Introduction
Aspirin-exacerbated respiratory disease (AERD) is characterized by
clinical features of persistent asthma, sinonasal inflammation with
nasal polyposis, and hypersensitivity reactions to cyclooxygenase-1
inhibitors.1 Patients with AERD are known to have more
severe airway obstruction and frequent asthma exacerbation than those
with aspirin tolerant asthma (ATA). A recent report has suggested that
the prevalence of AERD is 7% in adult asthmatics, while 14% in severe
asthmatics.2
Immunological pathophysiology of AERD is not fully understood; however,
a number of studies have provided evidence that numerous kinds of immune
cells (eosinophils, mast cells, innate lymphoid cells, and
platelet-adherent leukocytes) and mediators (leukotriene E4,
prostaglandin E2, prostaglandin D2, IL-25, and IL-33) are
involved.3 Dysregulation of arachidonic acid
metabolism is a well-known pathophysiology in AERD. Reduced levels of
prostaglandin E2, increased levels of prostaglandin D2 and leukotriene
E4 play important roles in airway inflammation and bronchoconstriction
in AERD.4 In this context, the level of urinary
leukotriene E4 has been proposed as a potential biomarker to determine
AERD, and leukotriene receptor antagonists (e.g. montelukast or
pranlukast) are widely used in AERD treatment.5, 6Meanwhile, the levels of leukotriene E4 were reported to be remained
high with increased eosinophil inflammation and impaired asthma control
despite of the leukotriene receptor antagonist treatment in AERD
patients.7 To attenuate the activation status of
eosinophils, mast cells and innate lymphoid cells in AERD pathogenesis,
previous studies have suggested anti-IL4R (e.g. dupilumab),
anti-IL-5 (e.g. mepolizumab or reslizumab), anti-IgE (e.g.omalizumab), and anti-IL-33/TSLP antibody treatment of severe type 2
asthma in addition to inhaled corticosteroids with long-acting
beta2-agonists.1, 8 Although these
biologics are closely related to pathologic mediators in AERD, the high
medical cost and incomplete blockage of non-steroidal anti-inflammatory
drug-induced reactions should be carefully considered.
To identify novel causal pathways and therapeutic targets of AERD, we
performed RNA and methylation sequencing using nasal epithelial
scrapings from AERD patients as compared to ATA patients.