Biomarkers predicting nasal polyp recurrence in aspirin-exacerbated respiratory disease

The proposed investigations focus on identification of biomarkers associated with nasal polyp recurrence in patients with aspirin-exacerbated respiratory disease (AERD) who fail endoscopic sinus surgery and aspirin therapy after desensitization. Nasal polyps are inflammatory outgrowths of sinonasal mucosa that lead to significant medical resource consumption, impairment in quality of life, and are particularly severe and rapidly recur after endoscopic sinus surgery in AERD, even with adjuvant treatment with aspirin therapy after desensitization which can prevent nasal polyp recurrence in some patients. This proposal details proteomic analysis of both Type (T) 2 and non-T2 biomarkers in the sinonasal tissue and non-invasively sampled nasal fluid of patients with AERD. The investigators have observed that non-T2 proteins including oncostatin M, interleukin 10, and macrophage colony stimulating factor are elevated in the nasal mucus of patients with AERD who have rapid post- endoscopic sinus surgery nasal polyp regrowth despite aspirin therapy after desensitization. Additionally, the investigators have identified nasal tissue macrophages as a likely source of the proteins associated with nasal polyp recurrence. Employing proteomic, lipidomic and cellular techniques, the investigators will test the hypotheses that complex T2/non-T2 inflammatory interactions within the respiratory tract drive post-surgical NP recurrence and that a combination of T2/non-T2 markers can be used as a predictive model for NP recurrence, and also that an activated phenotype of macrophages drives nasal polyp recurrence in AERD. The aims are to: 1) Establish a biomarker-based predictive model of NP recurrence in patients with AERD based on polyp tissue samples, utilizing levels of T2 and non-T2 markers of inflammation, and 2) characterize the macrophage subsets that produce tissue proteins associated with nasal polyp recurrence, specifically oncostatin M and interleukin 10, and establish relationship between macrophage phenotype and nasal polyp severity in patients with AERD. These studies will advance our understanding of the pathogenesis of AERD leading to the identification of novel therapeutic targets for this disease.