A document by Marcela Valverde. Click on the document to view its contents.

Background: Anaphylaxis is the most severe manifestation of allergic disorders. Diagnostic and understanding of molecular mechanisms need to improve. Extracellular vesicles (EVs) play a key role in cellular communication offering new possibilities to unravel patient-based particularities. The aim of this study is to analyze the protein profile of anaphylaxis-derived EVs providing a resource of potential markers for anaphylactic reactions, and to characterize their molecular mechanisms. Methods: EVs were isolated from 86 plasma samples (collected from 43 patients) during the acute phase of anaphylaxis (AnEVs) and at their baseline (BEVs). For comparison, EVs were characterized and their protein patterns were analyzed by mass spectrometry-based quantitative proteomics (LC-MS/MS). System Biology Analysis (SBA) was applied to identify main canonical pathways and molecules involved. In addition, in vitro permeability assays based on EVs-endothelial cells (ECs) were performed. Results: Differential proteomic analysis performed in 10 EVs paired patients’ samples identified 1206 proteins of which 99 were modulated in the AnEVs signature. CDC42, Ficolin-2 and S100A9 enrichment was confirmed in a larger cohort of patients. SBA revealed diverse group of immune proteins as the main canonical pathways altered in AnEVs. Thus, leukocyte extravasation and granulocyte adhesion-diapedesis processes stand out. In addition, marked-EVs from anaphylactic patients were captured by ECs decreasing the resistance of human endothelial monolayers. Conclusion: Our findings identify for the first time a differential EVs pattern signature in anaphylaxis revealing a source of potential biomarkers. Furthermore, these vesicles could participate in altered immune molecular mechanisms and present a role increasing vascular permeability.

Background. Chronic rhinosinusitis with nasal polyps (CRSwNP), characterized by partial (hyposmia) or total (anosmia) loss of smell, is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), worsens disease severity and quality of life. The objective of this study was to determine whether, in real-life conditions, biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare smell improvement in N-ERD and non-N-ERD subgroups. Methods. A multicenter, non-interventional, retrospective, observational study was performed, including 206 patients with severe asthma undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab) with CRSwNP. Results. Improved olfaction was found after treatment with all monoclonal antibodies: omalizumab (35.8%), mepolizumab (35.4%), reslizumab (35.7%), and benralizumab (39.1%), with no differences between groups. Patients with atopy, greater use of short course systemic corticosteroids, and larger polyp size were more likely to experience improvement in smell. The proportion of patients experiencing smell improvement was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. Conclusions. This is the first study to compare real-life improvement in sense of smell among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in sense of smell (with non-significant differences between biologic drugs). No differences were found in smell improvement between the N-ERD and non-N-ERD group.