Nasal Polyposis and its Management: Pathogenesis, Medical and Surgical Treatment

Preface
Acknowledgment
Contents
History of Nasal Polyposis
	1	 Introduction
	2	 The History of Rhinology and Nasal Polyps
	3	 Etiology and Pathophysiology
	4	 Diagnosis of Nasal Polyps
	5	 Treatment of Nasal Polyps
		5.1	 Medical Treatment
		5.2	 Surgical Treatment
	6	 Conclusions
	References
Epidemiology of Nasal Polyps
	1	 Introduction
	2	 Allergy
	3	 Asthma
	4	 Gender and Age
	5	 Genetics
	6	 Churg–Strauss Syndrome (CSS)
	7	 Intolerance to Nonsteroidal Anti-inflammatory Drugs
	8	 Gastroesophageal Reflux Disease (GERD)
	9	 Allergic Fungal Rhinosinusitis
	10	 Ethnicity and Geography
	References
Phenotypes and Endotypes of Nasal Polyps in the Asian Population
	1	 Endotypes of CRSwNP Based on Inflammatory Cellular Patterns
	2	 Eosinophilia Shift of Nasal Polyps in Asian Population
	3	 Diagnostic Criteria of ECRSwNP and Non-ECRSwNP
	4	 Prognosis of ECRSwNP/Non-ECRSwNP and Predictive Indicators
	5	 Endotypes of CRSwNP Based on Profiles of Key Cytokines
	References
Pathology of Nasal Polyps
	1	 Introduction
		1.1	 Normal Sinonasal Histology
			1.1.1	 Structural Components
			1.1.2	 Non-structural Components
	2	 Nasal Polyp Pathology
		2.1	 Chronic Rhinosinusitis with Nasal Polyps (CRSwNPs)
			2.1.1	 Macroscopic Pathology
			2.1.2	 Microscopic Pathology
	3	 Bone Changes
		3.1	 Mucus Histopathology, Including Eosinophilic Mucus
		3.2	 Antrochoanal Polyps
		3.3	 Non-inflammatory Polypoid Lesions
	4	 Conclusions
	References
B-Cell and T-Cell Immunity in Nasal Polyposis
	1	 Introduction
	2	 B Cells in Nasal Polyps
		2.1	 B-Cell Enrichment and Germinal Center-Like Reactions in Nasal Polyp Tissues
		2.2	 B-Cell-Mediated Pathogenicity in CRSwNPs
			2.2.1	 Superantigen-Mediated Activation of B Cells and Antibody Production
			2.2.2	 B-Cell Activation and Increased Autoantibody and Complement in Nasal Polyps
	3	 T Cells in Nasal Polyps
		3.1	 T-Cell Populations in Nasal Polyps
		3.2	 CD8+ T Cells are a Source of Cytokines in Nasal Polyps
		3.3	 CD4+ T Cells
			3.3.1	 Th1/Th17 Cell Polarization in Nasal Polyps
			3.3.2	 Th2 Cell Polarization in Nasal Polyps Promoted by Dendritic Cells and Sinonasal Epithelial Cell Signaling
			3.3.3	 T-Follicular Helper Cells Support Ectopic Lymphoid Structures Within Nasal Polyps
			3.3.4	 Regulatory T Cells
	4	 Summary and Future Directions
	References
Eosinophilic Chronic Rhinosinusitis with Nasal Polyps and the JESREC Study
	1	 Chronic Rhinosinusitis (CRS) in Japan from 1925 to 1995
	2	 The Appearance of Eosinophilic Sinusitis
	3	 Epidemiological Study of Eosinophilic Rhinosinusitis
	4	 Determination of the Cutoff Values for Tissue Eosinophil Counts
	5	 Determination of the JESREC Score
	6	 Severity Classification
	7	 Usefulness of the JESREC Study
	8	 Classification of Chronic Rhinosinusitis and Comparison with Europe and the United States
	9	 Next-Generation Sequencing Analysis
	10	 Periostin and ECRS
	11	 Protease Inhibitors and Eosinophilic Sinusitis
	12	 TRPV3 and Eosinophilic Sinusitis
	13	 Fibrin and ECRS
	14	 Eosinophils and ECRS
	15	 Conclusions
	References
Radiologic Imaging of Nasal Polyposis
	1	 Introduction
	2	 Radiologic Appearance of Sinonasal Polyps
	3	 Special Types of Sinonasal Polyps
	4	 Complications
	5	 Radiologic Differential Diagnosis
		5.1	 Acute Rhinosinusitis
		5.2	 Mucus Retention Cysts
		5.3	 Other Benign Masses
		5.4	 Malignancy
		5.5	 Dense Secretions
		5.6	 Cystic Fibrosis (CF)
	6	 Radiologic Modalities
	References
Pathogenesis and Pathophysiology of Nasal Polyps
	1	 Introduction
	2	 Adenoma and Fibroma Theory
	3	 Necrotizing Ethmoiditis Theory
	4	 Glandular-Cyst Theory
	5	 Mucosal Exudate Theory
	6	 Theory on Cystic Dilatation of the Excretory Duct of Nasal Glands and Vessel Obstruction
	7	 Blockade Theory
	8	 Peri-Phlebitis and Peri-Lymphangitis Theory
	9	 Glandular Hyperplasia Theory
	10	 Epithelial Rupture Theory
	11	 Mucous Glands in Nasal Polyps
	12	 Formation and Growth of Glands
	13	 Gland Degeneration
	14	 Cellular Infiltration in the Pathophysiology of Nasal Polyps
	References
Mucin Expression in Nasal Polyps
	1	 Introduction
	2	 Mucin Genes
	3	 Sources of Mucus Hyper-Secretion in Nasal Polyps
	4	 Studies of Mucin Gene Expression in Nasal Polyps
		4.1	 Techniques
		4.2	 Control Mucosa for Mucin Gene Studies in Nasal Polyps
		4.3	 Main Studies
	5	 Mucin Gene Expression in Nasal Polyps
		5.1	 General Mucin Gene Expression Profile
		5.2	 Individual Mucin Genes
			5.2.1	 MUC1
			5.2.2	 MUC2
			5.2.3	 MUC3 and 6
			5.2.4	 MUC4
			5.2.5	 MUC5AC
			5.2.6	 MUC5B and 7
			5.2.7	 MUC8
	6	 Steroids and Mucin Expression in Nasal Polyps
	7	 Discussion
	8	 Future Work
	References
Impairment of Nasal Epithelial Barrier Function in Nasal Polyps
	1	 Introduction
	2	 Histology and Physiological Functions of Nasal Epithelium
	3	 Histopathological and Pathogenic Alterations in Nasal Epithelium of Nasal Polyps
		3.1	 Epithelial Hyperplasia
		3.2	 Architectural and Functional Impairments of Ciliary Function
		3.3	 Overproduction of the Mucus
		3.4	 Impairment of Tight Junction
	4	 Conclusion
	References
Biofilms in Chronic Rhinosinusitis
	1	 Introduction
	2	 What Is a Biofilm?
	3	 Biofilms and Chronic Rhinosinusitis: What Is the Evidence?
	4	 Microbiology of Biofilms in Chronic Rhinosinusitis
	5	 Pathophysiology
	6	 Effect of Biofilms in Patients with Chronic Rhinosinusitis
	7	 Strategies for Biofilm Eradication
	8	 Conclusions
	References
Treatment of Nasal Polyposis with Biologics
	1	 Introduction
	2	 Targeting the IgE Pathway
	3	 Targeting the IL-5 Pathway
	4	 Targeting the IL-4/IL-13 Pathway
	5	 Other Biologics
	6	 Conclusion
	References
The Impact of the Microbiome in Chronic Rhinosinusitis with Nasal Polyps
	1	 Introduction: The Impact of CRSwNP
	2	 Recent Advances in Characterization of the Human Microbiome
	3	 Understanding Microbial Communities
	4	 The Microbiome of the Human Aerodigestive Tract
		4.1	 The Microbiome of the Nasal Cavity and Paranasal Sinuses
		4.2	 The Microbiome in CRS
	5	 The Microbiome in CRSwNP
		5.1	 Microbiome Perturbations in Patients with CRSwNP
		5.2	 The Role of Staphylococcus aureus in CRSwNP
	6	 Conclusions
	References
Staphylococcus aureus, Superantigens, and Nasal Polyps
	1	 Introduction
	2	 Inflammatory Mechanisms
	3	 Sinus Microbiome and Biofilms
	4	 Epithelial Barrier Dysfunction
	5	 Clinical Implications and Treatment
	6	 Summary
	References
Fungal-Induced Inflammation and Nasal Polyps
	1	 Introduction
	2	 Fungus Is Among Us
	3	 The Immune Response to Fungi
		3.1	 IgE-Mediated Allergy
		3.2	 Aspirin-Exacerbated Respiratory Disease (AERD)
	4	 The Destructive Power of Eosinophils
	5	 An Immunologic Defense?
	6	 Alternaria-Induced Eosinophil Degranulation
	7	 Summary
	References
Categorization of Nasal Polyps
	1	 Categorization by Clinical Profile
		1.1	 Symptom Scores
		1.2	 Computed Tomography (CT) Imaging
		1.3	 Nasal Endoscopy
		1.4	 Specific Nasal Polyp Scoring
		1.5	 Objective Measures of Nasal Function
	2	 Categorisation by Inflammatory Profile
		2.1	 Inflammatory Disease Associations
		2.2	 Histology and Culture
		2.3	 Inflammatory Cytokine Milieu and Endotyping
	3	 Categorization by Response to Therapy
	References
Endotyping of Nasal Polyposis
	1	 Introduction
	2	 Traditional Categorization of CRS by Phenotype: CRSsNP versus CRSwNP
	3	 Endotyping in CRS
		3.1	 Type 2 Endotype or “Eosinophilic CRS (eCRS)”
		3.2	 Non-Type 2 Endotypes
			3.2.1	 Type 1 Endotype
			3.2.2	 Type 3/17 Endotype
	4	 Endotype Biomarkers
		4.1	 Eosinophilia
		4.2	 IgE
		4.3	 Other Biomarkers
	5	 Clinical Associations with Endotype
		5.1	 Association Between Endotypes and Nasal Polyposis
		5.2	 Geographic and Genetic Variability in Endotypes
		5.3	 Association of Endotype with Clinical Features
		5.4	 Association of Endotypes with Asthma and Allergy
		5.5	 Association with Epithelial Barrier Function
	6	 Application of Endotypes to Treatment
		6.1	 Primary Diffuse Type 2: Central Compartment Atopic Disease (CCAD)
			6.1.1	 Immunotherapy
		6.2	 Primary Diffuse Type 2 CRS: Eosinophilic CRS (eCRS)
			6.2.1	 Corticosteroids
			6.2.2	 Biologics
		6.3	 Primary Diffuse Non-Type 2 CRS: Type 1 or Type 3 Airway Inflammation
			6.3.1	 Macrolides
	7	 Limitations of Endotyping
		7.1	 Endotype Definitions
		7.2	 Endotype Biomarkers
	8	 Conclusion
	References
Nasal Polyposis and Nonsteroidal Anti-inflammatory Drug-Exacerbated Respiratory Disease
	1	 Introduction
	2	 Histopathology
	3	 Bronchial Hyperreactivity, Asthma, and NERD
	4	 Clinical Features, Associated Conditions, and Quality of Life
	5	 Diagnosis of AI and BHR
	6	 Treatment
	References
Allergic Fungal Sinusitis
	1	 Introduction/History
	2	 Epidemiology and Microbiology
	3	 Clinical Presentation
	4	 Diagnostic Criteria
	5	 Radiologic Features
	6	 Pathophysiology
	7	 Treatment
	8	 Natural Course
	References
Vasculitis Including Churg–Strauss Syndrome
	1	 Introduction
	2	 Vasculitic Diseases
		2.1	 Small-Vessel Vasculitis (SVV)
			2.1.1	 Granulomatosis with Polyangiitis
			2.1.2	 Eosinophilic Granulomatosis with Polyangiitis
			2.1.3	 Microscopic Polyangiitis (MPA)
		2.2	 Immune Complex Small-Vessel Vasculitis (SVV)
			2.2.1	 Cryoglobulinemic Vasculitis (CV)
		2.3	 Medium-Vessel Vasculitis (MVV)
			2.3.1	 Polyarteritis Nodosa (PAN)
	References
Cystic Fibrosis Chronic Rhinosinusitis
	1	 Introduction
	2	 Epidemiology of Chronic Rhinosinusitis in Cystic Fibrosis
	3	 Etiology
		3.1	 Genetics
		3.2	 Microbiology
		3.3	 Allergy
	4	 Pathophysiology
	5	 Clinical Presentation
	6	 Investigations
		6.1	 Radiology
	7	 Management
		7.1	 Medical
			7.1.1	 Ibuprofen
			7.1.2	 Dornase Alfa
		7.2	 Surgery
			7.2.1	 Extent of Surgery
		7.3	 Novel Treatments
			7.3.1	 CFTR Modulator Therapy
			7.3.2	 Antibiofilm Therapies
		7.4	 Management of Nasal Polyps Prior to Lung Transplantation
	8	 Conclusion
	References
Nasal Polyposis in Children: A Differential Diagnosis and Algorithm
	1	 Introduction
	2	 Antrochoanal Polyp
	3	 Cystic Fibrosis
	4	 Encephaloceles or Meningoencephalocele
	5	 Idiopathic Nasal Polyposis
	6	 Primary Ciliary Dyskinesia (PCD)
	7	 Saccharin Test
	8	 Ciliary Beat Frequency
	9	 Electron Microscopy
	10	 Immunodeficiency
	11	 Allergic Aspergillosis
	12	 Tumours
	References
Olfaction and Nasal Polyposis
	1	 Introduction
		1.1	 Bullet Messages
	2	 Impaired Olfaction: An Important Primary Symptom in CRS with Nasal Polyposis
	3	 Clinical Olfactory Testing
	4	 Taste and Smell
	5	 Subjective Test Methods
	6	 Trigeminal Nerve Assessment
	7	 Objective Test Methods
		7.1	 Bullet Messages
	8	 Nasal Airflow Patterns and Olfaction
		8.1	 Bullet Messages
	9	 Location of the Olfactory Epithelium
		9.1	 Bullet Messages
	10	 The Medical Management of Disordered Smell in CRS with Nasal Polyposis
	11	 Sinus Surgery and Olfaction in CRS with Nasal Polyposis
	12	 Tailor the Surgery to the Extent of the Problem
		12.1	 Bullet Messages
	13	 Impact of Endoscopic Sinus Surgery on Olfactory Function in CRS with Nasal Polyposis
		13.1	 Bullet Messages
	14	 Conclusions and Perspectives
	References
Sinonasal Innate Immunity
	1	 Introduction
	2	 The Nose and Paranasal Sinuses as the First Defenders of the Airways
	3	 The Nasal Cycle
		3.1	 Sneezing
		3.2	 Mucociliary Clearance and the Structure of the Respiratory Mucosa
		3.3	 Sinonasal Mucus and Mucus Production
	4	 Regulation of the Mucociliary Transport
	5	 Patterns of Sinonasal Mucociliary Clearance
	6	 The Role of Antimicrobial Products in Sinonasal Mucus
	7	 Conclusion
	References
Relapses After Surgery and Their Prevention
	1	 Introduction
	2	 Clinical Prevention
	3	 Prevention of Eosinophilic Inflammation
	4	 Prevention of Changes in Arachidonic Acid Metabolism
	5	 Prevention of Edema Formation
	6	 Prevention of Tissue Growth/Remodeling
	7	 Antimicrobial Prevention
	8	 Antifungal Prevention
	References
Cortisone Therapy in Nasal Polyposis
	1	 Introduction
	2	 Intranasal Steroids (INS)
		2.1	 Postoperative Use of Topical Corticosteroids
		2.2	 Side Effects of Intranasal Steroids
		2.3	 Oral Corticosteroids and Maximal Medical Therapy
	3	 Perioperative Use of Oral Corticosteroids
	4	 Risks and Side Effects of Oral Corticosteroids
		4.1	 Risks of Corticosteroid Use
	References
Antifungal Treatment (Topical/Systemic)
	1	 Introduction
	2	 Topical Antimycotics
	3	 Systemic Oral Antimycotics
	4	 Antimycotics After Endoscopic Sinus Surgery
	5	 Effects of Amphotericin B
	6	 Side Effects of Antimycotics
	7	 Conclusions
	References
Antibiotic Treatment (Topical/Systemic)
	1	 Background
	2	 Potential Therapeutic Actions of Antibiotic Agents
	3	 Topical Intranasal Antibiotic Agents (Table 1)
	4	 Systemic Antibiotic Agents
		4.1	 Do Short-Term Antibiotic Treatment Confer a Benefit? (Table 2)
		4.2	 How Do Different Antibiotics Compare? (Table 2)
		4.3	 Do Long-Term Macrolide and Other Antibiotic Treatments Confer a Benefit? (Table 3)
	5	 Antibiotic Agents after Endoscopic Sinus Surgery (Tables 1 and 3)
	6	 Side Effects of Antibiotic Agents
	7	 Conclusions
	References
Aspirin Intolerance
	1	 Introduction
	2	 Postoperative Care and Long-Term Medical Management to Prevent Recurrence
	3	 Characteristics of AI in Polypous CRS
		3.1	 Role of an In Vitro Assay
	4	 Aspirin Desensitization
	5	 Implications of Eicosanoid Imbalance on the Pathophysiology of Nasal Polyps
	6	 Conclusion
	References
Where Are We in the Medical Treatment of CRS with Nasal Polyps/Eosinophilic Chronic Rhinosinusitis
	1	 Introduction
	2	 Corticosteroids (1a) (See Also “Antibiotic Treatment (Topical/Systemic)”)
	3	 Saline Irrigation (1a)
	4	 Aspirin Treatment After Desensitization (ATAD) with Oral Aspirin in NSAID-Exacerbated Respiratory Disease (N-ERD) (Ia)
	5	 Biologics
		5.1	 Omalizumab (Anti-IgE) (1b)
		5.2	 Meoplizumab (Anti-Il-5) (1b)
		5.3	 Dupilumab (Anti IL-4/IL-13) (1a)
	6	 Overview
	References
Anesthetic Management in Nasal Polypectomy
	1	 Anesthetic Management in Nasal Polypectomy
	2	 Pathophysiology and Clinical Course of Samter’s Triad
	3	 Leading Features of Anesthesia Management
		3.1	 Asthma
		3.2	 Pain Management
		3.3	 Anesthesia for Endoscopic Sinus Surgery (ESS)
		3.4	 Total Intravenous Anesthesia (TIVA) vs. Inhalational Anesthesia
		3.5	 Nasal Polypectomy in Childhood
	References
Surgical Treatment of Nasal Polyposis
	1	 Introduction
	2	 Pathogenesis
		2.1	 Nasal Polyps
		2.2	 Antrochoanal Polyps
	3	 Examination
	4	 Imaging Studies
		4.1	 Computed Tomography
		4.2	 Magnetic Resonance Imaging
	5	 Surgical Therapy
		5.1	 General Principles
		5.2	 Functional Endoscopic Sinus Surgery
		5.3	 Image-Guided Surgery
		5.4	 Surgical Steps
		5.5	 Special Situations
			5.5.1	 Deviated Nasal Septum
			5.5.2	 Concha Bullosa
	6	 Postoperative Management
		6.1	 Steroid Injection
	7	 Conclusions
	References
Nasalisation in the Surgical Treatment of Nasal Polyposis
	1	 Introduction
	2	 Philosophy of the Nasalisation Surgical Procedure
	3	 Nasalisation Technique
		3.1	 Anatomical Considerations
		3.2	 Set-Up
		3.3	 Surgical Dissection (Video)
		3.4	 Post-operative Care
	4	 Results
		4.1	 Improvement in Symptoms and Quality of Life
		4.2	 Stabilisation of the Disease-Specific Evolution
		4.3	 Avoiding Recurrence of Nasal Polyps
		4.4	 Complications
	5	 Discussion: Controlling the Underlying Pathophysiological Mechanism
	References
Reasons for Failure and Complications of Surgery in Diffuse Nasal Polyposis
	1	 Postoperative Care
	2	 Nasal Polyposis in Children
	3	 Complications
	4	 Conclusion
	References
Nasal Polyposis: Aggressive Sinus Marsupialization Including the Frontal Drillout (Modified Lothrop) Procedure
	1	 Introduction
	2	 Evaluation of the Frontal Sinus Complexity
	3	 Frontal Drillout/Endoscopic Modified Lothrop/Draf 3 Procedure
	4	 Results of Frontal Sinus Surgery
		4.1	 Restenosis and Risk Factors
		4.2	 Frontal Drill-Out Outcomes
		4.3	 The Middle Turbinate in Nasal Polyposis
	5	 Surgical Plan
	6	 Surgical Technique
		6.1	 Management of Other Diseased Sinuses
		6.2	 Frontal Recess Clearance
		6.3	 Grade 6 EFSS, Frontal Drillout, EMLP, Draf 3
	7	 Conclusion
	References
Evaluation of Surgical Treatments
	1	 Introduction
	2	 New EPOS2020 Classification for CRS
	3	 Evidence-Based Surgical Treatment
	4	 How Do We Measure the Effectiveness of Sinus Surgery
	5	 Efficacy of Surgery in Diffuse Bilateral Type 2 CRS
		5.1	 CRSwNP: Which Evidence Do We Have to Operate?
		5.2	 Indications for Surgery: What Evidence Do We Have for When to Operate in Patients with CRSwNP?
		5.3	 Functional Endoscopic Sinus Surgery vs. Polypectomy in Patients with CRSwNP
		5.4	 Revision Sinus Surgery in Patients with CRSwNP
		5.5	 Which Factors Predict Outcomes of Surgery in CRSwNP
		5.6	 Does the Type or Extent of Endoscopic Sinus Surgery Affect Outcomes in Patients with CRSwNP?
		5.7	 AFRS
	6	 Nasal Polyps in Secondary CRS
		6.1	 Diffuse Mechanical Secondary CRS
		6.2	 Cystic Fibrosis (CF)
		6.3	 Primary Ciliary Dyskinesia
		6.4	 Diffuse Inflammatory Secondary CRS
	References
Index