Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction 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 olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Serum microRNAs Catalog Asthma Patients by Phenotype.

BACKGROUND AND OBJECTIVES: Asthma is a chronic inflammatory condition of the airways with a complex pathophysiology. Stratification of asthma subtypes into phenotypes and endotypes should move the field forward, making treatment more effective and personalized. Eosinophils are the key inflammatory cells involved in severe eosinophilic asthma. Given the health threat posed by eosinophilic asthma, there is a need for reliable biomarkers to identify affected patients and treat them properly with novel biologics. microRNAs (miRNAs) are a promising diagnostic tool. The aim of this study was to identify serum miRNAs that can phenotype asthma patients. METHODS: Serum miRNAs of patients with eosinophilic asthma (N=40) and patients with noneosinophilic asthma (N=36) were evaluated using next-generation sequencing, specifically miRNAs-seq, and selected miRNAs were validated using RT-qPCR. Pathway enrichment analysis of deregulated miRNAs was performed. RESULTS: Next-generation sequencing revealed 15 miRNAs that were expressed differentially between eosinophilic and noneosinophilic asthma patients, although no differences were observed in the miRNome between atopic and nonatopic asthma patients. Of the 15 miRNAs expressed differentially between eosinophilic and noneosinophilic asthma patients, hsa-miR-26a-1-3p and hsa-miR-376a-3p were validated by RT-qPCR. Expression levels of these 2 miRNAs were higher in eosinophilic than in noneosinophilic asthma patients. Furthermore, expression values of hsa-miR-26a-1-3p correlated inversely with peripheral blood eosinophil count, and hsa-miR-376a-3p expression values correlated with FeNO values and the number of exacerbations. Additionally, in silico pathway enrichment analysis revealed that these 2 miRNAs regulate signaling pathways associated with the pathogenesis of asthma. CONCLUSIONS: hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used to differentiate between eosinophilic and noneosinophilic asthma.

Eosinophil Response Against Classical and Emerging Respiratory Viruses: COVID-19.

Eosinophils were discovered more than 140 years ago. These polymorphonuclear leukocytes have a very active metabolism and contain numerous intracellular secretory granules that enable multiple effects on both health and disease status. Classically, eosinophils have been considered important immune cells in the pathogenesis of inflammatory processes (eg, parasitic helminth infections) and allergic or pulmonary diseases (eg, asthma) and are always associated with a type 2 immune response. Furthermore, in recent years, eosinophils have been linked to the immune response by conferring host protection against fungi, bacteria, and viruses, which they recognize through several molecules, such as toll-like receptors and the retinoic acid-inducible gene 1-like receptor. The immune protection provided by eosinophils is exerted through multiple mechanisms and properties. Eosinophils contain numerous cytoplasmatic granules that release cationic proteins, cytokines, chemokines, and other molecules, all of which contribute to their functioning. In addition to the competence of eosinophils as effector cells, their capabilities as antigen-presenting cells enable them to act in multiple situations, thus promoting diverse aspects of the immune response. This review summarizes various aspects of eosinophil biology, with emphasis on the mechanisms used and roles played by eosinophils in host defence against viral infections and response to vaccines. The review focuses on respiratory viruses, such as the new coronavirus, SARS-CoV-2.

Eosinophils: Old Players in a New Game.

Eosinophils are terminal polymorphonuclear cells with a high number of cytoplasmic granules that originate in bone marrow. Some are exosomes, which contain multiple molecules, such as specific eosinophilic proteins, cytokines, chemokines, enzymes, and lipid mediators that contribute to the effector role of these cells. Moreover, exosomes present a large number of receptors that allow them to interact with multiple cell types. Eosinophils play an important role in defense against infestations and are a key element in asthma and allergic diseases. Eosinophils are recruited to the inflamed area in response to stimuli, modulating the immune response through the release to the extracellular medium of their granule-derived content. Various mechanisms of degranulation have been identified. Polymorphonuclear leukocytes contain multivesicular bodies that generate exosomes that are secreted into the extracellular environment. Eosinophilic exosomes participate in multiple processes and mechanisms. Eosinophils participate actively in asthma and are hallmarks of the disease. The cells migrate to the inflammatory focus and contribute to epithelial damage and airway remodeling. Given their relevance in this pathology, new therapeutic tools have been developed that target mainly eosinophils and their receptors. In this manuscript, we provide a global, updated vision of the biology of eosinophils and the role of eosinophils in respiratory diseases, particularly asthma. We also summarize asthma treatments linked to eosinophils and new therapeutic strategies based on biological products in which eosinophils and their receptors are the main targets.

Eosinophil-derived exosomes contribute to asthma remodelling by activating structural lung cells.

BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the ability to secrete exosomes. However, the precise role played by exosomes in the biological processes leading up to asthma has not been fully defined. OBJECTIVE: We hypothesized that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils from asthmatic patients and healthy volunteers were purified from peripheral blood, and exosomes were isolated from eosinophils of asthmatic and healthy individuals. All experiments were performed with eosinophil-derived exosomes from healthy and asthmatic subjects. Epithelial damage was evaluated using primary small airway epithelial cell lines through 2 types of apoptosis assays, that is, flow cytometry and TUNEL assay with confocal microscopy. Additionally, the epithelial repair was analysed by performing wound healing assays with epithelial cells. Functional studies such as proliferation and inhibition-proliferation assays were carried out in primary bronchial smooth muscle cell lines. Also, gene expression analysis of pro-inflammatory molecules was evaluated by real-time PCR on epithelial and muscle cells. Lastly, protein expression of epithelial and muscle cell signalling factors was estimated by Western blot. RESULTS: Asthmatic eosinophil-derived exosomes induced an increase in epithelial cell apoptosis at 24 hour and 48 hour, impeding wound closure. In addition, muscle cell proliferation was increased at 72 hours after exosome addition and was linked with higher phosphorylation of ERK1/2. We also found higher expression of several genes when both cell types were cultured in the presence of exosomes from asthmatics: CCR3 and VEGFA in muscle cells, and CCL26, TNF and POSTN in epithelial cells. Healthy eosinophil-derived exosomes did not exert any effect over these cell types. CONCLUSIONS AND CLINICAL RELEVANCE: Eosinophil-derived exosomes from asthmatic patients participate actively in the development of the pathological features of asthma via structural lung cells.