = 1.000), RP-EBUS findings (concentric vs. others; 97% [28/29] vs. 81% [17/21]; P = 0.148), and acute angle location (apical segment of both upper lobes vs. others; 92% [12/13] vs. 89% [33/37]; P = 1.000). The cumulative diagnostic yields of the first, second, and third TBCB were 82% (41/50), 88% (44/50), and 90% (45/50), respectively. Mild bleeding was developed in 56% (28/50), and moderate bleeding was found in 26% (13/50). CONCLUSION: TBCB using a 1.1-mm diameter cryoprobe is an effective, reasonable method for the diagnosis of PLLs regardless of its size, RP-EBUS finding, and anatomical location without serious complication. TRIAL REGISTRATION: Clinical Trials.Gov (NCT05046093).

Development and Application of an Active Pharmacovigilance Framework Based on Electronic Healthcare Records from Multiple Centers in Korea.

INTRODUCTION: With the availability of retrospective pharmacovigilance data, the common data model (CDM) has been identified as an efficient approach towards anonymized multicenter analysis; however, the establishment of a suitable model for individual medical systems and applications supporting their analysis is a challenge. OBJECTIVE: The aim of this study was to construct a specialized Korean CDM (K-CDM) for pharmacovigilance systems based on a clinical scenario to detect adverse drug reactions (ADRs). METHODS: De-identified patient records (n = 5,402,129) from 13 institutions were converted to the K-CDM. From 2005 to 2017, 37,698,535 visits, 39,910,849 conditions, 259,594,727 drug exposures, and 30,176,929 procedures were recorded. The K-CDM, which comprises three layers, is compatible with existing models and is potentially adaptable to extended clinical research. Local codes for electronic medical records (EMRs), including diagnosis, drug prescriptions, and procedures, were mapped using standard vocabulary. Distributed queries based on clinical scenarios were developed and applied to K-CDM through decentralized or distributed networks. RESULTS: Meta-analysis of drug relative risk ratios from ten institutions revealed that non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of gastrointestinal hemorrhage by twofold compared with aspirin, and non-vitamin K anticoagulants decreased cerebrovascular bleeding risk by 0.18-fold compared with warfarin. CONCLUSION: These results are similar to those from previous studies and are conducive for new research, thereby demonstrating the feasibility of K-CDM for pharmacovigilance. However, the low quality of original EMR data, incomplete mapping, and heterogeneity between institutions reduced the validity of the analysis, thus necessitating continuous calibration among researchers, clinicians, and the government.

The prevalence of multiple chronic conditions and medical burden in asthma patients.

BACKGROUND: The prevalence of multiple chronic conditions (MCC), defined as several coexisting chronic conditions, has increased with the aging of society. MCC is associated with poor outcomes, but most comorbid diseases in asthma patients have been evaluated as asthma-associated diseases. We investigated the morbidity of coexisting chronic diseases in asthma patients and their medical burdens. METHODS: We analyzed data from the National Health Insurance Service-National Sample Cohort for 2002-2013. We defined MCC with asthma as a group of one or more chronic diseases in addition to asthma. We analyzed 20 chronic conditions, including asthma. Age was categorized into groups 1-5 (< 10, 10-29, 30-44, 45-64, and ≥ 65 years, respectively). The frequency of medical system use and associated costs were analyzed to determine the asthma-related medical burden in patients with MCC. RESULTS: The prevalence of asthma was 13.01%, and the prevalence of MCC in asthmatic patients was 36.55%. The prevalence of MCC with asthma was higher in females than males and increased with age. The significant comorbidities were hypertension, dyslipidemia, arthritis, and diabetes. Dyslipidemia, arthritis, depression, and osteoporosis were more common in females than males. Hypertension, diabetes, COPD, coronary artery disease, cancer, and hepatitis were more prevalent in males than females. According to age, the most prevalent chronic condition in groups 1 and 2 was depression, dyslipidemia in group 3, and hypertension in groups 4 and 5. Older age, low income, and severe disability were independent risk factors for MCC in patients with asthma. The frequency of asthma-related medical system use and asthma-associated costs increased with increasing numbers of coexisting chronic diseases. CONCLUSION: Comorbid chronic diseases in asthma patients differed according to age and sex. The asthma-related-medical burdens were highest in patients with five or more chronic conditions and groups 1 and 5.

Reducing Microbial Contamination in Hematopoietic Stem Cell Products and Quality Improvement Strategy: Retrospective Analysis of 1996-2021 Data.

Background: Sterility and safety assurance of hematopoietic stem cell (HSC) products is critical in transplantation. Microbial contamination can lead to product disposal and increases the risk of unsuccessful clinical outcomes. Therefore, it is important to implement and maintain good practice guidelines and regulations for the HSC collection and processing unit in each hospital. We aimed to share our experiences and suggest strategies to improve the quality assurance of HSC processing. Methods: We retrospectively analyzed microbial culture results of 11,743 HSC products processed over a 25-year period (January 1996 to May 2021). Because of reorganization of the HSC management system in 2008, the 25-year period was divided into periods 1 (January 1996 to December 2007) and 2 (January 2008 to May 2021). We reviewed all culture results of the HSC products and stored aliquot samples and collected culture results for peripheral blood and catheter samples. Results: Of the 11,743 products in total, 35 (0.3%) were contaminated by microorganisms, including 19 (0.5%) of 3,861 products during period 1 and 16 (0.2%) of 7,882 products during period 2. Penicillium was the most commonly identified microorganism (15.8%) during period 1 and coagulase-negative Staphylococcus was the most commonly identified (31.3%) during period 2. HSC product contamination occurred most often during HSC collection and processing. Conclusions: The contamination rate decreased significantly during period 2, when the HSC management system was reorganized. Our results imply that handling HSC products by trained personnel and adopting established protocols, including quality assurance programs, aid in decreasing the contamination risk.

Real-world evaluation of atezolizumab and etoposide-carboplatin as a first-line treatment for extensive-stage small cell lung cancer.

BACKGROUND/AIMS: Despite the obvious benefits of adding immune checkpoint inhibitors to platinum-etoposide chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC), real-world data remain scarce. METHODS: This retrospective study included 89 patients with ES-SCLC treated with platinum-etoposide chemotherapy alone (chemo-only group; n = 48) or in combination with atezolizumab (atezolizumab group; n = 41) and compared the survival outcomes between these two groups. RESULTS: Overall survival (OS) was significantly longer in the atezolizumab group than in the chemo-only group (15.2 months vs. 8.5 months; p = 0.047), whereas the median progression-free survival was almost the same (5.1 months vs. 5.0 months) in both groups (p = 0.754). Subsequent multivariate analysis revealed that thoracic radiation (hazard ratio [HR], 0.223; 95% confidence interval [CI], 0.092-0.537; p = 0.001) and atezolizumab administration (HR, 0.350; 95% CI, 0.184-0.668; p = 0.001) were favorable prognostic factors for OS. In the thoracic radiation subgroup, patients who received atezolizumab demonstrated favorable survival outcomes and no grade 3-4 adverse events (AEs). CONCLUSION: The addition of atezolizumab to platinum-etoposide resulted in favorable outcomes in this real-world study. Thoracic radiation was associated with improved OS and acceptable AE risk in combination with immunotherapy in patients with ES-SCLC.

Clinical aspects of severe cutaneous adverse reactions caused by beta-lactam antibiotics: A study from the Korea SCAR registry.

Background: Although beta-lactams are 1 of the major causative agents of severe cutaneous adverse reactions (SCAR), their epidemiology and clinical aspects have been poorly studied. This study aimed to investigate the characteristics of SCAR caused by beta-lactams in the Korean SCAR registry. Methods: We retrospectively analyzed beta-lactam-induced SCAR cases collected from 28 tertiary university hospitals in Korea between 2010 and 2015. The SCAR phenotypes included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap, and drug reaction with eosinophilia and systemic symptoms (DRESS). Beta-lactams were classified according to their chemical structures: penicillins, cephalosporins, and carbapenems. The causative beta-lactams, clinical and laboratory features, treatments, and outcomes were evaluated. Results: Among the 275 antibiotic-induced SCAR cases, 170 patients developed SCAR induced by beta-lactams. Beta-lactam antibiotic-induced SCAR showed more frequent SJS/TEN compared to SCAR induced by non-beta-lactam antibiotics (SJS/TEN/SJS-TEN overlap/DRESS: 36.5/11.2/5.9/46.5% vs. 23.8/10.5/2.9/62.9%, P = 0.049). Cephalosporin was the most common culprit drug. Particularly, 91 and 79 patients presented with SJS/TEN and DRESS, respectively. The odds ratio (OR) for poor prognosis, such as sequelae and death, was significantly increased in subjects with SJS-TEN overlap and TEN and carbapenem as culprit drug in the multivariate analysis (OR, 35.61; P = 0.016, OR, 28.07; P = 0.006, OR 30.46; P = 0.027). Conclusion: Among antibiotic-induced SCAR, clinical features were different depending on whether the culprit drug was a beta-lactam antibiotic or SCAR type. The poor prognosis was related to SJS-TEN overlap, TEN type, and carbapenem as the culprit drug.

Toll-like receptor 2 mediates Acanthamoeba-induced allergic airway inflammatory response in mice.

BACKGROUND: Repeated intranasal exposure to Acanthamoeba has been revealed to induce allergic airway inflammatory responses in mice. Based on the role of toll-like receptors (TLRs) in the pathogenesis of allergic asthma, TLRs form a link between innate and adaptive immune responses, and play an important role in the activation of various cells in the innate immune system. METHODOLOGY/PRINCIPAL FINDINGS: To determine the TLRs that are related to these immune responses, we assessed the expression levels of inflammation-related genes in mouse lung epithelial (MLE)-12 cells treated with excretory-secretory proteins (ES-P) of the Acanthamoeba strain (KA/E2) with or without the TLR antagonists. The expression levels of inflammation-related genes, such as eotaxin, TARC, macrophage-derived chemokine (MDC), and TSLP, in the TLR2 and TLR9 antagonist treatment groups were decreased, compared to those in the ES-P alone or other TLR antagonist treatment groups. In particular, a greater decrease in the relevant gene expression levels was found in the TLR2 antagonist treatment group than in the TLR9 antagonist treatment group. Allergic airway inflammation was evaluated in the wild-type (WT) and TLR2 knockout (KO) groups following KA/E2 exposure. Based on the results, allergic airway inflammatory responses (airway resistance value, inflammatory cell infiltration, Th2-related cytokine expression, mucin production, and metaplasia of lung epithelial cells and goblet cells) by KA/E2 were reduced in the TLR2 KO groups. In addition, TLR2 knockout BMDCs displayed lower activation of surface markers owing to ES-P stimulation than normal BMDCs, and KA/E2 ES-P-treated TLR2-depleted BMDCs produced fewer Th2 cytokine-expressing cells from naïve T cells than WT BMDCs. When ES-P was administered after primary lung cells were obtained from WT and TLR2 KO mice, the expression levels of inflammation-related genes were found to be significantly decreased in TLR2 KO cells compared to those in WT cells. CONCLUSIONS: These results suggest that TLR2 is involved in lung inflammatory response activation in KA/E2 intranasal infection, especially in airway tissue.

The Additive Impact of Transbronchial Cryobiopsy Using a 1.1-mm Diameter Cryoprobe on Conventional Biopsy for Peripheral Lung Nodules.

PURPOSE: The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs). Materials and Methods: From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022. RESULTS: The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm2) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm2, p < 0.001) and 1.9-mm forceps (3.7 mm2, p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications. CONCLUSION: Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: From multicenter real-world cohort data in Korea.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. Methods: We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. Results: The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6-47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8-161.5, P = 0.024], and 3) initial ACT score <20 [OR = 24.1, 95% CI: 5.45-158.8, P < 0.001] for ACT responders. FEV1 responders also showed a longer exacerbation-free period than those with no FEV1 increase (P = 0.014), yielding a hazard ratio for the first asthma exacerbation of 0.5 (95% CI: 0.3-0.9, P = 0.016). Conclusions: The results of this study suggest that tiotropium add-on for uncontrolled asthma with ICS-LABA would be more effective in patients with positive BDR or ACO. Additionally, an increase in FEV1 following tiotropium may predict a lower risk of asthma exacerbation.

Adverse drug events leading to emergency department visits: A multicenter observational study in Korea.

Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is lacking. This multicenter retrospective observational study evaluated the prevalence and features of adverse drug event-related emergency department visits across ages. We reviewed emergency department medical records obtained from three university hospitals between July 2014 and December 2014. The proportion of adverse drug events among total emergency department visits was calculated. The cause, severity, preventability, and causative drug(s) of each adverse drug event were analyzed and compared between age groups (children/adolescents [<18 years], adults [18-64 years], and the elderly [≥65 years]). Of 59,428 emergency department visits, 2,104 (3.5%) were adverse drug event-related. Adverse drug event-related emergency department visits were more likely to be female and older. Multivariate logistic regression analysis revealed that compared to non- adverse drug event-related cases, adverse drug event-related emergency department visitors were more likely to be female (60.6% vs. 53.6%, p<0.001, OR 1.285, 95% CI 1.025-1.603) and older (50.8 ± 24.6 years vs. 37.7 ± 24.4 years, p<0.001, OR 1.892, 95% CI: 1.397-2.297). Comorbidities such as diabetes, chronic kidney disease, chronic liver disease, and malignancies were also significantly associated with adverse drug event-related emergency department visits. Side effects were the most common type of adverse drug events across age groups, although main types differed substantially depending on age. Serious adverse drug events, hospitalizations, and adverse drug event-related deaths occurred more frequently in the elderly than in adults or children/adolescents. The proportion of adverse drug event-related emergency department visits that were preventable was 15.3%. Causative drugs of adverse drug events varied considerably depending on age group. Adverse drug event features differ substantially according to age group. The findings suggest that an age-specific approach should be adopted in the preventive strategies to reduce adverse drug events.

TonEBP in Myeloid Cells Promotes Obesity-Induced Insulin Resistance and Inflammation Through Adipose Tissue Remodeling.

The phenotypic and functional plasticity of adipose tissue macrophages (ATMs) during obesity plays a crucial role in orchestration of adipose and systemic inflammation. Tonicity-responsive enhancer binding protein (TonEBP) (also called NFAT5) is a stress protein that mediates cellular responses to a range of metabolic insults. Here, we show that myeloid cell-specific TonEBP depletion reduced inflammation and insulin resistance in mice with high-fat diet-induced obesity but did not affect adiposity. This phenotype was associated with a reduced accumulation and a reduced proinflammatory phenotype of metabolically activated macrophages, decreased expression of inflammatory factors related to insulin resistance, and enhanced insulin sensitivity. TonEBP expression was elevated in the ATMs of obese mice, and Sp1 was identified as a central regulator of TonEBP induction. TonEBP depletion in macrophages decreased induction of insulin resistance-related genes and promoted induction of insulin sensitivity-related genes under obesity-mimicking conditions and thereby improved insulin signaling and glucose uptake in adipocytes. mRNA expression of TonEBP in peripheral blood mononuclear cells was positively correlated with blood glucose levels in mice and humans. These findings suggest that TonEBP in macrophages promotes obesity-associated systemic insulin resistance and inflammation, and downregulation of TonEBP may induce a healthy metabolic state during obesity.

The First Case of Erythritol-Induced Anaphylaxis in Korea.

Erythritol is a natural sugar alcohol found in some fruits and fermented foods, which is used as a dietary sweetener because it has few calories. Here, we describe a 36-year-old woman who experienced anaphylaxis upon ingestion of an erythritol-containing drink. She presented to the emergency department with dyspnea and angioedema after drinking a peach-containing diet beverage. Her blood pressure dropped to 70/40 mmHg and the symptoms improved after administration of an antihistamine, glucocorticoid, and epinephrine. After 10 days, she drank another peach-containing diet beverage and experienced urticaria. No serum-specific immunoglobulin E findings were observed, including against peach components. A skin prick test (SPT) was performed using a peach, the two ingested diet beverages, and another peach-containing beverage. The SPT results for the peach and the peach-containing product were negative, but the wheal sizes for the two diet beverages were > 3 mm. The diet beverages contained erythritol as a food additive. The SPT result was positive for erythritol. The patient was diagnosed with anaphylaxis to erythritol and was instructed to avoid foods containing erythritol. She was prescribed a self-injectable epinephrine pen. To our knowledge, this is the first case of erythritol-induced anaphylaxis in Korea. Physicians should be aware of the possibility of allergic reactions to food additives, and additives should be evaluated to prevent the recurrence of symptoms.

Association Between Clinical Burden and Blood Eosinophil Counts in Asthma: Findings From a Korean Adult Asthma Cohort.

BACKGROUND: Some reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort. METHODS: Clinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated. RESULTS: In total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266-23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083-11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL. CONCLUSION: The baseline blood eosinophil count may predict the future clinical burden of asthma.

Safety and Diagnostic Yield of Radial Probe Endobronchial Ultrasound-Guided Biopsy for Peripheral Lung Lesions in Patients with Idiopathic Pulmonary Fibrosis: A Multicenter Cross-Sectional Study.

BACKGROUND: Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) is widely used for diagnosis of peripheral lung lesions (PLLs). To date, there have been no reports regarding the clinical outcomes of RP-EBUS-TBLB for PLLs in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: This study was performed between October 2017 and December 2019 to identify the safety and diagnostic performance of RP-EBUS-TBLB in IPF patients. METHODS: Patients were divided into the usual interstitial pneumonia (UIP) group (n = 39, 4%), the probable UIP group (n = 12, 1%), and the noninterstitial lung disease (non-ILD) group (n = 903, 95%). RESULTS: The diagnostic yield was significantly lower in the UIP group than in the non-ILD group (62% vs. 76%; p = 0.042), but there were no significant differences between the UIP and probable UIP groups (62% vs. 83%; p = 0.293) or the probable UIP and non-ILD groups (83% vs. 76%; p = 0.741). Multivariate logistic analysis showed that the mean diameter of PLLs, positive bronchus sign on CT, and "within the lesion" status on EBUS were independently associated with success of the procedure. Especially, the presence of the UIP pattern on CT (OR, 0.385; 95% CI: 0.172-0.863; p = 0.020) was independently associated with failed diagnosis. Among patients with UIP, "within the lesion" status on EBUS (OR, 25.432; 95% CI: 2.321-278.666; p = 0.008) was shown to be a factor contributing to a successful diagnosis. Overall, there were no significant differences in complication rates among the 3 study groups. CONCLUSION: RP-EBUS-TBLB can be performed safely with an acceptable diagnostic yield, even in patients with IPF.

Association between obesity and lung function changes by sex and age in adults with asthma.

OBJECTIVE: The lung function changes presenting before and after asthma treatment in obese people remain largely unknown. This study aimed to investigate the association between obesity and lung function changes before and after treatment in adults with asthma. METHODS: We enrolled 937 newly diagnosed asthma patients from Cohort for Reality and Evolution of Adult Asthma in Korea cohort in 2015-2017, who performed follow-up spirometry after three months of asthma treatment. The percentage changes (Δ) between the spirometry results before and after treatment were calculated. Patients were categorized into four body mass index (BMI) groups; underweight (<18.5), normal (18.5-22.9), overweight (23.0-24.9), and obese (≥25.0). Association between percent change of pulmonary function and BMI was analyzed according to sex and/or age (< 45 yrs, 45-65 yrs, ≥ 65 yrs), which were statistically corrected for age, sex, smoking status, and medication history. RESULTS: There was no consistent correlation between BMI and each lung function parameter. However, there were significant differences between BMI and ΔFEV1/FVC before and after 3 months of controller treatment. The obese asthmatics showed significantly lower ΔFEV1/FVC (6.0 ± 13.5%) than the underweight (12.6 ± 21.4%, P = 0.044) or normal weight (9.1 ± 14.6%, P = 0.031). Middle-aged women had higher BMI (24.11 ± 3.60 vs. 22.39 ± 3.52) and lower ΔFEV1/FVC (5.7 ± 11.9% vs. 8.9 ± 14.3%, P = 0.012) than young women. CONCLUSIONS: Obesity is negatively correlated with the ΔFEV1/FVC before and after controller treatment. Sex and age differentially contribute to lung function changes in response to asthma medications in adult asthmatics, showing a significant decrease in the ΔFEV1/FVC in middle-aged women.

Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma.

Asthma is a chronic eosinophilic airway disease characterized by type 2 helper T cell-driven inflammation. Adipose stem cells (ASCs) and the ASC culture supernatant are known to improve allergic airway inflammation; however, the immunomodulatory effects of ASC-derived extracellular vesicles (EVs) on allergic airway diseases remain unclear. Thus, we assessed the effects of ASC-derived EVs on allergic airway inflammation in a mouse model of asthma. EVs were isolated from the culture supernatant of murine ASCs and characterized. Six-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. Before the OVA challenge, 10 µg/50 µl of ASC-derived EVs was administered intranasally to the experimental group. ASC-derived EVs significantly attenuated airway hyperresponsiveness (AHR) in asthmatic mice (p = 0.023). ASC-derived EVs resulted in a remarkable reduction of the total number of inflammatory cells (p = 0.005) and eosinophils (p = 0.023) in the bronchoalveolar lavage fluid (BALF), the degree of eosinophilic lung inflammation (p < 0.001), and the serum total and OVA-specific immunoglobulin (Ig)E (p = 0.048 and p = 0.001) and total IgG1 (p < 0.001). Interleukin- (IL-) 4 was significantly inhibited with ASC-derived EV pretreatment in the BALF and lung draining lymph nodes (LLNs) (p = 0.040 and p = 0.011). Furthermore, ASC-derived EV administration resulted in a significant increase of the regulatory T cell (Treg) populations in LLNs. ASC-derived EVs alleviated AHR and allergic airway inflammation caused by the induction of Treg expansion in a mouse model of asthma. There seems to be a role for ASC-derived EVs as a modifier in allergic airway disease.

Risk factors of beta-lactam anaphylaxis in Korea: A 6-year multicenter retrospective adult case-control study.

BACKGROUND: Beta-lactams (BLs) are commonly used antibiotics and leading causative agents of drug-induced anaphylaxis. Few studies on the culprit drugs and risk factors of BL-induced anaphylaxis are available. Our goal was to evaluate the culprit drugs and compare the risk factors in patients with BL-induced anaphylaxis to matched tolerant controls in a hospital setting. METHODS: We retrospectively enrolled all patients who developed anaphylaxis from intravenous BL during hospitalization from 9 Korean hospitals. We compared clinical parameters between patients with BL-induced anaphylaxis and 4-fold BL-tolerant controls matched by age, sex, BL use, and the purpose of BL administration. RESULTS: Seventy-four cases of BL-induced anaphylaxis and 296 BL-tolerant controls were enrolled. Cephalosporin accounted for 77% of total BL-induced anaphylaxis, and the top derivatives were ceftriaxone (23.0%), cefazedone (10.8%), and cefbuperazone (9.5%). Among penicillin derivatives, piperacillin (16.2%) was the most common, followed by ampicillin (2.7%). History of drug allergy (odds ratio [OR], 19.91; 95% confidence interval [CI] 5.33-74.44), previous exposure to the causative BL (OR, 7.71; 95% CI, 1.62-36.76), and concurrent administration of angiotensin-converting enzyme inhibitors (ACEIs) (OR, 5.97; 95% CI, 1.28-27.91) were independent risk factors associated with BL-induced anaphylaxis. Food allergy (OR, 13.93; 95% CI 1.31-148.9) and previous exposure to BL (OR, 6.59; 95% CI, 1.30-33.31) were identified as risk factors for cephalosporin-induced anaphylaxis. CONCLUSIONS: To prevent BL-induced anaphylaxis, attention should be paid to histories of drug or food allergy, previous exposure to BLs, and ACEI use. The risk factors and clinical outcomes might vary according to the BL classes.

Development and Validation of a Trigger Tool for Identifying Drug-Related Emergency Department Visits.

There are various trigger tools for detecting adverse drug events (ADEs), however, a drug-related emergency department (ED) visit trigger tool (DrEDTT) has not yet been developed. We aimed to develop and validate a DrEDTT with a multi-center cohort. In this cross-sectional study, we developed the DrEDTT consisting of 28 triggers through a comprehensive literature review and three phase expert group discussion. Next, we evaluated the performance of the DrEDTT by applying it to relevant medical records retrieved from four hospitals from January 2016 to June 2016. Two experts performed an in-depth chart review of a 25% of random sample of trigger flagged and unflagged ED visits and a true ADE was determined through causality assessment. Among 66,564 patients who visited the ED for reasons other than traffic accident and trauma during the study period, at least one trigger was found in 21,268 (32.0%) patients. A total of 959 true ADE cases (5.8%) were identified from a randomly selected 25% of ED visit cases. The overall positive predictive value was 14.0% (range: 8.3-66.7%). Sensitivity and specificity of DrEDTT were 77.7% and 70.4%, respectively. In conclusion, this newly developed trigger tool might be helpful to detect ADE-related ED visits.