Pathobiology of Type 2 Inflammation in Asthma and Nasal Polyposis

Abstract

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). In addition to the above cytokines, other proinflammatory mediators involved in the pathobiology of asthma and nasal polyposis include prostaglandin D₂ and cysteinyl leukotrienes. Within this context of 'united airway diseases', nasal polyposis encompasses several nosological entities such as chronic rhinosinusitis with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD). Because of the common pathogenic origins of asthma and nasal polyposis, it is not surprising that the more severe forms of both these disorders can be successfully treated by the same biologic drugs, targeting many molecular components (IgE, IL-5 and its receptor, IL-4/IL-13 receptors) of the type 2 inflammatory trait.

Keywords: nasal polyposis; severe asthma; united airway diseases.

Figure 1

Pathobiologic mechanisms underlying type 2 airway inflammation in asthma and nasal polyposis. Released by damaged airway epithelium, alarmins (IL-25, IL-33, TSLP) activate dendritic cells, ILC2, and airway fibroblasts. As a consequence, an overproduction of type 2 cytokines (IL-4, IL-5, IL-13) occurs within both upper and lower airways, being responsible for the development of nasal polyposis and asthma. In addition to proinflammatory features, the type 2 trait also includes structural changes underpinning airway remodeling mediated by TGF-β and other growth factors. TSLP: thymic stromal lymphopoietin; Th: T helper; ILC2: group 2 innate lymphoid cells; IL: interleukin; TGF-β: transforming growth factor-β. This original figure was created by the authors using “BioRender.com”.