Integrative Cross-Talk in Asthma: Unraveling the Complex Interactions Between Eosinophils, Immune, and Structural Cells in the Airway Microenvironment.

Asthma is a chronic inflammatory process that leads to airway narrowing, causing breath loss followed by spasms, wheezing, and shortness of breath. Within the asthmatic lungs, interaction among various immune cells and structural cells plays a significant role in orchestrating an inflammatory response in which eosinophils hold central importance. In these settings, allergens or other environmental exposures commonly drive the immune response to recruit eosinophils to the airways.

Clinical Remission Criteria and Serum Levels of Type 2 Inflammation Mediators during 24 Weeks of Treatment with the Anti-IL-5 Drug Mepolizumab in Patients with T2-High Severe Asthma.

Anti-interleukin (IL) 5 is an effective treatment modality for inhibiting eosinophilic inflammation in patients with T2-high severe asthma. The aim of this study was to determine the clinical efficacy and serum levels of type 2 inflammatory mediators during 24 weeks of mepolizumab treatment in patients with T2-high severe asthma. Eighteen patients with T2-high severe asthma were enrolled in this study.

IL-5 and GM-CSF, but Not IL-3, Promote the Proliferative Properties of Inflammatory-like and Lung Resident-like Eosinophils in the Blood of Asthma Patients.

Blood eosinophils can be described as inflammatory-like (iEOS-like) and lung-resident-like (rEOS-like) eosinophils. This study is based on the hypothesis that eosinophilopoetins such as interleukin (IL)-3 and IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) alter the proliferative properties of eosinophil subtypes and may be associated with the expression of their receptors on eosinophils. We investigated 8 individuals with severe nonallergic eosinophilic asthma (SNEA), 17 nonsevere allergic asthma (AA), and 11 healthy subjects (HS).

Changes in Left Heart Geometry, Function, and Blood Serum Biomarkers in Patients with Obstructive Sleep Apnea after Treatment with Continuous Positive Airway Pressure.

Background: Cardiovascular remodeling is essential in patients with obstructive sleep apnea (OSA), and continuous positive airway pressure (CPAP) therapy could improve these processes. Two-dimensional (2D) speckle-tracking (ST) echocardiography is a useful method for subclinical biventricular dysfunction diagnosis and thus might help as an earlier treatment for OSA patients. It is still not clear which blood serum biomarkers could be used to assess CPAP treatment efficacy.

Asthmatic Eosinophils Alter the Gene Expression of Extracellular Matrix Proteins in Airway Smooth Muscle Cells and Pulmonary Fibroblasts.

The impaired production of extracellular matrix (ECM) proteins by airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) is a part of airway remodeling in asthma. This process might be influenced by eosinophils that migrate to the airway and abundantly secrete various cytokines, including TGF-β. We aimed to investigate the effect of asthmatic eosinophils on the gene expression of ECM proteins in ASMC and PF.

αβ and αβ Integrin Expression and Pro-Proliferative Properties of Eosinophil Subtypes in Asthma.

Eosinophilic inflammation is one of the main pathophysiological features in asthma. Two subtypes of eosinophils exist in the lung and systemic circulation: lung-resident eosinophils (rEOS) and inflammatory eosinophils (iEOS). We evaluated the expression of αβ and αβ integrins of eosinophil subtypes and their influence on airway smooth muscle (ASM) cell proliferation and viability in asthma.

Asthmatic Eosinophils Promote Contractility and Migration of Airway Smooth Muscle Cells and Pulmonary Fibroblasts In Vitro.

Enhanced contractility and migration of airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) are part of airway remodeling in asthma. Eosinophils are the central inflammatory cells that participate in airway inflammation. However, the role of asthmatic eosinophils in ASMC and PF contractility, migration, and differentiation to contractile phenotype has not yet been precisely described.

Blood Eosinophils Subtypes and Their Survivability in Asthma Patients.

Eosinophils subtypes as lung-resident (rEOS) and inflammatory (iEOS) eosinophils are different in surface protein expression, functions, response to IL-5 and localization in lungs. rEOS- and iEOS-like eosinophils are found in blood; thus, we aimed to investigate their quantity and survivability in asthma patients. A total of 40 individuals were included: 10 steroid-free non-severe allergic asthma (AA), and 18 severe non-allergic eosinophilic asthma (SNEA) patients, the control group consisted of 12 healthy non-smoking subjects (HS).

In Vivo Allergen-Activated Eosinophils Promote Collagen I and Fibronectin Gene Expression in Airway Smooth Muscle Cells via TGF-1 Signaling Pathway in Asthma.

Eosinophils infiltration and releasing TGF-1 in the airways has been implicated in the pathogenesis of asthma, especially during acute episodes provoked by an allergen. TGF-1 is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodeling in asthma. We aimed to evaluate the effect of in vivo allergen-activated eosinophils on the expression of and in ASM cells in asthma.

Serum Levels of Epithelial-Derived Cytokines as Interleukin-25 and Thymic Stromal Lymphopoietin after a Single Dose of Mepolizumab in Patients with Severe Non-Allergic Eosinophilic Asthma: A Short Report.

The bronchial epithelium has continuous contact with environmental agents initiating and maintaining airway type 2 inflammation in asthma. However, there is a lack of data on whether reduced airway eosinophilic inflammation can affect the production of epithelial-derived mediators, such as interleukin-25 (IL-25) and thymic stromal lymphopoietin (TSLP). The aim of this study was to investigate the changes in serum levels of IL-25 and TSLP after a single dose of mepolizumab, a humanized monoclonal antibody to interleukin-5 (IL-5), in patients with severe non-allergic eosinophilic asthma (SNEA).

Serum levels of epithelial-derived mediators and interleukin-4/interleukin-13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma.

Allergens are the main trigger that enhances airway type 2 inflammation, and the epithelium is the first line of defense that reacts to its exposure. Therefore, epithelial-derived mediators, such as interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP) and ezrin, may play a role as alarmins in IL-4/IL-13 signaling in allergic asthma (AA). We investigated the serum levels of IL-25, IL-33, TSLP, ezrin, IL-4 and IL-13, after bronchial challenge with Dermatophagoides pteronyssinus in patients with AA.

The Enhanced Adhesion of Eosinophils Is Associated with Their Prolonged Viability and Pro-Proliferative Effect in Asthma.

Before eosinophils migrate into the bronchial lumen, they promote airway structural changes after contact with pulmonary cells and extracellular matrix components. We aimed to investigate the impact of eosinophil adhesion to their viability and pro-proliferative effect on airway smooth muscle (ASM) cells and pulmonary fibroblasts during different asthma phenotypes. A total of 39 individuals were included: 14 steroid-free non-severe allergic asthma (AA) patients, 10 severe non-allergic eosinophilic asthma (SNEA) patients, and 15 healthy control subjects (HS).

Expression of eosinophil β chain-signaling cytokines receptors, outer-membrane integrins, and type 2 inflammation biomarkers in severe non-allergic eosinophilic asthma.

Background: Severe non-allergic eosinophilic asthma (SNEA) is a rare asthma phenotype associated with severe clinical course, frequent exacerbations, and resistance to therapy, including high steroid doses. The key feature is type 2 inflammation with predominant airway eosinophilia. Eosinophil maturation, activation, survivability, and recruitment are mainly induced by interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) through their receptors on eosinophil surface and related with integrins activation states.

Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma.

Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact through integrin-ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell-cell and cell-extracellular matrix interactions.

Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma.

Background: Recent studies have suggested that eosinophils may have a direct effect on airway smooth muscle cells (ASMC), causing their proliferation in patients with asthma, but the precise mechanism of the interaction between these cells remains unknown. We propose that changes in Wnt signaling activity and extracellular matrix (ECM) production may help explain these findings. Therefore, the aim of this study was to investigate the effect of eosinophils from asthmatic and non-asthmatic subjects on Wnt-5a, transforming growth factor β1 (TGF-β1), and ECM protein (fibronectin and collagen) gene expression and ASMC proliferation.