Upper airways in aspirin-exacerbated respiratory disease

Abstract

Recent findings further support the notion that arachidonic acid metabolism is dysregulated in AERD patients. This is reflected by resistance to PGE₂, overproduction of CysLTs by enhanced numbers of platelet-adherent leukocytes, and cellular stimulation by INF-γ released from eosinophils. Aspirin desensitization may be a useful treatment option in AERD patients exhibiting recalcitrant CRSwNP.

Identification of phenotypic clusters of nonsteroidal anti-inflammatory drugs exacerbated respiratory disease

“…In the present study, the overall prevalence of CRS in patients with NERD was 65.2%; all the subtype 1 or 2 patients had CRS, while none of the subtype 3 patients and 48.4% of the subtype 4 patients had CRS. Moreover, mean peripheral and sputum eosinophil counts were higher in all the patients with NERD, both of which were significantly higher in subtypes 1 and 2, indicating that subtypes 1 and 2 may represent the clinical phenotype of NERD as previously described by Samter's triad . In subtype 1, all the patients were atopic; therefore, the allergen‐Th2‐driven pathway could be a major mechanism for the activation of eosinophils.…”

“…Each subtype showed distinct features in terms of the female proportion, the degree of eosinophilia, LTE4 metabolite levels, asthma exacerbation, and severity. It is well known that NERD occurs more commonly in females, especially in middle‐aged women . In the present study, although the female proportion was higher in total patients with NERD, it showed significant differences among the four subtypes; the highest female proportion was noted in subtype 2 (73.8%), followed by subtype 3 (64.4%), and subtype 4 (61.3%).…”

“…The clinical features of NERD include middle‐age onset, female predominance, and common comorbid conditions, including CRS . Patients with NERD present as moderate‐to‐severe asthma, in which eosinophils are activated in the upper and lower airway mucosa . Compared to aspirin‐tolerant asthma (ATA), NERD is less associated with atopy; however, atopy is often present in patients with NERD .…”

Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling

“…The mechanism by which repeated challenges modulate gene expression is being investigated. We undertook studies to examine whether animals are sensitized to 8-oxoG, similar to allergens such as ragweed pollen extract (atopic) [48, 49] or those occurring in response to agents like aspirin (nonatopic) [50]. These studies showed no hyperreactivity-type responses (data not shown).…”

A novel treatment adjunct for aspirin exacerbated respiratory disease: the low‐salicylate diet: a multicenter randomized control crossover trial

“…The ASA intolerance seen in AERD is non–immunoglobulin E (IgE)‐mediated and has been described as a “nonallergic hypersensitivity reaction.” Altered metabolism of arachidonic acid results in prostaglandin (PG) and leukotriene (LT) imbalance that may result in overproduction and overresponsiveness to cysteinyl leukotrienes (cys‐LT) and underproduction and underresponsiveness to prostaglandin E2 (PGE 2 ) leading to predominantly eosinophilic inflammation . In fact, almost 100 genetic variants of AERD have been identified, which are responsible for various alterations in the metabolism of arachidonic acid …”