Characterisation of Nasal Polyps in Patients With and Without Aspirin-exacerbated Respiratory Disease

Overview

Prevalence of aspirin-exacerbated respiratory disease (AERD) is 16% amongst patients suffering from chronic rhinosinusitis with nasal polyps (CRSwNP). The mechanisms underlying the observed dysregulation of pro and anti-inflammatory pathways in AERD are still not fully understood. To address this and also to identify potential factors characterizing the disease the investigators plan to prospectively collect blood samples, nasal secretions as well as nasal biopsies from allergic, non-allergic and AERD patients suffering from CRSwNP. Initially, polyps of aforementioned patients will be subjected to RNA sequencing analysis using microarray technology. Once distinct factors are identified in nasal polyp tissue, their presence will be assessed in nasal secretions and serum of the respective patients to investigate their potential role as biomarkers. Furthermore presence of these parameters will be confirmed in situ in biopsies by confocal microscopy. Knowledge about factors differently upregulated in polyp tissue from AERD may contribute to a better understanding of the underlying mechanism of the disease.

Chronic rhinosinusitis (CRS) with (w) and without (s) nasal polyps (NP) in its different shapes is currently affecting up to 16% of the total population of the United States and around 11% of the population in Europe. However CRS may also be associated with hypersensitivity to aspirin and other non-selective cyclooxygenase inhibitors. This syndrome of combined CRSwNP, asthma and intolerance to inhibitors of the cyclooxygenase-1 enzyme was termed Samter's triad or aspirin-exacerbated respiratory disease (AERD). AERD is thought to affect around 16% of patients suffering from CRSwNP, around 7% of adult asthmatic patients and 0.3-2.5% of the general population. One characteristic feature of this disease is the presence of nasal polyps that frequently relapse after surgery rendering this disease difficult to manage. Despite its relatively high prevalence, the pathophysiologic mechanisms are yet not fully understood. In this respect, an overproduction of and overresponsiveness to cysteinyl leukotrienes accompanied by and underproduction of and underresponsiveness to prostaglandins was observed in AERD patients.This indicates a dysregulation of pro and anti-inflammatory pathways. However the mechanism and the cells involved in causing this imbalance are still not clear. The availability of gene-chip microarray technology allows for quantitatively and simultaneously monitoring of the expression of thousands of genes and has greatly contributed to the understanding of pathological mechanisms. In this context, analysis of nasal polyps from allergic patients has shown that genes involved in deregulated cell growth similar to neoplastic growth are upregulated in this tissue. Furthermore very recently, profiling of CRS samples by single-cell RNA sequencing revealed a significant loss of epithelial ecological diversity in nasal polyps. The authors suggest that basal cells form memories of chronic exposure to an inflammatory environment and shift the cellular ecosystem towards propagating the disease. However polyps from AERD patients which show a different clinical and most likely also pathophysiological profile have not been included in this study. Given the prevalence of 15% amongst CRSwNP patients and the impaired quality of life of AERD patients it would be desirable to understand the difference between AERD and CRSwNP without AERD at a molecular level and also to potentially find biomarkers that uniquely identify patients suffering from AERD disease. Therefore, the investigators plan to prospectively collect blood samples, nasal secretions as well as nasal biopsies from allergic, non-allergic and AERD patients suffering from CRSwNP. Initially, RNA sequencing will be performed using microarray technology in biopsies of those patients. Once parameters are identified, the investigators will investigate if a similar pattern can also be detected in nasal secretions and/or serum of the respective patients to investigate their potential as biomarkers. Furthermore presence of these parameters will be confirmed in situ in biopsies by confocal microscopy.