Characterisation of the Nasal Microbiome in Patients With N-ERD
Condition: Aspirin Exacerbated Respiratory Disease; Chronic Rhinitis
MeSH terms: Rhinitis; Respiratory Tract Diseases; Respiration Disorders
Study type: Interventional

Summary: 
      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. It may also be associated with a hypersensitivity to
      non-steroidal anti-inflammatory (NSAID) drugs in a syndrome called NSAID-exacerbated
      respiratory disease (N-ERD) characterized by highly recurrent polyps and concomitant asthma.
      The pathophysiological mechanisms especially with regards to the potential role of the
      microbiome in driving N-ERD are so far not fully understood. Here, the investigators plan to
      analyse the nasal microbiome in these patients and to compare it to nasal samples from CRSwNP
      and CRSsNP patients as well as healthy controls (in total 80 subjects). This will provide
      insights into potential differences in the microbiome as compared to other CRS patients and
      the impact of the microbiome in driving this 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, aspirin-exacerbated respiratory disease (AERD) and recently
      NSAID-exacerbated respiratory disease (N-ERD). N-ERD 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 N-ERD patients.This indicates a dysregulation of pro and anti-inflammatory
      pathways.

      Our mucosal body surfaces are colonized by a large variety of microbes organized within
      complex community structures. Novel sequencing techniques (e.g. 16SrRNA sequencing) have
      facilitated in-depth analysis of the nasal microbiome in health and disease. Recent studies
      show amongst other an enrichment in Haemophilus and Streptococcus in the nose of CRS
      patients, whereas nasal microbiome of healthy patients is rich in Propionibacterium acnes .
      So far, differences in microbiome were observed in healthy versus CRS patients, but the
      impact of the microbial environment in N-ERD has not been assessed yet and is thus aim of the
      study.

      The investigators will collect nasal microbiome and nasal secretions from patients suffering
      from N-ERD and will compare them to the microbiome of CRSwNP, CRSsNP and healthy controls
      (n=20 per group). Additionally, cytokines in nasal secretions, protein expression at mRNA
      levels in nasal mucosa, and serum of these patients and clinical parameters (e.g. total nasal
      polyp score, quality of life questionnaire, olfactory performance) will be determined.
    

Intervention name(s): Microbiome swabs
Intervention type(s): Other
Intervention description(s): Swabs for analysis of microbiome
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: aerd, microbiome