An update on the pathogenesis of the upper airways in aspirin-exacerbated respiratory disease

Abstract

Chronic rhinosinusitis with nasal polyps is a major comorbid condition of AERD patients that is closely associated with severe asthmatic symptoms. Significant pathologic findings in nasal polyp tissues include intense eosinophilic inflammation, which is caused by elevated production of eosinophil-related cytokines and chemokines, specific immunoglobulin E responses to staphylococcal enterotoxins, and altered arachidonic acid metabolism. This could affect the current treatments and methodologies that are used to control asthma, leading to a more severe and intractable AERD phenotype.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…Also, the production of PGE2 is reduced and COX-2 as well as E-prostanoid receptor subtype-2 are downregulated. 953 All of these effects add to an aggravation of the eicosanoid imbalance. Recently, gene profiling studies have suggested that periostin is the most upregulated gene in NP tissue of AERD patients.…”

“…Recently, gene profiling studies have suggested that periostin is the most upregulated gene in NP tissue of AERD patients. 953,957 The complexity in the interaction of inflammatory mediators in AERD is underlined by the dysregulation of the PG2-dependent control of LT production in peripheral granulocytes. When compared to those of patients with ASA-tolerant asthma or those of controls, granulocytes of patients with AERD generate more LTB4 and cysLTs, and are resistant to the PGE2-mediated suppression of LT generation.…”

“…Key cytokines and chemokines such as IL-5 and eotaxin are also elevated, leading to intense airway mucosal eosinophilic infiltration and activation. 953 Comparative histopathological analysis reveals the strongest tissue eosinophilia in patients with AERD, when comparing different clinical subgroups in a patient population with CRSsNP, inhalant allergies, and/or CRSwNP. 954 However, much of the described pathophysiology of AERD is likely explained by genetic variations, of which a number of polymorphisms have been identified that potentially play a causative role.…”

Periostin in bronchial asthma – a brief update

“…Periostin is also able to activate T cells and their differentiation into Th2 or neutrophils recruitment in bronchial mucosa [25,28]. Activated Th2 cells produce also IL-5 which intervenes in eosinophilic line development.…”

Expression of cysteinyl leukotriene receptor GPR17 in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps

“…11 In recent years, there has been increasing interest in the potential role of cysLTs in the pathogenesis of CRSwNP. For instance, Steinke et al 11 showed that cysLTs levels are significantly increased in ECRS patients but not in non-ECRS patients and healthy controls. Our previous study also revealed the differential expression of cysLTs and its receptors (CysLT1R and CysLT2R) between the two CRSwNP subsets.…”