Search Results (419)

Bronchial asthma is a heterogeneous disease characterized by chronic airway inflammation. Oxidative stress arises when the production of free radicals exceeds the antioxidant defense system’s capacity, leading to a redox imbalance. Under oxidative stress, airway inflammation is activated, leading to airway remodeling and maintenance of bronchial hyperreactivity. Airway epithelial remodeling can cause irreversible tissue fibrosis in asthma patients, thereby contributing to a severe course of asthma. A comprehensive literature review was performed using medical database “PubMed” and specialized search engine “Google Scholar” using the PICO model. A total of 51 scientific studies published in English from 2020–2025 were analyzed. Out of the initial 561 articles, 510 articles were excluded due to incomplete articles, studies involving animals, or articles not in English. New studies show that oxidative stress can be objectively measured using various biomarkers. This research aims to provide a better understanding of how oxidative stress affects the airways of asthma patients and what information can be obtained by measuring oxidative stress biomarkers. Full article

Bronchial thermoplasty (BT) is a non-pharmacological treatment for severe asthma. The working mechanism and response determinants of BT remain partly unknown. This study aims to investigate whether a systemic transcriptomic response to BT can be detected and contextualized against a control cohort. Whole blood was collected at baseline and six months after BT from severe asthma patients (n = 31) and a control cohort (n = 126). RNA was isolated and sequenced. The following comparisons were made: before and after BT, responders and non-responders, and severe asthma (at baseline) versus controls. Differentially expressed genes were identified across 179 samples using DESeq2. Pathway enrichment was investigated using gene set enrichment and overrepresentation analyses. Following BT, pathways related to nervous system development, ion channel activity, muscle tissue development, and cilia function were downregulated. In responders specifically, gene sets involved in nervous system and muscle development were downregulated. Compared with the control cohort, pathways related to nervous system development and ion channel activity were upregulated in the severe asthma cohort at baseline. In conclusion, systemic blood-derived transcriptomic changes can be detected in severe asthma patients six months after BT and may provide insight into BT mechanisms and its responder profile. Full article

Background/Objectives: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder classically associated with emphysema and COPD. However, emerging evidence indicates that its clinical spectrum extends to airway-predominant diseases such as bronchiectasis and asthma, where protease–antiprotease imbalance and neutrophilic inflammation may drive tissue injury. This narrative review aims to synthesize current evidence on the relationship between AATD and airway diseases beyond emphysema, focusing on epidemiological patterns, underlying mechanisms, diagnostic strategies, and therapeutic implications. Methods: A narrative synthesis of the literature was performed, integrating data from registries, with observational and translational studies addressing the prevalence, pathobiology, and therapeutic implications of AATD in bronchiectasis, asthma, and severe asthma. Epidemiologic and mechanistic insights were analyzed to identify overlapping pathways and evidence gaps. Results: Evidence supports a non-negligible prevalence of bronchiectasis and asthma among AATD individuals, particularly in severe or heterozygous genotypes. Neutrophil elastase overactivity, impaired mucociliary clearance, and chronic neutrophilic inflammation emerge as shared mechanisms promoting bronchial remodeling and airflow limitation. In asthma, AATD appears linked to T2-low, steroid-resistant phenotypes and persistent obstruction, whereas in severe asthma cohorts, up to 20% may carry non-PiMM SERPINA 1 variants. No randomized trials have evaluated augmentation therapy and standardized screening algorithms are lacking. Conclusions: AATD represents a systemic disorder with clinically relevant airway manifestations beyond COPD and emphysema. Targeted testing should be considered in patients with idiopathic bronchiectasis or severe asthma. Future genotype-stratified, prospective studies are required to clarify causality, define biomarkers of disease activity, and evaluate the potential role of anti-protease-based therapeutic strategies. Full article

Small intestinal bacterial overgrowth (SIBO) is an increasingly recognized condition that influences immune responses. It may be linked to atopic disorders such as bronchial asthma (BA), food allergies (FA), chronic spontaneous urticaria (CSU), and mast cell activation syndrome (MCAS). The aim of our study was to perform a structured literature search to assess the possible correlation between SIBO and the presentation of atopic disorders. The prevalence of SIBO was highest in patients with BA (60–100%) and FA (50–87.5%), followed by MCAS (30.9%) and CSU (27.9%). The diagnosis of SIBO was based on lactulose or glucose breath tests. SIBO exacerbated symptoms of atopic diseases, and treating it within BA and MCAS improved the symptoms, in contrast to CSU. The present evidence suggests a possible crosslink between SIBO and atopic manifestations. Bacterial overgrowth appears to trigger the Th2 immune response via the mucosal pathway and low-grade endotoxemia. These result in the increased synthesis of interleukins involved in allergic reactions (IL-4, IL-5, IL-13). Further studies are essential to confirm the clinical significance of this association. The “gut–allergy axis” may offer new therapeutic options and possibly improve quality of life in patients with atopy. Full article

Advanced glycation end-products (AGEs) are a variety of endogenous and exogenous substances that play an important role in inflammation, allergies, and autoimmune diseases. AGEs’ pathogenicity, alongside advanced oxidation protein products (AOPPs) and other ligands, lies in their ability to bind the receptor for advanced glycation end-products (RAGE) and trigger pro-inflammatory signaling pathways and cytokine release. The literature reports numerous studies on the role of the AGE-RAGE axis in various allergic conditions, including bronchial asthma, atopic dermatitis, food allergies, and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or Hashimoto’s thyroiditis, where the significant role of the AGE–RAGE axis in the immunopathogenesis of both allergic and autoimmune conditions is largely discussed and demonstrated. They suggest promising opportunities for the development of new diagnostic markers and targeted therapeutic strategies. However, further large-scale studies are needed to fully understand this multifaceted pathway and translate these insights into effective clinical interventions. Full article

Background: Impedance pneumography (IP) is a non-invasive technique for assessing tidal breathing in young children and enables home-based recordings without active patient cooperation. By deriving tidal breathing flow–volume (TBFV) curves and indices such as the expiratory variability index (EVI), IP has been proposed as a tool for identifying obstructive breathing patterns and monitoring airway function in early childhood. However, its clinical role in asthma and wheezing disorders has not been systematically evaluated. This review aimed to assess the evidence of IP in differentiating healthy children from those with asthma or recurrent wheeze, in reflecting treatment-related changes or acute bronchial obstruction, and in relation to other lung function tests. Methods: A systematic literature search of PubMed, Medline, Embase, and the Cochrane Library databases was conducted on 5 January 2026. Original studies using IP in children aged 0–7 years with asthma or wheeze were eligible. Study selection followed PRISMA guidelines, and risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale (NOS). Due to substantial heterogeneity in study design, populations, and outcome measures, results were synthesized narratively. Results: Five studies were included, with a total of 376 participants aged 0.5–7.0 years. Three studies reported significantly lower EVI values and TBFV profile variation in children with asthma or recurrent wheeze compared with healthy controls. Two studies found an association between EVI and markers of airway obstruction. Changes in IP measures following inhaled corticosteroid treatment or medication withdrawal were reported, suggesting sensitivity to treatment-related changes. However, study quality was moderate to low, with small sample sizes, heterogeneous outcome definitions, and limited diagnostic validation. Conclusions: Current evidence suggests that IP-derived indices, particularly EVI, capture clinically relevant features of obstructive breathing patterns in young children and may be useful for longitudinal monitoring of airway function. However, evidence supporting a diagnostic role for IP in childhood asthma remains limited. Larger, independent, and methodologically robust studies are needed before IP can be integrated into routine clinical practice. Full article

Background/Objectives: Allergic asthma (AA) is a common chronic respiratory disease characterized by airway inflammation and bronchial hyperreactivity triggered by environmental allergens such as pollen and dust mites. Allergen-specific immunotherapy (AIT), particularly its sublingual formulation (SLIT), is the only treatment capable of modifying the disease’s natural course by targeting IgE-mediated sensitization mechanisms. Methods: We analyzed demographic, clinical, functional (FEV₁, FVC, FEV₁/FVC), and immunological data (specific IgE for Phl p1, Phl p5, Der p1, Der p2, Der p23), alongside asthma control parameters (ACT score), reliever use, and exacerbation frequency, in patients undergoing SLIT for grass pollen and dust mite allergens. Results: After at least twelve months of treatment, we observed significant reductions in exacerbation rate (p < 0.01) and reliever use (p = 0.0002). These improvements were particularly evident in the subgroup receiving grass pollen SLIT (p = 0.03 and p = 0.01, respectively). An increase in ACT score was observed but did not reach statistical significance (p = 0.07), likely due to already high baseline control. All patients reported improved rhinitis symptoms. Lung function parameters showed no significant changes. SLIT was well tolerated, with no serious adverse events or discontinuations. The subgroup of patients treated with dust mite SLIT was small, limiting the statistical power and generalizability of these findings. Consequently, the dust mite results should be interpreted cautiously and considered exploratory. The more robust and statistically supported findings pertain to the grass pollen SLIT group, reflecting a more consolidated evidence base for this allergen. Conclusions: SLIT for grass pollen demonstrated promising, statistically supported benefits in reducing exacerbations and improving disease control, supporting its role as an effective adjunct therapy in AA. While dust mite SLIT also showed positive trends, the limited sample size warrants further investigation to confirm these preliminary findings. Overall, SLIT appears to be a safe and potentially beneficial option for patients with AA and allergic rhinitis, but larger studies are needed to substantiate its efficacy across different allergens. Full article

Background/Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) involves a sudden onset of a perfusion-pressure injury from the initial insult combined with a secondary injury phase produced by delayed cerebral ischemia, cerebrospinal fluid circulation disturbances, and generalized instability of the patient’s physiological state. The situation may be further complicated when there has been rupture of the aneurysm at the site of the carotid–posterior communicating (PCom) artery junction that occurs in conjunction with a fetal configuration of the posterior cerebral artery (fPCA), thereby making definitive treatment dependent on preserving the critical nature of the branches of the posterior circulation since the aneurysm’s neck plane coincides with the dominant posterior circulation conduit. Case Presentation: A 65-year-old female patient who was obese (Grade III BMI = 42), had chronic bronchial asthma, and arterial hypertension experienced a “thunderclap” type of headache in the right retro-orbital area followed by a syncopal episode and developed acute confusion with agitation. Upon admission to the hospital, her Glasgow Coma Scale (GCS) was 13, her FOUR score was 15, her Montreal Cognitive Assessment (MoCA) score was 12/30, her Hunt–Hess grade was 3, WFNS grade 2, and Fisher grade 4 SAH with intraventricular extension. Digital subtraction angiography (DSA) and three-dimensional rotational angiography revealed a posteriorly directed right carotid communicating aneurysm that had a relatively compact neck (approximately 2.5 mm) and sac size of approximately 7.7 × 6.6 mm, with the fPCA originating at the neck plane. Microsurgical treatment was performed with junction-preserving reconstruction with skull base refinement, temporary occlusion of the internal carotid artery for a few minutes, placement of clips reconstructing the carotid–PCom interface, and micro-Doppler verification of patent vessel. Postoperatively, the blood pressure was kept within the range of 110–130 mmHg with nimodipine and closely monitored. The neurological recovery was sequential (GCS of 15 by POD 2; MoCA of 22 by POD 5). By POD 5 CT scan, the clip remained positioned in a stable fashion without evidence of infarct, hemorrhage, or hydrocephalus; at three months she was neurologically intact (mRS 0; Barthel 100; MoCA 28/30), and CTA confirmed persistent exclusion of the aneurysm and preservation of fPCA flow. Conclusions: In cases where the ruptured aneurysm is located at the carotid communicating junction with the PCom artery in a configuration of the posterior cerebral artery that is described as fetal, clip treatment should be viewed as a form of branch-preserving junction reconstruction of the carotid–PCom junction supported by adherence to controlled postoperative physiology and close ppostoperativesurveillance. Full article

Chronic rhinitis is induced by endotype-diverse inflammatory processes, which complicates effective therapeutic management. According to the current principles of personalized medicine, which also apply to the management of rhinological disorders, the best therapeutic results can be achieved after targeted treatment preceded by analysis of the patient’s endotype. Analysis of immune and cellular mechanisms allows for the use of biological treatment, and its effects provide new information on inflammatory processes in the nasal mucosa. The effects of biological treatment may be particularly interesting in the case of mixed endotypes, which pose a difficult therapeutic challenge. In eosinophilic asthma co-occurring with allergic rhinitis, as well as in eosinophilic asthma associated with non-allergic rhinitis, eosinophils represent a key effector cell population driving the underlying type 2-mediated inflammatory response. The aim of this study is to analyze the efficacy of anti-IL5 or anti-ILR5 therapy in patients with severe eosinophilic asthma and persistent allergic or non-allergic rhinitis. Methods: In this single-center real-life study, the authors analyzed the effects of biological treatment on rhinological symptoms in patients over the age of 18 with severe uncontrolled eosinophilic bronchial asthma with coexisting persistent allergic or non-allergic rhinitis treated with mepolizumab or benralizumab. In all patients, the otolaryngologist performed anterior rhinoscopy. Evaluation of rhinological symptoms and quality of life in patients treated with anti-IL5 or anti-IL5 therapy before and six months after biological treatment was performed using the TNSS and SNOT-22 scales. Results: In total, 67 patients with eosinophilic severe bronchial asthma were included in the study; among them 39 (58.2%) suffered from persistent allergic rhinitis and 28 (41.8%) suffered from chronic non-allergic rhinitis. After six months of treatment, higher absolute differences for SNOT and TNSS were observed in the persistent allergic rhinitis group. Conclusions: Biological treatment with mepolizumab and benralizumab may reduce the severity of rhinological symptoms in both endotypes of inflammation. However, higher therapeutic benefits were observed in patients with co-existing persistent allergic rhinitis. It was demonstrated that, in addition to IgE-mediated responses, the eosinophil represented an important component of the inflammatory reaction in allergic rhinitis. Full article

Background: Gut microbiota dysbiosis has been associated with childhood asthma; however, its role in adult bronchial asthma (BA), particularly in Japanese populations, remains unclear. The potential influence of sex-based differences also warrants investigation. We aimed to investigate the association between gut microbiota composition and adult BA in a Japanese cohort, focusing on sex-specific differences. Methods: Stool samples from 108 Japanese adults with BA (48 male and 60 female individuals) and 210 healthy controls (90 male and 120 female individuals) were analyzed using 16S rRNA gene sequencing. Analyses were stratified by sex. β-diversity was assessed using non-metric multidimensional scaling and permutational multivariate analysis of variance. Genus-level taxonomic comparisons were conducted using the ANOVA-Like Differential Expression version 2 tool on centered log-ratio-transformed data. Results: β-diversity significantly differed between the groups among both male and female individuals. In male individuals, 11 taxa had absolute effect sizes of ≥0.2. In female individuals, 19 taxa met this threshold, with 8 reaching significance after Benjamini–Hochberg correction. Streptococcus and Blautia were enriched in the BA group in both sexes, whereas other taxa showed sex-specific patterns, such as Veillonella in male and Flavonifractor and Eggerthella in female individuals. Several short-chain fatty acid (SCFA)-producing taxa were depleted in the BA group. Conclusions: Our findings suggest that gut microbiota dysbiosis occurs in Japanese adults with BA, characterized by enrichment of taxa associated with respiratory diseases and depletion of SCFA-producing bacteria. The observed patterns highlight the importance of considering sex-specific differences in future research. Full article

Vitamin D deficiency is associated with the risk of atopic diseases and respiratory infections. The activated vitamin D receptor (VDR) forms a dimer with the retinoid X receptor alpha (RXRA) and binds to VDR/RXRA composite elements (CEs) in enhancers of target genes. However, VDR/RXRA CEs are identified in only 11.5% of cases in ChIP-Seq peaks. Our hypothesis was that VDR could form a VDR-Partner complex with transcription factor for which CEs have not yet been identified. We utilized Web-MCOT to search for novel VDR/Partner CEs in regulatory DNA. The potential formation of the VDR-Partner protein complex was assessed using the AlphaFold machine learning model. Through real-time RT-PCR, we measured the expression of immune system genes in a culture of U937 macrophage-like cells incubated with the active metabolite of vitamin D, calcitriol. We have predicted novel VDR/NR2C2 and VDR/PPARG CEs in the regulatory regions of immune system genes. We found potential synergism of VDR/NR2C2 and VDR/RXRA CEs in relation to the IRF5 gene, as well as potential synergism of VDR/PPARG and VDR/RXRA CEs for MAPK13. Predicting new regulatory relationships through the identification of new potential VDR/Partner CEs may provide insight into the deep mechanisms of vitamin D involvement in the pathogenesis of atopic dermatitis, bronchial asthma, allergic rhinitis, and pulmonary infections. Full article

Current asthma therapies reduce inflammation and symptoms but there are concerns regarding adverse effects and the long-term treatment burden. The anti-asthmatic potential of Dictamnine (Dic) has not been investigated. The therapeutic effect of Dic on airway inflammation and remodeling was investigated by targeting the tumor growth factor (TGF)-β/Smad2/3 pathway. A murine model of ovalbumin (OVA)-induced asthma was used to evaluate the effects of orally-administered Dic on airway hyperresponsiveness, inflammatory cytokines in bronchoalveolar lavage fluid (BALF), OVA-specific IgE in the serum, and histopathological changes. The expression of TGF-β/Smad2/3 and epithelial markers was assessed. Human bronchial epithelial cells were used in vitro to examine the effects of Dic on TGF-β-induced Smad2/3 phosphorylation. Network pharmacology was conducted to predict Dic-associated targets and pathways. Dic substantially reduced the levels of Th2 cytokines, mucin 5AC in BALF, and OVA-specific IgE in the serum. Histology indicated reduced inflammatory cell infiltration, bronchial wall thickening, and peribronchial fibrosis in Dic-treated mice. Dic downregulated TGF-β and p-Smad2/3 expression and upregulated ZO-1 expression in the lung tissue. Dic downregulated TGF-β-induced Smad2/3 phosphorylation in bronchial epithelial cells. Network pharmacology indicated enrichment of Dic-related genes in the TGF-β pathway. Dic exhibited anti-asthmatic effects and is a potential therapeutic candidate. Full article

Understanding asthma’s endotypes is key to advancing precision medicine. Using omics techniques on sputum, bronchial epithelium, and blood have revealed T2 and non-T2 asthma, each which have been further categorized into T2 and non-T2 subgroups. Despite advances in understanding asthma’s molecular complexity, many questions remain. Future research could either enhance current multiomics approaches with sophisticated bioinformatics or integrate hypothesis-driven research. It is now widely accepted that the airway epithelium starts and regulates the inflammatory cascade in asthma. If asthma originates in the altered epithelium, concentrating research on epithelial dysfunction is logical. This approach is likely more straightforward than analyzing the multitude of genes affected by the inflammatory cascade triggered by this disturbed airway epithelium. The airway epithelium comprises various cell types, including basal cells, club cells, ciliated cells, goblet cells, pulmonary neuroendocrine cells, tuft cells, and pulmonary ionocytes, which are connected by junctional complexes including tight junctions, adherens junctions, gap junctions, and desmosomes. The healthy airway epithelium helps support homeostasis, defend against threats, and regulate immunity through innate and adaptive systems. Chronic airway epithelial barrier dysfunction can instigate and propagate excessive immune responses. Knowing the cellular makeup and differentiation of the airway epithelium is vital for creating treatments to restore airway integrity in established asthma. A new consensus highlights focusing research on airway epithelial dysfunction as the main driver of inflammation, marking the start of the “epithelium era” in asthma research. Full article

Der p 23 induces a high-frequency sensitization in allergic individuals. However, its allergenic activity and clinical impact are scarce. We aimed to evaluate the ability of rDer p 23 to induce allergic inflammation in a mouse model and to test IgE reactivity in humans. Female Balb/c mice were sensitized and challenged with rDer p 23 and Dermatophagoides pteronyssinus extract. Specific antibodies were determined by ELISA, inflammatory cell infiltration and goblet cells hyperplasia were evaluated by lung histology, and bronchial hyperreactivity (BHR) was assessed by the FinePoint RC System^TM and whole-body plethysmography (WBP). IgE reactivity was evaluated by ELISA, the basophils activation test (BAT) and the skin pick test (SPT) in humans. rDer p 23, produced in Escherichia coli, adopts a random coil structure, predominantly exists in a monomeric state, and exhibits high stability. rDer p 23-treated mice showed a significant increase in lung resistance and bronchial hyperreactivity, as well as in eosinophils, neutrophils, and T cell count in bronchoalveolar lavage fluid (BALF). Cytokine and antibodies profiles were biased to a Type-2 response. No significant difference was observed in group 2 Innate Lymphoid Cells (ILC-2s) in lung and regulatory T cells (Treg) in the spleen. In asthmatic individuals sensitized to D. pteronyssinus, serum IgE reactivity to rDer p 23 was 67.5%. BAT and SPT results were significantly higher in allergic patients. Our findings support the pro-allergenic role of rDer p 23 in the development of the pathological features of asthma. Full article

Background: Asthma and chronic obstructive pulmonary disease (COPD) are prevalent obstructive lung diseases with distinct inflammatory pathways but overlapping clinical features. Bronchodilator responsiveness (BDR) is a key diagnostic criterion, yet its metabolic determinants are poorly understood. Objective: This cross-sectional study investigated whether integrated profiling of exhaled volatile organic compounds (VOCs) and clinical biomarkers can differentiate BA, COPD, and health, and predict BDR. Methods: Exhaled breath from 160 BA patients, 128 COPD patients, and 254 healthy controls was analyzed in real-time using proton-transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) during tidal and forced expiration. Clinical assessment included spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil count, and total IgE. Machine-learning (XGBoost) was employed for feature selection and model development. Results: Distinct VOC signatures effectively discriminated disease groups from controls and from each other. The model for distinguishing asthma from healthy controls achieved an AUC of 0.747 during normal quiet breathing and 0.710 during forced exhale. For discriminating COPD from healthy controls, the model performance was higher, with an AUC of 0.821 for normal quiet breathing and 0.856 for forced exhale. A model integrating VOC profiles with clinical biomarkers (FeNO, eosinophils, IgE) demonstrated very high accuracy in internal validation in predicting BDR (AUC = 1.000 for tidal breathing; AUC = 0.970 for forced expiration). Specific mass spectral features (m/z 79, m/z 101) were significantly associated with a positive BDR test. Conclusions: This study delineates disease-specific VOC signatures and underscores the profound synergy between exhaled metabolomics and clinical immunology for identifying associations treatment response, advocating for the integration of real-time breath analysis into personalized management strategies for obstructive lung diseases. Full article