Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

PURPOSE: Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. METHODS: We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. RESULTS: Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). CONCLUSIONS: SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

A Comparative Study of Endoscopic versus Percutaneous Epidural Neuroplasty in Lower Back Pain: Outcomes at Six-Month Follow Up.

Background and Objectives: Endoscopic epidural neuroplasty (EEN) facilitates adhesiolysis through direct epiduroscopic visualization, offering more precise neural decompression than that exhibited by percutaneous epidural neuroplasty (PEN). We aimed to compare the effects of EEN and PEN for 6 months after treatment with lower back and radicular pain in patients. Methods: This retrospective study compared the visual analog scale (VAS) and Oswestry disability index (ODI) scores in patients with low back and radicular pain who underwent EEN or PEN with a steering catheter. The medical records of 107 patients were analyzed, with 73 and 34 undergoing EEN and PEN, respectively. Results: The VAS and ODI scores decreased at all time points after EEN and PEN. VAS and ODI scores decreased more in the EEN group than those in the PEN group at 1 day and 1- and 6-months post-procedure, indicating superior pain relief for both lower back and radicular pain through EEN. Conclusions: EEN is a superior treatment of pain control than PEN in lower back and radicular pain patients.

Safety, Tolerability, Pharmacokinetics, and pharmacodynamics of YH35324, a novel Long-Acting High-Affinity IgETrap-Fc protein in subjects with Atopy: Results from the First-in-Human study.

BACKGROUND: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy. METHODS: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30-700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab. RESULTS: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3-9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab. CONCLUSION: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions.

Anticancer Activity of Astaxanthin-Incorporated Chitosan Nanoparticles.

Astaxanthin (AST)-encapsulated nanoparticles were fabricated using glycol chitosan (Chito) through electrostatic interaction (abbreviated as ChitoAST) to solve the aqueous solubility of astaxanthin and improve its biological activity. AST was dissolved in organic solvents and then mixed with chitosan solution, followed by a dialysis procedure. All formulations of ChitoAST nanoparticles showed small diameters (less than 400 nm) with monomodal distributions. Analysis with Fourier transform infrared (FT-IR) spectroscopy confirmed the specific peaks of AST and Chito. Furthermore, ChitoAST nanoparticles were formed through electrostatic interactions between Chito and AST. In addition, ChitoAST nanoparticles showed superior antioxidant activity, as good as AST itself; the half maximal radical scavenging concentrations (RC50) of AST and ChitoAST nanoparticles were 11.8 and 29.3 µg/mL, respectively. In vitro, AST and ChitoAST nanoparticles at 10 and 20 µg/mL properly inhibited the production of intracellular reactive oxygen species (ROSs), nitric oxide (NO), and inducible nitric oxide synthase (iNOS). ChitoAST nanoparticles had no significant cytotoxicity against RAW264.7 cells or B16F10 melanoma cells, whereas AST and ChitoAST nanoparticles inhibited the growth of cancer cells. Furthermore, AST itself and ChitoAST nanoparticles (20 µg/mL) efficiently inhibited the migration of cancer cells in a wound healing assay. An in vivo study using mice and a pulmonary metastasis model showed that ChitoAST nanoparticles were efficiently delivered to a lung with B16F10 cell metastasis; i.e., fluorescence intensity in the lung was significantly higher than in other organs. We suggest that ChitoAST nanoparticles are promising candidates for antioxidative and anticancer therapies of B16F10 cells.

Metabolic Profiling of Primary and Secondary Metabolites in Kohlrabi (Brassica oleracea var. gongylodes) Sprouts Exposed to Different Light-Emitting Diodes.

Light-emitting diode (LED) technology is one of the most important light sources in the plant industry for enhancing growth and specific metabolites in plants. In this study, we analyzed the growth, primary and secondary metabolites of 10 days old kohlrabi (Brassica oleracea var. gongylodes) sprouts exposed to different LED light conditions. The results showed that the highest fresh weight was achieved under red LED light, whereas the highest shoot and root lengths were recorded below the blue LED light. Furthermore, high-performance liquid chromatography (HPLC) analysis revealed the presence of 13 phenylpropanoid compounds, 8 glucosinolates (GSLs), and 5 different carotenoids. The phenylpropanoid and GSL contents were highest under blue LED light. In contrast, the carotenoid content was found to be maximum beneath white LED light. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) of the 71 identified metabolites using HPLC and gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) showed a clear separation, indicating that different LEDs exhibited variation in the accumulation of primary and secondary metabolites. A heat map and hierarchical clustering analysis revealed that blue LED light accumulated the highest amount of primary and secondary metabolites. Overall, our results demonstrate that exposure of kohlrabi sprouts to blue LED light is the most suitable condition for the highest growth and is effective in increasing the phenylpropanoid and GSL content, whereas white light might be used to enhance carotenoid compounds in kohlrabi sprouts.

Role of IL-22 in acute asthma mouse model.

Introduction: Allergic asthma is often associated with eosinophilic inflammation, which is related to the T-helper cell type 2 (Th2) cytokines and responsive to corticosteroids. However, there are also phenotypes of non-Th2-mediated asthma, which have poor responsivity to corticosteroids. The leading phenotype of non-Th2-mediated asthma is neutrophilic asthma, which is considered difficult to treat. Recently, IL-22 has been found to be involved in neutrophilic inflammation in asthma. However, studies on the role of IL-22 in asthma are still controversial as IL-22 has both pro-inflammatory and anti-inflammatory roles in asthma. This study examined whether the IL-22 level increased in acute neutrophilic asthma in the mouse model. Herein, we aimed to demonstrate increased IL-22 levels in neutrophilic asthma and elucidate the pathways leading to elevated neutrophil counts.Methods: Six-week old female BALB/c mice were sensitized and challenged with PBS, ovalbumin (OVA) or OVA + lipopolysaccharide (LPS). The mice were then assigned to one of the following five groups: (1) control (PBS/ PBS), (2) OVA/PBS, (3) OVA/OVA, (4) OVA+LPS/PBS, (5) OVA+LPS/OVA+LPS.Results: The levels of Th2 cytokines, IL-17, and IL-22 were assessed, with investigation of the neutrophil chemokines. This study showed that in the acute neutrophilic asthma, the levels of IL-17 and IL-22 were significantly higher than those in the OVA/OVA group, which represents acute eosinophilic asthma. Moreover, the level of CCL20 increased in the neutrophilic asthma group.Conclusion: Thus, this study suggests that in the acute neutrophilic asthma mouse model, IL-17 and IL-22 may increase with CCL20, resulting in neutrophilic inflammation.

Genetic Characteristics of Canine Adenovirus Type 2 Detected in Wild Raccoon Dogs (Nyctereutes procyonoides) in Korea (2017-2020).

Adenovirus has been detected in a wide range of hosts like dogs, foxes, horses, bats, avian animals, and raccoon dogs. Canine adenoviruses with two serotypes host mammals and are members of the mastadenovirus family. Canine adenovirus type 1 (CAdV-1) and canine adenovirus type 2 (CAdV-2) cause infectious canine hepatitis and infectious bronchial disease, respectively. In this study, we investigated the prevalence of CAdV-1 and 2 in wild Nyctereutes procyonoides in Korea in 2017-2020 from 414 tissue samples, including the liver, kidney, lung, and intestine, collected from 105 raccoon dog carcasses. Only CAdV-2 was detected in two raccoon dogs, whereas CAdV-1 was not detected. Tissue samples from raccoon dogs were screened for CAdV-1 and CAdV-2 using conventional PCR. Adenovirus was successfully isolated from PCR positive samples using the Vero cell line, and the full-length gene sequence of the isolated viruses was obtained through 5' and 3' rapid amplification of cDNA ends (RACE). The major genes of the isolated CAdV-2/18Ra54 and CAdV-2/18Ra-65 strains showed the closest relationship with that of the CAdV-2 Toronto A26/61 strain isolated from Canada in 1976. There is no large mutation between CAdV-2, which is prevalent worldwide, and CAdV-2, which is prevalent in wild animals in Korea. In addition, it is still spreading and causing infections. The Toronto A26/61 strain, which showed the most similarity to CAdV-2/18Ra-54, was likely transmitted to wild animals through vaccinated companion animals, suggesting that further research is needed on safety measures surrounding animal vaccination. This study provides information on the genetic characteristics and prevalence of canine adenovirus in domestic wild animals and provides a better understanding of canine adenovirus.

Determination of the 95% effective dose of remimazolam to achieve loss of consciousness during anesthesia induction in different age groups.

BACKGROUND: Remimazolam is a new ultra short-acting benzodiazepine originally developed as an improved version of midazolam. Recent studies have demonstrated non-inferiority of remimazolam to propofol in general anesthesia. However, to date, few studies have investigated the induction bolus dose of remimazolam required to achieve general anesthesia. We aimed to determine the 95% effective dose (ED95) of remimazolam bolus required to achieve loss of consciousness (LOC) and the appropriate doses for different age groups. METHODS: Patients aged 20-79 years with the American Society of Anesthesiologists physical status of I or II were enrolled in this study. A total of 120 patients were included representing young, middle-aged, and elderly groups. Loss of eyelash reflex and verbal response after the administration of remimazolam was considered successful LOC. The ED95 of remimazolam was determined using a biased coin up-and-down design with sequential allocation and the isotonic regression method. RESULTS: The ED95 of remimazolam for induction of general anesthesia was 0.367 mg/kg (95% CI [0.277, 0.392]) in the young group, 0.369 mg/kg (95% CI [0.266, 0.394]) in the middle-aged group, and 0.249 mg/kg (95% CI [0.199, 0.288]) in the elderly group. During the study period, none of the patients required rescue medications for hypotension or bradycardia. CONCLUSIONS: This study investigated the ED95 of remimazolam bolus for anesthesia induction. The precise dosing of the ED95 can help maintain hemodynamic stability during the induction of anesthesia.

Comparison of Temperature and Pain Changes between the Drip and Topical Methods of Administering the Transnasal Sphenopalatine Ganglion Block.

The objective of this study was to compare facial temperatures and the visual analogue scale (VAS) between the drip method and the topical method of transnasal sphenopalatine ganglion block (SPGB). The transnasal SPGB is administered to patients with facial or head and neck pain. In the transnasal approach, the drip and topical methods are frequently used. We compared facial temperatures and VAS after transnasal SPGB. Medical records of 74 patients who visited the pain clinic and underwent transnasal SPGB were retrospectively reviewed. A total of 156 transnasal SPGB were performed. The patients were divided into the drip-method and topical-method groups. Facial temperatures were measured in six areas of the right and left forehead, maxilla, and mandible before and 30 min after completion of the transnasal SPGB. Temperatures were compared before and 30 min after SPGB in each group and between the two groups. VAS scores were compared at the same times of SPGB in each group and between the two groups. In the drip-method group, there were significant increases at four areas of the face in temperature changes at 30 min after SPGB. In the topical-method group, there was no significant difference in the temperature changes at 30 min after SPGB. There were statistically significant differences in the facial temperature changes between the two groups in the right forehead (p = 0.001), left forehead (p = 0.015), and right maxillary area (p = 0.046). In herpes zoster, there were statistically significant differences in the VAS scores between before and 30 min after SPGB in both groups (p < 0.001, p = 0.008) and between two groups (p < 0.001). In migraine, there were statistically significant differences in VAS scores between before and 30 min after SPGB in both groups (p < 0.001, p = 0.004) and between two groups (p = 0.014). Transnasal SPGB using two methods showed different temperature changes and VAS scores.

Biomedical Membrane of Fish Collagen/Gellan Gum Containing Bone Graft Materials.

The development of a guided bone regeneration (GBR) membrane with non-mammalian fish collagen has the advantage of low risk for transmission of infectious diseases in tissue regeneration. In this work, a fish collagen/gellan gum and bone graft material (FC/GG-BGM) composite GBR membrane were fabricated through solution blending and casting procedures in a vacuum. The membranes were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy observation (SEM), and atomic force microscope (AFM) analyses. FT-IR results suggested that ionic interactions were formed between FC and GG both in composite powder and membranes. In vivo experiments showed that these FC/GG-BGM composite membranes could generate osteoblast minerals and promote loose bone calcification, thus accelerating bone regeneration. At 2 weeks, the defected site of rats treated with FC/GG-BGM membrane (0.377 ± 0.012 mm3) showed higher regeneration than that of rats treated with the bovine collagen membrane (0.290 ± 0.015 mm3) and control rats without membrane (0.160 ± 0.008 mm3). Compared with bovine collagen membrane, the FC/GG-BGM composite membrane displays better bone regeneration ability. Therefore, FC/GG-BGM composite membrane is suitable as a GBR membrane for bone regeneration.

Genetic diversity of bat coronaviruses and comparative genetic analysis of MERS-related coronaviruses in South Korea.

Bats have been identified as a natural reservoir of several potentially zoonotic viruses, including Lyssavirus, Ebola virus, Marburg virus, Hendra virus, Nipah virus, as well as severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus (CoV). Here, we performed a molecular epidemiological investigation of South Korean bat viruses. Genetic comparative analysis was performed on the spike glycoprotein gene of the detected MERS-related CoVs. Among 1640 samples (348 oral swabs, 1199 faecal samples, 83 urine samples and 10 bat carcass) collected across 24 South Korean provinces during 2017-2019, CoV was detected in 82 samples (75 faeces and seven oral swab samples) from 11 provinces. Surveillance over the 3 years during which samples were collected revealed significantly higher CoV detection rates between spring and autumn, and a high detection rate in Vespertillionidae and Rhinolophidae bats. Our phylogenetic analysis shows that Korean bat CoVs are genetically diverse regardless of their spatiotemporal distribution and their host species, and that the discovered bat CoVs belong to various subgenera within the Alpha- and Betacoronavirus genera. Twenty detected MERS-related CoVs belonging to the genus Betacoronavirus were similar to the Ia io bat CoV NL140422 and NL13845 strains. A comprehensive genetic analysis of two Korean bat MERS-related CoV spike receptor binding domain (RBDs) (176 and 267 strains) showed that the 18 critical residues that are involved in interactions with the human DPP4 receptor are most similar to the NL13845 strain, which is known to not bind with hDPP4. A deeper analysis of the interfacing residues in the Korean bat MERS-related CoVs RBD-hDPP4 complexes showed that the Korean bat CoVs has fewer polar contacts than the NL13845 strain. Although further study will be needed, these results suggest that Korean bat MERS-related CoVs are unlikely to bind with hDPP4. Nevertheless, these findings highlight the need for continuous monitoring to identifying the origin of new infectious diseases, specifically mutant CoV.

Experimental infection of dogs with severe fever with thrombocytopenia syndrome virus: Pathogenicity and potential for intraspecies transmission.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by infection with Dabie bandavirus [formerly SFTS virus (SFTSV)] and is an emerging zoonotic disease. Dogs can be infected with SFTSV, but its pathogenicity and transmissibility have not been fully elucidated. In experiment 1, immunocompetent dogs were intramuscularly inoculated with SFTSV. In experiment 2, immunosuppressed dogs (immunosuppressed group; oral azathioprine 5 mg/kg/day for 30 days) were intramuscularly inoculated with SFTSV. Both immunosuppressed and immunocompetent contact dogs were co-housed with the SFTSV-inoculated dogs that had been immunosuppressed. Immunocompetent SFTSV-infected dogs did not show any clinical symptom. However, immunosuppressed SFTSV-infected dogs showed high fever and weight loss without lethality. In all SFTSV-infected dogs, viral RNA could be measured in the serum only after 3 days post infection (DPI) and neutralizing antibodies were detected in the serum beginning 9 DPI. SFTSV shedding in the urine and faeces of some infected dogs occurred between 4 and 6 DPI. The immunocompromised SFTSV-infected dogs showed thrombocytopenia beginning 3 DPI to the end of the experiment (24 DPI). We confirmed SFTSV transmission to one of three immunocompetent co-housed dogs. This dog showed a high fever, weight loss, and shed viral RNA by urine. Viral RNA and neutralizing antibodies were also detected in the serum. These results demonstrated that intramuscular inoculation with SFTSV induced minor clinical symptoms in dogs, and intraspecies SFTSV transmission in dogs can occur by contact.

Platycodin D attenuates airway inflammation via suppression Th2 transcription factor in a murine model of acute asthma.

Introduction: Bronchial asthma is a common chronic inflammatory condition of the airway tissue. Platycodin D (PLD) has antiinflammatory effects in a mouse model of allergic asthma. In this work, the anti-asthma potential of PLD was studied by investigation of its effect to suppress airway inflammation and mucin production, a murine model of asthma and the possible mechanisms.Methods: Mice were randomly assigned to five experimental groups: control, ovalbumin (OVA), OVA+ICS (intranasal fluticasone), OVA+PLD and OVA+PLD/ICS. Airway histological studies were evaluated by the H&E staining; IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid were evaluated by ELISA; GATA3 and IRF4 mRNA of airway were measured by RT-PCR and their protein level were measured by Western blotting.Results: Our study showed that PLD suppressed eosinophilic inflammation and mucin production in bronchial mucosa. Moreover, PLD inhibited production of Th2 cytokines such as IL-4, IL-5, and IL-13. Protein production of GATA3 and IRF4, were also decreased in PLD treated OVA asthma model. Taken together, our results provided evidence that PLD inhibits the airway inflammation via suppression of Th2 transcription factor production.Conclusion: These findings suggest that PLD may effectively ameliorate the progression of asthma. These results suggest that PLD could be used as a therapy for allergic asthma.

Bacterial Profiles of Brain in Downer Cattle with Unknown Etiology.

Downer cow can be caused by muscular paralysis, neurological damage, metabolic disorder, and/or the complication of microbial infection. However, downer cow with unknown etiology is issued because of the non-detection of its bacterial etiological agent. In this study, differences in the bacterial community in brain tissues between downer cattle with unknown etiology and healthy slaughtered cattle are investigated. Bacterial diversity and representative genera between downer and normal cattle were significantly different (p < 0.05). There are significant differences in representative genera of downer and normal cattle, especially the significance, fold change, and area under the receiver operating characteristic curve score (p < 0.05). Furthermore, the prediction of functional genes in brain microbiota between the downer and normal cattle revealed differences in the cluster of orthologous gene categories, such as lipid transport and metabolism, secondary metabolite biosynthesis, and signal transduction (p < 0.05). This study revealed a significant difference in microbiota between the downer and normal cattle. Thus, we demonstrate that representative genera from downer cattle through 16S rRNA gene amplicon sequencing and microbiota analysis have the potential as candidates for bacterial etiological agents for downer cow.

Association between Lung Function and New-Onset Diabetes Mellitus in Healthy Individuals after a 6-Year Follow-up.

BACKGROUND: We analyzed hemoglobin A1c (HbA1c) levels and various lung function test results in healthy individuals after a 6-year follow-up period to explore the influence of lung function changes on glycemic control. METHODS: Subjects whose HbA1c levels did not qualify as diabetes mellitus (DM) and who had at least two consecutive lung function tests were selected among the people who visited a health promotion center. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV/FVC ratio, and forced expiratory flow 25% to 75% (FEF25%-75%), were divided into four groups based on their baseline quantiles. To evaluate future DM onset risk in relation to lung function changes, the correlation between baseline HbA1c levels and changes in lung function parameters after a 6-year follow-up period was analyzed. RESULTS: Overall, 17,568 individuals were included; 0.9% of the subjects were diagnosed with DM. The individuals included in the quartile with FEV1/FVC ratio values of 78% to 82% had lower risk of DM than those in the quartile with FEV1/FVC ratio values of ≥86% after adjusting for age, sex, and body mass index (P=0.04). Baseline percent predicted FEV1, FVC, FEV1/FVC ratio, and FEF25%-75%, and differences in the FEV1/FVC ratio or FEF25%-75%, showed negative linear correlations with baseline HbA1c levels. CONCLUSION: Healthy subjects with FEV1/FVC ratio values between 78% and 82% had 40% lower risk for future DM. Smaller differences and lower baseline FEV1/FVC ratio or FEF25%-75% values were associated with higher baseline HbA1c levels. These findings suggest that airflow limitation affects systemic glucose control and that the FEV1/FVC ratio could be one of the factors predicting future DM risk in healthy individuals.

Cyclo-VEGI inhibits bronchial artery remodeling in a murine model of chronic asthma.

Purpose/Aim: In the context of asthma, airway bronchial remodeling and angiogenesis in the bronchial mucosa are well established. Cyclopeptidic-vascular endothelial growth inhibitor (cyclo-VEGI) is an inhibitor of the vascular endothelial growth factor (VEGF) receptor that increases the proliferation of endothelial cells and the formation of new vessels. However, changes in the bronchial arteries of patients with asthma have not been clearly elucidated. We investigated whether structural changes occurred in bronchial arteries, as well as the effects of cyclo-VEGI in a mouse model of chronic asthma (in vivo) and human fibroblasts (in vitro). Materials and Methods: A validated mouse model of allergic airway inflammation with ovalbumin (OVA) as the causative allergen was used for the study. Mice were treated with cyclo-VEGI or fluticasone during OVA challenge. In vitro experiments were conducted to determine whether fibroblasts proliferated following elastin exposure and the effects of cyclo-VEGI on them. Results: OVA sensitization and challenge led to greater perivascular smooth muscle area, more elastic fibers, and elevated expression of vascular cell adhesion molecule (VCAM)-1 antigen. These phenomena indicated changes to bronchial arteries. Cyclo-VEGI and fluticasone treatment both inhibited airway hyper-responsiveness and inflammation. Cyclo-VEGI-treated mice exhibited decreased perivascular smooth muscle area, elastin fibers, and VCAM-1 expression. Fluticasone-treated mice exhibited reductions in perivascular smooth muscle but not in perivascular elastin or VCAM-1 expression. In vitro, fibroblast proliferation was enhanced by elastin treatment, which was inhibited by cyclo-VEGI treatment. Eotaxin expression was elevated in elastin-treated fibroblasts and decreased with cyclo-VEGI treatment. Conclusions: Vascular remodeling occurred in our mouse model of chronic asthma. Cyclo-VEGI could reduce airway inflammation and hyper-responsiveness by inhibiting VCAM-1 expression and elastin deposition around the bronchial arteries.

Astrovirus Infection in Cattle with Nonsuppurative Meningoencephalitis in South Korea.

Neurological diseases in cattle can be caused by several infectious agents. Astroviruses are increasingly recognized as the causative agent of encephalitis in various animals, including humans. In this study, a neuroinvasive astrovirus (BoAstV 20B05) was discovered in the brain tissues of an 81-month-old Korean native cattle with neurological symptoms. Lymphocyte infiltration and multifocal perivascular cuffing were observed in the cerebrum and brain stem, and viral antigens were also detected in the meninges. In particular, the concentration of the astroviral genome was high in the brain tissues. Korean BoAstV 20B05 was classified into the CH13/NeuroS1 clade and was closely related to the Neuro-Uy and KagoshimaSR28-462 strains. Our evolutionary analysis showed that Korean BoAstV 20B05 belongs to the sub-lineage NeuroS1 and evolved independently of BoAstV KagoshimaSR28-462. These results suggest that neuroinvasive astroviruses were first introduced in Korea. However, analysis is limited by the lack of reference astrovirus sequences reported in various countries within Asia, and further analysis should be performed using more strains. In this study, we identified a neuroinvasive astrovirus infection with neurological symptoms for the first time in South Korea and confirmed that BoAstV 20B05 may have been introduced in South Korea a long time ago.

The association between serum apolipoprotein B and fractional exhaled nitric oxide in bronchial asthma patients.

BACKGROUND: Asthma and lipid metabolism are associated with systemic inflammation. However, the studies about the relationship between lipid profile, fractional exhaled nitric acid (FeNO) and pulmonary function test (PFT) results are currently lacking. METHODS: We enrolled asthma patients who had serum lipid profiles including apolipoprotein levels from March 1, 2019 to December 31, 2019. We classified the asthma patients into two groups according to the diagnosis method: (I) patients who were diagnosed based on clinical symptoms/signs and PFT results and (II) patients diagnosed with clinical symptoms/signs. Clinical characteristics including age, underlying diseases, smoking status, allergy test results and treatment agents were compared between the two groups. The associations between blood cholesterol levels including apolipoprotein and pulmonary functions were analyzed. Moreover, patients were divided into two groups according to the median value of apolipoprotein B (Apo B), and lung function test results were compared between the patients who had high and low Apo B levels. RESULTS: Among the 167 patients, 93 (55.7%) were PFT-proven asthma patients. In PFT-proven asthma patients, the levels of total cholesterol (TC) (r =0.37, P=0.03), low-density lipoprotein (LDL) (r =0.46, P=0.01) and Apo B (r =0.38, P=0.02) showed a significant correlation with FeNO, which had no statistical significance in physician-diagnosed asthma group. In multivariate regression analysis, log (FeNO) showed a significant correlation with Apo B (P<0.01) after adjustment for presence of PFT-proven asthma (P=0.01) and current smoking (P=0.01). Patients with high Apo B levels had a lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (69.8 vs. 74.9, P=0.02) and lower post-BD FEV1 (%) (77.5 vs. 85.0, P=0.04) compared with those showing low Apo B levels. CONCLUSIONS: The levels of Apo B and FeNO had positive correlations and high Apo B levels were associated with severe airflow obstruction and low FEV1 (%). Apo B could reflect the uncontrolled status of bronchial asthma and poor lung function.