Neutrophilic Asthma-From Mechanisms to New Perspectives of Therapy

中性粒细胞性哮喘——从机制到新的治疗视角

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Abstract

Neutrophilic asthma (NA) is an inflammatory phenotype of asthma, characterized by predominantly neutrophilic infiltrations in bronchial mucosa. It is usually diagnosed on the basis of high neutrophil count in induced sputum (from >40% to >76%) with low eosinophils (<2%). The prevalence of NA ranges from 16% to 28% of the adult asthma population depending on the definitions and study methods applied. A clinical picture of NA is characterized by late onset of symptoms, higher exacerbation rate, lower level of symptoms control, and poorer response to steroids compared to eosinophilic phenotype. Comorbidities such as obesity and GERD as well as the influence of environmental factors (air pollution, smoking, bacterial infections) contribute to the development and severe course of the disease. NA is T2-low disease with predominantly Th1/Th17-type inflammation. Neutrophils are key cells responsible for initiating and sustaining inflammation. In addition to their primary functions like phagocytosis, degranulation, and NETosis, neutrophils release several pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF) and chemokines (CXCL-1, -2, -8, -9, -10) responsible for the recruitment of other neutrophils or T cells. Increasing knowledge about the biology of neutrophiles and their role in asthma results in new potential therapies that could improve control of NA, particularly new biologicals targeting Th1/Th17-related cytokines. In this review, we discuss the prevalence, mechanisms, and clinical features of neutrophilic asthma. Furthermore, current therapeutic options and some promising perspectives for the near future are presented.

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