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.

The Role of ACT Score in Mepolizumab Discontinuation

“…After the randomized controlled trial, SYNAPSE, mepolizumab was approved for nasal polyps in the setting of severe chronic rhinosinusitis (18). However, those with greater type 2 inflammation often have concomitant CRSwNP, so it is not surprising that clinicians chose mepolizumab for those with this comorbidity (19). Since the people started on mepolizumab have a higher incidence of CRSwNP in this study, these people likely have greater Th2 inflammation which suggests that the population on mepolizumab, regardless of when they discontinue the medication, are going to have more severe asthma at baseline than the people placed on other biologics, which is supported by the higher use of prednisone (62% vs 36%, P < 0.001).…”

Airways Type-2 Related Disorders: Multiorgan, Systemic or Syndemic Disease?

“…In recent years, due to the progress in scientific research, we have come to recognize CRS not merely as a localized disease but as an immunological alteration with local and systemic manifestations. Consequently, the concept of inflammatory endotype, particularly type 2 inflammation in our case, has been introduced in this field [2]. Therefore, the recognition of the pathobiological mechanisms driving the disease's development has led to a paradigm shift.…”

Effect of Obesity on the Expression of Genes Associated with Severe Asthma—A Pilot Study

“…Importantly, several studies indicate that asthma endotypes are also shared by other allergic diseases, such as chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with asthma and CRSwNP are frequently characterized by a predominant T2 airway inflammation, affecting the lower and upper airways, respectively [ 4 ]. The T2-low endotype is counterbalanced by a high number of neutrophils in bronchoalveolar fluid (BALF) and sputum and high clinical severity as seen in late onset non-allergic asthma or obesity-associated asthma [ 3 ].…”