Omalizumab may decrease the thickness of the reticular basement membrane and fibronectin deposit in the bronchial mucosa of severe allergic asthmatics

Zastrzeżyńska, Weronika; Przybyszowski, Marek; Bazan-Socha, Stanisława; Gawlewicz‐Mroczka, Agnieszka; Sadowski, Piotr; Okoń, Krzysztof; Jakieła, Bogdan; Plutecka, Hanna; Ćmiel, Adam; Sładek, Krzysztof; Musiał, Jacek; Soja, Jerzy

doi:10.1080/02770903.2019.1585872

Cited by 23 publications

(16 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, there is no effective cure for airway remodelling in asthma, although reports on biological therapy bring an emerging hope . The identification of simple and non‐invasive imaging or laboratory biomarkers, however, is critical for its assessment.…”

Section: Discussionmentioning

confidence: 99%

The relationship of airway structural changes to blood and bronchoalveolar lavage biomarkers, and lung function abnormalities in asthma

Koźlik

Zuk

Bartyzel

et al. 2019

Clin Experimental Allergy

Self Cite

View full text Add to dashboard Cite

Background: Airway structural changes are important in asthma pathology and require further investigations.Objective: We sought to evaluate which computed tomography (CT) indices, bronchial histological traits, or blood and bronchoalveolar lavage (BAL) biomarkers correlate best with lung function abnormalities in asthma. Methods:In 105 white adult asthmatics (53 with a component of fixed airflow obstruction), we determined airway cross-sectional geometry of two proximal (the right upper lobe apical segmental and the left apicoposterior) and two distal (the right and the left basal posterior) bronchi, quantified the low-attenuation lung area (LAA%), and analysed clusters based on airway CT-metrics. We also performed bronchofiberoscopy with BAL and endobronchial biopsy, assessed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, IL-23, interferon (INF)γ and periostin, together with circulating a disintegrin and metalloproteinase domain-containing protein (ADAM)33, and investigated interplays between analysed variables.Results: Patients with fixed airflow limitation were characterized by lower lumen area and increased wall area and wall thickness ratios in distal airways, accompanied by raised LAA%. They had also higher blood neutrophilia, blood and BAL eosinophilia, increased circulating fibrinogen, periostin, and ADAM33. Blood neutrophilia, serum high density lipoproteins, thyroid-stimulating hormone, and shortened activated partial thromboplastin time were determinants of thicker reticular basement membrane (RBM). BAL eosinophilia was the only positive predictor of collagen I accumulation. Surprisingly, we observed a negative correlation between RBM thickening and collagen I deposit. Cluster analysis based on CT-metrics of the right lower lobe basal posterior bronchus revealed three well-separated clusters similar in age, asthma duration, and BMI, but different in RBM thickness, collagen I accumulation, and inflammatory markers.Conclusions and clinical relevance: Airway remodelling traits are mainly related to the Th 2 profile, higher circulating ADAM33, and blood neutrophilia. Lung function

show abstract

Section: Discussionmentioning

confidence: 99%

The relationship of airway structural changes to blood and bronchoalveolar lavage biomarkers, and lung function abnormalities in asthma

Koźlik

Zuk

Bartyzel

et al. 2019

Clin Experimental Allergy

Self Cite

View full text Add to dashboard Cite

show abstract

“…As omalizumab has been used for more than 15 years, there are some data indicating that it may decrease unfavorable structural airway changes in allergic asthmatics, with respect to the fibronectin deposit, the increased thickness of the basal lamina and the bronchial wall thickness. [172][173][174] Treatment with mepolizumab significantly reduced the expression of three extracellular matrix proteins: tenascin, lumican and procollagen III in the reticular basement membrane. 171 Benralizumab caused the consequent 29% relative reduction of airways smooth muscle mass and number of tissues myofibroblasts.…”

Section: The Effect Of Treatment Of Asthma and Allergy On Epithelial ...mentioning

confidence: 99%

The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development

Noureddine¹,

Chałubiński²

2022

JAA

View full text Add to dashboard Cite

The respiratory epithelium constitutes the physical barrier between the human body and the environment, thus providing functional and immunological protection. It is often exposed to allergens, microbial substances, pathogens, pollutants, and environmental toxins, which lead to dysregulation of the epithelial barrier and result in the chronic inflammation seen in allergic diseases and asthma. This epithelial barrier dysfunction results from the disturbed tight junction formation, which are multi-protein subunits that promote cell-cell adhesion and barrier integrity. The increasing interest and evidence of the role of impaired epithelial barrier function in allergy and asthma highlight the need for innovative approaches that can provide new knowledge in this area. Here, we review and discuss the current role and mechanism of epithelial barrier dysfunction in developing allergic diseases and the effect of current allergy therapies on epithelial barrier restoration.

show abstract

“…However, Rijt et al [29] demonstrated in the murine model of chronic airway inflammation that a thicker basement membrane might promote dendritic cell activation and enhance further sensitization. Therefore, novel therapies aimed at stabilizing RBM to some extent, such as biological therapy or kinase inhibitors, might be a therapeutic option for particularly severe asthma individuals [30]. However, such an approach needs comprehensive elucidation of the role of thicker RBM in asthma, its determinants, and dynamics in progression.…”

Section: Discussionmentioning

confidence: 99%

Interactions via α2β1 Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma

Bazan-Socha

Jakieła

Zuk

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.

show abstract

Omalizumab may decrease the thickness of the reticular basement membrane and fibronectin deposit in the bronchial mucosa of severe allergic asthmatics

Cited by 23 publications

References 39 publications

The relationship of airway structural changes to blood and bronchoalveolar lavage biomarkers, and lung function abnormalities in asthma

The relationship of airway structural changes to blood and bronchoalveolar lavage biomarkers, and lung function abnormalities in asthma

The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development

Interactions via α2β1 Cell Integrin May Protect against the Progression of Airway Structural Changes in Asthma

Contact Info

Product

Resources

About