Pathogenesis of nonsteroidal antiinflammatory drug-induced asthma.
OBJECTIVE
To summarize recent findings related to the pathogenic mechanisms of aspirin-induced asthma with emphasis on molecular genetic mechanisms.


RESULTS
The overproduction of cysteinyl leukotrienes with the increased expression of cysteinyl leukotriene receptor 1 (CYSLTR1) is a consistent finding in aspirin-induced asthma patients. Recent data have suggested a dysregulation of cyclooxygenase-2 and prostaglandin E2, increased levels of 15-hydroxyeicosatetranoic acid, and decreased lipoxin generation as characteristics of the condition. The HLA allele DPB10301 was documented as a strong genetic marker for susceptibility in an Asian population. Leukotriene C4 synthase has been established as a key genetic determinant of aspirin-induced asthma, but recent studies have demonstrated that several single nucleotide polymorphisms in the promoters of prostaglandin E2 receptor subtype 2, CYSLTR1 and CYSLTR2 and T-box expressed in T cells (TBX21) could increase risk for the condition. Although cyclooxygenase-2 and thromboxane A2 receptor polymorphisms were not associated with aspirin-induced asthma phenotype, they may exert functional effects.


CONCLUSIONS
The identification of genetic markers for aspirin-induced asthma susceptibility along with in-vitro functional studies would help to elucidate the pathogenesis of the condition. Further studies of the interactions among genes and between genes and the environment will be essential.
Kim
Seung-Hyun
SH
Department of Allergy & Rheumatology, Ajou University School of Medicine, Suwon, South Korea.
Park
Hae-Sim
HS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin