Advertisement

The Role of Staphylococcus aureus in Patients with Chronic Sinusitis and Nasal Polyposis

  • Thad W. Vickery
  • Vijay R. Ramakrishnan
  • Jeffrey D. SuhEmail author
Rhinitis, Conjunctivitis, and Sinusitis (John J. Oppenheimer & Jonathan Corren, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Rhinitis, Conjunctivitis, and Sinusitis

Abstract

Purpose of Review

Staphylococcus aureus (S. aureus) is correlated with the development of persistent severe inflammatory disease of the upper airway including chronic rhinosinusitis with nasal polyps (CRSwNP). The presence of S. aureus is associated with atopic disease including allergic rhinitis and atopic dermatitis and is associated with poor outcomes.

Recent Findings

Several different strains of S. aureus generate different toxins and gene products that can account for organism pathogenicity. S. aureus bacteria and its antigens shape the bacterial and fungal microbiome and the mucosal niche which generates host responses that can account for inflammation. The multiple disease phenotypes and molecular endotypes seen in CRSwNP can be characterized by T-helper cell environment within the inflammatory milieu, the presence of epithelial barrier dysfunction, aberrant eicosanoid metabolism, poor wound healing, and dysfunctional host-bacteria interactions which lead to recalcitrant disease and worse surgical outcomes.

Summary

Understanding the pathomechanisms that S. aureus utilizes to promote nasal polyp formation, prolonged tissue inflammation, and bacterial dysbiosis are essential in our efforts to identify new therapeutic approaches to resolve this chronic inflammatory process.

Keywords

Chronic rhinosinusitis Nasal polyps Staphylococcus aureus Innate and adaptive immune system Superantigens 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical practice guideline (update): adult sinusitis executive summary. Otolaryngol Head Neck Surg. 2015;152:598–609.CrossRefGoogle Scholar
  2. 2.
    Fokkens WJ et al European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinol Suppl. 2012;3. Preceding table of contents–1–298Google Scholar
  3. 3.
    DeConde AS, Soler ZM. Chronic rhinosinusitis: epidemiology and burden of disease. Am J Rhinol Allergy. 2016;30:134–9.CrossRefGoogle Scholar
  4. 4.
    Stevens WW, Peters AT, Suh L, Norton JE, Kern RC, Conley DB, et al. A retrospective, cross-sectional study reveals that women with CRSwNP have more severe disease than men. Immun Inflamm Dis. 2015;3:14–22.CrossRefGoogle Scholar
  5. 5.
    •• Derycke L, Perez-Novo C, Van Crombruggen K, Corriveau M-N, Bachert C. Staphylococcus aureus and chronic airway disease. World Allergy Organ J. 2010;3:223–8 Comprehensive overview of the role of S. aureus. in upper airway disease. Google Scholar
  6. 6.
    Van Zele T, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006;61:1280–9.CrossRefGoogle Scholar
  7. 7.
    Mygind N, Dahl R, Bachert C. Nasal polyposis, eosinophil dominated inflammation, and allergy. Thorax. 2000;55(Suppl 2):S79–83.CrossRefGoogle Scholar
  8. 8.
    Foreman A, Holtappels G, Psaltis AJ, Jervis-Bardy J, Field J, Wormald PJ, et al. Adaptive immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis. Allergy. 2011;66:1449–56.CrossRefGoogle Scholar
  9. 9.
    Suh JD, Ramakrishnan V, Palmer JN. Biofilms. Otolaryngol Clin N Am. 2010;43:521–30 viii.CrossRefGoogle Scholar
  10. 10.
    van Zele T, Gevaert P, Watelet JB, Claeys G, Holtappels G, Claeys C, et al. Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis. J Allergy Clin Immunol. 2004;114:981–3.CrossRefGoogle Scholar
  11. 11.
    Zhang N, van Zele T, Perez-Novo C, van Bruaene N, Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol. 2008;122:961–8.CrossRefGoogle Scholar
  12. 12.
    Ba L, Zhang N, Meng J, Zhang J, Lin P, Zhou P, et al. The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps. Allergy. 2011;66:1296–303.CrossRefGoogle Scholar
  13. 13.
    • Wang X, et al. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol. 2016;138:1344–53. Multicenter study examining geographic variation of inflammatory cytokine profiles of CRS. CrossRefGoogle Scholar
  14. 14.
    Frank DN, Feazel LM, Bessesen MT, Price CS, Janoff EN, Pace NR. The human nasal microbiota and Staphylococcus aureus carriage. PLoS One. 2010;5:e10598.CrossRefGoogle Scholar
  15. 15.
    Drilling A, Coombs GW, Tan HL, Pearson JC, Boase S, Psaltis A, et al. Cousins, siblings, or copies: the genomics of recurrent Staphylococcus aureus infections in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014;4:953–60.CrossRefGoogle Scholar
  16. 16.
    Doyle PW, Woodham JD. Evaluation of the microbiology of chronic ethmoid sinusitis. J Clin Microbiol. 1991;29:2396–400.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Manarey CRA, Anand VK, Huang C. Incidence of methicillin-resistant Staphylococcus aureus causing chronic rhinosinusitis. Laryngoscope. 2004;114:939–41.CrossRefGoogle Scholar
  18. 18.
    Schubert MS. A superantigen hypothesis for the pathogenesis of chronic hypertrophic rhinosinusitis, allergic fungal sinusitis, and related disorders. Ann Allergy Asthma Immunol. 2001;87:181–8.CrossRefGoogle Scholar
  19. 19.
    Zhang N, Gevaert P, van Zele T, Perez-Novo C, Patou J, Holtappels G, et al. An update on the impact of Staphylococcus aureus enterotoxins in chronic sinusitis with nasal polyposis. Rhinology. 2005;43:162–8.PubMedGoogle Scholar
  20. 20.
    van Zele T, Vaneechoutte M, Holtappels G, Gevaert P, van Cauwenberge P, Bachert C. Detection of enterotoxin DNA in Staphylococcus aureus strains obtained from the middle meatus in controls and nasal polyp patients. Am J Rhinol. 2008;22:223–7.CrossRefGoogle Scholar
  21. 21.
    Pérez Novo CA, Waeytens A, Claeys C, Cauwenberge PV, Bachert C. Staphylococcus aureus enterotoxin B regulates prostaglandin E2 synthesis, growth, and migration in nasal tissue fibroblasts. J Infect Dis. 2008;197:1036–43.CrossRefGoogle Scholar
  22. 22.
    Pérez-Novo CA, et al. Eicosanoid metabolism and eosinophilic inflammation in nasal polyp patients with immune response to Staphylococcus aureus enterotoxins. Am J Rhinol. 2006;20:456–60.CrossRefGoogle Scholar
  23. 23.
    Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2009;27:451–83.CrossRefGoogle Scholar
  24. 24.
    Calus L, Derycke L, Dullaers M, van Zele T, de Ruyck N, Pérez-Novo C, et al. IL-21 is increased in nasal polyposis and after stimulation with Staphylococcus aureus enterotoxin B. Int Arch Allergy Immunol. 2017;174:161–9.CrossRefGoogle Scholar
  25. 25.
    • Takeda K, et al. Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis. J Allergy Clin Immunol. 2018.  https://doi.org/10.1016/j.jaci.2018.07.006. Study suggesting that immunoglobulin class switching of B cells (from IgA and IgG to IgE) during the mucosal response against nasal bacteria contributes to the IgE phenotyope often observed in CRSwNP.
  26. 26.
    Lan F, Zhang N, Holtappels G, de Ruyck N, Krysko O, van Crombruggen K, et al. Staphylococcus aureus induces a mucosal type 2 immune response via epithelial cell-derived cytokines. Am J Respir Crit Care Med. 2018;198:452–63.CrossRefGoogle Scholar
  27. 27.
    Ramakrishnan VR, Feazel LM, Gitomer SA, Ir D, Robertson CE, Frank DN. The microbiome of the middle meatus in healthy adults. PLoS One. 2013;8:e85507.CrossRefGoogle Scholar
  28. 28.
    Sachse F, Becker K, von Eiff C, Metze D, Rudack C. Staphylococcus aureus invades the epithelium in nasal polyposis and induces IL-6 in nasal epithelial cells in vitro. Allergy. 2010;65:1430–7.CrossRefGoogle Scholar
  29. 29.
    Kern RC, Conley DB, Walsh W, Chandra R, Kato A, Tripathi-Peters A, et al. Perspectives on the etiology of chronic rhinosinusitis: an immune barrier hypothesis. Am J Rhinol. 2008;22:549–59.CrossRefGoogle Scholar
  30. 30.
    Altunbulakli C, et al. Staphylococcus aureus enhances the tight junction barrier integrity in healthy nasal tissue, but not in nasal polyps. J Allergy Clin Immunol. 2018;142:665–668.e8.CrossRefGoogle Scholar
  31. 31.
    • Valera FCP, et al. Staphylococcus aureus impairs sinonasal epithelial repair: effects in patients with chronic rhinosinusitis with nasal polyps and control subjects. J Allergy Clin Immunol. 2018.  https://doi.org/10.1016/j.jaci.2018.05.035. Study demonstrating the negative impact of Staphylococcus on wound healing in CRSwNP.
  32. 32.
    Singh P, Mehta R, Agarwal S, Mishra P. Bacterial biofilm on the sinus mucosa of healthy subjects and patients with chronic rhinosinusitis (with or without nasal polyposis). J Laryngol Otol. 2015;129:46–9.CrossRefGoogle Scholar
  33. 33.
    Sanderson AR, Leid JG, Hunsaker D. Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis. Laryngoscope. 2006;116:1121–6.CrossRefGoogle Scholar
  34. 34.
    Sanclement JA, Webster P, Thomas J, Ramadan HH. Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis. Laryngoscope. 2005;115:578–82.CrossRefGoogle Scholar
  35. 35.
    Dlugaszewska J, Leszczynska M, Lenkowski M, Tatarska A, Pastusiak T, Szyfter W. The pathophysiological role of bacterial biofilms in chronic sinusitis. Eur Arch Otorhinolaryngol. 2016;273:1989–94.CrossRefGoogle Scholar
  36. 36.
    Prince AA, et al. Prevalence of biofilm-forming bacteria in chronic rhinosinusitis. Am J Rhinol. 2008;22:239–45.CrossRefGoogle Scholar
  37. 37.
    Foreman A, Holtappels G, Psaltis AJ, Jervis-Bardy J, Field J, Wormald PJ, et al. Adaptive immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis. Allergy. 2011;66:1449–56.CrossRefGoogle Scholar
  38. 38.
    • Vickery TW, Ramakrishnan VR. Bacterial pathogens and the microbiome. Otolaryngol Clin N Am. 2017;50:29–47. Review article summarizing the current understanding of host-microbe interactions and their role in CRS. CrossRefGoogle Scholar
  39. 39.
    Abreu NA, et al. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med. 2012;4:151ra124.CrossRefGoogle Scholar
  40. 40.
    Ramakrishnan VR, Feazel LM, Abrass LJ, Frank DN. Prevalence and abundance of Staphylococcus aureus in the middle meatus of patients with chronic rhinosinusitis, nasal polyps, and asthma. Int Forum Allergy Rhinol. 2013;3:267–71.CrossRefGoogle Scholar
  41. 41.
    Ramakrishnan VR, et al. Sinus microbiota varies among chronic rhinosinusitis phenotypes and predicts surgical outcome. J Allergy Clin Immunol. 2015;136:334–42.e1.CrossRefGoogle Scholar
  42. 42.
    Chalermwatanachai T, Vilchez-Vargas R, Holtappels G, Lacoere T, Jáuregui R, Kerckhof FM, et al. Chronic rhinosinusitis with nasal polyps is characterized by dysbacteriosis of the nasal microbiota. Sci Rep. 2018;8:7926.CrossRefGoogle Scholar
  43. 43.
    Koutsourelakis I, Halderman A, Khalil S, Hittle LE, Mongodin EF, Lane AP. Temporal instability of the post-surgical maxillary sinus microbiota. BMC Infect Dis. 2018;18:441.CrossRefGoogle Scholar
  44. 44.
    Frank DN, Zhu W, Sartor RB, Li E. Investigating the biological and clinical significance of human dysbioses. Trends Microbiol. 2011;19:427–34.CrossRefGoogle Scholar
  45. 45.
    Chong LY, et al. Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis. Cochrane Database Syst Rev. 2016;4:CD011996.PubMedGoogle Scholar
  46. 46.
    Marcela FC, Macdonald KI, Lee J, Witterick IJ. The use of postoperative topical corticosteroids in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis. Am J Rhinol Allergy. 2013;27:e146–57.CrossRefGoogle Scholar
  47. 47.
    Yoon HY, Lee HS, Kim IH, Hwang SH. Post-operative corticosteroid irrigation for chronic rhinosinusitis after endoscopic sinus surgery: a meta-analysis. Clin Otolaryngol. 2018;43:525–32.CrossRefGoogle Scholar
  48. 48.
    Hissaria P, Smith W, Wormald PJ, Taylor J, Vadas M, Gillis D, et al. Short course of systemic corticosteroids in sinonasal polyposis: a double-blind, randomized, placebo-controlled trial with evaluation of outcome measures. J Allergy Clin Immunol. 2006;118:128–33.CrossRefGoogle Scholar
  49. 49.
    van Zele T, et al. Oral steroids and doxycycline: two different approaches to treat nasal polyps. J Allergy Clin Immunol. 2010;125:1069–1076.e4.CrossRefGoogle Scholar
  50. 50.
    Watelet JB, Bachert C, Claeys C, van Cauwenberge P. Matrix metalloproteinases MMP-7, MMP-9 and their tissue inhibitor TIMP-1: expression in chronic sinusitis vs nasal polyposis. Allergy. 2004;59:54–60.CrossRefGoogle Scholar
  51. 51.
    Shin J-M, et al. Effect of doxycycline on transforming growth factor-beta-1-induced matrix metalloproteinase 2 expression, migration, and collagen contraction in nasal polyp-derived fibroblasts. Am J Rhinol Allergy. 2016;30:385–90.CrossRefGoogle Scholar
  52. 52.
    Shin J-M, Park J-H, Park I-H, Lee H-M. Doxycycline inhibits TGF-β1-induced extracellular matrix production in nasal polyp-derived fibroblasts. Int Forum Allergy Rhinol. 2016;6:256–63.CrossRefGoogle Scholar
  53. 53.
    Rudmik L, Soler ZM. Medical therapies for adult chronic sinusitis: a systematic review. JAMA. 2015;314:926–39.CrossRefGoogle Scholar
  54. 54.
    Jervis-Bardy J, Boase S, Psaltis A, Foreman A, Wormald P-J. A randomized trial of mupirocin sinonasal rinses versus saline in surgically recalcitrant staphylococcal chronic rhinosinusitis. Laryngoscope. 2012;122:2148–53.CrossRefGoogle Scholar
  55. 55.
    Solares CA, Batra PS, Hall GS, Citardi MJ. Treatment of chronic rhinosinusitis exacerbations due to methicillin-resistant Staphylococcus aureus with mupirocin irrigations. Am J Otolaryngol. 2006;27:161–5.CrossRefGoogle Scholar
  56. 56.
    • Halderman AA, Lane AP. Immunomodulators in the treatment of nasal polyposis. Adv Otorhinolaryngol. 2016;79:103–13. Comprehensive review on the current data utilizing biologic immunomodulators for the treatment of CRSwNP. PubMedGoogle Scholar
  57. 57.
    Bachert C, et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial. J Allergy Clin Immunol. 2017;140:1024–1031.e14.CrossRefGoogle Scholar
  58. 58.
    Ference EH, Suh JD, Tan BK, Smith SS. How often is sinus surgery performed for chronic rhinosinusitis with versus without nasal polyps? Am J Rhinol Allergy. 2018;32:34–9.CrossRefGoogle Scholar
  59. 59.
    Le PT, et al. Systematic review and meta-analysis of SNOT-22 outcomes after surgery for chronic rhinosinusitis with nasal polyposis. Otolaryngol Head Neck Surg. 2018;159:414–23.CrossRefGoogle Scholar
  60. 60.
    Miglani A, Divekar RD, Azar A, Rank MA, Lal D. Revision endoscopic sinus surgery rates by chronic rhinosinusitis subtype. Int Forum Allergy Rhinol. 2018;8:1047–51.CrossRefGoogle Scholar
  61. 61.
    Singhal D, Foreman A, Jervis-Bardy J, Bardy J-J, Wormald P-J. Staphylococcus aureus biofilms: nemesis of endoscopic sinus surgery. Laryngoscope. 2011;121:1578–83.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Thad W. Vickery
    • 1
  • Vijay R. Ramakrishnan
    • 2
  • Jeffrey D. Suh
    • 1
    Email author
  1. 1.Department of Head and Neck SurgeryDavid Geffen School of Medicine, University of California Los AngelesLos AngelesUSA
  2. 2.Department of Otolaryngology-Head and Neck SurgeryUniversity of ColoradoAuroraUSA

Personalised recommendations