title: Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct VEGF and GM-CSF signatures during symptomatic exacerbations.
abstract: BACKGROUND
  The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease.
  
  
  OBJECTIVE
  To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls.
  
  
  METHODS
  This was a non-interventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post-visit 2 weeks later. The sinonasal outcome test-22 (SNOT-22) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis.
  
  
  RESULTS
  Both CRSwNP patients and control subjects showed a significant increase in SNOT-22 scores during acute exacerbation. Increased nasal levels of IL-6, IL-5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM-CSF levels were notable and were validated by a conventional analysis.
  
  
  CONCLUSIONS
  CRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM-CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation.
authors.affiliation: Division of Allergic Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Divekar
authors.forename: S
authors.initials: S
authors.lastname: Samant
authors.forename: M A
authors.initials: MA
authors.lastname: Rank
authors.forename: J
authors.initials: J
authors.lastname: Hagan
authors.forename: D
authors.initials: D
authors.lastname: Lal
authors.forename: E K
authors.initials: EK
authors.lastname: O'Brien
authors.forename: H
authors.initials: H
authors.lastname: Kita
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D009298:Nasal Polyps / Q000150:complications*; D011446:Prospective Studies; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D012220:Rhinitis / Q000097:blood* / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D012852:Sinusitis / Q000097:blood* / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Chronic rhinosinusitis; GM-CSF; VEGF; exacerbation; human rhinovirus; nasal polyposis