Biomaterial Database

Effect of omalizumab on bronchoalveolar lavage matrix metalloproteinases in severe allergic asthma. 2022

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

Department of Pulmonology, University Hospital, Krakow, Poland.

Airway inflammation in asthma is accompanied by reconstruction of the bronchial wall extracellular matrix that most likely occurs with a contribution of matrix metalloproteinases (MMPs). Recently we have reported that omalizumab may decrease reticular basement membrane (RBM) thickness together with fibronectin deposits in asthmatic airways, although mechanisms involved are unknown. In the present study, we have investigated the impact of omalizumab on MMPs concentrations in bronchoalveolar lavage fluid (BAL) of asthmatic subjects in relation to airway remodeling changes in histology. The study group consisted of 13 severe allergic asthmatics treated with omalizumab for at least 12 months. In each subject, clinical and laboratory parameters, bronchoscopy with BAL, and endobronchial biopsy were evaluated before and after the biologic therapy. RBM thickness, fibronectin, and collagen deposits in bronchial mucosa specimens were analyzed in histology. The investigations also included BAL cytology and BAL concentrations of MMP-2, -3, and -9. Omalizumab was related to a decrease in all measured MMPs in BAL (p < 0.001, each), although such declines were not observed in each patient. The depletions were associated with a lower asthma exacerbation rate and better asthma control. Interestingly, patients who showed a decline in at least one MMP (n = 10, 77%) were characterized by a higher decrease in the RBM thickness (-1.61 [-2.02 to -0.6] vs. -0.06 [-0.09 to +3.3], p = 0.03). Likewise, individuals with lower concentrations of MMP-9 after omalizumab (n = 7, 58%) had a greater reduction in the RBM layer as compared to those with steady MMP-9 levels (-1.8 [-2.4 to -1.14] vs. -0.13 [-0.6 to -0.06] μm, p = 0.03). Moreover, the latter group also had unfavorable higher collagen I accumulation after biologic (42 [20 to 55] vs. 0 [-10 to 20]%, respectively, p = 0.03). Higher concentrations of MMPs in BAL at baseline were related to the lower systemic steroid dose and better omalizumab response concerning the decline in RBM thickness. Our data suggest that omalizumab therapy is associated with decreased BAL MMPs concentration in the subgroup of asthma patients. The decline was linked with a reduction in the RBM thickness what might play a beneficial role in airway remodeling.

UI	MeSH Term	Description	Entries
D006967	Hypersensitivity	Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.	Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D001992	Bronchoalveolar Lavage Fluid	Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung.	Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D003094	Collagen	A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).	Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D005353	Fibronectins	Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.	Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069444	Omalizumab	An anti-IgE, recombinant, humanized monoclonal antibody which specifically binds to the C epsilon3 domain of IMMUNOGLOBULIN E, the site of high-affinity IgE receptor binding. It inhibits the binding of IgE to MAST CELLS and BASOPHILS to reduce the severity of the allergic response and is used in the management of persistent allergic ASTHMA.	Xolair
D001249	Asthma	A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	Asthma, Bronchial,Bronchial Asthma,Asthmas
D056151	Airway Remodeling	The structural changes in the number, mass, size and/or composition of the airway tissues.	Airway Remodelling,Asthmatic Airway Remodeling,Asthmatic Airway Remodelling,Asthmatic Airway Wall Remodeling,Asthmatic Airway Wall Remodelling,Small Airway Remodeling,Small Airway Remodelling,Airway Wall Remodelling,Airway Remodeling, Asthmatic,Airway Remodeling, Small,Airway Remodelings,Airway Remodelings, Asthmatic,Airway Remodelings, Small,Airway Remodelling, Asthmatic,Airway Remodelling, Small,Airway Remodellings,Airway Remodellings, Asthmatic,Airway Remodellings, Small,Airway Wall Remodellings,Asthmatic Airway Remodelings,Asthmatic Airway Remodellings,Remodeling, Airway,Remodeling, Asthmatic Airway,Remodeling, Small Airway,Remodelings, Airway,Remodelings, Asthmatic Airway,Remodelings, Small Airway,Remodelling, Airway,Remodelling, Airway Wall,Remodelling, Asthmatic Airway,Remodelling, Small Airway,Remodellings, Airway,Remodellings, Airway Wall,Remodellings, Asthmatic Airway,Remodellings, Small Airway,Small Airway Remodelings,Small Airway Remodellings,Wall Remodelling, Airway,Wall Remodellings, Airway
D020780	Matrix Metalloproteinase 9	An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.	Gelatinase B,92-kDa Gelatinase,92-kDa Type IV Collagenase,MMP-9 Metalloproteinase,MMP9 Metalloproteinase,Matrix Metalloproteinase-9,92 kDa Gelatinase,92 kDa Type IV Collagenase,MMP 9 Metalloproteinase,Metalloproteinase 9, Matrix,Metalloproteinase, MMP-9,Metalloproteinase, MMP9