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Rationale: Daily high-dose aspirin therapy benefits many patients with aspirin-exacerbated respiratory disease but provides no benefit for aspirin-tolerant patients with asthma. Type 2 inflammation characterizes aspirin-exacerbated respiratory disease. Objectives: To determine whether high-dose aspirin therapy changes biomarkers of type 2 inflammation in aspirin-exacerbated respiratory disease. Methods: Forty-two subjects with aspirin-exacerbated respiratory disease underwent an aspirin desensitization and were placed on high-dose aspirin (1,300 mg daily). Fifteen aspirin-tolerant subjects with asthma were also placed on high-dose aspirin. Biologic specimens and clinical parameters were collected at baseline and after 8 weeks on aspirin. Urinary eicosanoids, plasma tryptase and cytokine levels, platelet-leukocyte aggregates, and granulocyte transcripts were assessed. Measurements and Main Results: Eight weeks of high-dose aspirin decreased nasal symptoms and urinary prostaglandin E metabolite ( P  < 0.05) and increased urinary leukotriene E 4 ( P  < 0.01) levels in subjects with aspirin-exacerbated respiratory disease, but not in those with aspirin-tolerant asthma. Urinary prostaglandin D 2 and thromboxane metabolites decreased in both groups. Only in subjects with aspirin-exacerbated respiratory disease, exhaled nitric oxide ( P  < 0.05), plasma tryptase ( P  < 0.01), and blood eosinophil ( P  < 0.01) and basophil ( P  < 0.01) counts increased and plasma tryptase correlated with eosinophil counts (Pearson r  = 0.514; P  < 0.01) on aspirin. After correction for eosinophil counts, aspirin-induced changes in blood granulocyte transcripts did not differ between groups. Aspirin had no effect on platelet-leukocyte aggregates, platelet activation markers, or plasma cytokines in either group. Conclusions: High-dose aspirin therapy for 8 weeks paradoxically increases markers of type 2 inflammation in subjects with aspirin-exacerbated respiratory disease, despite reducing nasal symptoms. This effect of aspirin is unique to aspirin-exacerbated respiratory disease and not observed in subjects with aspirin-tolerant asthma.

Objectives/hypothesis: Clinically, inflammatory polyps are found in the middle turbinate (MT) in patients with chronic rhinosinusitis (CRS) but not in the inferior turbinate (IT). The purpose of this study was to investigate differences in protein expression between IT and MT tissue in patients with CRS., Study Design: Prospective cohort., Methods: Pathologic specimens obtained from patients with CRS undergoing functional endoscopic sinus surgery with IT reduction were evaluated by immunohistochemical analysis of inflammatory markers cysteinyl leukotriene 1 receptor (CysLT1R), toll-like receptor 2 (TLR2), and vascular cell adhesion molecule 1 (VCAM1). Protein expression was quantified with nuance multispectral analysis and results compared between MT and IT tissue., Results: The total expression of VCAM1 and CysLT1R was decreased in the IT compared to the MT. There was no difference in total TLR2 expression between the IT and MT. When comparing patients with eosinophilic CRS to noneosinophilic CRS (neCRS), there was decreased expression of VCAM1 in the IT of patients with neCRS. When comparing patients with nasal polyposis to those without polyps, there was decreased expression of VCAM1 in the IT of patients without polyps., Conclusions: There is a difference in protein receptor expression of VCAM1 and CysLT1R in MT compared to IT tissue. Although the leukotrienes are a well-known target for treatment of chronic sinusitis, this is the first study demonstrating an upregulation of VCAM1 expression in the MT and could be a potential future target for the treatment of CRS., Level of Evidence: NA Laryngoscope, 126:E179-E183, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To examine the expression of cysteinyl leukotriene receptor-1 (CysLTR-1) and cysteinyl leukotriene receptor-2 (CysLTR-2) in the adenoid tissues from children with adenoid hypertrophy (AH) and to explore the role of leukotrienes in the pathogenesis of AH., Methods: Sixty children with AH who were treated by adenoidectomy and/or tonsillectomy were classified into two groups: simple AH and AH plus allergic rhinitis (n=30 each). Twenty children who underwent tonsillectomy due to recurrent purulent tonsillitis were selected as the control group. The expression of CysLTR-1 and CysLTR-2 in the excised tonsil and/or adenoid tissues was determined by immunofluorescence histochemical labeling and integrated optical density measurement., Results: The expression of CysLTR-1 and CysLTR-2 in the adenoid and tonsil tissues increased significantly in both the simple AH group and AH plus allergic rhinitis group compared with the control group (P<0.01). The expression of CysLTR-1 and CysLTR-2 in the AH plus allergic rhinitis group increased more significantly compared with the simple AH group (P<0.01)., Conclusions: CysLTR-1 and CysLTR-2 are highly expressed in the adenoid tissues from children with AH, suggesting that leukotrienes are involved in the pathogenesis of AH.