Perspectives on the etiology of chronic rhinosinusitis: An immune barrier hypothesis

Robert C. Kern*, David B. Conley, William Walsh, Rakesh Chandra, Atsushi Kato, Anju Tripathi-Peters, Leslie C. Grammer, Robert P. Schleimer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

240 Scopus citations


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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)549-559
Number of pages11
JournalAmerican Journal of Rhinology
Issue number6
StatePublished - 2008


  • Adaptive immune system
  • Chronic rhinosinusitis
  • Fungal hypothesis
  • Immune barrier hypothesis
  • Innate immunesystem
  • Nasal polyps
  • Superantigen hypothesis

ASJC Scopus subject areas

  • Otorhinolaryngology


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