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

Abstract

PURPOSE OF REVIEW: The key features of aspirin-exacerbated respiratory diseases

(AERDs) include chronic, severe asthma and a high prevalence (60-80%) of chronic

rhinosinusitis with nasal polyps, all of which are exacerbated by exposure to

aspirin and other NSAIDs. Although the pathogenic mechanisms of AERD are not

completely understood, repeated instances have shown intense eosinophilic

infiltrations of upper and lower airway mucosa, and dysregulation of arachidonate

metabolisms. Here, recent updates on the pathogenic mechanisms of chronic

rhinosinusitis with nasal polyps in aspirin-exacerbated respiratory diseases are

summarized. RECENT FINDINGS: Intense eosinophilic infiltration is closely related

to the elevated production of cytokines and chemokines such as IL-5 and eotaxin.

The response of local immunoglobulin E to staphylococcal enterotoxins contributes

to eosinophilic inflammation in nasal polyp tissue. Other characteristics include

the overproduction of cysteinyl leukotrienes and increased expression of

cysteinyl leukotriene receptor-1, reduced production of prostaglandin E2, and the

down-regulation of cyclooxygenase-2 and E-prostanoid receptor subtype-2. A recent

gene expression profiling study has also suggested that periostin is the most

up-regulated gene in the nasal polyp tissue of AERD patients. SUMMARY: 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.