Introduction Allergic asthma, often triggered by house dust mites (HDMs), is characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. Among the major HDM allergens, Der pII plays a significant role in promoting inflammation. This study investigates the role of epidermal growth factor receptor (EGFR) inhibitors in modulating Der pII-induced cytokine production and inflammation in human immune cells. Methods Recombinant GST-Der pII protein was expressed and purified for subsequent studies. Human peripheral blood mononuclear cells (HPBMC), THP-1 monocytes, THP-1-derived macrophages, and pulmonary alveolar macrophages (NR8383) were exposed to Der pII, followed by treatment with EGFR inhibitors AZD-9291 and Tarceva. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of IL-6 and IL-8. Nitric oxide (NO) levels were determined using the Griess Reagent System. Results Der pII significantly induced pro-inflammatory cytokines, including IL-6, IL-8, and TNF-α in HPBMC and THP-1 cells. Both EGFR inhibitors reduced the secretion of IL-6 and IL-8 in these cell types. In THP-1 macrophages, AZD-9291 suppressed IL-6 expression and CD14/CD36 macrophage markers. Moreover, AZD-9291 significantly inhibited NO production in alveolar macrophages. Conclusions These findings suggest that EGFR plays a critical role in mediating Der pII-induced inflammation, and EGFR inhibitors may represent a potential therapeutic approach for controlling HDM-induced allergic inflammation.

Background Type 2-low asthma is a severe, steroid-resistant phenotype characterized by neutrophilic inflammation and limited treatment options. PTX3, an acute-phase protein involved in innate immunity, has been linked to inflammatory diseases; but its role in type 2-low asthma remains unclear. Methods A chronic HDM + c-di-GMP murine model was used to mimic type 2-low asthma. PTX3 −/− and WT mice were assessed for inflammation, cytokine profiles, antibody responses, and lung function. AHR was measured using FlexiVent. BALF inflammatory cells were analyzed by cytospin and flow cytometry. Cytokines were quantified using mesoscale assay, and serum immunoglobulins by ELISA. Results In mice, the type 2-low model exhibited increased systemic and airway PTX3 levels. PTX3 −/− mice exposed to the type 2-low protocol developed significantly greater airway inflammation, with higher total BALF cell counts and a 2-fold increase in neutrophils, but no change in eosinophils. PTX3 deficiency led to increased total and HDM-specific IgE levels. BALF cytokine analysis revealed elevated IL-17A in PTX3 −/− mice, while IL-4, IL-5, and IL-13 remained unchanged. PTX3 −/− mice also exhibited significantly higher AHR parameters. Conclusions PTX3 absence enhances neutrophilic inflammation, IL-17A production, IgE responses, and AHR, highlighting PTX3 as a potential biomarker and therapeutic target in type 2- low asthma.

Asthma is a chronic respiratory condition influenced by genetic, environmental, and sex-related factors. Women experience greater asthma severity, airway hyperresponsiveness (AHR), and inflammation than men, likely due to sex-linked genetic and hormonal differences. However, the independent contributions of sex chromosomes and gonadal sex to these responses remain unclear. This study examines their roles in allergic airway responses using the Four Core Genotype (FCG) mouse model, which distinguishes between chromosomal and gonadal influences. We hypothesized that XX-mice and those with female gonads would exhibit heightened airway inflammation and immune activation in response to house dust mite (HDM) challenge. Using a controlled, moderate five-week HDM exposure paradigm that reliably induced allergic airway inflammation, we aimed to capture biologically relevant sex- and genotype-dependent variations rather than a maximal inflammatory phenotype. FCG mice (XXF, XXM, XYF, XYM) underwent 5 weeks of HDM exposure, followed by assessments of airway lung function and inflammation. Our results showed that HDM challenge differentially increased airway resistance and elastance in FCG mice, with specific contributions of sex chromosomes and gonadal sex. Histological analysis showed higher lung inflammation and goblet cell hyperplasia in challenged mice with female gonads than those with male gonads. Flow cytometry assessment revealed elevated eosinophils in XXF mice. Combined, our findings show that both sex chromosomes and gonadal sex influence airway inflammation and immune responses to allergen challenge, with mice bearing XX chromosomes and female gonads exhibiting greater susceptibility.

Bronchial challenge testing with methacholine was applied to evaluate and quantify bronchial hyperresponsiveness (BHR) in asthma patients. We aimed to compare the clinical effectiveness between methacholine chloride and methacholine for methacholine challenge testing (MCT) in clinical practice, and investigate the adverse events associated with methacholine chloride. Patients who received methacholine and inhaled methacholine chloride for MCT were included in this retrospective study. All participants completed pulmonary function tests and MCT between January 2022 and February 2024. The provocative dose of methacholine that results in a 20% fall in FEV1 (PD20-FEV1) was used as quantitative measure of bronchial hyperresponsiveness. The primary outcome of the study was the proportion of positive MCT results and the degree of BHR, while the secondary outcome was the incidence rate of respiratory adverse events during methacholine chloride administration. A total of 17,352 participants were included. In patients with bronchial symptoms, those administrated methacholine chloride for MCT demonstrated a significantly higher percentage of positive results compared with those administrated conventional methacholine (36.7% vs. 30.8%, P < 0.001). Moreover, PD20-FEV1 values were significantly lower in methacholine chloride group than methacholine group (P < 0.001). Chest tightness was the most prevalent adverse symptom affecting 30.8% of patients who received methacholine chloride, followed by cough at 27.2%. No serious adverse events were reported in these patients. The data indicated that methacholine chloride yielded a higher positive test rate than methacholine in MCT. Given that only mild adverse symptoms of chest tightness and cough were observed, with no serious adverse events reported, it represents a safe and effective alternative for clinical BHR assessment.

Neutrophilic asthma is one of the main types of severe asthma. Our previous studies demonstrated that neutrophil extracellular traps (NETs) contribute to its pathological process. However, the underlying mechanisms remains unclear. This study aimed to investigate the potential mechanisms of NETs in neutrophilic asthma. Clinical samples were collected from patients with neutrophilic asthma and healthy controls. A neutrophil-dominant asthmatic murine model was established using ovalbumin (OVA), Freund's complete adjuvant (CFA) and lipopolysaccharide (LPS). Airway inflammation and remodeling were assessed by pathological staining. The expression of EMT markers and Hedgehog (Hh)/Gli1 pathway markers were measured by Western blot, qPCR, and immunofluorescence. We found that the expression of dsDNA, one of the skeleton components of NETs, was significantly higher in the peripheral plasma of patients with neutrophilic asthma than that of healthy controls, and neutrophils in neutrophilic asthma patients were more likely to induce the production of NETs. We further demonstrated that NETs induced EMT in airway epithelial cells. Both in vivo and in vitro, we confirmed that reducing NETs formation or enhancing NETs degradation reversed EMT process, attenuated airway hyperresponsiveness (AHR) and alleviated airway inflammation in neutrophil-dominant asthmatic mouse model. We also found that the Hh/Gli1 pathway was activated during this process, and inhibition of the Hh/Gli1 pathway also reversed the EMT process of airway epithelium. Similarly, AHR and airway inflammation in neutrophil-dominant asthmatic mice were reduced. We confirmed that NETs promote EMT in airway epithelium via activation the Hh/Gli1 signaling pathway, thus playing an important role in the pathogenesis of neutrophilic asthma. Targeting NETs or the Hh/Gli1 pathway may provide a promising therapeutic strategy for the treatment of severe neutrophilic asthma.

scRNA-sequencing Reveals Bu-Shen-Yi-Qi formula (BSYQF) ameliorates airway remodeling via regulating imbalanced M1/M2 macrophage subtypes in chronic asthmatic mice.

Zhichuanling oral liquid attenuates airway inflammation in asthma by targeting the STIM1/CHOP/JNK axis.

Introduction: Bronchial Asthma is a frequent disease in children and young adults, characterized by airway obstruction caused by bronchial hyperresponsiveness. The condition can be cured with the use of bronchodilators or can be treated naturally, by applying Respiratory Physical Therapy (PT) in both cases. The purpose of this study is to evaluate the effect of Respiratory Physical Therapy, through the training of nasal and diaphragmatic breathing through activities. Method: A 5-year-old boy of Greek origin was treated with Respiratory PT, to reduce symptoms of Bronchial Asthma. Evaluation measurements were carried out before and after the end of the physiotherapeutic Intervention. Questionnaires were used to check asthma exacerbation and body posture. Spirometry was performed to estimate pulmonary volumes and capacities, abdomen and chest circumference were also measured during inhalation and exhalation phases. 24 sessions, lasting 60 minutes each, were performed during 8 weeks period, through training diaphragmatic and controlled nasal breathing, and Relaxation Techniques. The child and caregiver were trained to apply these techniques at home in a self-treatment form. Results: Forced Expiratory Volume (FEV) and Peak Expiratory Flow Rate reduced, Forced Vital Capacity slightly increased after treatment, however, spirometry volumes are not considered as statistically significant (p&gt;0.1). Abdominal breathing circumference while inhaling, increased by 9.75% (mobility of diaphragm increased). Asthma symptom control improved and fatigue during activity reduced. Conclusion: Respiratory Physical Therapy (PT) focused on Diaphragmatic Breathing Training, when combined with breathing exercises performed at home, contributes to overall improvement of asthma symptoms. However, research should be conducted in a larger population sample to consolidate findings on the effectiveness of Respiratory Physical Therapy.

NLRP3-mediated epithelial pyroptosis involved in airway hyperresponsiveness in combined eosinophilic and neutrophilic asthma.

Objective: Asthma results from an amalgamation of three essential features: airflow obstruction, hyperresponsiveness of airways to endogenous or exogenous stimuli and inflammation. Inadequate knowledge of inhalation techniques is a major cause of therapeutic failure in asthma. This study aimed to evaluate the knowledge of medical students and medical staff regarding the correct use of metered-dose inhalers (MDIs). The main purpose of this study was to evaluate the use of medical students from the college of medicine at Alnahrin University and college of pharmacy Baghdad university and medical staff who working at a secondary general Iraqi hospital (Alkadimia teaching hospital) in term of their knowledge regarding to metered dose inhalers (MDI). Methods: A cross-sectional observational study was conducted using written and practical assessment tools. The participants’ student from the college of medicine at Alnahrin University and college of pharmacy Baghdad University and medical staff who working at a secondary general Iraqi hospital (Alkadimia teaching hospital) were followed the use of written practice tests, about the use of metered dose inhalers. Score from (0-10) was given to each test and median score were calculated for each answer. Question with higher and lower correct values were identified and a descriptive comparison was made regarding the performance of various group. Statistical analysis was performed using the Kruskal- Wallis method for comparison medians. A sequential logistic multiple regression analysis was also performed. Results: Doctors and clinical pharmacists achieved significantly higher median scores than medical and pharmacy students. Conclusions: The study highlights significant gaps in MDI technique knowledge. Demonstrated insufficient knowledge in several critical steps of MDI use.

Background: Vasicine (Vas) is a quinazoline alkaloid derived from Adhatoda vasica Nees, which has good anti-allergic asthma and anti-inflammatory effects. However, its specific functional mechanism on allergic asthma is unclear. This study aims to investigate the protective effect of Vas on allergic asthma and its underlying mechanisms. Methods: Initially, the therapeutic effects of Vas were assessed in ovalbumin-sensitized BALB/c mice using airway hyperresponsiveness (AHR), histopathological examinations, immunohistochemistry, and enzyme-linked immunosorbent assays (ELISA). Subsequently, a non-targeted metabolomic analysis was performed to examine the influence of Vas on lung metabolites, while molecular docking was utilized to clarify the mechanisms by which Vas intervenes in allergic asthma. Lastly, RBL-2H3 cells were employed in vitro to validate the metabolomic findings by measuring intracellular Ca2+ concentrations, in addition to conducting ELISA and Western blot analyses. Results: In vivo, Vas alleviates AHR in mice with allergic asthma, enhances histopathological conditions, and reduces inflammatory factors. Non-targeted metabolomics analyses indicate that the primary pathway implicated in its intervention in allergic asthma may be the FcεRI pathway. Furthermore, molecular docking techniques were utilized to evaluate the binding affinity between Vas and proteins associated with this pathway. In vitro, Vas effectively inhibits degranulation in RBL-2H3 cells and diminishes the release of inflammatory factors by modulating the FcεRI/Lyn + Syk/MAPK pathway. Conclusions: These findings indicate that Vas may effectively alleviate allergic asthma by reducing inflammatory responses, decreasing AHR, and improving histopathological features. Furthermore, Vas seems to inhibit mast cell degranulation and modulate the FcεRI/Lyn + Syk/MAPK pathway.

Obstructive sleep apnea (OSA) is increasingly recognized as a major comorbidity in chronic respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). The coexistence of OSA with asthma or COPD significantly complicates the clinical course, leading to poorer disease control, more frequent exacerbations, reduced lung function, impaired sleep quality, and increased cardiovascular and overall mortality. In asthma, OSA exacerbates airway inflammation, enhances bronchial hyperresponsiveness, and decreases responsiveness to standard therapies. In COPD, the "overlap syndrome" is associated with profound nocturnal hypoxemia, chronic hypercapnia, pulmonary hypertension, and a markedly elevated risk of hospitalization and death. Underlying mechanisms include chronic airway inflammation, oxidative stress induced by intermittent hypoxia, instability of ventilatory control (high loop gain), structural upper-airway alterations, and the burden of obesity and metabolic dysfunction. These interactions highlight the urgent need for integrated and proactive management strategies. Thus, we propose an Asthma-COPD-OSA Outpatient Unit (ACOSOU)-a care-delivery model, not a disease entity-designed to integrate systematic screening, diagnosis, treatment initiation, and long-term follow-up of OSA in patients with asthma and COPD. Optimal care requires systematic screening in respiratory outpatient settings, appropriate diagnostic pathways using polysomnography or home sleep apnea testing, and individualized treatment approaches. Continuous positive airway pressure (CPAP) remains the cornerstone therapy for OSA-asthma and OSA-COPD overlap, improving gas exchange, reducing exacerbations, and enhancing disease control. Comprehensive management also includes optimization of inhaled therapies, pulmonary rehabilitation, weight reduction, sleep hygiene, and multidisciplinary collaboration. This review proposes an integrated ACOSOU model to streamline screening, diagnosis, CPAP titration, and long-term follow-up. However, implementation in low- and middle-income countries faces challenges including limited trained sleep-medicine personnel, unequal access to diagnostic tools, and high CPAP costs without insurance coverage. Strengthening infrastructure, training, and policy support will be essential to improve outcomes for patients with chronic respiratory diseases and OSA comorbidity.

Epithelial-mesenchymal transition (EMT) is amajor pathological characteristic of airway remodellingin severe asthma. Interleukin (IL)-36 belongs to the IL-1 family and is associated with allergic disease, but the role of IL-36 in airway remodelling in asthma remains unclear. We aimed to explore the effect of IL-36 on EMT and to verify whether blocking IL-36-induced EMT can alleviate the airway remodeling in severe asthma. In this study, BEAS-2B cells were stimulated with IL-36 receptor (IL-36R) agonist. The expression of epithelial‒mesenchymal transition (EMT) markers and the migration capacity of cells were determined. A chronic asthma mouse model was established to evaluate the effects of IL-36 signalling on airway inflammation and remodelling. In vitro, EMT and cell migration in BEAS-2BcellswereinducedbyIL-36. In addition, IL-36 facilitated the phosphorylation of NF-κB and STAT3. In vivo, blocking IL-36R via treatment with an IL-36 receptor antagonist (IL-36Ra) inhibited the infiltration of inflammatory cells, decreased airway hyper-responsiveness (AHR) and alleviated airway remodelling (by inhibiting processes, such as EMT) in asthmatic mice. Compared with the administration of IL-36Ra alone, the coadministration of IL-36R agonist with IL-36Ra restored pathological changes related to airway remodelling. These data indicated that IL-36 signalling may participate in airway remodelling by inducing EMT. IL-36 may be a new therapeutic target for airway remodelling in severe asthma.

Diverse IL-9-secreting T helper cells direct responses in the allergic lung.

Asthma prevalence has been increasing, particularly among children and in populations transitioning to Western lifestyle. According to the hygiene hypothesis, early-life exposure to microorganisms may protect against asthma and other allergic conditions. Previous studies demonstrated that Saccharomyces cerevisiae UFMG A-905 reduce bronchial hyperresponsiveness, airway and lung inflammation, and restore IL-10 and IFN-γ. However, the underlying mechanisms remain unclear. To investigate the potential pathways by which S. cerevisiae UFMG A-905 modulates asthma. Wild-type and Il17a⁻/⁻ mice were treated daily with live yeast or its supernatant (postbiotic) by oral gavage, starting ten days before OVA sensitization and maintained during sensitization and challenge. Control groups received saline. Lung tissues were analyzed by flow cytometry to assess dendritic cells and regulatory T cells. Gene expression of TLR-9, NLRP3, Dectin-1, and Mincle was quantified by qPCR. Short-, medium-, and long-chain fatty acids were measured in feces using gas chromatography, while gut cytokine were evaluated by ELISA. Treatment with S. cerevisiae UFMG A-905 led to an increase in CD11c⁺MHCII⁺CD11b⁺CD103⁻ dendritic cells, regulatory T cells (CD4⁺CD25⁺FOXP3⁺), and NLRP3 gene expression in the lung, and the fecal levels of dihomo-γ-linolenic acid. Neither gut cytokines nor OVA specific IgE were affected, and the supernatant did not significantly alter cell counts. The beneficial effects were partially dependent on IL-17A. The effects observed with S. cerevisiae UFMG A-905 correlated with modulation of Th17, dendritic-cell and regulatory T-cell responses, upregulation of NLRP3, and increased fatty acid production, suggesting gut-lung axis involvement.

Gut-lung axis: a novel mechanism involving microbiota dysbiosis-coordinated PLA2-TRPV1 neuroimmune crosstalk in nanoplastic-induced asthma exacerbation.

BackgroundEndothelin-1 (ET-1) is a proinflammatory mediator that plays a crucial role in regulating airway tone by activating G protein-coupled endothelin receptors A (ETA) and B (ETB). The endothelin system has been linked to asthma, but the impact of ETB receptor deficiency on allergic airway inflammation remains uncharted. This study explores how the endothelin system influences allergic airway inflammation and hyperresponsiveness.MethodsWe used rescued ETB receptor-deficient (ETB−/−) mice to obviate lethal inherited Hirschsprung disease, prepro-ET-1 overexpressing (preETtg), and wild-type (WT) mice. Basal airway resistance and responsiveness to broncho-constrictive stimuli were assessed in isolated, perfused and ventilated lungs of naïve mice. Additionally, we analysed the humoral immune response and airway hyperresponsiveness following induction of type 2 airway inflammation induced by systemic ovalbumin (OVA) sensitisation and repeated airway challenge with aerosolised OVA.ResultsNaïve ETB−/− mice exhibited significantly heightened airway responsiveness compared to naïve WT mice. After OVA sensitisation and challenge, ETB−/− mice displayed increased OVA-specific immunoglobulin E levels, intensified allergic airway inflammation and hyperresponsiveness compared to WT mice. Conversely, preETtg mice displayed reduced immunoglobulin E levels, airway inflammation and hyperresponsiveness.ConclusionOur findings suggest ETB receptors have a protective role in asthma-associated allergic airway inflammation and hyperresponsiveness. The increased asthma phenotype in sensitised and challenged ETB−/− mice is attributed to ETB-specific immunomodulatory mechanisms, rather than to elevated levels of ET-1 resulting from impaired ETB-mediated ET-1 clearance. This conclusion is supported by the diminished asthma-phenotype observed in sensitised and challenged preETtg mice. Therefore, adjusting endothelin signalling could offer a promising approach to managing asthma.

HuangLong oral liquid alleviates cough variant asthma in mice via inhibiting M2 macrophage chemotaxis and polarization by regulating the PI3K/AKT/ERK pathway.

Mediating roles of oxidative stress and nuclear factor kappa B signaling in benzyl butyl phthalate-aggravated allergic asthma.

Objective To investigate the role of nerve growth factor (NGF) and its high-affinity receptor tyrosine kinase A (TrkA) in the pathogenesis of bronchial asthma (BA), and to evaluate their association with asthma severity and type 2 T helper (Th2) inflammatory factors, and to validate the intervention efficacy and mechanism of nebulized targeted therapy using poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with anti-NGF antibodies in severe asthma. Methods Serum samples were collected from asthma patients of varying severity and non-asthmatic individuals. Levels of NGF, TrkA, interleukin 4(IL-4), IL-5, and IL-13 were measured. An ovalbumin (OVA)-induced severe asthma mouse model was established and randomly divided into blank control, severe asthma, conventional antibody therapy, and nebulized anti-NGF microsphere groups. Differences in inflammatory factors in bronchoalveolar lavage fluid (BALF), lung tissue pathology, and NGF/TrkA/NF-κB protein expression levels were compared among groups via ELISA, pulmonary function testing, HE/Masson staining, and Western blot analysis. Results Clinical testing revealed elevated serum NGF (82.52±4.01 vs 22.92±5.25)pg/mL and TrkA (53.93±8.97 vs 15.76±3.60)pg/mL levels in the severe asthma group compared to the non-asthmatic control group; IL-4 (44.23±9.88 vs 20.88±3.90)pg/mL, IL-5 (147.1±14.92 vs 47.13±5.63)pg/mL, and IL-13 (106.9±11.64 vs 51.93±8.55)pg/mL levels were significantly elevated. In animal experiments, the nebulized anti-NGF microsphere group exhibited significantly lower levels of IL-4 (36.08±6.08 vs 87.35±9.13)pg/mL, IL-5 (35.41±4.52 vs 81.53±4.94)pg/mL, and IL-13 (36.37±4.57 vs 92.37±6.53)pg/mL. Forced expiratory volume in one second(FEV1) (84.68±5.33 vs 60.87±3.93)% increased, and airway hyper reactivity(AHR) (152.8±7.36 vs 233.8±8.77)% decreased. Pulmonary tissue pathological damage and collagen deposition were alleviated. Western blot analysis revealed that relative protein levels of NGF, TrkA, and NF-κB in lung tissues of mice treated with nebulized anti-NGF microspheres were lower than those in the severe asthma group. Conclusion The NGF/TrkA signaling pathway is closely associated with asthma severity. Nebulized anti-NGF microsphere therapy effectively targets the lungs, inhibits the NF-κB pathway, alleviates airway inflammation, and significantly improves pulmonary function.