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Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except “cough,” were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

This study aims to find an eco-friendly dual material to apply toward energy and antibacterial industry, and to identify their active sites. Cu0.1Zn0.9O nanoparticles (NPs) containing 10 % Cu ions into ZnO framework are synthesized using a facile hydrothermal method, and 10, 20, 30, or 40 nm-sized Ag NPs are loaded to obtain Ag@Cu0.1Zn0.9O particles. From the time-dependent increase in photocurrent density, it is confirmed that the Ag NPs has a photoelectron harvesting ability. Unlike ZnO and Cu0.1Zn0.9O, the Ag@Cu0.1Zn0.9O catalyst well splits water to generate hydrogen. Particularly, the catalyst loaded with 30 nm Ag NPs achieves the highest hydrogen production efficiency of 424.54 μmolg−1. This proves that the active sites generating hydrogen during water splitting are the Ag NP surfaces grafted onto the conduction band of the Cu0.1Zn0.9O particles. Contrastingly, antibacterial performances against Bacillus manliponensis are expressed in all samples of ZnO, Cu0.1Zn0.9O, and Ag@Cu0.1Zn0.9O. The antibacterial performance for the Ag NP-loaded sample slightly increases but it is not significant, indicating that the active site exhibiting the antibacterial activity is the hole+ of the valence band of Cu0.1Zn0.9O. In the end, this study revealed that the advantageous photocatalytic activity does not always express effective antibacterial activity because the active sites exhibiting photocatalytic and antibacterial properties may not be the same.

Oncolytic viruses are of significant clinical interest due to their ability to directly infect and kill tumors and enhance the anti-tumor immune response. Previously, we developed KLS-3010, a novel oncolytic virus derived from the International Health Department-White (IHD-W) strain vaccinia virus, which has robust tumoricidal effects. In the present study, we generated a recombinant oncolytic virus, KLS-3020, by inserting three transgenes (hyaluronidase [PH-20], interleukin-12 [IL-12], and soluble programmed cell death 1 fused to the Fc domain [sPD1-Fc]) into KLS-3010 and investigated its anti-tumor efficacy and ability to induce anti-tumor immune responses in CT26.WT and B16F10 mouse tumor models. A single injection of KLS-3020 significantly decreased tumor growth. The roles of the transgenes were investigated using viruses expressing each single transgene alone and KLS-3020. PH-20 promoted virus spread and tumor immune cell infiltration, IL-12 activated and reprogrammed T cells to inflammatory phenotypes, and sPD1-Fc increased intra-tumoral populations of activated T cells. The tumor-specific systemic immune response and the abscopal tumor control elicited by KLS-3020 were demonstrated in the CT26.WT tumor model. The insertion of transgenes into KLS-3020 increased its anti-tumor efficacy, supporting further clinical investigation of KLS-3020 as a novel oncolytic immunotherapy.

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) 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.

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.

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

Background: Asthma is a heterogeneous inflammatory airway disorder with various phenotypes. Quantitative computed tomography (QCT) methods can differentiate among lung diseases through accurate assessment of the location, extent, and severity of the disease. The purpose of this study was to identify asthma clusters using QCT metrics of airway and parenchymal structure, and to identify associations with visual analyses conducted by radiologists. Methods: This prospective study used input from QCT-based metrics including hydraulic diameter (Dh), luminal wall thickness (WT), functional small airway disease (fSAD), and emphysematous lung (Emph) to perform a cluster analysis and made comparisons with the visual grouping analysis conducted by radiologists based on site of airway involvement and remodeling evaluated. Results: A total of 61 asthmatics of varying severities were grouped into 4 clusters. From C1 to C4, more severe lung function deterioration, higher fixed obstruction rate, and more frequent asthma exacerbations were observed in the 5-year follow-up period. C1 presented non-severe asthma with increased WT, Dh of proximal airways, and fSAD. C2 was mixed with non-severe and severe asthmatics, and showed bronchodilator responses limited to the proximal airways. C3 and C4 included severe asthmatics that showed a reduced Dh of the proximal airway and diminished bronchodilator responses. While C3 was characterized by severe allergic asthma without fSAD, C4 included ex-smokers with high fSAD% and Emph%. These clusters correlated well with the grouping done by radiologists and clinical outcomes. Conclusions: Four QCT imaging-based clusters with distinct structural and functional changes in proximal and small airways can stratify heterogeneous asthmatics and can be a complementary tool to predict clinical outcomes.

Neuropathic pain is a chronic pain state characterized by nerve damage, inflammation, and nociceptive neuron hyperactivity. As the underlying pathophysiology is complex, a more effective therapy for neuropathic pain would be one that targets multiple elements. Here, we generated recombinant adeno-associated viruses (AAVs) encoding three therapeutic genes, namely, glutamate decarboxylase 65, glial cell-derived neurotrophic factor, and interleukin-10, with various combinations. The efficacy for pain relief was evaluated in a rat spared nerve injury model of neuropathic pain. The maximal analgesic effect was achieved when the AAVs expressing all three genes were administered to rats with neuropathic pain. The combination of two virus constructs expressing the three genes was named KLS-2031 and evaluated as a potential novel therapeutic for neuropathic pain. Single transforaminal epidural injections of KLS-2031 into the intervertebral foramen to target the appropriate dorsal root ganglion produced notable long-term analgesic effects in female and male rats. Furthermore, KLS-2031 mitigated the neuroinflammation, neuronal cell death, and dorsal root ganglion hyperexcitability induced by the spared nerve injury. These results suggest that KLS-2031 represents a promising therapeutic option for refractory neuropathic pain.

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.