title: Perspectives on the etiology of chronic rhinosinusitis: an immune barrier hypothesis.
abstract: BACKGROUND
  Chronic rhinosinusitis (CRS) has been defined as persistent symptomatic inflammation of the nasal and sinus mucosa resulting from the interaction of multiple host and environmental factors. Recent studies have implicated Alternaria fungi or toxigenic Staphylococcus aureus as critical agents in CRS pathogenesis. The emphasis on environmental agents in CRS etiology has focused interest toward elimination of those agents as the prime mechanism of therapy. This viewpoint is in marked contrast to the current perspective on some other chronic inflammatory epithelial disorders that afflict the skin, lungs, and gut, wherein host factors are believed to predispose to disease expression in the presence of ubiquitous environmental agents.
  
  
  METHODS
  The current review evaluates CRS etiology from this perspective and considers that CRS develops, in part, as an outcome of a dysfunctional host response. Specifically, evidence from our laboratory and others will be reviewed indicating that CRS is associated with a failure of the mechanical and immunologic barriers across the nasal mucosa. The hypothesis would further propose that genetic and epigenetic variation predisposes susceptible individuals to barrier failure in the presence of environmental stress leading to CRS.
  
  
  RESULTS
  From this unifying perspective, bacteria and fungi are seen as disease modifiers rather than primary etiologic agents.
  
  
  CONCLUSIONS
  The goal is to place concepts of CRS pathophysiology in a framework consistent with a current understanding of chronic inflammation in general and epithelial disease in particular.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. r-kern@northwestern.edu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.forename: William
authors.initials: W
authors.lastname: Walsh
authors.forename: Rakesh
authors.initials: R
authors.lastname: Chandra
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Anju
authors.initials: A
authors.lastname: Tripathi-Peters
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000528:Alternaria / Q000276:immunology; D002908:Chronic Disease; D006801:Humans; D009297:Nasal Mucosa / Q000276:immunology; D012220:Rhinitis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D012852:Sinusitis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D018089:Superantigens / Q000276:immunology
chemical_list: D018089:Superantigens
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