Polyp Sinus Clinical Trial
Official title:
In Depth Characterisation of Nasal Polyps in Patients With and Without Aspirin-exacerbated Respiratory Disease - a Pilot Study
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.
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