Rhinosinusitis (Polypoid)

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Rhinosinusitis (Polypoid)

Rhinology
Author Credentials 

Andrew Thomas, MD
Resident
Department of Surgery, Division of Otolaryngology
University of Utah
Salt Lake City, Utah

Jeremiah Alt, MD, PhD
Assistant Professor 
Surgery, Division of Otolaryngology
University of Utah
Salt Lake City, Utah

Module Summary

Chronic rhinosinusitis with nasal polyps (CRSwNP) is diagnosed based on the presence of nasal polyps in addition to meeting criteria for CRS. Although not known to be associated with mortality risk, the morbidity and severe impact on quality of life reported by patients with severe CRS is worse than major illness such as COPD, CHF, and Parkinsons disease. Though quality of life improvements after treatment appear to be most substantial for patients with CRSwNP. CRSwNP is most commonly associated with a Th2 driven inflammatory process. The underlying pathophysiology is not entirely understood but related to chronic inflammation and may be seen in conditions that result in chronic sinonasal inflammation such as allergic fungal sinusitis, CF, PCD, and AERD. Other benign and malignant masses may present as unilateral “polyps” and must be considered in the differential. Topical nasal steroids are the cornerstone of medical therapy for CRSwNP. Oral therapeutics with an anti-inflammatory mechanism of action serve an adjunct role to topical steroids and the most evidence exists for use of a short course of oral corticosteroids. Other options include macrolide class antibiotics and leukotriene antagonists. Evidence is growing for a potential role of immunotherapies in the treatment of this disease. Aspirin desensitization is an effective treatment for CRSwNP in the setting of AERD and additional benefit can be seen with diet modification and leukotriene antagonists. Surgical treatment is indicated when appropriate medical management (generally a trial of intranasal corticosteroids, saline irrigations, and short course oral corticosteroid) fails to control symptoms. The duration of medical management is not firmly defined but generally 3- to 4-weeks is recommended as minimum. The principals of surgical management for CRSwNP are to remove sinus outflow obstruction, reduce inflammatory load of polypoid tissue, and create a patent passage for topical anti-inflammatories and rinses. The appropriate extent of surgery is unclear though it does appear that more extensive endoscopic sinus surgery (compared to conservative approaches such as MIST or balloon which may be adequate for minimal disease) provides improved long term outcomes for patients with more severe disease. Our understanding of the pathophysiology of this condition and its subtypes remains quite limited though is continuing to grow with new research. The underlying principle of therapy remains reducing an underlying chronic inflammatory process both with anti-inflammatory medical therapy and surgical relief of obstruction and inflammatory load. 
 

Module Learning Objectives 
  1. Recognize the differences between acute, subacute, and chronic rhinosinusitis.
  2. Explain the concept of the unified airway theory and how this relates to the pathogenesis of polypoid rhinosinusitis.
  3. Summarize current theories of the pathogenesis of polypoid rhinosinusitis. 
  4. Cite the key elements of the clinical workup for a patient with polypoid rhinosinusitis.
  5. Explain options of medical management of polypoid rhinosinusitis, and the data which exists on their respective efficacy.
  6. Recognize the indications for surgical management of polypoid rhinosinusitis, as well as potential risks and benefits.
  7. Identify other conditions associated with polypoid rhinosinusitis and how this impacts management.

Anatomy

Learning Objectives 
  1. Understand the anatomy of the paranasal sinuses.
  2. Describe common characteristics of sinonasal polyps.
  3. Appreciate important anatomic relationships of the orbit and cranial vault and the potential for both orbital and intracranial complications of CRSwNP.1
  4. Identify the anatomic difference that distinguishes pediatric CRS (PCRS) from adult CRS.2
     
References 
  1. Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. Feb 2016;6 Suppl 1:S22-209.
  2. Bernstein JM, Dryja D, Murphy TF. Molecular typing of paired bacterial isolates from the adenoid and lateral wall of the nose in children undergoing adenoidectomy: implications in acute rhinosinusitis. Otolaryngol Head Neck Surg. Dec 2001;125(6):593-597.

Pathogenesis

Learning Objectives 
  1. Be familiar with the united airway concept and the potential relationship of CRSwNP to other upper airway inflammatory conditions.1-3
  2. Understand the theoretical immunologic relationship of allergy and CRSwNP.4,5
  3. Be familiar with the potential relationship of vitamin D levels and CRSwNP.6
  4. Understand the potential relationship of S. aureus and superantigens to CRSwNP pathogenesis.7
  5. Be familiar with the relationship of fungus to CRS.8,9
     
References 
  1. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008 Apr;63 Suppl 86:8-160.
  2. Braunstahl GJ, Kleinjan A, Overbeek SE, Prins JB, Hoogsteden HC, Fokkens WJ. Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients. Am J Respir Crit Care Med. 2000 Jun;161(6):2051-2057.
  3. Gaga M, Lambrou P, Papageorgiou N, et al. Eosinophils are a feature of upper and lower airway pathology in non-atopic asthma, irrespective of the presence of rhinitis. Clin Exp Allergy. 2000 May;30(5):663-669.
  4. Bachert C, Gevaert P, Holtappels G, Johansson SG, van Cauwenberge P. Total and specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy Clin Immunol. 2001 Apr;107(4):607-614.
  5. Hamilos DL, Leung DY, Wood R, et al. Chronic hyperplastic sinusitis: association of tissue eosinophilia with mRNA expression of granulocyte-macrophage colony-stimulating factor and interleukin-3. J Allergy Clin Immunol.1993;92(1 Pt 1):39-48.
  6. Mulligan JK, Bleier BS, O'Connell B, Mulligan RM, Wagner C, Schlosser RJ. Vitamin D3 correlates inversely with systemic dendritic cell numbers and bone erosion in chronic rhinosinusitis with nasal polyps and allergic fungal rhinosinusitis. Clin Exp Immunol. 2011;164(3):312-320.
  7. Ou J, Wang J, Xu Y, et al. Staphylococcus aureus superantigens are associated with chronic rhinosinusitis with nasal polyps: a meta-analysis. Eur Arch Otorhinolaryngol. 2014;271(10):2729-2736.
  8. Kim ST, Choi JH, Jeon HG, Cha HE, Hwang YJ, Chung YS. Comparison between polymerase chain reaction and fungal culture for the detection of fungi in patients with chronic sinusitis and normal controls. Acta Otolaryngol. 2005;125(1):72-75.
  9. Murr AH, Goldberg AN, Vesper S. Fungal speciation using quantitative polymerase chain reaction (QPCR) in patients with and without chronic rhinosinusitis. Laryngoscope. 2006;116(8):1342-1348.

Basic Science

Learning Objectives 
  1. Describe the balance of Th1 and Th2 T cell activation associated with CRSwNP.1
  2. In addition to Th1 and Th2 T cells, name another T cell type which may be involved in CRSwNP pathogenesis as well as other upper airway inflammatory disease.2
  3. Be able to identify the inflammatory cytokines that are typically secreted by Th1 cells and those secreted by Th2 cells:
    1. Interferon-γ (IFN-γ)
    2. Tumor necrosis factor-α (TNF-α)
    3. Interleukin (IL)-4
    4. IL-5
    5. IL-9
    6. IL-13
  4. List two inflammatory cytokines associated with the inflammatory process of polyposis and which are found to be elevated in polyp tissue.1,3
  5. Evaluate the relationship between allergy and nasal polyposis, and identify a specific subtype of CRSwNP in which the inflammatory process is driven by an allergic response.4
References 
  1. Van Zele T, Claeys S, Gevaert P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006;61(11):1280-1289.
  2. Liu Y, Zeng M, Liu Z. Th17 response and its regulation in inflammatory upper airway diseases. Clin Exp Allergy. 2015;45(3):602-612.
  3. Bachert C, Gevaert P, Holtappels G, Johansson SG, van Cauwenberge P. Total and specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy Clin Immunol. 2001;107(4):607-614.
  4. Lee S, Lane AP. Chronic rhinosinusitis as a multifactorial inflammatory disorder. Curr Infect Dis Rep. 2011;13(2):159-168.
     

Incidence

Learning Objectives 
  1. Know the incidence of CRSwNP.1
  2. Describe the relationship of disease incidence for asthma and CRSwNP, and understand the importance of evaluating CRSwNP patients for asthma.2,3
  3. Identify other comorbid diseases that are associated with nasal polyps.4,5
References 
  1. Tan BK, Chandra RK, Pollak J, et al. Incidence and associated premorbid diagnoses of patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2013;131(5):1350-1360.
  2. Settipane GA, Chafee FH. Nasal polyps in asthma and rhinitis. A review of 6,037 patients. J Allergy Clin Immunol. 1977;59(1):17-21.
  3. Ragab A, Clement P, Vincken W. Objective assessment of lower airway involvement in chronic rhinosinusitis. Am J Rhinol. 2004;18(1):15-21.
  4. Hadfield PJ, Rowe-Jones JM, Mackay IS. The prevalence of nasal polyps in adults with cystic fibrosis. Clin Otolaryngol Allied Sci. 2000;25(1):19-22.
  5. Picado C. Aspirin intolerance and nasal polyposis. Curr Allergy Asthma Rep. 2002;2(6):488-493.

Genetics

Learning Objectives 
  1. Be familiar with potential genetic differences between polypoid and non-polypoid CRS.1
  2. Be familiar with how genetically based differences in immunity may influence bacterial colonization of the sinuses and how this may contribute to sinonasal inflammation and disease.2
  3. Identify a disease of specific known genetic defects which is associated with nasal polyposis. Recognize that this relationship is unique, without other clear relationships between polyposis genetic conditions.3
     
References 
  1. Zhang Y, Endam LM, Filali-Mouhim A, et al. Polymorphisms in RYBP and AOAH genes are associated with chronic rhinosinusitis in a Chinese population: a replication study. PLoS One. 2012;7(6):e39247.
  2. Cormier C, Mfuna Endam L, Filali-Mouhim A, et al. A pooling-based genomewide association study identifies genetic variants associated with Staphylococcus aureus colonization in chronic rhinosinusitis patients. Int Forum Allergy Rhinol. 2014;4(3):207-215.
  3. Van Zele T, Claeys S, Gevaert P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006;61(11):1280-1289.

Patient Evaluation

Learning Objectives 
  1. Know the definition of acute rhinosinusitis (ARS), subacute rhinosinusitis (subacute RS), and chronic rhinosinusitis (CRS). Acute rhinosinusitis (ARS) in adults may be defined as sinonasal inflammation lasting less than 4 weeks associated with the sudden onset of symptoms.1-3
  2. How is the diagnosis of CRSwNP defined and made clinically?2,3
  3. Identify additional benign processes and masses that should be considered in the case of finding unilateral polyps.4,6
  4. List a differential diagnosis for malignant neoplasms that should be considered in finding of a unilateral nasal polyp.4
  5. Describe features that would be suggestive of sinonasal tumor or encephalocele, rather than nasal polyp.6,7
  6. Recognize the symptoms of CRS, and the four main categories they belong to.1
  7. Identify the most common symptoms associated with polypoid CRS.8
  8. Know the value and reasons of importance for nasal endoscopy in the evaluation of patients with CRS.9
References 
  1. Meltzer EO, Hamilos DL, Hadley JA, et al. Rhinosinusitis: establishing definitions for clinical research and patient care. J Allergy Clin Immunol. 2004;114(6 Suppl):155-212.
  2. Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European Position Paper on Rhinosinusitis and Nasal Polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar;50(1):1-12.
  3. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): Adult Sinusitis Executive Summary. Otolaryngol Head Neck Surg. 2015;152(4):598-609.
  4. London NR, Jr., Reh DD. Differential Diagnosis of Chronic Rhinosinusitis with Nasal Polyps. Adv Otorhinolaryngol. 2016;79:1-12.
  5. Nicolai P CP. Benign tumors of the sinonasal tract. In: Flint PW HB, Lund, VJ, eds. Cummings Otolaryngology Head and Neck Surgery. Vol 1. 5 ed. Philadelphia: Mosby Elsevier; 2005:717–727.
  6. Arslan HH, Hidir Y, Durmaz A, Karslioglu Y, Tosun F, Gerek M. Unexpected tumor incidence in surgically removed unilateral and bilateral nasal polyps. J Craniofac Surg. 2011;22(2):751-754.
  7. Tirumandas M, Sharma A, Gbenimacho I, et al. Nasal encephaloceles: a review of etiology, pathophysiology, clinical presentations, diagnosis, treatment, and complications. Childs Nerv Syst. 2013;29(5):739-744.
  8. Bachert C, Pawankar R, Zhang L, et al. ICON: chronic rhinosinusitis. World Allergy Organ J. 2014;7(1):25.
  9. Bhattacharyya N, Lee LN. Evaluating the diagnosis of chronic rhinosinusitis based on clinical guidelines and endoscopy. Otolaryngol Head Neck Surg. 2010;143(1):147-151.

Measurement of Functional Status

Learning Objectives 
  1. Recognize the dramatic impact of CRSwNP on patient quality of life1
  2. Identify two different CRS-specific quality of life measures and be familiar with their subdomains
    1. RSDI2
      1. Physical
      2. Functional
      3. Emotional
    2. SNOT-223
      1. Rhinologic symptoms
      2. Extranasal rhinologic symptoms
      3. Ear/Facial symptoms
      4. Psychological dysfunction
      5. Sleep dysfunction
  3. Identify a common subjective measure of nasal obstruction and understand the component subdomains
    1. NOSE4
      1. Nasal congestion
      2. Nasal blockage
      3. Trouble breathing
      4. Trouble sleeping
      5. Inability to get air through nose during exercise
  4. Compare the valuation of the health state of CRS, in patients with CRS who have failed medical therapy and elected to have endoscopic sinus surgery, to the health state valuation of patients with other chronic disease. Select which health states are valued higher (better), and which are valued lower (worse) than having CRS:5
    1. End stage renal disease (ESRD) on hemodialysis 
    2. Moderate chronic obstructive pulmonary disease (COPD)
    3. Congestive heart failure (CHF)
    4. Parkinsons disease
    5. Coronary artery disease (CAD) without medications
    6. Moderately severe hearing loss
       
References 
  1. Alobid I, Benitez P, Bernal-Sprekelsen M, et al. Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy. 2005 Apr;60(4):452-458.
  2. Benninger MS, Senior BA. The development of the Rhinosinusitis Disability Index. Arch Otolaryngol Head Neck Surg. 1997 Nov;123(11):1175-1179.
  3. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009 Oct;34(5):447-454.
  4. Stewart MG, Witsell DL, Smith TL, Weaver EM, Yueh B, Hannley MT. Development and validation of the Nasal Obstruction Symptom Evaluation (NOSE) scale. Otolaryngol Head Neck Surg. 2004 Feb;130(2):157-163.
  5. Soler ZM, Wittenberg E, Schlosser RJ, Mace JC, Smith TL. Health state utility values in patients undergoing endoscopic sinus surgery. Laryngoscope. 2011 Dec;121(12):2672-2678.
     

Imaging

Learning Objectives 
  1. Recognize that CT is the diagnostic imaging modaulity of choice for evaluating suspected CRS.1
  2. Describe indications for CT imaging in CRSwNP.
  3. Identify instances in which an MRI may aid in the evaluation of a patient with CRSwNP.2
  4. Be familiar with the Lund-Mackay scoring system of CRS severity (see further information under staging section).3
References 
  1. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): Adult Sinusitis Executive Summary. Otolaryngol Head Neck Surg. 2015 Apr;152(4):598-609.
  2. Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016 Feb;6 Suppl 1:S22-209.
  3. Lund VJ, Mackay IS. Staging in rhinosinusitus. Rhinology. 1993 Dec;31(4):183-184.
     

Pathology

Learning Objectives 
  1. Name most common histopathologic type of nasal polyp.1
  2. Describe the histologic appearance of an eosinophilic nasal polyp specimen stained with hematoxylin and eosin (H&E).1
  3. Choose which of the following cell types are increased in nasal tissue of patients with CRSwNP relative to CRSsNP (antibody specific).2
    1. Activated T-lymphocytes (CD25)
    2. Plasma cells (CD138)
    3. Neutrophils (MPO)
    4. Naïve B lymphocytes (CD20)
    5. T-lymphocytes (CD3)
    6. Eosinophils
    7. Macrophages (CD68)
  4. What inflammatory cell type and cytokine is elevated in nasal tissue of patients with nasal polyposis and CF relative to patients with CRSwNP.2
References 
  1. Hellquist HB. Nasal polyps update. Histopathology. Allergy Asthma Proc.1996 Sept-Oct;17(5):237-242.
  2. Van Zele T, Claeys S, Gevaert P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006 Nov;61(11):1280-1289.

Treatment

Learning Objectives 

Be familiar with medical and surgical treatments for CRSwNP (see sections for medical and surgical therapies below).1

References 
  1. Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016 Feb;6 Suppl 1:S22-209.

Medical Therapies

Learning Objectives 
  1. Know the role of saline irrigations in CRSwNP management.1
    1. Evidence for benefit over placebo and as a useful adjunct to other treatments
    2. Inferior to inhaled nasal coritcosteroids (INCS)
    3. High volume normal saline irrigations are better than low volume
    4. Hypertonic solutions may have a greater effect on objective measurements than hypotonic solutions2,3
  2. Know the options for topical therapy of CRSwNP, evidence for benefits, potential risks, and overall recommendations.4,7
    1. Intranasal corticosteroids (ICNS)
      1. Types of corticosteroids used for CRSwNP:
        1. Fluticasone propionate
        2. Beclomethasone dipropionate
        3. Betamethasone sodium phosphate
        4. Mometasone furoate
        5. Flunisolide
        6. Budesonide
        7. Triamcinolone
      2. Evidence
      3. Risks
      4. Recommendations
    2. Antifungals8,9
      1. Evidence
  3. Know the options for oral therapy of CRSwNP, evidence for benefits, potential risks, and overall recommendations.10
    1. Antifungals11
      1. Evidence for efficacy
      2. Side-effects 
      3. Length of treatment
    2. Oral steroids12-15
      1. Evidence for efficacy
      2. Side-effects 
      3. Length of treatment
    3. Non-macrolide antibiotics16
      1. Evidence for efficacy
      2. Side-effects 
      3. Length of treatment
    4. Macrolide antibiotics16,17
      1. Evidence for efficacy
      2. Side-effects 
      3. Length of treatment
    5. Anti-leukotriene therapy18,19
      1. Evidence for efficacy
      2. Side-effects 
      3. Length of treatment
    6. Aspirin desensitization for patients with AERD
      1. Evidence for efficacy20
      2. Side-effects and compliance20,21
      3. Considerations prior to initiating therapy (pulmonary)
      4. Length of maintenance therapy22
  4. Identify which additional medical therapy should be considered for AERD and CRSwNP which has evidence for improving symptoms in these patients, and when started prior to aspirin provocation testing may actually improve the safety of testing without impairing the diagnostic utility of the test?23
  5. Describe the role for a low-salicylate diet in patients with AERD and CRSwNP.24
  6. Be aware of growing evidence to support the potential use of biologic therapies such as monoclonal antibodies targeting the TH2 limb of the immune system.25,27
    1. IL-5
    2. IL-4R
    3. IgE
  7. Know the appropriate duration of medical therapy to complete prior to surgical intervention.28,29
References 
  1. Harvey R, Hannan SA, Badia L, Scadding G. Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD006394.
  2. van den Berg JW, de Nier LM, Kaper NM, et al. Limited evidence: higher efficacy of nasal saline irrigation over nasal saline spray in chronic rhinosinusitis--an update and reanalysis of the evidence base. Otolaryngol Head Neck Surg. 2014 Jan;150(1):16-21.
  3. Pynnonen MA, Mukerji SS, Kim HM, Adams ME, Terrell JE. Nasal saline for chronic sinonasal symptoms: a randomized controlled trial. Arch Otolaryngol Head Neck Surg. 2007 Nov;133(11):1115-20.
  4. Dingsor G, Kramer J, Olsholt R, Soderstrom T. Flunisolide nasal spray 0.025% in the prophylactic treatment of nasal polyposis after polypectomy. A randomized, double blind, parallel, placebo controlled study. Rhinology. 1985 Mar;23(1):49-58.
  5. Drettner B, Ebbesen A, Nilsson M. Prophylactive treatment with flunisolide after polypectomy. Rhinology. 1982 Sep;20(3):149-58.
  6. Holopainen E, Grahne B, Malmberg H, Makinien J, Lindqvist N. Budesonide in the treatment of nasal polyposis. Eur J Respir Dis Suppl. 1982;122:221-8.
  7. Jankowski R, Schrewelius C, Bonfils P, et al. Efficacy and tolerability of budesonide aqueous nasal spray treatment in patients with nasal polyps. Arch Otolaryngol Head Neck Surg. 2001 Apr;127(4):447-52.
  8. Weschta M, Rimek D, Formanek M, Polzehl D, Podbielski A, Riechelmann H. Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: a randomized, double-blind clinical trial. J Allergy Clin Immunol. 2004 Jun;113(6):1122-1128.
  9. Ebbens FA, Scadding GK, Badia L, et al. Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2006 Nov;118(5):1149-1156.
  10. Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016 Feb;6 Suppl 1:S22-209.
  11. Kennedy DW, Kuhn FA, Hamilos DL, et al. Treatment of chronic rhinosinusitis with high-dose oral terbinafine: a double blind, placebo-controlled study. Laryngoscope. 2005 Oct;115(10):1793-1799.
  12. Martinez-Devesa P, Patiar S. WITHDRAWN: Oral steroids for nasal polyps. Cochrane Database Syst Rev. 2016 Apr;4:CD005232.
  13. Martinez-Devesa P, Patiar S. Oral steroids for nasal polyps. Cochrane Database Syst Rev. Jul 06 2011(7):CD005232.
  14. Poetker DM, Jakubowski LA, Lal D, Hwang PH, Wright ED, Smith TL. Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013 Feb;3(2):104-20.
  15. Hissaria P, Smith W, Wormald PJ, 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 Jul;118(1):128-33.
  16. Soler ZM, Oyer SL, Kern RC, et al. Antimicrobials and chronic rhinosinusitis with or without polyposis in adults: an evidenced-based review with recommendations. Int Forum Allergy Rhinol. 2013 Jan;3(1):31-47.
  17. Varvyanskaya A, Lopatin A. Efficacy of long-term low-dose macrolide therapy in preventing early recurrence of nasal polyps after endoscopic sinus surgery. Int Forum Allergy Rhinol. 2014 Jul;4(7):533-541.
  18. Smith TL, Sautter NB. Is montelukast indicated for treatment of chronic rhinosinusitis with polyposis? Laryngoscope. 2014 Aug;124(8):1735-1736.
  19. Schaper C, Noga O, Koch B, et al. Anti-inflammatory properties of montelukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis. J Investig Allergol Clin Immunol. 2011;21(1):51-58.
  20. Fruth K, Pogorzelski B, Schmidtmann I, et al. Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease. Allergy. 2013;68(5):659-665.
  21. Baker TW, Quinn JM. Aspirin therapy in aspirin-exacerbated respiratory disease: a risk-benefit analysis for the practicing allergist. Allergy Asthma Proc. 2011 Sep-Oct;32(5):335-340.
  22. Gosepath J, Schafer D, Mann WJ. [Aspirin sensitivity: long term follow-up after up to 3 years of adaptive desensitization using a maintenance dose of 100 mg of aspirin a day]. Laryngorhinootologie. 2002 Oct;81(10):732-738.
  23. White A, Ludington E, Mehra P, Stevenson DD, Simon RA. Effect of leukotriene modifier drugs on the safety of oral aspirin challenges. Ann Allergy Asthma Immunol. 2006 Nov;97(5):688-693.
  24. Sommer DD, Rotenberg BW, Sowerby LJ, et al. A novel treatment adjunct for aspirin exacerbated respiratory disease: the low-salicylate diet: a multicenter randomized control crossover trial. Int Forum Allergy Rhinol. 2016 Apr;6(4):385-391.
  25. Gevaert P, Calus L, Van Zele T, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013 Jan;131(1):110-116 e111.
  26. Pinto JM, Mehta N, DiTineo M, Wang J, Baroody FM, Naclerio RM. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology. 2010 Sep;48(3):318-324.
  27. Gevaert P, Lang-Loidolt D, Lackner A, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006 Nov;118(5):1133-1141.
  28. Marple BF, Stankiewicz JA, Baroody FM, et al. Diagnosis and management of chronic rhinosinusitis in adults. Postgrad Med. 2009 Nov;121(6):121-139.
  29. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): Adult Sinusitis Executive Summary. Otolaryngol Head Neck Surg. 2015 Apr;152(4):598-609.
     

Pharmacology

Learning Objectives 
  1. Understand which topical steroids are most potent based on pharmacologic studies of potency, while recognizing the lack of data to support differences in clinical efficacy.1
  2. Which topical steroids are associated with the lowest rates of systemic absorption? Which are associated with higher rates?1
  3. Recognize the lack of evidence for clinical systemic effects of INCS (despite bioavailability of older agents), including the lack of identified changes in cortisol levels, nor significant changes in growth of children treated with INCS.2
  4. List the two most common side-effects of INCS therapy.
  5. Understand the mechanisms by macrolide antibiotics are believed to impact CRSwNP.3-5
  6. Understand the potential risks of macrolide therapy for CRSwNP.6
  7. Identify the respective mechanisms of the leukotriene inhibitors montelukast and zileuton.
  8. Zileuton: a selective 5-lipoxygenase enzyme inhibitor
  9. Montelukast: CysLT receptor antagonist
  10. Identify the particular adverse effect associated with zileuton, which is not associated with montelukust (montelukast having limited associated risks).7
References 
  1. Derendorf H, Meltzer EO. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications. Allergy. 2008 Oct;63(10):1292-1300.
  2. Welch KC, Thaler ER, Doghramji LL, Palmer JN, Chiu AG. The effects of serum and urinary cortisol levels of topical intranasal irrigations with budesonide added to saline in patients with recurrent polyposis after endoscopic sinus surgery. Am J Rhinol Allergy. 2010 Jan-Feb;24(1):26-28.
  3. Suzuki H, Shimomura A, Ikeda K, Oshima T, Takasaka T. Effects of long-term low-dose macrolide administration on neutrophil recruitment and IL-8 in the nasal discharge of chronic sinusitis patients. Tohoku J Exp Med. 1997 Jul;182(2):115-124.
  4. Wallwork B, Coman W, Mackay-Sim A, Cervin A. Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis. Laryngoscope. 2004 Feb;114(2):286-290.
  5. Peric A, Vojvodic D, Matkovic-Jozin S. Effect of long-term, low-dose clarithromycin on T helper 2 cytokines, eosinophilic cationic protein and the 'regulated on activation, normal T cell expressed and secreted' chemokine in the nasal secretions of patients with nasal polyposis. J Laryngol Otol. 2012 May;126(5):495-502.
  6. Wentzel JL, Soler ZM, DeYoung K, Nguyen SA, Lohia S, Schlosser RJ. Leukotriene antagonists in nasal polyposis: a meta-analysis and systematic review. Am J Rhinol Allergy. 2013 Nov-Dec;27(6):482-489.
  7. Reques FG, Rodriguez JL. Tolerability of leukotriene modifiers in asthma: a review of clinical experience. BioDrugs. 1999 Jul;11(6):385-394.

Surgical Therapies

Learning Objectives 
  1. Recognize the role for preoperative steroids (systemic and topical) in the surgical management of CRSwNP.
  2. Know the advantages and disadvantages of conservative approaches, minimally invasive sinus technique (MIST) and balloon dilation, compared to traditional endoscopic sinus surgery (ESS).1-3
  3. Understand the potential benefits of middle turbinate resection, the lack of apparent improvement in QOL indicators, and recognize the potential risks associated with loss of this landmark for revision sinus surgery.4,5
  4. Understand the potential role for image guidance in ESS, and it’s particular utility in difficult or revision cases, though also recognize that evidence for reduction of complications and improved outcomes with this technology is very limited.6
  5. Recognize the benefits of ESS for treatment of CRSwNP, and potential differences in post-operative outcomes compared to CRSsNP.7,8
References 
  1. Brumund KT, Graham SM, Beck KC, Hoffman EA, McLennan G. The effect of maxillary sinus antrostomy size on xenon ventilation in the sheep model. Otolaryngol Head Neck Surg. 2004 Oct;131(4):528-533.
  2. Catalano P, Roffman E. Outcome in patients with chronic sinusitis after the minimally invasive sinus technique. Am J Rhinol. 2003 Jan-Feb;17(1):17-22.
  3. Albu S, Tomescu E. Small and large middle meatus antrostomies in the treatment of chronic maxillary sinusitis. Otolaryngol Head Neck Surg. 2004 Oct;131(4):542-547.
  4. Soler ZM, Hwang PH, Mace J, Smith TL. Outcomes after middle turbinate resection: revisiting a controversial topic. Laryngoscope. 2010 Apr;120(4):832-837.
  5. Wu AW, Ting JY, Platt MP, Tierney HT, Metson R. Factors affecting time to revision sinus surgery for nasal polyps: a 25-year experience. Laryngoscope. 2014 Jan;124(1):29-33.
  6. Ramakrishnan VR, Orlandi RR, Citardi MJ, Smith TL, Fried MP, Kingdom TT. The use of image-guided surgery in endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013 Mar;3(3):236-241.
  7. Smith TL, Mendolia-Loffredo S, Loehrl TA, Sparapani R, Laud PW, Nattinger AB. Predictive factors and outcomes in endoscopic sinus surgery for chronic rhinosinusitis. Laryngoscope. 2005 Dec;115(12):2199-2205.
  8. Smith TL, Litvack JR, Hwang PH, et al. Determinants of outcomes of sinus surgery: a multi-institutional prospective cohort study. Otolaryngol Head Neck Surg. 2010 Jan;142(1):55-63.
  9. Patel ZM, Thamboo A, Rudmik L, Nayak JV, Smith TL, Hwang PH. Surgical therapy vs continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2017 Feb;7(2):119-127. 
     

Rehabilitation

Learning Objectives 
  1. Recognize the importance of post-operative cares following ESS to ensure an optimal result, and the literature supporting these practices.
    1. Outpatient debridement1
    2. Saline irrigations
    3. Intranasal corticosteroids
  2. Identify additional potential post-operative interventions which lack sufficient evidence of benefit to recommend, though are reasonable options for appropriate cases.
    1. Systemic corticosteroids 
    2. Oral antibiotics
    3. Packing and spacers2
  3. Know which post-operative interventions are actually recommended against due to lack of evidence for benefit and the potential for side-effects. 
    1. Topical decongestants 
    2. Mitomycin C3
References 
  1. Rudmik L, Soler ZM, Orlandi RR, et al. Early postoperative care following endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2011 Nov-Dec ;1(6):417-430.
  2. Lee JM, Grewal A. Middle meatal spacers for the prevention of synechiae following endoscopic sinus surgery: a systematic review and meta-analysis of randomized controlled trials. Int Forum Allergy Rhinol.  2012Nov ;2(6):477-486.
  3. Weldon CS. The Blalock-Hanlon operation: an anachronism. Ann Thorac Surg. 1987 Apr;43(4):448-449.
  4. Thamboo A, Patel ZM. Office Procedures in Refractory Chronic Rhinosinusitis. Otolaryngol Clin North Am. 2017 Feb;50(1):113-128. 
     

Staging

Learning Objectives 
  1. Be familiar with the Lund-Kennedy (LK) endoscopic staging system and the component categories scored with this system.1
    1. Nasal polyps
    2. Discharge
    3. Edema
    4. Scarring
    5. Crusting
  2. Describe the potential benefits of the Modified Lund-Kennedy staging system (MLK), and list the three components of the original LK system included in this modification.2
    1. Nasal polyps
    2. Discharge
    3. Edema
  3. Be familiar with the Lund-Mackay (LM) CT scoring system of CRS severity and its component categories3,4. Each sinus receives a score of 0, 1, or 2, with the exception of the ostiomeatal complex which is assigned a score of either 0 (not obstructed) or 2 (obstructed).
    1. 0: No opacification/abnormality
    2. 1: Partial opacification
    3. 2: Complete opacification
References 
  1. Lund VJ, Kennedy DW. Quantification for staging sinusitis. The Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995 Oct;167:17-21.
  2. Psaltis AJ, Li G, Vaezeafshar R, Cho KS, Hwang PH. Modification of the Lund-Kennedy endoscopic scoring system improves its reliability and correlation with patient-reported outcome measures. Laryngoscope. 2014 Oct;124(10):2216-2223.
  3. Lund VJ, Mackay IS. Staging in rhinosinusitus. Rhinology. 1993 Dec;31(4):183-184.
  4. Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict? Otolaryngol Head Neck Surg. 2007 Oct;137(4):555-561.

Case Studies

  1. A 15 year old girl presents with a history of constant sinus infections. A recent car accident, though with no significant injuries sustained, had brought the child to medical attention as CT imaging incedentaly revealed diffuse pan sinusitis. You note that the sinuses seem quite underdeveloped on this imaging. Her father states that the child always seems to be sick and they would like to get some medicine for the patient as well as her sibling who seems to have the same illness. What other history would be helpful in this case? What additional findings might you expect on endoscopy? How would you expect polyps in this disease process to differ from other polypoid sinusitis in regard to dominant cell types and inflammatory mediators? What additional testing would be useful? How would you approach management? 
  2. A 35 year old man presents with frequent sinus infections and upper respiratory illness. He endorses facial pressure and pain, congestion, and purulent nasal drainage for greater severity the past 6 months which fluctuates in severity but never seems to resolve. Some temporary improvement with antibiotics. He reports that he has always had frequent upper respiratory illnesses and cough. In asking about family history he notes that he and his wife have been attempting pregnancy for 12 months without success. What conditions are you considering based on the history? What should you look for on exam? What relevant imaging should you obtain? How would you make the diagnosis, and what would be the particular findings on pathology? 
  3. A 56 year old man presents with difficulty breathing through his nose, facial pressure, constant fatigue, a decreased sense of smell. He has has “the sinus” for over 4 months now and has been taking over the counter decongestants and allergy medications but can’t get rid of it. He saw his primary care provider and received an antibiotic twice which seemed to decrease symptoms for up to a week but then they returned again. Are symptoms alone sufficient to make your diagnosis? What would be your next step in the workup of this patient? What type of imaging might be helpful? Once you have made a diagnosis, what would you try first for treatment? What medical therapies could be helpful? When would you elect to proceed with surgery?
  4. A 53 year old woman with difficulty breathing through her nose and frequent sinus infections have been worsening over the past year. She has had daily asthma symptoms and uses an inhaled corticosteroid as well as a short acting beta agonist inhaler daily. She has had exacerbations requiring oral steroids about 1-2 times per year. She is followed by pulmonology and most recent pulmonary function tests demonstrated an FEV1 of 75%. In conversation about the patient’s recent travels to Hawaii she comments that although she enjoyed herself “she could never live there because her asthma and allergies were so bad.” She recounts a particularly severe asthma exacerbation after having a small amount of a pina colada.  What diagnosis seems most likely from the patient’s history? She is interested in allergy shots for suspected food allergies – how would you advise her on this and what recommendations would you make on diet modification? She is found to extensive nasal polyposis – what is the role of surgery? What is the role of medical therapy? How would you counsel her on aspirin desensitization in regard to her nasal polyps? 
References 
  1. Cardet JC, White AA, Barrett NA, et al. Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2014 Mar-Apr ;2(2):208-213.
  2. Fruth K, Pogorzelski B, Schmidtmann I, et al. Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease. Allergy. 2013;68(5):659-665.
  3. Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016 Feb;6 Suppl 1:S22-209.
  4. Orlandi RR, Wiggins RH, 3rd. Radiological sinonasal findings in adults with cystic fibrosis. Am J Rhinol Allergy. 2009 May-Jun ;23(3):307-311.
  5. Sommer DD, Rotenberg BW, Sowerby LJ, et al. A novel treatment adjunct for aspirin exacerbated respiratory disease: the low-salicylate diet: a multicenter randomized control crossover trial. Int Forum Allergy Rhinol. 2016 Apr;6(4):385-391.
  6. Van Zele T, Claeys S, Gevaert P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006 Nov;61(11):1280-1289.

Complications

Learning Objectives 
  1. Describe the process of orbital and skull base involvement from CRSwNP and risk of dural and periorbital involvement.
  2. Understand the difference in incidence of skull base and orbital involvement between allergic fungal rhinosinusitis (AFRS) and other CRSwNP and inflammatory sinusitis.1
  3. Be familiar with the risk of mucocele formation, most common site of occurrence, and the impact of surgical intervention on this risk. Recognize how a diagnosis of AERD could impact this risk.2
     
References 
  1. Ghegan MD, Lee FS, Schlosser RJ. Incidence of skull base and orbital erosion in allergic fungal rhinosinusitis (AFRS) and non-AFRS. Otolaryngol Head Neck Surg. 2006 Apr;134(4):592-595.
  2. Chobillon MA, Jankowski R. Relationship between mucoceles, nasal polyposis and nasalisation. Rhinology. 2004 Dec;42(4):219-224.

Review

Review Questions 
  1. How is the diagnosis of CRSwNP made?
  2. What conditions are associated with CRSwNP?
  3. Describe findings of CRSwNP on endoscopy and what other diagnoses should be considered in case of unilateral polyp.
  4. What is the common airway theory? How does this related to CRSwNP?
  5. What is the role of diagnostic imaging in the evaluation of a patient with CRSwNP?
  6. What medical therapies have efficacy for treatment of CRSwNP?
  7. How is CRSwNP felt to differ from CRSsNP on a molecular and histological level?
  8. What is the role of allergy and allergy treatment in CRSwNP?
  9. What are the major hypotheses for the underlying pathogenesis of CRSwNP?
  10. What genetic condition(s) should be considered in relation to CRSwNP?
  11. Is there a relationship between asthma and CRSwNP? Describe this relationship and how to approach treatment of patients with AERD.
References 
  1. Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. Feb 2016;6 Suppl 1:S22-209.
Resources 

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