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.