Exploring the In Vitro and In Vivo Therapeutic Efficacy of Juniperus oxycedrus Cade Oil: Antioxidant, Anti-inflammatory, and Anti-asthmatic Effects in an Allergic Asthma Model.

This investigation aimed to explore the antioxidant, anti-inflammatory effects of Cade oil and its efficacy within a Wistar allergic asthma model. The antioxidant activity was assessed through various in vitro tests using chain-breaking antioxidant effects (radical scavenging and reducing abilities assays).  In vivo experiments involved Wistar rats categorized into four groups: negative control group, Ovalbumin-sensitised/challenged group, Cade oil-treated group, and Ovalbumin-sensitised/challenged Cade oil-treated group. These experiments aimed to evaluate oxidative stress parameters in the lungs and erythrocytes. The results indicated that the Cade oil exhibited significant antioxidant capabilities, evidenced by its radical scavenging activity against DPPH, ABTS, and Galvinoxyl radicals, with IC50 values ranging from 21.92 to 24.44 µg/mL. Besides, the reducing abilities methods showed A0,5 value ranging from 11.51 to 30.40  µg/mL for reducing power, Cupric ion reducing antioxidant capacity, and O-phenanthroline assays. Additionally, the IC50 value for ß-carotene scavenging was found to be (8.2 ± 0.25 µg/ml). Analysis revealed high levels of polyphenols and flavonoids in Cade oil, indicating rich polyphenol (275.21 ± 3.14 mg GAE/g DW) and flavonoid (28.23 ± 1.91 µg QE/mg) content. In vivo findings highlighted Cade oil's efficacy in reducing inflammatory cell recruitment, enhancing antioxidant status, reducing lipid peroxidation, and improving histopathological alterations within the allergic asthma model. These results demonstrated that Cade oil has a potent antioxidant, anti-inflammatory, and anti-asthmatic properties, suggesting its potential therapeutic application in asthma treatment.

Risk and protective factors of asthma and mental health condition multimorbidity in a national sample of Canadian children.

BACKGROUND: The coexistence of childhood asthma and mental health (MH) conditions can impact management and health outcomes but we need to better understand the etiology of multimorbidity. We investigated the association between childhood asthma and MH conditions as well as the determinants of their coexistence. METHODS: We used data from the Canadian Health Survey of Children and Youth 2019 (3-17 years; n = 47,871), a cross-sectional, nationally representative Statistics Canada dataset. Our primary outcome was condition status (no asthma or MH condition; asthma only; MH condition only; both asthma, and a MH condition (AMHM)). Predictors of condition status were assessed using multiple multinomial logistic regression. Sensitivity analyses considered individual MH conditions. RESULTS: MH condition prevalence was almost two-fold higher among those with asthma than those without asthma (21.1% vs. 11.6%, respectively). There were increased risks of each condition category associated with having allergies, other chronic conditions, and family members smoking in the home while there were protective associations with each condition status category for being female and born outside of Canada. Four additional variables were associated with AMHM and MH condition presence with one additional variable associated with both AMHM and asthma. In sensitivity analyses, the associations tended to be similar for most characteristics, although there was some variability. CONCLUSION: There are common risk factors of asthma and MH conditions along with their multimorbidity with a tendency for MH risk factors to be associated with multimorbidity. MH condition presence is common and important to assess among children with asthma.

Potential association between obstructive lung diseases and cognitive decline.

Introduction: Chronic obstructive lung diseases, such as asthma and COPD, appear to have a more extensive impact on overall functioning than previously believed. The latest data from clinical trials suggests a potential link between cognitive deterioration and chronic obstructive inflammatory lung disease. This raises the question of whether these diseases affect cognitive functions and whether any relevant biomarker may be identified. Methods: This prospective observational study included 78 patients divided equally into asthma, COPD, and control groups (n=26, 27 and 25 respectively). The participants underwent identical examinations at the beginning of the study and after at least 12 months. The test battery comprised 16 questionnaires (11 self-rated, 5 observer-rated, assessing cognition and mental state), spirometry, and blood samples taken for PKA and CREB mRNA evaluation. Results: A 2.3-fold increase in CREB mRNA was observed between examinations (p=0.014) for all participants; no distinctions were observed between the asthma, COPD, and control groups. Pooled, adjusted data revealed a borderline interaction between diagnosis and CREB expression in predicting MMSE (p=0.055) in COPD, CREB expression is also associated with MMSE (ß=0.273, p=0.034) like with the other conducted tests (ß=0.327, p=0.024) from COPD patients. No correlations were generally found for PKA, although one significant negative correlation was found between the first and second time points in the COPD group (ß=-0.4157, p=0.049),. Discussion: Chronic obstructive lung diseases, such as asthma and COPD, may have some linkage to impairment of cognitive functions. However, the noted rise in CREB mRNA expression might suggest a potential avenue for assessing possible changes in cognition, especially in COPD; such findings may reveal additional transcription factors linked to cognitive decline.

SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma.

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

The Role of Transforming Growth Factor-ß (TGF-ß) in Asthma and Chronic Obstructive Pulmonary Disease (COPD).

Asthma and chronic obstructive pulmonary disease (COPD) represent chronic inflammatory respiratory disorders that, despite having distinct pathophysiological underpinnings, both feature airflow obstruction and respiratory symptoms. A critical component in the pathogenesis of each condition is the transforming growth factor-ß (TGF-ß), a multifunctional cytokine that exerts varying influences across these diseases. In asthma, TGF-ß is significantly involved in airway remodeling, a key aspect marked by subepithelial fibrosis, hypertrophy of the smooth muscle, enhanced mucus production, and suppression of emphysema development. The cytokine facilitates collagen deposition and the proliferation of fibroblasts, which are crucial in the structural modifications within the airways. In contrast, the role of TGF-ß in COPD is more ambiguous. It initially acts as a protective agent, fostering tissue repair and curbing inflammation. However, prolonged exposure to environmental factors such as cigarette smoke causes TGF-ß signaling malfunction. Such dysregulation leads to abnormal tissue remodeling, marked by excessive collagen deposition, enlargement of airspaces, and, thus, accelerated development of emphysema. Additionally, TGF-ß facilitates the epithelial-to-mesenchymal transition (EMT), a process contributing to the phenotypic alterations observed in COPD. A thorough comprehension of the multifaceted role of TGF-ß in asthma and COPD is imperative for elaborating precise therapeutic interventions. We review several promising approaches that alter TGF-ß signaling. Nevertheless, additional studies are essential to delineate further the specific mechanisms of TGF-ß dysregulation and its potential therapeutic impacts in these chronic respiratory diseases.

Development and validation of a novel questionnaire to describe and assess sensations and triggers associated with refractory and unexplained chronic cough.

INTRODUCTION: Refractory or unexplained chronic cough (RUCC) is a common clinical problem with no effective diagnostic tools. The Sensations and Triggers Provoking Cough questionnaire (TOPIC) was developed to characterise cough in RUCC versus cough in other conditions. METHODS: Content analysis of participant interviews discussing the sensations and triggers of chronic cough informed TOPIC development. Participants with chronic cough completed the draft-TOPIC (a subset repeating 5-7 days later), St George's Respiratory Questionnaire (SGRQ), Cough Severity Diary (CSD) and Global Rating of Change Scale. The draft-TOPIC item list was reduced in hierarchical and Rasch analysis to refine the questionnaire to the TOPIC. RESULTS: 49 items describing the triggers and sensations of cough were generated from participant interviews (RUCC n=14, chronic obstructive pulmonary disease (COPD) n=11, interstitial lung disease (ILD) n=10, asthma n=11, bronchiectasis n=3, cystic fibrosis n=7). 140 participants (median age 60.0 (19.0-88.0), female 56.4%; RUCC n=39, ILD n=38, asthma n=45, COPD n=6, bronchiectasis n=12) completed draft-TOPIC, where items with poor 'fit' for RUCC were removed to create TOPIC (8 trigger items, 7 sensation items). Median TOPIC score was significantly higher in RUCC (37.0) vs ILD (24.5, p=0.009) and asthma (7.0, p<0.001), but not bronchiectasis (20.0, p=0.318) or COPD (18.5, p=0.238), likely due to small sample sizes. The Rasch model demonstrated excellent fit in RUCC (χ2=22.04, p=0.85; PSI=0.88); as expected. When all participant groups were included, fit was no longer demonstrated (χ2=66.43, p=0.0001, PSI=0.89) due to the increased heterogeneity (CI=0.077). TOPIC correlated positively with SGRQ (r=0.47, p<0.001) and CSD (r=0.63, p<0.001). The test-retest reliability of TOPIC (intraclass correlation coefficient) was excellent (r=0.90, p<0.001). CONCLUSIONS: High TOPIC scores in the RUCC patients suggest their cough is characterised by specific sensations and triggers. Validation of TOPIC in cough clinics may demonstrate value as an aid to identify features of RUCC versus cough in other conditions.

The analysis of lung sounds in infants and children with a history of wheezing/asthma using an automatic procedure.

BACKGROUND: Lung sound analysis parameters have been reported to be useful biomarkers for evaluating airway condition. We developed an automatic lung sound analysis software program for infants and children based on lung sound spectral curves of frequency and power by leveraging machine learning (ML) technology. METHODS: To put this software program into clinical practice, in Study 1, the reliability and reproducibility of the software program using data from younger children were examined. In Study 2, the relationship between lung sound parameters and respiratory flow (L/s) was evaluated using data from older children. In Study 3, we conducted a survey using the ATS-DLD questionnaire to evaluate the clinical usefulness. The survey focused on the history of wheezing and allergies, among healthy 3-year-old infants, and then measured lung sounds. The clinical usefulness was evaluated by comparing the questionnaire results with the results of the new lung sound parameters. RESULTS: In Studies 1 and 2, the parameters of the new software program demonstrated excellent reproducibility and reliability, and were not affected by airflow (L/s). In Study 3, infants with a history of wheezing showed lower FAP0 and RPF75p (p < 0.001 and p = 0.025, respectively) and higher PAP0 (p = 0.001) than healthy infants. Furthermore, infants with asthma/asthma-like bronchitis showed lower FAP0 (p = 0.002) and higher PAP0 (p = 0.001) than healthy infants. CONCLUSIONS: Lung sound parameters obtained using the ML algorithm were able to accurately assess the respiratory condition of infants. These parameters are useful for the early detection and intervention of childhood asthma.

Longitudinal association of exclusive and dual use of cigarettes and cigars with asthma exacerbation among US adults: a cohort study.

BACKGROUND: Cigar use among adults in the United States has remained relatively stable in the past decade and occupies a growing part of the tobacco marketplace as cigarette use has declined. While studies have established the detrimental respiratory health effects of cigarette use, the effects of cigar use need further characterization. In this study, we evaluate the prospective association between cigar use, with or without cigarettes, and asthma exacerbation. METHODS: We used data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study to run generalized estimating equation models examining the association between time-varying, one-wave-lagged cigarette and cigar use and self-reported asthma exacerbation among US adults (18+). We defined our exposure as non-established (reference), former, exclusive cigarette, exclusive cigar, and dual use. We defined an asthma exacerbation event as a reported asthma attack in the past 12 months necessitating oral or injected steroid medication or asthma symptoms disrupting sleep at least once a week in the past 30 days. We adjusted for age, sex, race and ethnicity, household income, health insurance, established electronic nicotine delivery systems use, cigarette pack-years, secondhand smoke exposure, obesity, and baseline asthma exacerbation. RESULTS: Exclusive cigarette use (incidence rate ratio (IRR): 1.26, 95% confidence interval (CI): 1.03-1.54) and dual use (IRR: 1.41, 95% CI: 1.08-1.85) were associated with a higher rate of asthma exacerbation compared to non-established use, while former use (IRR: 1.01, 95% CI: 0.80-1.28) and exclusive cigar use (IRR: 0.70, 95% CI: 0.42-1.17) were not. CONCLUSION: We found no association between exclusive cigar use and self-reported asthma exacerbation. However, exclusive cigarette use and dual cigarette and cigar use were associated with higher incidence rates of self-reported asthma exacerbation compared to non-established use. Studies should evaluate strategies to improve cigarette and cigar smoking cessation among adults with asthma who continue to smoke.

Cathepsin B-Activatable Bioactive Peptide Nanocarrier for High-Efficiency Immunotherapy of Asthma.

Introduction: Asthma, a chronic respiratory disease closely associated with inflammation, presents ongoing treatment challenges. IALLIPF (le-Ala-Leu-Leu-Ile-Pro-Phe) is one of millet prolamins peptides (MPP) which shows anti-oxidant bioactivity by reducing the production of reactive oxygen species (ROS). Tryptophan (Trp, W) is an amino acid that has been demonstrated to possess anti-inflammatory effects. We introduce a novel cathepsin B-activatable bioactive peptides nanocarrier, PEG-IALLIPF-GFLG-W (MPP-Trp), designed for immunotherapy of asthma. Methods: MPP-Trp is synthesized, purified, and its characteristics are investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) are examined to evaluate anti-inflammatory effects of IALLIPF, Trp and MPP-Trp. The immunomodulatory effects of IALLIPF, Trp and MPP-Trp on Th1/Th2 cell populations and cytokines are investigated by flow cytometry, qRT-PCR and ELISA assays. We explore the therapeutic effect of MPP-Trp in the mouse model of asthma by the analysis of lung histology and ELISA. It is necessary to study the biocompatibility of MPP-Trp by CCK8 assay and histopathologic analysis using hematoxylin and eosin (HE) staining. Results: In asthmatic peripheral blood mononuclear cells (PBMCs), IALLIPF, Trp and MPP-Trp are able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), especially MPP-Trp. MPP-Trp significantly upregulates Th1 cell levels while notably reducing Th2 cell levels. Furthermore, MPP-Trp effectively elevates the expression and production of interferon-gamma (IFN-γ), an essential cytokine from Th1 cells. Additionally, MPP-Trp markedly diminishes the mRNA expression and levels of key asthma pathogenesis cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), in asthma PBMCs. MPP-Trp ameliorates pulmonary pathological alterations and significantly inhibits OVA-induced inflammation in mice with asthma. It has little influence on the cell viability in Asthma-PBMCs treated with various concentrations or durations of MPP-Trp. No pathological changes, including in the heart, liver, spleen, lung, and kidney tissues, are observed in non-sensitized and non-challenged mice treated with MPP-Trp (20 mg/kg). Discussion: Our research demonstrates that MPP-Trp has immunomodulatory effects on Th1/Th2 cell populations, essential in managing asthma. It considerably alleviates OVA-induced asthma by shifting the immune response towards a Th1-dominant profile, thereby reducing Th2-driven inflammation. Therefore, this novel bioactive peptide nanocarrier, MPP-Trp, holds promise as a candidate for asthma immunotherapy.

Small airway dysfunction links asthma exacerbations with asthma control and health-related quality of life.

BACKGROUND: Small airway dysfunction not only affects asthma control, but also has adverse effects on the psychological and/or social activities of asthma patients. However, few long-term observational studies have explored the complex relationship between small airway dysfunction and asthma control and health-related quality of life in patients with asthma exacerbations. METHODS: The study recruited 223 patients with exacerbations of asthma (i.e. those with at least one asthma attack over the past year) and 228 patients without exacerbations of asthma (i.e. those without asthma attacks over the past year). We evaluated SAD in patients with asthma exacerbations using impulse oscillometry method. At each evaluation time point within one year of follow-up, the attending physician conducts a case investigation of the patients. We analyzed the correlation between SAD and general characteristics (age, obesity, smoking history), type 2 inflammation (blood eosinophils, exhaled nitric oxide), FEV1, as well as asthma control (ACT) and health-related quality of life (mini-AQLQ) in patients with asthma exacerbations, and constructed a structural equation model to evaluate the causality of these clinical variables. RESULTS: The SAD prevalence in patients with asthma exacerbation is as high as 75%. SAD is connected with poor asthma control and poor health-related quality of life. The structural equation model indicates that age, obesity, FeNO, and FEV1 are independent predictive factors of SAD. SAD is the main determinant factor of asthma control, which in turn affected health-related quality of life. FEV1 and age directly affect asthma control and affect health-related quality of life through asthma control. In addition, there is a bidirectional relationship between FEV1 and small airway dysfunction and between asthma control and health-related quality of life. CONCLUSIONS: Small airways are involved from an early stage in asthma. Abnormal function of the small airways can significantly increase airway resistance in asthma patients, while worsening their clinical symptoms. In addition, aging is also a key risk factor for asthma control. Especially, small airway dysfunction links asthma control with health-related quality of life.

In mouse model of mixed granulocytic asthma with corticosteroid refractoriness, Bronchom mitigates airway hyperresponsiveness, inflammation and airway remodeling.

BACKGROUND: Asthma is a heterogeneous, inflammatory disease with several phenotypes and endotypes. Severe asthmatics often exhibit mixed granulocytosis with reduced corticosteroid sensitivity. Bronchom is a newly developed Ayurvedic prescription medicine, indicated for the treatment of obstructive airway disorders. The purpose of the present study was to evaluate the in-vivo efficacy of Bronchom in mouse model of mixed granulocytic asthma with steroidal recalcitrance. METHODS: High-performance thin layer chromatography (HPTLC) and Ultra-high performance liquid chromatography (UHPLC) were employed to identify and quantitate the phytometabolites present in Bronchom. The preclinical effectiveness of Bronchom was assessed in house dust mite (HDM) and Complete Freund's adjuvant (CFA)-induced mixed granulocytic asthma model in mice. High dose of dexamethasone was tested parallelly. Specific-pathogen-free C57BL/6 mice were immunized with HDM and CFA and nineteen days later, they were intranasally challenged with HDM for four consecutive days. Then the mice were challenged with nebulized methacholine to evaluate airway hyperresponsiveness (AHR). Inflammatory cell influx was enumerated in the bronchoalveolar lavage fluid (BALF) followed by lung histology. Additionally, the concentrations of Th2 and pro-inflammatory cytokines was assessed in the BALF by multiplexed immune assay. The mRNA expression of pro-inflammatory cytokines and Mucin 5AC (MUC5AC) was also evaluated in the lung. RESULTS: HPTLC fingerprinting and UHPLC quantification of Bronchom revealed the presence of bioactive phytometabolites, namely, rosmarinic acid, gallic acid, methyl gallate, piperine, eugenol and glycyrrhizin. Bronchom effectively reduced AHR driven by HDM-CFA and the influx of total leukocytes, eosinophils and neutrophils in the BALF. In addition, Bronchom inhibited the infiltration of inflammatory cells in the lung as well as goblet cell metaplasia. Further, it also suppressed the elevated levels of Th2 cytokines and pro-inflammatory cytokines in the BALF. Similarly, Bronchom also regulated the mRNA expression of pro-inflammatory cytokines as well as MUC5AC in mice lungs. Reduced effectiveness of a high dose of the steroid, dexamethasone was observed in the model. CONCLUSIONS: We have demonstrated for the first time the robust pharmacological effects of an herbo-mineral medicine in an animal model of mixed granulocytic asthma induced by HDM and CFA. The outcomes suggest the potential utility of Bronchom in severe asthmatics with a mixed granulocytic phenotype.

PM2.5 Exposure Inhibits Transepithelial Anion Short-circuit Current by Downregulating P2Y2 Receptor/CFTR Pathway.

Fine particulate matter (PM2.5) can damage airway epithelial barriers. The anion transport system plays a crucial role in airway epithelial barriers. However, the detrimental effect and mechanism of PM2.5 on the anion transport system are still unclear. In this study, airway epithelial cells and ovalbumin (OVA)-induced asthmatic mice were used. In transwell model, the adenosine triphosphate (ATP)-induced transepithelial anion short-circuit current (Isc) and airway surface liquid (ASL) significantly decreased after PM2.5 exposure. In addition, PM2.5 exposure decreased the expression levels of P2Y2R, CFTR and cytoplasmic free-calcium, but ATP can increase the expressions of these proteins. PM2.5 exposure increased the levels of Th2-related cytokines of bronchoalveolar lavage fluid, lung inflammation, collagen deposition and hyperplasisa of goblet cells. Interestingly, the administration of ATP showed an inhibitory effect on lung inflammation induced by PM2.5. Together, our study reveals that PM2.5 impairs the ATP-induced transepithelial anion Isc through downregulating P2Y2R/CFTR pathway, and this process may participate in aggravating airway hyperresponsiveness and airway inflammation. These findings may provide important insights on PM2.5-mediated airway epithelial injury.

Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.

Asthma poses a major public health burden. While existing asthma drugs manage symptoms for many, some patients remain resistant. The lack of a cure, especially for severe asthma, compels exploration of novel therapies. Cancer immunotherapy successes with CAR-T cells suggest its potential for asthma treatment. Researchers are exploring various approaches for allergic diseases including membrane-bound IgE, IL-5, PD-L2, and CTLA-4 for asthma, and Dectin-1 for fungal asthma. NK cells offer several advantages over T cells for CAR-based immunotherapy. They offer key benefits: (1) HLA compatibility, meaning they can be used in a wider range of patients without the need for matching tissue types. (2) Minimal side effects (CRS and GVHD) due to their limited persistence and cytokine profile. (3) Scalability for "off-the-shelf" production from various sources. Several strategies have been introduced that highlight the superiority and challenges of CAR-NK cell therapy for asthma treatment including IL-10, IFN-γ, ADCC, perforin-granzyme, FASL, KIR, NCRs (NKP46), DAP, DNAM-1, TGF-ß, TNF-α, CCL, NKG2A, TF, and EGFR. Furthermore, we advocate for incorporating AI for CAR design optimization and CRISPR-Cas9 gene editing technology for precise gene manipulation to generate highly effective CAR constructs. This review will delve into the evolution and production of CAR designs, explore pre-clinical and clinical studies of CAR-based therapies in asthma, analyze strategies to optimize CAR-NK cell function, conduct a comparative analysis of CAR-T and CAR-NK cell therapy with their respective challenges, and finally present established novel CAR designs with promising potential for asthma treatment.

Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Self-management practice and associated factors among asthmatic patients on follow-up care at public tertiary hospitals, south west, Ethiopia, 2022.

INTRODUCTION: Bronchial asthma is a major public health issue that affects patients, families, and communities worldwide. Despite the growing importance of self-management and its clear link to better health outcomes, the uptake and use of self-management among asthmatic patients is not well understood. Thus, the study aimed to determine the level of self-management practice and associated factors among asthmatic patients on follow-up care at public tertiary hospitals found in south-west Ethiopia. METHOD: An institutional-based cross-sectional study design was employed from August 1 to September 30, 2022. The study included all asthmatic patients on follow-up care at public tertiary hospitals found in south west Ethiopia, among whom 274 were interviewed. All asthmatic patients who were registered at the chronic follow-up unit of each hospital and fulfilled inclusion criteria were included and interviewed consecutively. The data were collected using a structured interviewer-administered questionnaire adapted from previous studies, entered into EpiData version 4.6, and exported to SPSS version 25 for analysis. Descriptive statistics were used to summarize the participant's characteristics. Linear regression was used to identify variables associated with asthma self-management practice, and variables with a p-value of 0.05 were considered statistically significant. Finally, tables, graphs, and text were used to present the data. RESULT: Out of 274 interviewed asthmatic patients, 45.26% 95% CI (39, 51) had good asthma self-management practices. Advancing in age (ß = -0.009, P = 0.043), being a smoker (ß = -0.346, 95%, P = 0.03, being alcohol drinker (ß = -0.217, P = 0.001), having depression (ß = -0.038, P = 0.005), having anxiety (ß = -0.029, P = 0.02) and having social support (ß = 0.022, P<0.001) were identified as factors affecting asthma self-management practice. CONCLUSION: The finding revealed that four of every nine asthmatic patients had good asthma self-management practices. Age, alcohol consumption, smoking, anxiety, depression, and social support were significantly associated with asthma self-management practice. Ongoing self-management support and collaborative target interventions aimed at improving asthma self-management practices and identified factors are very crucial.

Body Mass Index and the Risk of Adult-Onset Asthma: A Prospective Observational Study among 59,668 Middle-Aged Men and Women in Finland.

Introduction: Obesity, in addition to many other negative health consequences, affects pulmonary function and is a potential risk factor for asthma. Methods: We analyzed the association of body mass index (BMI) with incident asthma among 60,639 Finnish men and women aged 25 to 74 years who participated in a population-based chronic disease risk factor survey in 1972, 1977, 1982, 1987, 1992, 1997, 2002, 2007, or 2012. Data on lifestyle factors such as smoking and physical activity, as well as medical history, were obtained, and various physical measurements, including height and weight, were taken at baseline. Incident asthma events were ascertained from the National Social Insurance Institution's register data. The study cohorts were followed-up until the end of 2017 through registers. Results: During the follow-up, 4612 (14%) women and 2578 (9.3%) men developed asthma. The risk of asthma was analyzed in the following three BMI categories: <24.9 (reference category), 25-29.9 (overweight) and ≥30 kg/m2 (obesity). Hazard ratios (95% CI) were 1.34 (1.24-1.43) and 1.57 (1.44-1.71) in women and 1.25 (1.14-1.37) and 1.63 (1.44-1.83) in men. The observed association was independent of smoking, height and leisure-time physical activity. In women, 30.8% (19.2% in men) of the total asthma incidence was attributed to overweight and obesity. Conclusions: Overweight and obesity are important risk factors for asthma.

FOXK2 facilitates the airway remodeling during chronic asthma by promoting glycolysis in a SIRT2-dependent manner.

Asthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as "airway remodeling", are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus-mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS-2B) were increasingly upregulated upon TGF-ß1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF-ß1-induced epithelial-mesenchymal transition (EMT) and glycolysis in BEAS-2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) inhibited the EMT in TGF-ß1-induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown-mediated inhibition of EMT and glycolysis in TGF-ß1-treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF-ß1-treated cells in a SIRT2-dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.

[Molecular allergen IgE tests show neosensitizaions occurring during house dust mite specific immunotherapy].

Objective:Neosensitizations may be occur during the allergen specific immunotherapy（AIT） due to the differences between allergen vaccine's content and a patient's molecular sensitization profile. This study investigates whether AIT with HDM extract changes the sensitization profile, whether de novo sensitization occurs, and the clinical importance of the neosensitization. Methods:Fifty-three patients with HDM allergic rhinitis ,with/without asthma, patients were received one year HDM subcutaneous AIT . Fourteen patients were recruited as control group and received only necessary medications. Serum samples were collected at baseline, 6thmoths and 12thof AIT, respectively. Serum samples were tested specific IgE against Der p, Der p 1/2/3 and Der f, Der f 1/2/3, as well as IgG4 against Der p, Der p 1/2 and Der f, Der f 1/2. VAS were collected at the time-points as well. Results:In AIT group, Der p, Der p 1/3, and Der f 1/3 specific IgE levels were significantly higher after one-year treatment, especially for Der p 3. There were 69.2%（18/26） patients whose Der p 3 specific IgE below 0.35 kU/L at baseline but became positive（>0.35 kU/L） after treatment, that is, neosensitization occurred. All tested allergen specific IgG4 level significantly increased after one year AIT treatment and the VAS declined dramatically. However, for patients with neosensitization and without neosensitization, there were no significantly changes concerning to IgG4 level and VAS. Conclusion:Patients undergoing AIT might have a risk of neosensitization to the allergen components in the vaccines. However, the clinical importance of the neosensitization remains unclear and warrants further studies.

Jolkinolide B attenuates allergic airway inflammation and airway remodeling in asthmatic mice.

Asthma is a widely prevalent chronic disease that brings great suffering to patients and may result in death if it turns severe. Jolkinolide B (JB) is one diterpenoid component separated from the dried roots of Euphorbia fischeriana Steud (Euphorbiaceae), and has anti--inflammatory, antioxidative, and antitumor properties. However, the detailed regulatory role and associated regulatory mechanism in the progression of asthma remain elusive. In this work, it was demonstrated that the extensive infiltration of bronchial inflammatory cells and the thickening of airway wall were observed in ovalbumin (OVA)-induced mice, but these impacts were reversed by JB (10 mg/kg) treatment, indicating that JB relieved the provocative symptoms in OVA-induced asthma mice. In addition, JB can control OVA-triggered lung function and pulmonary resistance. Moreover, JB attenuated OVA-evoked inflammation by lowering the levels of interleukin (IL)-4, IL-5, and IL-13. Besides, the activated nuclear factor kappa B (NF-κB) and transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGFß/smad3) pathways in OVA-induced mice are rescued by JB treatment. In conclusion, it was disclosed that JB reduced allergic airway inflammation and airway remodeling in asthmatic mice by modulating the NF-κB and TGFß/smad3 pathways. This work could offer new opinions on JB for lessening progression of asthma.

[Current situation and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023].

Objective: To explore the incidence and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023. Methods: From October 2022 to August 2023, 11 cities including Xishuangbanna in Yunnan Province, Suqian in Jiangsu Province, Chifeng and Hohhot in Inner Mongolia, Tangshan in Hebei Province, Changzhi in Shanxi Province, Yinchuan in Ningxia Province, Lanzhou and Dingxi in Gansu Province, Linyi in Shandong Province, and Tonghua in Jilin Province were selected as research sites to recruit kindergarten children and primary and secondary school adolescents in local urban areas. A total of 21 959 children and adolescents were included in this study. Demographic information, wheezing data (whether wheezing has occurred in the past and whether wheezing attacks have occurred in the past one year), personal history, family history and other information were collected through questionnaires. The multivariate logistic regression model was used to analyze the influencing factors of wheezing attacks in the past one year. Results: The mean age of 21 959 children and adolescents was (12.09±3.65) years old, and 52.3% (11 480) were boys. The incidence of wheezing history was 3.7% (816 cases), and the incidence of wheezing attacks in the past year was 2.5% (556 cases). The multivariate logistic regression model analysis results showed that compared with older age, girls, full-term natural delivery, no allergic rhinitis, no family history of allergic diseases, no passive smoking, partial diet, natural conception and childbirth, the children aged 3-18 years with young age, male, partial diet, passive smoking, family history of allergic diseases, allergic rhinitis, cesarean section, premature birth, and assisted reproduction had a higher risk of wheezing [OR (95%CI): 0.86(0.84-0.88), 1.27(1.07-1.51), 2.31(1.95-2.75), 2.09(1.76-2.47), 3.5(2.80-4.37), 4.05(3.39-4.83), 1.20(1.02-1.43), 2.26(1.66-3.09), and 1.67(1.01-2.78)]. Conclusion: From 2022 to 2023, the incidence of wheezing among children aged 3-18 years in China is not significantly higher than before, and childhood wheezing may be related to factors such as children's age, gender, dietary habits, family and personal history of allergic diseases, passive smoking, and perinatal period.