Successful Treatment of Mucus Plug Due to Allergic Bronchopulmonary Aspergillosis Using Dupilumab.

Allergic bronchopulmonary aspergillosis (ABPA) often necessitates treatment with systemic steroids and antifungals, which are associated with relapses and side effects. We report an 82-year-old woman with eosinophilic asthma, experiencing sputum production and dyspnea, who was diagnosed with ABPA based on her chest CT, pulmonary function tests, and elevated blood eosinophils and immunoglobulin E. Due to the presence of osteoporosis and diabetes, standard steroid therapy was considered a high risk. Instead, we administered dupilumab, an interleukin 4 receptor alpha (IL4-Rα) antibody targeting Th2 cytokine signaling. Remarkable improvements were observed within two weeks, including reduced sputum and dyspnea. After 12 weeks, significant enhancements in asthma control and lung function, along with decreased fractional exhaled nitric oxide (FeNO) levels were noted, with chest CT showing resolution of most of the mucus plugs. This case demonstrates dupilumab's potential as a viable ABPA treatment alternative, particularly for patients who are unsuitable for systemic steroids. More research on the long-term effectiveness and safety of such biologics is needed.

Study on Predicting Clinical Stage of Patients with Bronchial Asthma Based on CT Radiomics.

Objective: To explore the value of a new model based on CT radiomics in predicting the staging of patients with bronchial asthma (BA). Methods: Patients with BA from 2018 to 2021 were retrospectively analyzed and underwent plain chest CT before treatment. According to the guidelines for the prevention and treatment of BA (2016 edition), they were divided into two groups: acute attack and non-acute attack. The images were processed as follows: using Lung Kit software for image standardization and segmentation, using AK software for image feature extraction, and using R language for data analysis and model construction (training set: test set = 7: 3). The efficacy and clinical effects of the constructed model were evaluated with ROC curve, sensitivity, specificity, calibration curve and decision curve. Results: A total of 112 patients with BA were enrolled, including 80 patients with acute attack (range: 2-86 years old, mean: 53.89±17.306 years old, males of 33) and 32 patients with non-acute attack (range: 4-79 years old, mean: 57.38±19.223 years old, males of 18). A total of 10 imaging features are finally retained and used to construct model using multi-factor logical regression method. In the training group, the AUC, sensitivity and specificity of the model was 0.881 (95% CI:0.808-0.955), 0.804 and 0.818, separately; while in the test group, it was 0.792 (95% CI:0.608-0.976), 0.792 and 0.80, respectively. Conclusion: The model constructed based on radiomics has a good effect on predicting the staging of patients with BA, which provides a new method for clinical diagnosis of staging in BA patients.

Potential Impact of SOD2 (rs4880; p.Val16Ala) Variant with the Susceptibility for Childhood Bronchial Asthma.

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.

Impacto pronóstico de la enfermedad pulmonar obstructiva crónica y el asma bronquial en pacientes con insuficiencia cardiaca / Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure

Propósito Analizar el impacto de la enfermedad pulmonar obstructiva crónica (EPOC) y el asma bronquial sobre el manejo terapéutico y el pronóstico de los pacientes con insuficiencia cardiaca (IC). Métodos Análisis de la información contenida en un registro clínico de pacientes remitidos a una unidad especializada de IC entre enero de 2010 y junio de 2022. Se compararon su perfil clínico, el tratamiento y el pronóstico en base a la presencia de EPOC o asma bronquial. El análisis de supervivencia se realizó mediante los métodos de Kaplan-Meier y Cox. La mediana de seguimiento fue de 1.493 días. Resultados Se estudiaron 2.577 pacientes, de los cuales 251 (9,7%) presentaban EPOC y 96 (3,7%), asma bronquial. Observamos diferencias significativas entre los tres grupos con respecto a la prescripción de betabloqueantes (EPOC=89,6%; asma=87,5%; no broncopatía=94,1%; p=0,002) e inhibidores del cotransportador de sodio-glucosa tipo2 (EPOC=35,1%; asma=50%; no broncopatía=38,3%; p=0,036). Además, los pacientes con patología bronquial recibieron con menor frecuencia un desfibrilador (EPOC=20,3%; asma=20,8%; no broncopatía=29%; p=0,004). La presencia de EPOC se asoció de forma independiente con mayor riesgo de muerte por cualquier causa (HR=1,64; IC95%: 1,33-2,02), muerte u hospitalización por IC (HR=1,47; IC95%: 1,22-1,76) y muerte cardiovascular o trasplante cardiaco (HR=1,39; IC95%: 1,08-1,79) en comparación con la ausencia de broncopatía. La presencia de asma bronquial no se asoció a un impacto significativo sobre los desenlaces analizados. Conclusiones La EPOC, pero no el asma bronquial, es un factor pronóstico adverso e independiente en pacientes con IC. (AU)

Purpose To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). Methods Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. Results We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; P=.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; P=.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; P=.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95%CI: 1.33-2.02), all-cause death or HF admission (HR=1.47; 95%CI: 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95%CI: 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. Conclusions COPD, but not asthma, is an adverse independent prognostic factor in patients with HF. (AU)

Assessment of bronchodilator responsiveness to salbutamol or ipratropium using different criteria in treatment-naïve patients with asthma and COPD.

Background: The criteria for significant bronchodilator responsiveness (BDR) were published in 2005 by the European Respiratory Society/American Thoracic Society, which were revised in 2021, however, data on the agreement between these two recommendations in untreated patients with airflow limitation are missing. Aims: We aimed to study BDR to salbutamol (SABA) or ipratropium bromide (SAMA) in patients with suspected bronchial asthma or COPD at initial clinical presentation using the 2005 and 2021 criteria and explore clinical factors associated with BDR+. Methods: Symptomatic, treatment-naïve patients with expiratory airflow limitation (n = 105, 57 men, age (mean ± standard deviation): 65 ± 10 years) underwent BDR testing with 400 mcg salbutamol (day 1) or 80 mcg ipratropium bromide (day 2) and BDR was measured after 15 and 30 minutes. Clinical factors with risk for BDR+ were assessed with binomial logistic regression analysis. Results: We found a good agreement between the number of 2005-BDR+ and 2021-BDR+ patients at 15 and 30 minutes post-salbutamol and post-ipratropium (88.6-94.8%). More patients showed BDR+ after 30 minutes than following 15 minutes using either criterion. When results at 30 minutes are considered, the number of patients with 2005-BDR+ (82%) was higher than that of 2021-BDR+ (75%), with the proportion of SAMA+ patients being higher than that of SABA+ (2005: 70% vs. 49%, Fisher exact p < 0.01; 2021: 64% vs. 41%, p = 0.001). 2005-BDR+ and 2021-BDR+ to SABA were associated with decreasing pre-BD FEV1% predicted and the presence of cough. More patients with asthma were in the SABA+ group compared to the SAMA+ group (2005: 71% vs. 53%, Fischer exact p = 0.04; 2021: 77% vs. 52%, p = 0.02). Conclusions: Fewer patients show BDR+ according to the 2021 criteria in comparison with the 2005 recommendations, and protocols for BDR testing may consider the assessment of response to both SABA and SAMA after 30 minutes.

Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Effectiveness of allergen immunotherapy with house dust mite extract for pediatric bronchial asthma.

Aim: We compared the effectiveness of rush subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) using standardized house dust mite (HDM) extract for pediatric bronchial asthma (BA). Methods: We followed the pediatric BA treatment score during 3 years of treatment. We assessed the median time to no longer requiring long-term control pharmacotherapy (LTCP) for BA (LTCP-free). We compared the outcomes after adjustment for confounding factors and propensity score matching. Results: Patients in the HDM SCIT group achieved the LTCP-free status significantly earlier than those in the HDM SLIT group after adjustment for confounding factors and propensity score matching. Conclusion: Patients treated for pediatric BA with rush HDM SCIT had earlier onset of therapeutic effects than those with HDM SLIT.

Integration of metabolomics and transcriptomics to reveal the mechanism of Gerberae piloselloidis herba in alleviating bronchial asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Gerberae Piloselloides Herba (GPH) is derived from Gerbera piloselloides (Linn.) Cass. It is a commonly used traditional medicine in China, featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial and anti-tumor. It is often used as an effective treatment for cough and sore throat as well as bronchial asthma (BA) in China. It was demonstrated in our previous studies that GPH exerted significant effects on the treatment of BA, but its underlying mechanism remains unclear. AIM OF THE STUDY: This study was aimed at revealing the mechanism through which GPH protects against BA. MATERIALS AND METHODS: The protective effect of GPH against BA was evaluated in a mouse model of BA induced by ovalbumin. Through integrated metabolomics and transcriptomics analysis, the most critical pathways were discovered. The effects of GPH in regulating these pathways was verified through molecular biology experiments and molecular docking. RESULTS: GPH have anti-BA effects. In plasma and lung tissue, 5 and 17 differentially expressed metabolites (DEMs), respectively, showed a reversed tendency in the GPH group compared with the model group; apart from gamma-aminobutyric acid and butyrylcarnitine, these DEMs might aid in BA diagnosis. The DEMs were involved primarily in the regulation of lipid metabolism, followed by glucose metabolism and amino acid metabolism. Transcriptomic analysis indicated that GPH modulated 268 differentially expressed genes (DEGs). Integration analysis of metabolomics and transcriptomics revealed that GPH might regulate the PPAR signaling pathway, thus affecting the expression of key gene targets such as Cyp4a12a, Cyp4a12b, Adh7, Acaa1b and Gpat2; controlling fatty acid degradation, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and other lipid metabolic pathways; and ameliorating BA. This possibility was confirmed through reverse-transcription quantitative polymerase chain reaction, western blotting, immunofluorescence and molecular docking. CONCLUSION: GPH was found to activate the PPAR signaling pathway, decrease the levels of Cyp4a12a and Cyp4a12b, and increase the levels of Adh7, Acaa1b and Gpat2, thereby regulating lipid metabolism disorder, decreasing the generation of inflammatory mediators and limiting lung injury.

Genetic Diversity in Bronchial Asthma Susceptibility: Exploring the Role of Vitamin D Receptor Gene Polymorphisms in Varied Geographic Contexts.

Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.

Ayurveda management of a patient having bronchial asthma and hemorrhoids- A case report.

Ayurveda is a holistic science that treats root cause of diseases. One disease can become a causative factor for another disease. This concept is fundamentally described as Nidanarthakar Vyadhi in Ayurveda. In the same way, treating causative diseases is helpful in managing another diseases. However, many published clinical trials on Ayurveda management of Bronchial asthma and Hemorrhoids exist. There is a dearth of published case reports or clinical trials showing an association between Arsha (hemorrhoids) and Shwasa (bronchial asthma). This case report gives important viewpoints about the role of hemorrhoids and its treatment in pathogenesis and treatment of bronchial asthma. This case report of a 38-year-old female patient known case of bronchial asthma who came to the OPD of Kayachikitsa Government Ayurved College and Hospital, Nagpur with complaints of cough with sputum, breathlessness, chest pain (on/off) for three years. The severity of these symptoms increased for three months. The patient was treated with conventional Shwasghna Chikitsa (treatment of bronchial asthma) for five days, but the response was unsatisfactory. After five days of Shwasghna treatment, the patient gave a history of hemorrhoids. Considering Nidanarthakar Roga (one disease can cause of another disease), treatment was planned. The treatment principle is the treatment of causative disease (Arsha). Hence, Arshoghna treatment was added. Significant increases in peak expiratory flow rate (PEFR), Sustained minimal inspiration (SMI), and Modified Medical Research Council Dyspnoea scale (mMRC) were observed. The respiratory rate was also reduced from 28/min to 18/min. Improvement in the subjective and objective parameters of the patient was observed. The inclusion of Arsha treatment can be helpful in the management of Tamakshwas (Bronchial Asthma). The need for further research in this direction is warranted.

The prevalence of obstructive sleep apnea in Japanese asthma patients.

BACKGROUND: Obstructive sleep apnea (OSA) occurs more commonly in asthma patients than in the general population because these conditions share some comorbidities. In Japan, the prevalence of OSA in the general population is reported to be approximately 20%; however, few reports have described the prevalence of OSA in asthma patients. Furthermore, the characteristics of Japanese patients with OSA and asthma are not clear. METHODS: Adult asthma patients were recruited from the outpatient departments of our institution between August 31, 2017, and March 31, 2019. In all included patients, the presence and severity of OSA were evaluated by the Epworth Sleepiness Scale (ESS) and a home sleep test (HST) using portable polysomnography (PSG). The rate of coexisting OSA in asthma patients and the characteristics of those patients according to the severity of OSA were investigated. RESULTS: Fifty-three patients were included. OSA was detected in 36 (67.9%) patients (mild, n = 15; moderate, n = 14; and severe, n = 7). Patients with OSA had significantly higher body mass index, Brinkman index, apnea-hypopnea index (AHI), and 3% oxygen desaturation index (ODI) values in comparison to those without OSA, while the percentage of the predicted value of forced vital capacity (%FVC) and lowest SpO2 levels were significantly lower. As the severity of OSA increased, age, brain natriuretic peptide level, AHI, and 3%ODI increased, and in contrast, FVC, %FVC, forced expiratory volume in one second (FEV1), percentage of the predicted value of FEV1 (%FEV1), Epworth Sleepiness Scale (ESS), 3%ODI, and lowest SpO2 levels decreased. In particular, the fact that the ESS value was inversely correlated with the severity of OSA in our patients was different from the general characteristics of OSA. Moreover, the AHI value was negatively correlated with FVC, %FVC, FEV1, and %FEV1. BMI was the only independent factor for the presence of OSA, and for asthma severity (FEV1, % of predicted), there was a weak correlation with smoking history. CONCLUSIONS: This is the first report to investigate the prevalence of OSA in Japanese asthma patients, using an HST. This study suggests that an HST should be performed in addition to the sleep interview for asthma patients with refractory disease, a low pulmonary function, advanced age, and high BMI because the more severe the OSA, the lower the ESS value may be.

Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure.

PURPOSE: To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). METHODS: Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. RESULTS: We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; p=0.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; p=0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; p=0.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95% CI 1.33-2.02), all-cause death or HF admission (HR=1.47; 95% CI 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95% CI 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. CONCLUSIONS: COPD, but not asthma, is an adverse independent prognostic factor in patients with HF.

Why is Pet (cat/dog) allergen immunotherapy (ait) such a controversial topic? current perspectives and future directions.

Summary: Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals."

Modulation by Withania somnifera of stress-induced anxiogenesis and airway inflammation in rats.

OBJECTIVES: Stress is an aversive stimulus which disrupts the biological milieu of the organism and a variety of emotional and environmental stressors are known to influence allergic and immunological disorders like bronchial asthma but the pharmacological basis of such interactions is not clearly defined. Withania somnifera (ashwagandha) is a potent anti-stress agent used widely in Indian traditional medicine and the present experimental study evaluated the effects of W. somnifera extract (WSE) on chronic stress-induced neurobehavioral and immunological responses in an experimental model of allergic asthma in rats. METHODS: Wistar rats (200-250 g) were immunized and challenged with ovalbumin (OVA) and exposed to restraint stress (RS) and WSE treatments for 15 days. Following this, anxiety behavior was assessed by the elevated plus maze (EPM) test, and blood and BAL fluid samples were collected for measuring of inflammatory/immune markers by ELISA and biochemical assay. The data of the various treatment groups were analyzed by ANOVA and Tukey's test. RESULTS: Restraint stress (RS) induced anxiogenic behavior in the (EPM) test in OVA immunized rats, and this was attenuated by WSE (200 and 400 mg/kg), in a dose related manner. Examination of blood and BAL fluid in these RS exposed rats also resulted in elevations in IgE, TNF-α and IL-4 levels, which were also attenuated by WSE pretreatments. Further, WSE pretreatment neutralized the such RS induced changes in oxidative stress markers viz. elevated MDA and reduced GSH levels. CONCLUSIONS: The data pharmacologically validates role of stress in asthma and suggests that adaptogens like WSE could be a potential complementary agent for reducing anxiety as well as airway inflammation by a multi-targeted and holistic approach. The study also highlights the significance of integration of traditional and modern medical concepts in such chronic disorders.

Tumor markers for lipid metabolism-related genes: Based on small cell lung cancer and bronchial asthma dual analysis.

Numerous studies have elucidated the intricate relationship between bronchial asthma and small cell lung cancer (SCLC), as well as the role lipid metabolism genes play in transitioning from bronchial asthma to SCLC. Despite this, the predictive power of single gene biomarkers remains insufficient and necessitates the development of more accurate prognostic models. In our study, we downloaded and preprocessed scRNA-seq of SCLC from the GEO database GSE164404 and severe asthma scRNA-seq from GSE145013 using the Seurat package. Using the MSigDB database and geneCard database, we selected lipid metabolism-related genes and performed scRNA-seq data analysis from the gene expression GEO database, aiming to uncover potential links between immune signaling pathways in bronchial asthma and SCLC. Our investigations yielded differentially expressed genes based on the scRNA-seq dataset related to lipid metabolism. We executed differential gene analysis, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. In-depth GSEA pathway activation analysis, crucial target gene predictions via protein-protein interactions, and key cluster gene evaluations for differential and diagnostic ROC values correlation analysis confirmed that key cluster genes are significant predictors for the progression of bronchial asthma to SCLC. To validate our findings, we performed wet laboratory experiments using real-time quantitative PCR to assess the expression of these relevant genes in SCLC cell lines. In conclusion, this research proposes a novel lipid metabolism-related gene marker that can offer comprehensive insights into the pathogenesis of bronchial asthma leading to SCLC. Although this study does not directly focus on senescence-associated molecular alterations, our findings in the lipid metabolism genes associated with inflammation and cancer progression offer valuable insights for further research targeting senescence-related changes in treating inflammatory diseases.

Correlation between changes in serum YKL-40, LXRs, PPM1A, and TGF-ß1 levels and airway remodeling and lung function in patients with bronchial asthma.

OBJECTIVE: This study investigates the correlation between serum levels of YKL-40, LXRs, PPM1A, and TGF-ß1 and airway remodeling and lung function in bronchial asthma patients. METHODS: The study involved 80 bronchial asthma patients and 92 healthy individuals. Serum cytokines, airway remodeling, and lung function markers were compared across mild, moderate, and severe asthma cases using high-resolution CT, t-tests, ANOVA, and Pearson correlation analysis. RESULTS: Asthmatic patients exhibited higher levels of serum YKL-40, LXRα, LXRß, TGF-ß1, airway wall thickness (T)/outer diameter (D), and WA% of total cross-sectional area compared to controls. Conversely, their serum PPM1A, Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1 s (FEV1) were lower. Serum YKL-40 and TGF-ß1 levels were positively correlated with T/D and WA%, and negatively correlated with PEF and FEV1. PPM1A levels were strongly associated with T/D, WA%, PEF, and FEV1. CONCLUSION: The severity of bronchial asthma is associated with increased serum levels of YKL-40, LXRα, LXRß, and TGF-ß1 and decreased PPM1A. The levels of YKL-40, PPM1A, and TGF-ß1 have a significant correlation with airway remodeling and lung function.

Suppressed pediatric asthma hospitalizations during the COVID-19 pandemic in Japan, from a national survey.

BACKGROUND: Acute asthma exacerbation in children is often caused by respiratory infections. In this study, a coordinated national surveillance system for acute asthma hospitalizations and causative respiratory infections was established. We herein report recent trends in pediatric acute asthma hospitalizations since the COVID-19 pandemic in Japan. METHODS: Thirty-three sentinel hospitals in Japan registered all of their hospitalized pediatric asthma patients and their causal pathogens. The changes in acute asthma hospitalization in children before and after the onset of the COVID-19 pandemic and whether or not COVID-19 caused acute asthma exacerbation were investigated. RESULTS: From fiscal years 2010-2019, the median number of acute asthma hospitalizations per year was 3524 (2462-4570), but in fiscal years 2020, 2021, and 2022, the numbers were 820, 1,001, and 1,026, respectively (the fiscal year in Japan is April to March). This decrease was observed in all age groups with the exception of the 3- to 6-year group. SARS-CoV-2 was evaluated in 2094 patients from fiscal years 2020-2022, but the first positive case was not detected until February 2022. Since then, only 36 of them have been identified with SARS-CoV-2, none of which required mechanical ventilation. Influenza, RS virus, and human metapneumovirus infections also decreased in FY 2020. In contrast, 24% of patients had not been receiving long-term control medications before admission despite the severity of bronchial asthma. CONCLUSION: SARS-CoV-2 was hardly detected in children with acute asthma hospitalization during the COVID-19 pandemic. This result indicated that SARS-CoV-2 did not induce acute asthma exacerbation in children. Rather, infection control measures implemented against the pandemic may have consequently reduced other respiratory virus infections and thus acute asthma hospitalizations during this period. However, the fact that many hospitalized patients have not been receiving appropriate long-term control medications is a major problem that should be addressed.

Yanghe Pingchuan granules mitigates oxidative stress and inflammation in a bronchial asthma rat model: role of the IKK/IκB/NF-κB signalling pathway.

Background: Bronchial asthma (BA) is a chronic inflammatory airway disease. Previous research has shown that Yanghe Pingchuan granules (YPG), among the granules formulated by the First Affiliated Hospital of the Anhui University of Chinese Medicine, exerts a precise therapeutic effect on BA. We previously showed that YPG improves airway inflammation in BA rats. Other studies have shown that the inhibitor of kappa-B kinase (IKK)/inhibitor of NF-κB (IκB)/nuclear factor kappa-B (NF-κB) signalling pathway plays a key role in inflammation mediation. Therefore, this study explored whether YPG could intervene in BA through the IKK/IκB/NF-κB signalling pathway. Methods: Ovalbumin-induced method was used to established BA rat model. After successful modelling, the authors used YPG to intervene the rats in BA rats. Hematoxylin-eosin (HE) staining was used to detect the bronchial pathological changes in BA rats, enzyme-linked immunosorbent assay (ELISA) was used to detect the changes of inflammatory factors (IL-1ß and IL-6) and oxidative stress indexes malondialdehyde (MDA), superoxide dismutase (SOD) and nitrogen monoxide (NO), Quantitative real-time polymerase chain reactionCR and western blot were used to detect the expression of IKK/IκB/NF-κB signalling pathway. Results: In BA model rats, YPG significantly improved the inflammatory response in bronchial tissues, reduced inflammatory factors IL-1ß and IL-6, alleviated oxidative stress, reduced MDA and NO, and increased SOD. Quantitative real-time polymerase chain reaction and western blot results showed that YPG could block the IKK/IκB/NF-κB signalling pathway. Conclusion: These findings showed that YPG had a definite therapeutic effect on BA, which may be related to blocking the IKK/IκB/NF-κB signalling pathway and improving inflammation and oxidative stress.

"Patient remodeling" as a consequence of uncontrolled and prolonged OCS use in severe asthma: how biologic therapy can reverse a dangerous trend.

INTRODUCTION: Asthma is a chronic inflammatory disease that can lead to airways remodeling. Despite their well-known side-effects, oral corticosteroids (OCS) continue to be used to reduce exacerbations and control asthma symptoms in many patients. CASE STUDY: We describe two cases of uncontrolled severe asthma characterized by systemic clinical consequences of prolonged OCS use, such as diabetes, weight gain, and osteoporosis. RESULTS: Both patients were treated with Dupilumab. During follow-up both patients showed an improvement in asthma control and were able to gradually taper the OCS dose, thus reducing the clinical burden associated with hypercortisolism. CONCLUSION: Dupilumab was able to control both the inflammatory-induced "airway remodeling" as well as the OCS-induced "patient remodeling".