Person:

Bhattacharyya, Neil

Background: Chronic rhinosinusitis (CRS) and allergic rhinitis are associated with functional limitations, but these impacts are not known on a population basis. Our objective was to epidemiologically determine functional limitations and workdays lost that are associated with CRS and allergic rhinitis in adults. Methods: The Medical Expenditure Panel Survey for calendar year 2007 was examined to identify cases of CRS and allergic rhinitis. Functional limitation variables for activity limitation, work limitation, social limitation, and cognitive limitation determined by the survey also were extracted. Using multivariate models adjusting for age, gender, race, ethnicity, education level, insurance status, geographic region, as well as the Charlson comorbidity index, incremental differences in workdays lost and these functional limitations were determined for patients with and without CRS and allergic rhinitis. Results: Among 225.1 million adults, the prevalences of CRS and allergic rhinitis were 4.9 ± 0.2% and 7.9 ± 0.3%, respectively. Patients with CRS demonstrated an incremental 1.04 ± 0.3 workdays lost per year along with significant increased adjusted odds ratios for activity limitation (odds ratio, 1.54), work limitation (1.50), and social limitation (1.49, all p < .005) but not cognitive limitation (1.05, p = .213). Patients with allergic rhinitis demonstrated an incremental 0.60 ± 0.45 workdays lost along with significant increased adjusted odds ratios for activity limitation (1.42), work limitation (1.43), social limitation (1.47), and cognitive limitation (1.32, all p < .019). Conclusions: Both CRS and allergic rhinitis impart significantly increased odds ratios for activity, work, and social limitations. Allergic rhinitis also carries with it statistically significant odds of functional cognitive limitation. The total aggregate workdays missed in the United States may be estimated at 11.5 million workdays and 10.7 million workdays for CRS and allergic rhinitis, respectively.

Background: Prostaglandin D2 (PGD2) is the dominant cyclooxygenase product of mast cells and is an effector of aspirin-induced respiratory reactions in aspirin-exacerbated respiratory disease (AERD). Objective: We evaluated the role of the innate cytokine thymic stromal lymphopoietin (TSLP) acting on mast cells to generate PGD2 and facilitate tissue eosinophilia and nasal polyposis in AERD. Methods: Urinary eicosanoids were measured in aspirin-tolerant controls and patients with AERD. Nasal polyp specimens from subjects with AERD and chronic rhinosinusitis were analyzed via qPCR, western blot, and immunohistochemistry. Human cord blood-derived and peripheral blood-derived mast cells were stimulated with TSLP in vitro to assess PGD2 generation. Results: Urinary levels of a stable PGD2 metabolite (uPGD-M) were 2-fold higher in subjects with AERD relative to controls, and increased further during aspirin-induced reactions. Peak uPGD-M levels during aspirin reactions correlated with reductions in blood eosinophil counts and lung function, and with increases in nasal congestion. Mast cells sorted from nasal polyps expressed PGD2 synthase (hPGDS) mRNA at higher levels than did eosinophils from the same tissue. Whole nasal polyp TSLP mRNA expression correlated strongly with mRNA encoding hPGDS (r = .75), the mast cell-specific marker carboxypeptidase A3 (r = .74), and uPGD-M (r=0.74). The cleaved, active form of TSLP was increased in AERD nasal polyps relative to aspirin-tolerant controls. Recombinant TSLP induced PGD2 generation by cultured human mast cells. Conclusions: Our study demonstrates that mast cell-derived PGD2 is a major effector of type 2 immune responses driven by TSLP, and suggests that dysregulation of this innate system contributes significantly to the pathophysiology of AERD.