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The methanolic extract of the fruits of Cornus officinalis S et Z. (Cornaceae) showed the significant neuroprotective activity against glutamate-induced toxicity in HT22 hippocampal cells. Chemical profile of n-BuOH fraction of the methanolic extract of C. officinalis fruits, which showed the most potent activity, was established using HPLC-diode array detector-electrospray-MS (HPLC-DAD-ESI-MS). Through bioactivity-guided isolation, five iridoid glycosides including one new compound, 7-O-butylmorroniside (1), loganin (2), morroniside (3), 7R-O-methylmorroniside (4), 7S-O-methylmorroniside (5) were isolated from the n-BuOH fraction. The protective activities of the isolated compounds, themselves, were not statistically significant. However, the hydrolyzed products of compounds 1, 4 and 5 significantly protected glutamate-injured HT22 cells up to 78±2.2%, 60±3.2% and 59±2.5% of non-treated control, respectively. [ABSTRACT FROM AUTHOR]

Scope: Hepatitis E Virus (HEV) is a significant global health issue, impacting both low- and middle-income countries (LMICs) and industrialized nations. HEV genotypes 1 and 2, primarily transmitted through contaminated water, are endemic in LMICs, while genotypes 3 and 4 are zoonotically transmitted in industrialized regions. Acute HEV infection poses severe risks, particularly to pregnant women and immunocompromised individuals, while chronic HEV infection leads to serious complications in those with pre-existing liver disease and transplant recipients. The development of an HEV vaccine offers new prevention opportunities, though its availability and integration into global immunization programs remain limited., Methods: This position paper was developed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Viral Hepatitis Study Group (ESGVH) through an extensive review of clinical data, safety profiles, efficacy, and immunogenicity of HEV vaccines. The study group focused particularly on high-risk and special populations, synthesizing global health insights and incorporating recommendations from the Strategic Advisory Group of Experts (SAGE) to formulate strategies for wider HEV vaccination use., Questions Addressed in the Position Paper: The position paper evaluates the efficacy and safety of HEV vaccines in both general and special populations. It identifies key barriers to the integration of HEV vaccines into routine immunization programs, including infrastructure limitations, costs, and vaccine accessibility. The paper also proposes strategies to overcome these challenges and improve vaccine distribution. Furthermore, it addresses ways to enhance public awareness and international cooperation to promote HEV vaccination efforts globally., Implications: ESGVH-ESCMID recommends HEV vaccination for high-risk groups, including women of childbearing age, patients with chronic liver diseases, and immunosuppressed individuals. Prioritizing investments in vaccine logistics, integrating diagnostics, and educational outreach can enhance uptake., Competing Interests: Conflict of interest disclosure The authors declare that they have no competing interests. Neither the authors nor their institutions have at any time received payment or services from a third party for any aspect of the submitted work (data monitoring board, study design, manuscript preparation, statistical analysis, or other aspects). In the last 3 years, and not related to the current work, the authors have the following relevant financial disclosures: Susanne Dudman: No payment or support from third parties. Arjana Zerja: No payment or support from third parties. İmran Hasanoğlu: Research grants from Roche Diagnostics and Biotest. Speaker honoraria received from Pfizer and Gilead Sciences. Simona Ruta: No payment or support from third parties. Berend van Welzen: Research grant and speaker fees from Gilead Health Sciences, and speaker and advisory board fees from ViiV Healthcare, all paid to his institution. Laura Ambra Nicolini: No payment or support from third parties. Paul Yonga: Speaker honoraria from Novartis, bioMerieux, Pfizer, Terumo Blood and Cell Technologies. Advisory Boards payment from Pfizer, MSD. Industry sponsored trials as Principal Investigator for Atea Pharmaceuticals. Joakim Øverbø: No payment or support from third parties. Sumit Rawat: No payment or support from third parties. Selma Habibovic: No payment or support from third parties. Tan Bou Kim: No payment or support from third parties. Antonio Rivero-Juarez: Research grants from Gilead Sciences, Roche Diagnostics, AbbVie, Janssen Cilag, and Vircell. Speaker honoraria received from Pfizer, Gilead Sciences, Merck Sharp & Dohme, and Roche., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Asthma is a common respiratory condition with various phenotypes, non-specific symptoms and variable clinical course. The occurrence of other respiratory conditions with asthma, respiratory co-morbidities (RCs), is not unusual. A literature search was performed for asthma and a variety of respiratory co-morbidities using Pub-Med for the years 2019-2024. The 5 conditions with the largest number of references, other than rhinitis and rhinosinusitis addressed in another paper in this issue, or which are the most problematic in the authors' clinical experience are summarized. Others are briefly discussed. The diagnosis and treatment of both asthma and RCs are complicated by the overlap of symptoms and signs. Recognizing RCs is especially problematic in adult onset, non-type 2 asthma as there are no biomarkers to assist in confirming non-type 2 asthma. Treatment decisions in subjects with suspected asthma and RCs are complicated by the potential similarities between the symptoms or signs of the RC and asthma, the absence of a sine quo non for the diagnosis of asthma, the likelihood that many RCs improve with systemic corticosteroids, and the possibility that the manifestations of the RCs are misattributed to asthma or vice versa. Recognition of RCs is critical to the effective management of asthma, particularly severe or difficult to treat asthma., (Copyright © 2024. Published by Elsevier Inc.)

Background: Episodic angioedema with eosinophilia, also known as Gleich's syndrome, is a differential diagnosis in patients with recurrent angioedema with higher blood eosinophils. Meanwhile, less has been elucidated regarding non-episodic angioedema with eosinophilia (NEAE). This study aimed to examine the prevalence, clinical characteristics, and disease course of NEAE., Methods: By reviewing the electronic medical records, we identified patients with NEAE among those referred to allergy clinics due to eosinophilia from January 2021 to December 2023 at Asan Medical Center., Results: Among 687 patients with eosinophilia, 58 (8.4%) were diagnosed with and treated for NEAE. All patients were females, with a mean age of 31.79 years. The mean absolute blood eosinophil count was 4468.76 cells/μL. All patients reported symmetric angioedema of the lower legs, and 37 (63.8%) had additional angioedema of the upper arms. Twenty-five (43.1%) patients reported a preceding event prior to onset of angioedema. Systemic corticosteroids (mean total dose 1745 ± 508.49 mg) were prescribed to all patients, with a treatment duration of approximately 40 days to achieve resolution. Following the resolution of angioedema, 6 patients experienced persistent arthralgia, 1 developed chronic spontaneous urticaria, and 1 developed hypereosinophilic syndrome., Conclusions: NEAE is an essential differential diagnosis in young female patients with eosinophilia, particularly those presenting with symmetric peripheral angioedema., Competing Interests: The authors declare that there is no conflict of interest to declare., (© 2024 The Author(s).)

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39 + CD9 + interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39 + CD9 + IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39 + CD9 + IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39 + CD9 + IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39 + CD9 + IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma., (© 2024. The Author(s).)

Background: Limited data are available on the prescription patterns and efficacy of antitussives and expectorants for patients with acute and chronic cough. This study examined the use and efficacy of these medications in a nationally representative sample of Korean patients., Methods: We examined 4,206,016 individuals from the National Health Insurance Service (NHIS)-National Health Information Database (NHID) between 2015 and 2017. Among them, a sample of 10% (n=420,602) was retrieved for the diagnosis of respiratory diseases using the International Classification of Diseases, 10 th edition (ICD-10; J00-J99), or the prescription of antitussives and expectorants for cough (ICD-10; R05). The acute cough group included those who were prescribed medications within 4 weeks of initial diagnosis (prescription within 14 days), whereas the chronic cough group included patients who were prescribed medications within 16 weeks of initial diagnosis (prescription within 56 days). If the prescription was discontinued or not changed to an alternative drug after the initial prescription, these cases were considered to have achieved symptom relief., Results: This study included 288,460 patients (971,065 cases) with acute cough and 5,888 patients (15,399 cases) with chronic cough. 'Expectorants, excluding combinations with cough suppressants' had the highest prescription rates in both groups (acute cough, 63.8%; chronic cough, 61.7%), and showed the highest symptom relief regardless of the number of medications prescribed (acute cough, 84.3%; chronic cough, 70.4%)., Conclusions: 'Expectorants, excluding combinations with cough suppressants' were the most prescribed and effective medications for relieving cough symptoms in Korea patients. Further studies are needed to determine the optimal duration for using antitussives and expectorants in cough management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1744/coif). The series “Cough Section” was commissioned by the editorial office without any funding or sponsorship. W.J.S. served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Journal of Thoracic Disease. The authors have no other conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

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). The total scores and subscores of all domains of the QLQAKA, SAQ, and EQ-5D improved significantly 6 months after biologic therapy but not after conventional therapy. The total QLQAKA, SAQ, and EQ-5D scores improved after 6 months in the anti-IL-5 ( P  < 0.05) and anti-IL-4/IL-13 ( P  < 0.05) treatment groups with no significant difference between groups ( 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., Competing Interests: The authors declare that they have no relevant conflicts of interest., (© 2024 The Authors.)

Background:  The Accreditation Council for Graduate Medical Education suggests that Clinical Informatics (CI) fellowship programs foster broad skills, which include collaboration and project management. However, they do not dictate how to best accomplish these learning objectives., Objectives:  This study aimed to describe a standard approach to project-based learning for CI, to share its implementation, and to discuss lessons learned., Methods:  We created a standard approach to project-based learning based on concepts from adult learning theory, the project life cycle framework, the Toyota Production System, and Improvement Science., Results:  With this standard approach in place, we learned how best to support fellows in its use. In addition to this approach to supporting needs assessment, risk/change management, implementation, and evaluation/improvement skills, we found the need to develop fellow skills in collaboration, leadership, and time management/managing up. Supported by project-based learning using this standard approach, and with targeted project selection to meet topic-based learning objectives, fellows reached the ability to practice independently in 15 to 21 months., Discussion:  Fellows are uniquely positioned to ensure the success of projects due to their increased availability and protected time compared with attendings. They are readily available for project teams to draw upon their expertise with clinical workflows and understanding of technological solutions. Project-based learning addressing organizational priorities complements fellow project management coursework and improves fellows' ability to function successfully in large, complex, and dynamic organizations. Exposing fellows to contemporary problems, then addressing them through projects, provides fellows with up-to-date applied informatics knowledge., Conclusion:  Project-based learning can ensure that many general CI learning objectives are supported inherently. It reinforces project management teachings, while providing fellows with a marketable project portfolio to aid with future job applications. Having projects tightly aligned with organizational priorities supports ongoing investment in fellowship programs., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients., Objective: This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use., Methods: Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines., Results: In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients., Conclusion: These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively., Methods: The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma., Results: The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts., Conclusions: The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Objective: To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma., Materials and Methods: Korean participants enrolled in a prospective multicenter study, named the Precision Medicine Intervention in Severe Asthma study, from May 2020 to August 2021, underwent baseline and follow-up chest CT scans (inspiration/expiration) 10-12 months apart, before and after biologic treatment. Two radiologists scored bronchiectasis severity and mucus plugging extent. Quantitative parameters were obtained from each CT scan as follows: normal lung area (normal), air trapping without emphysema (AT without emph), air trapping with emphysema (AT with emph), and airway (total branch count, Pi10). Clinical parameters, including pulmonary function tests (forced expiratory volume in 1 s [FEV1] and FEV1/forced vital capacity [FVC]), sputum and blood eosinophil count, were assessed at initial and follow-up stages. Changes in CT parameters were correlated with changes in clinical parameters using Pearson or Spearman correlation., Results: Thirty-four participants (female:male, 20:14; median age, 50.5 years) diagnosed with severe asthma from three centers were included. Changes in the bronchiectasis and mucus plugging extent scores were negatively correlated with changes in FEV1 and FEV1/FVC (ρ = from -0.544 to -0.368, all P < 0.05). Changes in quantitative CT parameters were correlated with changes in FEV1 (normal, r = 0.373 [ P = 0.030], AT without emph, r = -0.351 [ P = 0.042]), FEV1/FVC (normal, r = 0.390 [ P = 0.022], AT without emph, r = -0.370 [ P = 0.031]). Changes in total branch count were positively correlated with changes in FEV1 ( r = 0.349 [ P = 0.043]). There was no correlation between changes in Pi10 and the clinical parameters ( P > 0.05)., Conclusion: Visual and quantitative CT parameters of normal, AT without emph, and total branch count may be effective for evaluating treatment response in patients with severe asthma., Competing Interests: Joon Beom Seo, who holds the respective position of Editorial Board Member of the Korean Journal of Radiology, was not involved in the editorial evaluation or decision to publish this article. The remaining author has declared no conflicts of interest., (Copyright © 2024 The Korean Society of Radiology.)

The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, P = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 ( P = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, P = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

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., Competing Interests: The authors have no conflict of interest relevant to this article to disclose., (© 2024 The Authors.)

Background: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy., Objective: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA., Methods: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time., Results: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group., Conclusion: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period., Trial Registration: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939)., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2023 American College of Allergy, Asthma & Immunology. All rights reserved.)

Background: Pulmonary hypertension (PH) is a complication of chronic kidney disease (CKD) that contributes to mortality. Sclerostin, a SOST gene product that reduces osteoblastic bone formation by inhibiting Wnt/β-catenin signaling, is involved in arterial stiffness and CKD-bone mineral disease, but scanty evidence to PH. This study explored the relationship between sclerostin and PH in CKD 5, pre-dialysis end-stage kidney disease (ESKD) patients., Methods: This cross-sectional prospective observational cohort study included 44 pre-dialysis ESKD patients between May 2011 and May 2015. Circulating sclerostin levels were measured using an enzyme-linked immunosorbent assay. PH was defined as an estimated pulmonary artery systolic pressure > 35 mmHg on echocardiography., Results: Patients with higher sclerostin levels ≥ 218.18pmol/L had echocardiographic structural cardiac abnormalities, especially PH (P < 0.01). On multivariate logistic analysis, sclerostin over 218.19pmol/L was significantly associated with PH (odds ratio [OR], 41.14; 95% confidence interval [CI], 4.53-373.89, P < 0.01), but multivariate Cox regression analysis showed the systemic vascular calcification score over 1 point (Hazard ratio [HR] 11.49 95% CI 2.48-53.14, P = 0.002) and PH ([HR] 5.47, 95% CI 1.30-23.06, P = 0.02) were risk factors for all-cause mortality in pre-dialysis ESKD patients., Conclusions: Serum sclerostin and PH have a positive correlation in predialysis ESKD patients. The higher systemic vascular calcification score and PH have an association to increase all-cause mortality in pre-dialysis ESKD patients., (© 2024. The Author(s).)

All-bands-flat topological photonic insulators are photonic lattices with all dispersionless bulk bands separated by nontrivial bandgaps. A distinct feature of these systems is that the edge modes can be excited across the flatband frequencies without scattering into the localized bulk modes, thus allowing the edge mode spectrum to extend beyond the gap size. Here we exploit the wide edge mode spectrum of a Floquet-Lieb topological insulator with all flatbands to achieve broadband frequency generation by four-wave mixing on a topological silicon photonic platform. Our all-bands-flat Floquet insulator is based on a Lieb lattice of microring resonators with perfect couplings, which provides a wide frequency generation bandwidth spanning more than six microring's free spectral ranges. The all-bands-flat microring lattice can also serve as a robust topological platform for other broadband nonlinear processes such as stimulated Raman scattering, frequency comb generation, supercontinuum generation, and soliton propagation based on topologically protected edge modes.

Background: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive., Objective: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT., Methods: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV 1 ). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment., Results: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV 1 after 1 month. A significant association was found between low baseline FEV 1 and high blood eosinophil count and sustained FEV 1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV 1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98])., Conclusion: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In previous studies, several asthma phenotypes were identified using clinical and demographic parameters. Transcriptional phenotypes were mainly identified using sputum and bronchial cells., Objective: We aimed to investigate asthma phenotypes via clustering analysis using clinical variables and compare the transcription levels among clusters using gene expression profiling of the blood., Methods: Clustering analysis was performed using 6 parameters: age of asthma onset, body mass index, pack-years of smoking, forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, and blood eosinophil counts. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples and RNA was extracted from selected PBMCs. Transcriptional profiles were generated (Illumina NovaSeq 6000) and analyzed using the reference genome and gene annotation files (hg19.refGene.gft). Pathway enrichment analysis was conducted using GO, KEGG, and REACTOME databases., Results: In total, 355 patients with asthma were included in the analysis, of whom 72 (20.3%) had severe asthma. Clustering of the 6 parameters revealed 4 distinct subtypes. Cluster 1 (n = 63) had lower predicted FEV1 % and higher pack-years of smoking and neutrophils in sputum. Cluster 2 (n = 43) had a higher proportion and number of eosinophils in sputum and blood, and severe airflow limitation. Cluster 3 (n = 110) consisted of younger subjects with atopic features. Cluster 4 (n = 139) included features of late-onset mild asthma. Differentially expressed genes between clusters 1 and 2 were related to inflammatory responses and cell activation. Th17 cell differentiation and interferon gamma-mediated signaling pathways were related to neutrophilic inflammation in asthma., Conclusion: Four clinical clusters were differentiated based on clinical parameters and blood eosinophils in adult patients with asthma form the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA) cohort. Gene expression profiling and molecular pathways are novel means of classifying asthma phenotypes., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Author(s).)

Background: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known., Methods: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea. Obesity was defined as a body mass index value of ≥ 30 kg/m²., Results: The most common disease was IgA nephropathy (IgAN) in both obese and non-obese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37-2.17; OR, 1.96, 95% CI, 1.21-3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62-0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01-2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36-8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09-5.64)., Conclusion: Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

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., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Author(s).)

Background: Artificial intelligence (AI) is changing our life, including the medical field. Repeated machine learning using big data made various fields more predictable and accurate. In medicine, IBM Watson for Oncology (WFO), trained by Memorial Slone Kettering Cancer Center (MSKCC), was first introduced and applied in 14 countries worldwide.Our study was designed to assess the feasibility of WFO in actual clinical practice. We aimed to investigate the concordance rate between WFO and multidisciplinary tumor board (MTB) in Urologic cancer patients., Materials and Methods: We reviewed retrospectively collected data for consecutive patients who underwent WFO and MTB simultaneously in the diagnosis of urologic malignancy before determining further treatment between August 2017 and September 2020. We compared the recommendation of the AI system, WFO (IBM Watson Health, Cambridge, MA), with the opinion of MTB for further managing all patients diagnosed with urologic malignancies such as prostate, bladder, and kidney cancer., Results: A total of 55 patients were enrolled in our study. The number of patients with prostate cancer was 48. The number of bladder and kidney cancer patients was 5 and 2, respectively. The overall concordance rate between WFO and MTB was 92.7%. Three patients could not suggest proper treatment options using WFO, and the recommended choice of WFO was not feasible in the Korean Health Insurance Review and Assessment Service., Conclusions: The decision of WFO showed a high concordance rate with a multidisciplinary tumor board for urologic oncology. However, some recommendations of WFO were not feasible in actual practice, and WFO still has some points to improve and modify. Interestingly, applying WFO is likely to facilitate a multidisciplinary team approach., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Background: Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning., Objective: To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast., Methods: This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting β2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group)., Results: There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls., Conclusions: We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period., (Copyright © 2023. Published by Elsevier Inc.)

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., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Smoking and sodium intake (SI) have been evaluated as risk factors for kidney disease; however, the data are inconsistent. We assessed the association between SI and cotinine-verified smoking status and the risk of albuminuria., Methods: An observational study using the Korea National Health and Nutrition Examination Survey (2008-2011 and 2014-2018) was performed. We included 37,410 adults with an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 . The smoking status was assumed based on the urine cotinine/creatinine ratio (Ucot/Ucrea). SI was estimated from spot urine sodium using the Kawasaki formula., Results: Ucot/Ucrea levels were significantly higher in current smokers (920.22 ± 9.00 ng/mg) than in ex-smokers and nonsmokers (48.31 ± 2.47 and 23.84 ± 1.30 ng/mg) (p < 0.001). Ucot/Ucrea levels were significantly higher in second-hand smokers than in participants without a history of smoking (p < 0.001). Ucot/ Ucrea levels were positively associated with SI (p for trend < 0.001). Smoking status was not associated with albuminuria. SI had a linear relationship with albuminuria (p < 0.001). In groups with the highest Ucot/Ucrea levels, the highest SI quartile indicated a significantly higher risk of albuminuria than that in the lowest quartile (risk ratio, 2.22; 95% confidence interval, 1.26-3.92; p = 0.006). The risk of albuminuria was not significant in groups with the lowest and middle tertile adjusted for multiple risk factors., Conclusion: Smokers consume higher dietary sodium and dietary SI was positively related to the risk of albuminuria. Smoking is not associated with albuminuria as a single factor. The risk of albuminuria is the higher in participants with smoking and high SI.

Background: More than 200 asthma-associated genetic variants have been identified in genome-wide association studies (GWASs). Expression quantitative trait loci (eQTL) data resources can help identify causal genes of the GWAS signals, but it can be difficult to find an eQTL that reflects the disease state because most eQTL data are obtained from normal healthy subjects., Methods: We performed a blood eQTL analysis using transcriptomic and genotypic data from 433 Korean asthma patients. To identify asthma-related genes, we carried out colocalization, Summary-based Mendelian Randomization (SMR) analysis, and Transcriptome-Wide Association Study (TWAS) using the results of asthma GWASs and eQTL data. In addition, we compared the results of disease eQTL data and asthma-related genes with two normal blood eQTL data from Genotype-Tissue Expression (GTEx) project and a Japanese study., Results: We identified 340,274 cis-eQTL and 2,875 eGenes from asthmatic eQTL analysis. We compared the disease eQTL results with GTEx and a Japanese study and found that 64.1% of the 2,875 eGenes overlapped with the GTEx eGenes and 39.0% with the Japanese eGenes. Following the integrated analysis of the asthmatic eQTL data with asthma GWASs, using colocalization and SMR methods, we identified 15 asthma-related genes specific to the Korean asthmatic eQTL data., Conclusions: We provided Korean asthmatic cis-eQTL data and identified asthma-related genes by integrating them with GWAS data. In addition, we suggested these asthma-related genes as therapeutic targets for asthma. We envisage that our findings will contribute to understanding the etiological mechanisms of asthma and provide novel therapeutic targets., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Motivation: Asthma is a heterogeneous disease where various subtypes are established and molecular biomarkers of the subtypes are yet to be discovered. Recent availability of multi-omics data paved a way to discover molecular biomarkers for the subtypes. However, multi-omics biomarker discovery is challenging because of the complex interplay between different omics layers., Results: We propose a deep attention model named Gene-level biomarker discovery from multi-Omics data using graph ATtention neural network (GOAT) for identifying molecular biomarkers for eosinophilic asthma subtypes with multi-omics data. GOAT identifies genes that discriminate subtypes using a graph neural network by modeling complex interactions among genes as the attention mechanism in the deep learning model. In experiments with multi-omics profiles of the COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) asthma cohort of 300 patients, GOAT outperforms existing models and suggests interpretable biological mechanisms underlying asthma subtypes. Importantly, GOAT identified genes that are distinct only in terms of relationship with other genes through attention. To better understand the role of biomarkers, we further investigated two transcription factors, CTNNB1 and JUN, captured by GOAT. We were successful in showing the role of the transcription factors in eosinophilic asthma pathophysiology in a network propagation and transcriptional network analysis, which were not distinct in terms of gene expression level differences., Availability and Implementation: Source code is available https://github.com/DabinJeong/Multi-omics&#95;biomarker. The preprocessed data underlying this article is accessible in data folder of the github repository. Raw data are available in Multi-Omics Platform at http://203.252.206.90:5566/, and it can be accessible when requested., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Empirical therapy with oral histamine-1 receptor antagonists (H1RAs) is often used for patients with suspected upper airway cough syndrome. No placebo-controlled trials with nonsedating H1RAs (nsH1RAs) have evaluated validated cough outcomes. The objective of the present study was to assess the effect of an nsH1RA, bepotastine, on cough outcomes in patients with allergic rhinitis and persistent cough., Methods: A randomised, double-blind, placebo-controlled trial was conducted. Adult patients with persistent cough (>3 weeks in duration) and symptomatic allergic rhinitis were recruited and randomly assigned to receive either bepotastine or placebo at a 1:1 ratio. The primary outcome was cough-specific quality of life assessed using the Leicester Cough Questionnaire (LCQ). Secondary outcomes included cough severity visual analogue scale (VAS), throat VAS, Cough Hypersensitivity Questionnaire, Sinonasal Outcome Test-22 score and drug adverse events., Results: Between October 2021 and September 2022, 50 participants (43 females; mean age 46.28 years; median cough duration 3 months) were assigned to either the bepotastine 10 mg twice daily or placebo group in a 1:1 ratio. After 2 weeks of treatment, both bepotastine and placebo groups showed significant improvements in the LCQ scores, but there was no significant difference in the magnitude of change between the groups (3.45±2.10 versus 3.04±2.94, p=0.576). Secondary outcomes were also comparable., Conclusions: Despite the relatively small sample size, our study clearly demonstrated that a 2-week treatment with bepotastine did not provide therapeutic benefits for cough outcomes. These findings suggest against the use of nsH1RAs with the intention of improving cough outcomes, even in patients with persistent cough and allergic rhinitis., Competing Interests: Conflict of interest: W-J. Song is deputy chief editor of this journal. The other authors declare that they have no competing interests., (Copyright ©The authors 2023.)

Background: Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity is common; however, many patients do not receive an accurate diagnosis and are using unnecessary alternative drugs or have medication restrictions., Objective: To establish a protocol for provocation tests that can be performed safely and effectively at home to give patients an accurate diagnosis, whereas also delabeling NSAID hypersensitivity., Methods: We retrospectively analyzed the medical records of 147 patients with NSAID hypersensitivity. All patients had NSAID-induced urticaria/angioedema with less than 10% body surface area skin involvement. One specialist developed the protocol through history taking and chart review. If NSAID hypersensitivity was confirmed, an oral provocation test was performed to confirm the safe alternative medications (group A). If it was undetermined, an oral provocation test was performed to confirm the diagnosis and alternative medications (group B). All oral provocation tests were performed by patients in their homes according to the protocol., Results: Approximately 26% of group A patients had urticaria or angioedema symptoms with alternative drugs, whereas the remaining 74% was safe. In group B, 34% of the patients were diagnosed with having NSAID hypersensitivity. However, 61% did not respond to the culprit drug; therefore, NSAID hypersensitivity had been misdiagnosed. During this at-home self-provocation test, no severe hypersensitivity reactions occurred., Conclusion: Many patients originally suspected of having NSAID hypersensitivity were confirmed to have been misdiagnosed. We successfully conducted an effective and safe at-home self-provocation test., (Copyright © 2023. Published by Elsevier Inc.)

Background: The rapid development and rollout of vaccines against coronavirus disease 2019 (COVID-19) has led to more than half of the world's population being vaccinated to date. Real-world data have reported various adverse cutaneous reactions, including delayed-onset urticaria, which was highly ranked as a common manifestation across studies. However, the impact of these novel mRNA or viral vector COVID-19 vaccines on preexisting chronic spontaneous urticaria (CSU) remains largely unknown., Objective: To investigate the impact of COVID-19 vaccination on the clinical status of patients with relatively stable CSU who are undergoing omalizumab treatment and to identify risk factors for exacerbation., Methods: We conducted a questionnaire-based cross-sectional study in a tertiary hospital. Adult patients with relatively stable CSU under regular omalizumab treatments who had received at least one COVID-19 vaccination were included., Results: There were 105 study subjects who received 230 COVID-19 vaccinations between March and December 2021. Fifteen patients (14.3%) experienced aggravation of urticaria at least once after COVID-19 vaccination. The demographics and clinical characteristics of the patients were comparable regardless of the exacerbation of CSU. However, case-level analysis revealed that the presence of urticaria (vs none) before vaccination (odds ratio [OR] = 4.99; 95% CI, 1.57-15.82) and the development of systemic reactogenicity (OR = 4.57; 95% CI, 1.62-12.90) were associated with a higher risk for exacerbation., Conclusions: The novel COVID-19 vaccination induced exacerbation in more than one-tenth of patients with well-controlled CSU. The establishment of a proper management strategy during COVID-19 vaccination is necessary for patients with CSU., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The extent of differences between genetic risks associated with various asthma subtypes is still unknown. To better understand the heterogeneity of asthma, we employed an unsupervised method to identify genetic variants specifically associated with asthma subtypes. Our goal was to gain insight into the genetic basis of asthma., Methods: In this study, we utilized the UK Biobank dataset to select asthma patients (All asthma, n = 50,517) and controls (n = 283,410). We excluded 14,431 individuals who had no information on predicted values of forced expiratory volume in one second percent (FEV1%) and onset age, resulting in a final total of 36,086 asthma cases. We conducted k-means clustering based on asthma onset age and predicted FEV1% using these samples (n = 36,086). Cluster-specific genome-wide association studies were then performed, and heritability was estimated via linkage disequilibrium score regression. To further investigate the pathophysiology, we conducted eQTL analysis with GTEx and gene-set enrichment analysis with FUMA., Results: Clustering resulted in four distinct clusters: early onset asthma normalLF (early onset with normal lung function, n = 8172), early onset asthma reducedLF (early onset with reduced lung function, n = 8925), late-onset asthma normalLF (late-onset with normal lung function, n = 12,481), and late-onset asthma reducedLF (late-onset with reduced lung function, n = 6508). Our GWASs in four clusters and in All asthma sample identified 5 novel loci, 14 novel signals, and 51 cluster-specific signals. Among clusters, early onset asthma normalLF and late-onset asthma reducedLF were the least correlated (r g  = 0.37). Early onset asthma reducedLF showed the highest heritability explained by common variants (h 2  = 0.212) and was associated with the largest number of variants (71 single nucleotide polymorphisms). Further, the pathway analysis conducted through eQTL and gene-set enrichment analysis showed that the worsening of symptoms in early onset asthma correlated with lymphocyte activation, pathogen recognition, cytokine receptor activation, and lymphocyte differentiation., Conclusions: Our findings suggest that early onset asthma reducedLF was the most genetically predisposed cluster, and that asthma clusters with reduced lung function were genetically distinct from clusters with normal lung function. Our study revealed the genetic variation between clusters that were segmented based on onset age and lung function, providing an important clue for the genetic mechanism of asthma heterogeneity., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

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., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Severe asthma, compared with mild to moderate asthma, has a larger impact on the quality of life (QOL) of the affected patients and their families. These findings underscore the need for patient-reported outcomes that are specific to severe asthma. The Severe Asthma Questionnaire (SAQ) is a validated disease-specific questionnaire that addresses the impact of severe asthma on patients. The present study aimed to develop the Korean language version of the SAQ (SAQ-K), with the translation and linguistic validation., Methods: The development of SAQ-K was achieved through a process of forward translation, reconciliation, back translation, reconciliation, cognitive debriefing involving severe asthmatics, proofreading, and the final report., Results: Two medical personnel who were fluent in Korean and English independently translated the original English version of the SAQ into Korean. After incorporating these translations into a single reconciled version, two other bilingual personnel translated the Korean draft back into English. Discrepancies between the original form and the first Korean translation were then reviewed by the panel. The translated questionnaire was then tested in cognitive debriefing interviews with 15 severe asthma patients. Through this cognitive debriefing process, the second version was verified and finally proofread to check for spelling, grammar, layout, and formatting as the final version., Conclusions: We have generated the SAQ-K to enable clinicians and researchers to assess the health status of severe asthma patients in Korea., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1415/coif). WJS serves as an unpaid editorial board member of Journal of Thoracic Disease, and declares academic grants from MSD, consulting fees from MSD, GSK, AstraZeneca, and Novartis, and honoraria from MSD, GSK, AstraZeneca, and Novartis. However, these companies are not directly related to this work. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

This prospective observational study examined whether Staphylococcus aureus (SA) nasal colonization and staphylococcal enterotoxin (SE)-specific IgE sensitization synergistically affect clinical outcomes of adults with late-onset asthma (onset age ≥ 40 years). Nasal swabs were taken to evaluate SA colonization. Serum SE-IgE level was measured. Subjects were classified into 4 groups according to SA colonization and SE-IgE sensitization positivity. Among 181 patients with late-onset asthma recruited, the proportions of SA/SE (‒/‒), SA/SE (+ /‒), SA/SE (‒/ +), and SA/SE (+ / +) were 33.7%, 15.5%, 28.2%, and 22.6%, respectively. Severe asthma was more frequent in the SA/SE (+ / +) group than in the SA/SE (‒/‒) group (41.5% vs. 13.1%). The relationship of SA/SE (+ / +) with severe asthma was significant in multivariate logistic regression (vs. SA/SE (‒/‒); adjusted odds ratio: 4.36; 95% confidence intervals: 1.50‒12.73; p = 0.007), whereas SA/SE (+ /‒) or SA/SE (‒/ +) was not. In conclusion, SA nasal colonization and SE-IgE sensitization may synergistically affect disease severity in late-onset asthmatics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cough is one of the most common symptoms of acute coronavirus disease 2019, but cough may persist for weeks or months. This study aimed to examine the clinical characteristics of patients with post-coronavirus disease (COVID) persistent cough in the Omicron era. We conducted a pooled analysis comparing 3 different groups: 1) a prospective cohort of post-COVID cough (> 3 weeks; n = 55), 2) a retrospective cohort of post-COVID cough (> 3 weeks; n = 66), and 3) a prospective cohort of non-COVID chronic cough (CC) (> 8 weeks; n = 100). Cough and health status was assessed using patient-reported outcomes (PROs). Outcomes, including PROs and systemic symptoms, were longitudinally evaluated in the prospective post-COVID cough registry participants receiving usual care. A total of 121 patients with post-COVID cough and 100 with non-COVID CC were studied. Baseline cough-specific PRO scores did not significantly differ between post-COVID cough and non-COVID CC groups. There were no significant differences in chest imaging abnormality or lung function between groups. However, the proportions of patients with fractional exhaled nitric oxide (FeNO) ≥ 25 ppb were 44.7% in those with post-COVID cough and 22.7% in those with non-COVID CC, which were significantly different. In longitudinal assessment of the post-COVID registry (n = 43), cough-specific PROs, such as cough severity or Leicester Cough Questionnaire (LCQ) scores, significantly improved between visits 1 and 2 (visit interval: median 35 [interquartile range, IQR: 23-58] days). In the LCQ score, 83.3% of the patients showed improvement (change ≥ +1.3), but 7.1% had worsened (≤ -1.3). The number of systemic symptoms was median 4 (IQR: 2-7) at visit 1 but decreased to median 2 (IQR: 0-4) at visit 2. In summary, post-COVID persistent cough was similar in overall clinical characteristics to CC. Current cough guideline-based approaches may be effective in most patients with post-COVID cough. Measurement of FeNO levels may also be useful for cough management., Competing Interests: W.-J.S. declares grants from Merck Sharp & Dohme Corp. and AstraZeneca, consulting fees from Merck, AstraZeneca, Shionogi and GSK, and lecture fees from Merck, AstraZeneca, GSK and Novartis. Other authors declare that they have no competing interests., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)