Airway remodelling in asthma and the epithelium: on the edge of a new era

European Respiratory Journal, Journal Year: 2024, Volume and Issue: 63(4), P. 2301619 - 2301619

Published: April 1, 2024

Asthma is a chronic, heterogeneous disease of the airways, often characterised by structural changes known collectively as airway remodelling. In response to environmental insults, including pathogens, allergens and pollutants, epithelium can initiate remodelling via an inflammatory cascade involving variety mediators that have downstream effects on both immune cells. These include epithelial cytokines thymic stromal lymphopoietin, interleukin (IL)-33 IL-25, which facilitate through cross-talk between cells fibroblasts, mast smooth muscle cells, well signalling with such macrophages. The also independently inflammation in mechanical stress present during bronchoconstriction. Furthermore, genetic epigenetic alterations components are believed influence Here, we review recent advances our understanding roles driving remodelling, facilitated developments sequencing imaging techniques. We explore how new existing therapeutics target could modify

Language: Английский

---

Mucus Structure, Viscoelastic Properties, and Composition in Chronic Respiratory Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1933 - 1933

Published: Feb. 5, 2024

The respiratory mucus, a viscoelastic gel, effectuates primary line of the airway defense when operated by mucociliary clearance. In chronic diseases (CRDs), such as asthma, obstructive pulmonary disease (COPD), and cystic fibrosis (CF), mucus is overproduced its solid content augments, changing structure properties determining derangement essential mechanisms against opportunistic microbial (virus bacteria) pathogens. This ensues in damaging airways, leading to vicious cycle obstruction infection responsible for harsh clinical evolution these CRDs. Here, we review features normal pathological (i.e., sputum CF, COPD, asthma), i.e., mucin content, (mesh size), micro/macro-rheology, pH, osmotic pressure, ending with awareness that biomarkers (mucins, inflammatory proteins peptides, metabolites) might serve indicate acute exacerbation response therapies. There are some indications old novel treatments may change structure, properties, biomarker sputum; however, wealth work still needed embrace measures correlates severity association (or even substitutes of) functional tests.

Language: Английский

---

The Role of WNT5a and TGF‐β1 in Airway Remodelling and Severe Asthma

Allergy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

ABSTRACT Background Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role WNT5a and TGF‐β 1 in asthmatic biopsies sputum bronchial brushings assessed their remodelling. Methods protein expression were lamina propria epithelium people (GINA 1–3, n‐8 GINA 4–5, n‐14) healthy subjects (n‐9), alongside relevant markers. The effects on BEAS‐2B cell wound healing differentiation vitro. Replication was performed Unbiased Biomarkers for Prediction Respiratory Disease Outcomes (U‐BIOPRED) study ( n = 120) brushes 147). Results significantly increased patients concurrent airflow limitation or disease. Furthermore, correlated tissue eosinophils vascular co‐localised predominantly to basal cells Th17 gene r 0.40, p 0.025) both % intact s 0.54, 0.001) denuded −0.39, 0.003). Experiments confirmed that at maximal physiological concentrations (1 μg/mL), promoted healing, independently , as well induction EMT‐like morphology. mRNA associated asthma, limitation, eosinophilia Th2, neutrophil activation transcriptomes U‐BIOPRED. Conclusion asthma. Trial Registration ClinicalTrials.gov identifier: NCT01982162

Language: Английский

---

Impact of particulate air pollution on airway injury and epithelial plasticity; underlying mechanisms

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 8, 2024

Air pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction air pollutants, studies have demonstrated that it can cause inflammation injury. The epithelium forms first barrier defense against inhaled toxicants, PM. Airway epithelial cells clear airways from irritants orchestrate inflammatory response to these by secreting various lipid mediators, growth factors, chemokines, cytokines. Studies suggest PM pathogenesis diseases impairing mucociliary function, deteriorating integrity, inducing production mediators while modulating proliferation death cells. Furthermore, modulate plasticity remodeling, which play central roles COPD. This review focuses on effects injury plasticity, underlying mechanisms involving activity, inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial remodeling.

Language: Английский

---

Type 2 airway inflammation in COPD

European Respiratory Journal, Journal Year: 2024, Volume and Issue: 63(5), P. 2400150 - 2400150

Published: March 14, 2024

Globally, nearly 400 million persons have COPD, and COPD is one of the leading causes hospitalisation mortality across world. While it has been long-recognised that an inflammatory lung disease, dissimilar to asthma, type 2 inflammation was thought play a minor role. However, recent studies suggest in approximately third patients with may be important driver disease potential therapeutic target. Importantly, immune cells molecules involved COPD-related immunity significantly different from those observed severe asthma. Here, we identify effector airway discuss trial results biologicals targeted these pathways explore future development modulators COPD.

Language: Английский

---

Quercetin improves epithelial regeneration from airway basal cells of COPD patients

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 11, 2024

Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated reduced expression of several genes involved in epithelial repair. Quercetin reduces remodeling inflammation COPD models, therefore we examined whether quercetin promotes normal regeneration BC by altering gene expression. treated DMSO or 1 µM for three days were cultured at air/liquid interface (ALI) up to 4 weeks. healthy donors ALI used as controls. Polarization determined 8 ALI. The cell types IL-8 differentiated cultures quantified flow cytometry ELISA respectively. Microarray analysis conducted on quercetin-treated 3 identify differentially regulated (DEG). Bronchial brushings obtained similar age status either placebo (4 subjects) 2000 mg/day (7 6 months confirm the effects Compared placebo-, showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet lower IL-8. upregulated tissue development differentiation BC. quercetin, but not two developmental HOXB2 ELF3, which also FDR < 0.001. Active smokers mRNA TGF-β (0.067) (22.0), 3.6 4.14 fold respectively after treatment. These results indicate that may improve increasing development/differentiation COPD. This study registered ClinicalTrials.gov 6-18-2019. number is NCT03989271.

Language: Английский

---

Development and validation of a risk prediction model related to inflammatory and nutritional indexes for postoperative pulmonary infection after radical colorectal cancer surgery

BMJ Open, Journal Year: 2025, Volume and Issue: 15(1), P. e087426 - e087426

Published: Jan. 1, 2025

Objective To develop and validate a risk prediction model related to inflammatory nutritional indexes for postoperative pulmonary infection (POI) after radical colorectal cancer (CRC) surgery. Design Cross-sectional study. Participants This study analysed 866 CRC patients surgery at tertiary hospital in China. Methods Univariable multivariable logistic regression (LR) analyses were used explore influence factors of POI. Predictive models constructed using LR, random forest, support vector machine, K-nearest neighbours, naive Bayes XGBoost. The LR was generate nomogram POI prediction. discrimination calibration the assessed receiver operating characteristic (ROC) curves curves. contributions evaluated through Net Reclassification Improvement integrated improvement, while clinical practicability decision curve analysis. Main outcome measures during hospitalisation. Results Independent identified from included age, respiratory disease, Systemic Inflammation Response Index, albumin-to-globulin ratio, operative method duration. demonstrated best performance, with an area under ROC 0.773 (95% CI: 0.674 0.872). has good differentiation ability, net benefit. Incorporating into enhanced predictive value compared excluding either factor. Conclusion may represent promising tool predicting patients.

Language: Английский

---

Interplay between extracellular vesicles and allergic diseases: Current insights and future perspectives

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract The field of extracellular vesicle (EV) research has rapidly evolved, revealing their significant roles in various biological processes and clinical applications. Allergic diseases are prevalent immunological disorders characterized by exaggerated hypersensitivity reactions to allergens, leading diverse manifestations that can severely impact quality life. Recently, studies have underscored the pivotal role EVs allergic conditions, including asthma, rhinitis, atopic dermatitis. In this review, we provide a comprehensive overview recent advances separation characterization EVs, diseases, diagnostic value as biomarkers. Additionally, explore therapeutic potential for treatment prevention conditions. Overall, emerging insights into present promising opportunities enhancing diagnosis, treatment, management diseases.

Language: Английский

---

Study on the changes of extracellular matrix morphology and components in COPD animal model by using lung decellularized scaffold

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 27, 2025

Abstract Airway remodeling is a critical pathological process that influences the progression of chronic obstructive pulmonary disease(COPD). To better study small airway in COPD, we employed advanced techniques such as decellularized scaffolds, immunofluorescence, scanning electron microscopy, and proteomics to analyze morphological compositional changes extracellular matrix (ECM). Our revealed significant ultrastructural abnormalities scaffolds from COPD group, including thinning alveolar septa, enlargement spaces, fusion multiple alveoli. Additionally, ECM composition group exhibited notable characterized by an increase collagen fibers, type I IV collagens, fibronectin, laminin ( p < .05), along with decrease elastin glycosaminoglycans .05). Proteomic analysis identified 70 differentially expressed proteins between control group. These included 34 upregulated Smarca2, Skt, Acvrl1, Myl2 (all ratios >10.64), 36 downregulated Col6a6, Col6a5, AnK3 <0.27). Pathway indicated activation apoptosis (Enrichment Score, ES = 0.23) epithelial–mesenchymal transition (ES 0.38) genes inhibition synthesis –0.43) degradation –0.63) were observed findings enhance our understanding mechanisms underlying provide scientific basis for developing novel therapeutic strategies COPD.

Language: Английский

---

The role of mitochondria in eosinophil function: implications for severe asthma pathogenesis

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 1, 2024

Mitochondria are key metabolic hubs involved in cellular energy production and biosynthesis. ATP is generated primarily by glucose fatty acid oxidation through the tricarboxylic (TCA) cycle oxidative phosphorylation (OXPHOS) mitochondria. During OXPHOS there also of reactive oxygen species (ROS), which regulation function. central regulating cell survival death, particularly intrinsic apoptosis pathway. Severe asthma a heterogeneous disease driven various immune mechanisms. eosinophilic entails type 2 inflammatory response peripheral lung eosinophilia, associated with severe airflow obstruction, frequent exacerbations poor to treatment. Mitochondrial dysfunction altered metabolism have been observed airway epithelial smooth muscle cells from patients asthma. However, role mitochondria development eosinophilia eosinophil-mediated inflammation unknown. In this review, we discuss currently limited literature on eosinophil function how it regulated asthma-relevant cytokines, including interleukin (IL)-5 granulocyte-macrophage colony-stimulating factor (GM-CSF), as well corticosteroid drugs. Moreover, summarise evidence eosinophils extracellular trap formation. Finally, possible mitochondrial suggest research avenues order better understand their pathogenesis, identify novel therapeutic targets.

Language: Английский

---