Characterisation of Nasal Polyps in Patients With and Without Aspirin-exacerbated Respiratory Disease
Condition: Polyp Sinus
MeSH terms: Respiratory Tract Diseases; Respiration Disorders; Nasal Polyps; Polyps
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): biopsy
Intervention type(s): Other
Intervention description(s): Biopsy of nasal polyp for RNA sequencing
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients suffering from chronic rhinosinusitis with nasal polyps with/without AERD and
        with/without allergy
      
Biospecimen description: 
      Polyp biopsy, blood, nasal secretion