Effect of omalizumab on bronchoalveolar lavage matrix metalloproteinases in severe allergic asthma

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

doi:10.1080/02770903.2021.1903917

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…Notably, the anti-IgE monoclonal antibody omalizumab reduced symptom duration and viral shedding in a cohort of children with RV-induced exacerbations [ 181 ]. Long term use of omalizumab for severe asthma was able to reduce features of airway remodeling associated with exacerbations, including decreases in MMP production, airway inflammation, and basement membrane thickness [ 182 – 184 ]. As IL-33 appears to play a role in inflammatory responses of the lung following RV exposure, newer biologic therapies targeting IL-33 signaling, such as astegolimab and itepekimab, may also be effective in preventing RV-induced asthma exacerbations and subsequent airway remodeling [ 180 , 185 , 186 ].…”

Section: Therapeutic Approaches For Rhinovirus-induced Airway Remodelingmentioning

confidence: 99%

Rhinovirus induces airway remodeling: what are the physiological consequences?

Spector,

De Sanctis,

Panettieri

et al. 2023

Respir Res

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Background Rhinovirus infections commonly evoke asthma exacerbations in children and adults. Recurrent asthma exacerbations are associated with injury-repair responses in the airways that collectively contribute to airway remodeling. The physiological consequences of airway remodeling can manifest as irreversible airway obstruction and diminished responsiveness to bronchodilators. Structural cells of the airway, including epithelial cells, smooth muscle, fibroblasts, myofibroblasts, and adjacent lung vascular endothelial cells represent an understudied and emerging source of cellular and extracellular soluble mediators and matrix components that contribute to airway remodeling in a rhinovirus-evoked inflammatory environment. Main body While mechanistic pathways associated with rhinovirus-induced airway remodeling are still not fully characterized, infected airway epithelial cells robustly produce type 2 cytokines and chemokines, as well as pro-angiogenic and fibroblast activating factors that act in a paracrine manner on neighboring airway cells to stimulate remodeling responses. Morphological transformation of structural cells in response to rhinovirus promotes remodeling phenotypes including induction of mucus hypersecretion, epithelial-to-mesenchymal transition, and fibroblast-to-myofibroblast transdifferentiation. Rhinovirus exposure elicits airway hyperresponsiveness contributing to irreversible airway obstruction. This obstruction can occur as a consequence of sub-epithelial thickening mediated by smooth muscle migration and myofibroblast activity, or through independent mechanisms mediated by modulation of the β2 agonist receptor activation and its responsiveness to bronchodilators. Differential cellular responses emerge in response to rhinovirus infection that predispose asthmatic individuals to persistent signatures of airway remodeling, including exaggerated type 2 inflammation, enhanced extracellular matrix deposition, and robust production of pro-angiogenic mediators. Conclusions Few therapies address symptoms of rhinovirus-induced airway remodeling, though understanding the contribution of structural cells to these processes may elucidate future translational targets to alleviate symptoms of rhinovirus-induced exacerbations.

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Section: Therapeutic Approaches For Rhinovirus-induced Airway Remodelingmentioning

confidence: 99%

Rhinovirus induces airway remodeling: what are the physiological consequences?

Spector,

De Sanctis,

Panettieri

et al. 2023

Respir Res

View full text Add to dashboard Cite

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“…The amount of MMP9 in BALF directly correlates with the disease severity and decline in lung function in asthma ( 39 , 40 ). A recent study using a treatment with omalizumab, an anti-IgE monoclonal antibody, demonstrated that a decrease in BALF levels of MMP9 correlates with a lower asthma exacerbation rate in SA patients ( 41 ). Interestingly, although the decrease of MMP9 abundance in BALF correlates with reduction in reticular basement membrane thickness, it does not alter collagen or fibronectin accumulation in SA patients ( 41 ).…”

Section: Introductionmentioning

confidence: 99%

“…A recent study using a treatment with omalizumab, an anti-IgE monoclonal antibody, demonstrated that a decrease in BALF levels of MMP9 correlates with a lower asthma exacerbation rate in SA patients ( 41 ). Interestingly, although the decrease of MMP9 abundance in BALF correlates with reduction in reticular basement membrane thickness, it does not alter collagen or fibronectin accumulation in SA patients ( 41 ). Proteomics and transcriptomics studies have demonstrated that the neutrophil-derived protein neutrophil elastase (NE) is upregulated in the sputum of SA patients ( 42 ).…”

Section: Introductionmentioning

confidence: 99%

Immunobiology of Steroid-Unresponsive Severe Asthma

2021

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Asthma is a heterogeneous respiratory disease characterized by airflow obstruction, bronchial hyperresponsiveness and airway inflammation. Approximately 10% of asthma patients suffer from uncontrolled severe asthma (SA). A major difference between patients with SA from those with mild-to-moderate asthma is the resistance to common glucocorticoid treatments. Thus, steroid-unresponsive uncontrolled asthma is a hallmark of SA. An impediment in the development of new therapies for SA is a limited understanding of the range of immune responses and molecular networks that can contribute to the disease process. Typically SA is thought to be characterized by a Th2-low and Th17-high immunophenotype, accompanied by neutrophilic airway inflammation. However, Th2-mediated eosinophilic inflammation, as well as mixed Th1/Th17-mediated inflammation, is also described in SA. Thus, existing studies indicate that the immunophenotype of SA is diverse. This review attempts to summarize the interplay of different immune mediators and related mechanisms that are associated with airway inflammation and the immunobiology of SA.

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Mepolizumab in Severe Pediatric Asthma: Certainties and Doubts through a Single-Center Experience and Review of the Literature

Maglione,

Borrelli,

Dorato

et al. 2024

Children

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Background: Although, in most children with asthma, good symptom control is achieved with a low to moderate dose of inhaled corticosteroids, a small group of patients still experiences frequent symptoms, and even severe exacerbations, impairment of lung function, and reduced quality of life. Some of these subjects with severe asthma require biologic drugs as add-on therapy. In the past decade, numerous monoclonal antibodies have been approved for children or adolescents with severe asthma, in addition to their increasing use in adult asthma. However, the available evidence on how to select the most appropriate biologic based on a single patient’s clinical, functional, and laboratory characteristics is still scant, and is insufficient to guide clinicians in the decision-making process of a personalized treatment. Materials and Methods: We report a case series of four patients with severe eosinophilic asthma treated with mepolizumab, an anti-interleukin-5 monoclonal antibody, and review the existing literature on this treatment in children and adolescents. Results: Our patients, all with blood eosinophilia and elevated fractional exhaled nitric oxide levels, developed poor symptom control despite prolonged treatment with high-dose inhaled corticosteroids plus a second controller, addressing the addition of a biologic drug. In all of them, a 12-month treatment with subcutaneous mepolizumab showed a reduction in the blood eosinophil count and in asthma exacerbations, as well as an improvement on the Asthma Control Test. The results of the literature search focused on the strengths and limitations of the pediatric use of mepolizumab and highlighted the areas worthy of further research. Conclusions: Mepolizumab has proven effective in improving symptom control in pediatric patients with severe asthma. Additional well-powered clinical trials will be helpful in developing evidence-based guidelines regarding biologic drugs in the pediatric population.

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Effect of omalizumab on bronchoalveolar lavage matrix metalloproteinases in severe allergic asthma

Cited by 3 publications

References 30 publications

Rhinovirus induces airway remodeling: what are the physiological consequences?

Rhinovirus induces airway remodeling: what are the physiological consequences?

Immunobiology of Steroid-Unresponsive Severe Asthma

Mepolizumab in Severe Pediatric Asthma: Certainties and Doubts through a Single-Center Experience and Review of the Literature

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