بیومارکرهای بالقوه برای بیماری تنفسی شدت یافته NSAID Potential Biomarkers for NSAID-Exacerbated Respiratory Disease

1. Introduction NSAID-exacerbated respiratory disease (NERD) is characterized by adult-onset chronic rhinosinusitis (CRS) with nasal polyps, intense eosinophilic infiltration in the upper and lower airway mucosa, and severe symptoms of exacerbation in response to aspirin/cyclooxygenase- (COX-) 1 inhibitors [1]. A previous systematic review had reported a NERD prevalence of 7% among typical adult asthmatic patients and twice among patients with severe asthma [2]. NERD is therefore considered a risk factor for severe asthma [3, 4]. Among patients with CRS and nasal polyps, the prevalence of NERD was 8.7% and 9.7%, respectively [2]. NERD is associated with severe CRS with nasal polyps, recurrence after sinus surgery, and airway remodeling [5–7], suggesting that NERD causes severe asthma with CRS/nasal polyps. NERD has a unique pathophysiology, with increased levels of lipid mediators, activated eosinophils, and mast cells, even without COX-1 inhibitor treatment. Thus, in most studies defining asthma endotypes, NERD has been identified as an independent endotype [8, 9]. However, all patients with NERD are not accompanied by severe asthma, and their clinical course is also known to be variable [10]. Confirmative diagnosis of NERD is based on provocation tests with aspirin. Oral aspirin challenge is considered the gold standard diagnostic method; however, its use is often limited by the risk of severe reactions during the test. The bronchial aspirin challenge is safer and consumes less time; however, it is limited by its low sensitivity [11]. In addition, oral or bronchial aspirin challenge test has limitations that cannot be used to predict the treatment or prognosis of NERD. Therefore, in vitro tests should be developed for diagnosing and monitoring NERD. In this review, we summarized three groups of known noninvasive biomarkers that can distinguish NERD from aspirin-tolerant asthma (ATA): lipid mediators, inflammatory cells and cytokines, and genetic markers. In addition, we reviewed the subtypes of NERD and the related biomarkers for developing precision medicine in the future.