Eosinophil-targeted treatment strategies for long-term outcomes in severe eosinophilic asthma.

Background: Airway eosinophilic inflammation is a key pathobiologic trait of severe asthma, a complex chronic disease which affects about 5-10% of asthmatic patients worldwide. Therefore, an in-depth knowledge of the immunopathologic mechanisms underlying severe eosinophilic asthma (SEA) is essential to understand the beneficial effects of currently available, eosinophil-targeted anti-asthma treatments, as well as to develop new therapeutic strategies.

Areas Covered: This narrative review article aims to provide a concise coverage of the pathophysiology of severe eosinophilic asthma, followed by an updated overview of current and newly emerging therapeutic approaches capable of counteracting airway eosinophilic inflammation.

Pathobiology of Type 2 Inflammation in Asthma and Nasal Polyposis.

Asthma and nasal polyposis often coexist and are frequently intertwined by tight pathogenic links, mainly consisting of the cellular and molecular pathways underpinning type 2 airway inflammation. The latter is characterized by a structural and functional impairment of the epithelial barrier, associated with the eosinophilic infiltration of both the lower and upper airways, which can be driven by either allergic or non-allergic mechanisms. Type 2 inflammatory changes are predominantly due to the biological actions exerted by interleukins 4 (IL-4), 13 (IL-13), and 5 (IL-5), produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2).

Molecular Targets for Biological Therapies of Severe Asthma.

Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). Within this context, during the last years several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation.

Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications.

The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages.