Long-Term Outcome of Endoscopic Sinus Surgery in Patients with Aspirin-Exacerbated Respiratory Disease / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Patients with aspirin-exacerbated respiratory disease (AERD) tend to have more severe clinical course and also tend to be recalcitrant to conventional medical and surgical treatment. This study aimed to assess the long-term outcome of endoscopic sinus surgery in AERD patients. SUBJECTS AND METHOD: Fifteen patients with AERD (n=15) were identified through a retro-spective chart review, and compared with 74 patients of CRSwNP (with asthma n=23; without asthma n=51) by analyzing preoperative and postoperative symptoms, endoscopic score, Lund-Mackay CT score, number of revision surgery or outpatient procedures, frequency of clinic visits and medications. The CRS control status was evaluated according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012 criteria and logistic regression analyses were conducted to investigate the determining factors of preoperative and postoperative symptoms. RESULTS: The AERD group showed higher disease severity than other groups preoperatively: endoscopic score (CRSwNP s asthma 6.3±2.6 vs. CRSwNP c asthma 6.5±2.3 vs. AERD 8.8±1.4, p<0.05), CT score (12.2±4.9 vs. 17.0±4.8 vs. 18.0±2.1, p<0.05), and overall symptom score (30.8±0.4 vs. 33.8±1.5 vs. 37.9±0.7, p<0.01). The rate of revision surgery and outpatient procedures, postoperative clinic visit and prescription rate were higher in the AERD group (p<0.05, respectively). However, postoperative symptom scores and CRS control status were not significantly different among three groups (p=0.267 and p=0.996, respectively). CONCLUSION: Although AERD patients showed higher preoperative endoscopic scores and revision surgery rates, postoperative subjective symptoms were comparable to those of other groups with long-term follow up, suggesting the importance of frequent outpatient care after endoscopic sinus surgery.

Cysteinyl Leukotrienes and Their Receptors; Emerging Concepts

Cysteinyl leukotrienes (cys-LTs) are potent mediators of inflammation derived from arachidonic acid through the 5-lipoxygenase/leukotriene C4 synthase pathway. The derivation of their chemical structures and identification of their pharmacologic properties predated the cloning of their classical receptors and the development of drugs that modify their synthesis and actions. Recent studies have revealed unanticipated insights into the regulation of cys-LT synthesis, the function of the cys-LTs in innate and adaptive immunity and human disease, and the identification of a new receptor for the cys-LTs. This review highlights these studies and summarizes their potential pathobiologic and therapeutic implications.

Polymorphisms of ATF6B Are Potentially Associated With FEV1 Decline by Aspirin Provocation in Asthmatics

PURPOSE: Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6beta (ATF6B) is known to regulate ATFalpha-mediated ER stress response. The aim of this study is to investigate the associations of ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and its major phenotype, % decline of FEV1 by aspirin provocation. METHODS: Four common single nucleotide polymorphisms (SNPs) of ATF6B were genotyped and statistically analyzed in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) as controls. RESULTS: Logistic analysis revealed that 2 SNPs (rs2228628 and rs8111, P=0.008; corrected P=0.03) and 1 haplotype (ATF6B-ht4, P=0.005; corrected P=0.02) were significantly associated with % decline of FEV1 by aspirin provocation, whereas ATF6B polymorphisms and haplotypes were not associated with the risk of AERD. CONCLUSIONS: Although further functional and replication studies are needed, our preliminary findings suggest that ATF6B may be related to obstructive phenotypes in response to aspirin exposure in adult asthmatics.

Diagnostic Value of Clinical Parameters in the Prediction of Aspirin-Exacerbated Respiratory Disease in Asthma

PURPOSE: Aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with increased asthma severity. However, oral aspirin challenge (OAC) to diagnose AERD is a time-consuming procedure, and some patients experience serious complications. Thus, we evaluated diagnostic values of non-invasive clinical parameters to predict AERD in asthmatic patients. METHODS: A total of 836 Korean subjects were recruited from an asthma cohort. They underwent OAC, and clinical parameters including the history of aspirin hypersensitivity, nasal polyposis, and chronic sinusitis of aspirin-tolerant asthma (ATA) and AERD asthmatic patients were compared. RESULTS: Significant differences (P<0.01) were found in eight parameters: age at diagnosis, body mass index, FEV1%, PC20, history of urticaria, nasal polyps, chronic sinusitis, and history of aspirin hypersensitivity. After logistic regression analysis based on the eight clinical parameters, nasal polyps, history of aspirin intolerance, sinusitis, and log [PC20 methacholine] remained significantly associated with AERD (P<0.05). The sensitivity and specificity of the history of aspirin hypersensitivity to predict AERD were 64.7% and 92.0%, respectively, and the positive and negative predictive values were 56.9% and 94.1%, respectively. Overall, the accuracy of the test was 88.2%. The accuracy of the tests for nasal polyps and chronic sinusitis were 67.3% and 60.4%, respectively. CONCLUSIONS: Among clinical parameters associated with AERD, the history of aspirin hypersensitivity has the best positive and negative predictive values for the oral aspirin challenge test. Because the false-positive and -negative rates were still high, additional non-invasive methods are needed to reduce the rate of false outcomes.