Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic.

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

The KAAACI Guidelines for Sublingual Immunotherapy.

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.

A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study.

Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (-117.50 ± 94.38 vs. -115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (-18.62 ± 24.68 vs. -14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (-3.40 ± 10.60 vs. -14.48 ± 24.01 %, P = 0.065), blood eosinophils (-36.47 ± 517.02 vs. -363.22 ± 1294.59, P = 0.013), and exacerbation frequency (-3.07 ± 4.42 vs. -3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

Postharvest Quality Improvement of Bell Pepper (Capsicum annuum L. cv Nagano) with Forced-Air Precooling and Modified Atmosphere Packaging.

Optimum postharvest storage conditions increase the postharvest quality and shelf life of horticultural crops. The effects of forced-air precooling (FAP) and modified atmosphere packaging (MAP) on shelf life, physicochemical quality, and health-promoting properties of bell pepper (Capsicum annuum L. cv. Nagano) harvested at 90 and 50% coloring stages in May and July respectively, stored at 11 °C, 95% relative humidity were assessed. Fruits were subjected to four treatments: FAP + 30 µm polyethylene liner (FOLO); FAP-only (FOLX); 30 µm polyethylene liner-only (FXLO); and control (FXLX). The quality attributes, viz. weight loss, firmness, color, soluble solids content (SSC), soluble sugars, total phenolic content (TPC), total flavonoid content (TFC), 2,2-dephenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) were evaluated. The investigated parameters differed significantly (p < 0.05) among treatments except for soluble sugars. FOLO maintained sensory quality (weight loss, firmness, and color), physicochemical (SSC and soluble sugars), and health-promoting properties compared to other treatments during storage. The 50% coloring fruits had a huge variation between treatments than 90% coloring. The results revealed more TPC and antioxidant capacity in the 50% than in the 90% coloring fruits. The study highlights the need to consider the ideal fruit coloring stage at harvest under the effect of FAP and MAP treatments in preserving bell pepper's postharvest quality and shelf life.

KAAACI Guidelines for Allergen Immunotherapy.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

Determination of Freshness of Mackerel (Scomber japonicus) Using Shortwave Infrared Hyperspectral Imaging.

Shortwave infrared (SWIR) hyperspectral imaging was applied to classify the freshness of mackerels. Total volatile basic nitrogen (TVB-N) and acid values, as chemical compounds related to the freshness of mackerels, were also analyzed to develop a prediction model of freshness by combining them with hyperspectral data. Fresh mackerels were divided into three groups according to storage periods (0, 24, and 48 h), and hyperspectral data were collected from the eyes and whole body, separately. The optimized classification accuracies were 81.68% using raw data from eyes and 90.14% using body data by multiple scatter correction (MSC) pretreatment. The prediction accuracy of TVB-N was 90.76%, and the acid value was 83.76%. These results indicate that hyperspectral imaging, as a nondestructive method, can be used to verify the freshness of mackerels and predict the chemical compounds related to the freshness.

Serum Zonulin Is a Biomarker for Severe Asthma.

Zonulin is a regulator of epithelial and endothelial barrier function. It regulates intestinal permeability through disrupting tight junctions. Defective epithelial barrier function is a hallmark of airway inflammation in asthma. This study aimed to investigate the role of zonulin in the pathogenesis of severe asthma. We enrolled 56 adult patients with asthma (29 severe asthma and 27 mild-to-moderate asthma) and 33 normal controls. The clinical data, sera, and lung tissues of the patients were provided by the Cohort for Reality and Evolution of adult Asthma in Korea (COREA) and the Biobank of Soonchunhyang University Bucheon Hospital, South Korea. Serum zonulin levels were estimated using an enzyme-linked immunosorbent assay, and zonulin expression in the bronchial tissue was evaluated by immunohistochemical staining. The serum zonulin levels were significantly higher in patients with severe asthma (51.98 ± 19.66 ng/mL) than in those with mild-to-moderate asthma and normal controls (26.35 ± 13.70 vs. 17.26 ± 10.29 ng/mL, P < 0.001). They significantly correlated with percent predicted forced expiratory volume in one second (%FEV1) (r = -0.35, P = 0.009). The zonulin expression in the bronchial epithelium was greater in patients with severe asthma. A serum zonulin cutoff value to distinguish between severe and mild-to-moderate asthmatics was 38.83 ng/mL. Zonulin may play an important role in the pathogenesis of severe asthma, and serum zonulin could be a potential biomarker for severe asthma.

Efficacy of Second-Line Treatments in Chronic Urticaria Refractory to Standard Dose Antihistamines.

PURPOSE: The prevalence of chronic urticaria (CU) is increasing worldwide, and it imposes a major burden on patients. Few studies have evaluated the efficacy of second-line treatments of CU, particularly for patients being considered for costly third-line treatments such as omalizumab. We compared the efficacy and safety of second-line treatments of CU refractory to standard doses of nonsedating H1-antihistamines (nsAHs). METHODS: This 4-week, prospective, randomized, open-label trial divided patients into 4 treatment groups: 4-fold updosing of nsAHs, multiple combination of 4 nsAHs, switching to other nsAHs, and adjunctive H2-receptor antagonist. The clinical outcomes included urticaria control status, symptoms, and rescue medication use. RESULTS: This study included 109 patients. After 4 weeks of second-line treatment, urticaria was well-controlled, partly controlled, and uncontrolled in 43.1%, 36.7%, and 20.2% of patients, respectively. Complete control of CU was achieved in 20.4% of patients. Among the patients with high-dose nsAHs, the proportion with well-controlled status was higher compared to the patients who received standard doses (51.9% vs. 34.5%, P = 0.031). No significant difference was observed in the proportion of well-controlled cases between the updosing and combination treatment groups (57.7% vs. 46.4%, P = 0.616). However, increasing the dose of nsAHs 4-fold was associated with a higher rate of complete symptom control compared to multiple combination treatment with 4 nsAHs (40.0% vs. 10.7%, P = 0.030). Logistic regression analysis confirmed the higher efficacy of updosing of nsAHs for complete control of CU compared to the other treatment strategies (odds ratio, 0.180; P = 0.020). CONCLUSIONS: In patients with CU refractory to standard doses of nsAHs, both updosing of nsAHs 4-fold and multiple combination treatment with 4 nsAHs increased the rate of well-controlled cases without causing significant adverse effects. Updosing of nsAHs is more effective for complete CU control than combination treatment.

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.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in Non-pharmacological Management.

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

KAAACI Allergic Rhinitis Guidelines: Part 1. Update in Pharmacotherapy.

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

Ni-Ion-Chelating Strategy for Mitigating the Deterioration of Li-Ion Batteries with Nickel-Rich Cathodes.

Ni-rich cathodes are the most promising candidates for realizing high-energy-density Li-ion batteries. However, the high-valence Ni4+ ions formed in highly delithiated states are prone to reduction to lower valence states, such as Ni3+ and Ni2+ , which may cause lattice oxygen loss, cation mixing, and Ni ion dissolution. Further, LiPF6 , a key salt in commercialized electrolytes, undergoes hydrolysis to produce acidic compounds, which accelerate Ni-ion dissolution and the interfacial deterioration of the Ni-rich cathode. Dissolved Ni ions migrate and deposit on the surface of the graphite anode, causing continuous electrolyte decomposition and threatening battery safety by forming Li dendrites on the anode. Herein, 1,2-bis(diphenylphosphino)ethane (DPPE) chelates Ni ions dissolved from the Ni-rich cathode using bidentate phosphine moieties and alleviates LiPF6 hydrolysis via complexation with PF5 . Further, DPPE reduces the generation of corrosive HF and HPO2 F2 substantially compared to the amounts observed using trimethyl phosphite and tris(trimethylsilyl) phosphite, which are HF-scavenging additives. Li-ion cells with Ni-rich cathodes and graphite anodes containing DPPE exhibit remarkable discharge capacity retentions of 83.4%, with high Coulombic efficiencies of >99.99% after 300 cycles at 45 °C. The results of this study will promote the development of electrolyte additives.

Effect of Moisture Content Difference on the Analysis of Quality Attributes of Red Pepper (Capsicum annuum L.) Powder Using a Hyperspectral System.

The variety of characteristics of red pepper makes it difficult to analyze at the production field through hyperspectral imaging. The importance of pretreatment to adjust the moisture content (MC) in the process of predicting the quality attributes of red pepper powder through hyperspectral imaging was investigated. Hyperspectral images of four types of red pepper powder with different pungency levels and MC were acquired in the visible near-infrared (VIS-NIR) and short-wave infrared (SWIR) regions. Principal component analysis revealed that the powders were grouped according to their pungency level, color value, and MC (VIS-NIR, Principal Component 1 = 95%; SWIR, Principal Component 1 = 91%). The loading plot indicated that 580-610, 675-760, 870-975, 1020-1130, and 1430-1520 nm are the key wavelengths affected by the presence of O-H and C-H bonds present in red pigments, capsaicinoids, and water molecules. The R2 of the partial least squares model for predicting capsaicinoid and free sugar in samples with a data MC difference of 0-2% was 0.9 or higher, and a difference of more than 2% in MC had a negative effect on prediction accuracy. The color value prediction accuracy was barely affected by the difference in MC. It was demonstrated that adjusting the MC is essential for capsaicinoid and free sugar analysis of red pepper.

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.

Changes in Volatile Compounds in Short-Term High CO2-Treated 'Seolhyang' Strawberry (Fragaria × ananassa) Fruit during Cold Storage.

'Seolhyang' strawberry is harvested before it is fully ripened and treated with CO2 to extend the shelf-life. However, the volatile changes in the 'Seolhyang' strawberry after short-term CO2 treatment have not been investigated, although the volatile profile is an important quality attribute. Herein, we investigated the effect of short-term high CO2 treatment on the changes in the composition of volatile compounds in 'Seolhyang' strawberries at two ripening stages (i.e., half-red and bright-red) during cold storage using headspace solid-phase microextraction and gas chromatography-mass spectrometry. Furthermore, the effect of CO2 treatment on fruit quality with respect to the aroma was investigated. A total of 30 volatile compounds were identified. Storage increased the volatile compound concentrations, and the total concentration of volatiles in the CO2-treated strawberries was lower than that of the untreated strawberries during storage. The production of some characteristic strawberry volatiles (e.g., 4-methoxy-2,5-dimethyl-3(2H)-furanone) was inhibited in CO2-treated strawberries. However, CO2 treatment helped maintain the concentrations of hexanal and 2-hexenal, which are responsible for the fresh odor in strawberries. Interestingly, CO2 treatment suppressed the production of off-odor volatiles, acetaldehyde, and hexanoic acid during strawberry storage. Thus, short-term CO2 treatment may help maintain the fresh aroma of strawberries during cold storage.

The burden of symptomatic patients with chronic spontaneous urticaria: a real-world study in Korea.

BACKGROUND/AIMS: Chronic spontaneous urticaria (CSU) poses a considerable burden both on the quality of life (QoL) of individual patients and on healthcare systems. Real­world data evaluating the disease burden of CSU are limited in this country. This study evaluated the disease burden and healthcare resource utilization (HRU) among symptomatic CSU patients. METHODS: This multicenter, noninterventional, retrospective, and cross-sectional study assessed CSU patients symptomatic for more than 6 months despite step-wise H1-antihistamine medications. Primary outcomes included Urticaria Activity Score over 7 days (UAS7) and Chronic Urticaria QoL scale (CU-QoL). Secondary outcomes included EuroQol 5-Dimension 5-Level (EQ-5D-5L), Dermatology Life Quality Index (DLQI), association of disease activity with QoL, medications used for the past 6 months, and HRU. RESULTS: Five hundred patients with CSU were enrolled. Mean disease duration was 3.7 years. Based on UAS7, 22.2% of patients were in well-controlled status and 31.2%, 28.4%, and 18.2% of them had mild, moderate, and severe disease, respectively. Mean CU-QoL and DLQI scores were 57.5 ± 29.7 and 10.2 ± 7.6, respectively, while the EQ-5D-5L utility score was 0.8 ± 0.2. H1-antihistamines were prescribed to 95% of patients, while omalizumab was prescribed to 33% of patients. Most patients (98%) had outpatient visits in the past 6 months. Negative correlations were noted between UAS7 and CU-QoL, EQ-5D-5L, EQ-5D-5L visual analog scale scores, but a positive correlation was noted with DLQI score (p < 0.001 for all). The number of outpatient department visits increased with disease activity (p = 0.001). CONCLUSION: CSU affects QoL, leading to increased HRU, particularly in patients with severe disease.

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.

BACKGROUND: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. METHODS: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. RESULTS: In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. CONCLUSIONS: Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.

HLA-A*24:02 increase the risk of allopurinol-induced drug reaction with eosinophilia and systemic symptoms in HLA-B*58:01 carriers in a Korean population; a multicenter cross-sectional case-control study.

Background: HLA-B*58:01 is a well-known risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA-B*58:01 carriers suffer SCARs after taking allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA-B*58:01. Methods: Subjects with B*58:01 were enrolled (21 allopurinol-induced DRESS and 52 allopurinol-tolerant control). HLA-A, -B, -C and -DRB1 alleles were compared. Comparison of risk between HLAs and allopurinol-induced SCAR in separate populations was performed to support the results. Kruskal-Wallis test, Pearson's chi-square test, Fisher's exact test and binary logistic regression were used to analyze the risk of SCAR development. Results: Frequencies of A*24:02 (71.4 vs. 17.3%, p < 0.001, odds ratio [OR] = 12.0; 95% confidence interval [CI], 3.6-39.2) were significantly higher in B*58:01 (+) DRESS than B*58:01 (+) tolerant controls. In addition, DRB1*13:02 further increased the risk of DRESS. The phenotype frequency of A*24:02/DRB1*13:02 was significantly higher in the B*58:01 (+) DRESS group than in the B*58:01 (+) tolerant controls (52.4% vs. 5.8%, p < 0.001, OR, 66.0; 95% CI, 6.1-716.2). In 2782 allopurinol user cohort, the overall prevalence of DRESS was 0.22%, which increased to 1.62% and 2.86% in the presence of B*58:01 and B*58:01/A*24:02, respectively. Conclusion: The additional secondary screening with A*24:02 and DRB1*13:02 alleles may identify those at further increased risk of allopurinol-induced DRESS in B*58:01 carriers.