Omalizumab Modulates Bronchial Reticular Basement Membrane Thickness and Eosinophil Infiltration in Severe Persistent Allergic Asthma Patients

Abstract

Severe persistent asthma causes a substantial morbidity and mortality burden and is frequently not well controlled, despite intensive guideline-based therapy. The unique monoclonal antibody approved for patients with severe allergic asthma is omalizumab: a recombinant humanised murine against IgE antibodies. The aim of the present study is to investigate the effect of long-term anti-IgE on the thickening of the reticular basement membrane (RBM) and eosinophil infiltration in bronchial biopsies from patients with severe persistent allergic asthma. Biopsies were obtained from 11 patients with severe persistent allergic asthma before and after (12 months) treatment with omalizumab. RBM thickness and eosinophils were measured by using light microscope image analysis. A significant mean reduction in RBM thickness and eosinophil infiltration were measured after one-year omalizumab treatment. No correlation between eosinophil reduction and RBM thickness reduction was found. No correlation between each of the previous two parameters and clinical parameters was detected. In conclusion, our study showed that a substantial proportion of severe asthmatics reduced the original bronchial RBM thickness and eosinophil infiltration after one-year treatment with anti-IgE, thus emphasizing the possible role of omalizumab in affecting airway remodeling in severe persistent allergic asthma.

Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives

“…In a randomised double-blind placebo-controlled study involving 25 allergic asthmatics, VAN RENSEN et al [63] provided additional evidence that sputum and airway eosinophils, as well as FcεRI + and CD4 + cells, are reduced after omalizumab treatment. A few more recent studies reported similar findings [64][65][66], possibly associated with decreased expression of IL-4 and IL-5 [62,67].…”

“…The aforementioned radiological findings were recently corroborated by histopathological observations of RICCIO et al [64] on bronchial biopsy samples obtained from 11 patients with severe persistent allergic asthma before and after 1 year of treatment with omalizumab. The authors observed a significant reduction in RBM thickness after treatment with omalizumab, accompanied by a marked but not statistically significant reduction in eosinophil infiltration.…”

Mesenchymal Stromal Cells Mediate Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation by Inhibition of the Th17 Signaling Pathway

“…This population of asthmatics tends to have interleukin-17 (IL-17)-mediated neutrophilic airway inflammation driven by antigen-specific Th17 CD4 T cells through mechanisms that are currently unclear [7][8][9][10]. Although some antibody-based therapies may be helpful [11][12][13], new therapeutic options are needed. Mesenchymal stromal cells (MSCs) are multipotent adult cells isolated from many source tissues, including bone marrow, adipose tissue, and umbilical cord blood, and are defined by expression of a panel of cell surface markers and the ability to differentiate into cartilage, fat, and bone tissues [14][15][16][17][18].…”

An insight into pharmacological and clinical basis of anti-IgE for add-on therapy of severe asthma

“…Recent preliminary findings, obtained in a limited number of asthmatic patients by means of computed tomography (CT) imaging, have shown that omalizumab reduced airway wall thickness and increased the bronchial luminal area (46). These findings have been recently corroborated by histopathological observations referring to bronchial biopsy samples obtained from patients with severe persistent allergic asthma before and 12 months after treatment with omalizumab, showing a significant reduction in the thickness of epithelial reticular basement membrane (47). Very recent reports suggest that omalizumab, in addition to being very effective for the treatment of allergic asthma, can be also useful in the management of apparently non-allergic phenotypes of this airway disease.…”