Chronic Rhinosinusitis: The mucosal concept

Preface
Contents
Contributors
1: Introduction
2: Epidemiology
2.1 Introduction
2.2 Variations in the Worldwide Prevalence of CRS
2.3 Risk Factors for CRS
2.4 Translation into Future Daily Practice
References
3: Quality of Life and Psychological Burden
3.1 Introduction
3.2 Psychometric Properties
3.2.1 Validity
3.2.2 Reliability
3.2.2.1 Test–Retest
3.2.2.2 Internal Consistency
3.2.3 Responsiveness
3.3 Patient Reported Outcomes (PRO) in CRS
3.3.1 Generic Questionnaires
3.3.2 Specific Questionnaires
3.3.2.1 SNOT-22: A Measure of Severity
3.3.2.2 SNOT-22: A Measure of Response to Medical Treatment
3.3.2.3 SNOT-22: A Measure of Response to Surgical Treatment
3.3.2.4 SNOT-22: A Measure of Response to Biologic Treatment
3.4 Translation into the Future Daily Practice
References
4: Genetics and Epigenetics
4.1 Heritability of CRS
4.2 Genetics of CRS
4.2.1 Candidate Gene Association Studies of CRS
4.2.2 Genome-Wide Association Studies of CRS
4.3 Epigenetics of CRS
4.3.1 DNA Methylation in CRS
4.3.2 Histone Modifications in CRS
4.3.3 Noncoding RNA in CRS
4.4 Translation into Future Daily Practice
References
5: Involvement of the Immune System in Airways Disease
5.1 Conclusions
References
6: T Cells and Group 2 Innate Lymphoid Cells 2
6.1 Introduction
6.2 Inflammatory Endotypes of CRS
6.3 Type 2 Cytokine-Induced Inflammation in Nasal Polyps
6.4 Th2 Cells
6.5 ILC2s
6.6 ILC2-Th2 Interaction in NPs
6.7 Conclusion and Translation into Future Daily Practice
References
7: B Cells and Plasma Cells
7.1 Introduction
7.2 B Cell
7.2.1 B Cell Development
7.2.2 B Cell Activation-Response to Antigen
7.2.3 Role of B Cells and Plasma Cells in CRS
7.3 CRSsNP
7.4 CRSwNP
7.4.1 Elevated B Cell Population in CRSwNP
7.4.2 Activation Mechanisms
7.5 Antibodies and Class Switching
7.5.1 Class Switching
7.5.2 Autoreactive Antibodies
7.5.3 IgE to Staphylococcus aureus
7.6 Conclusion
References
B Cell Glossary of Terms
8: Eosinophils
8.1 Clinical Manifestations and Diagnosis of Eosinophilic CRS
8.2 Eosinophil Development, Chemotaxis, and Activation in CRS
8.3 Functions of Eosinophils in CRS
8.3.1 Effector Functions
8.3.2 Extracellular Trap Formation and Charcot–Leyden Crystal Deposition
8.3.3 Other Roles of Eosinophils
8.4 Treatment Considerations
8.5 Translation into Future Daily Practice
References
9: Neutrophils
9.1 Clinical Manifestations of Neutrophilia in CRS
9.2 Neutrophil Recruitment and Activation in CRS
9.3 Functions of Neutrophils in CRS
9.4 Antibacterial Defense
9.5 Immune Regulation and Tissue Remodeling
9.6 Therapeutic Implications
9.7 Translation into Future Daily Practice
References
10: Remodeling Features
10.1 Introduction
10.2 The Features of Tissue Remodeling in Different Types of CRS
10.3 The Mechanism of Tissue Remodeling in CRS
10.4 Correlation Between Tissue Remodeling and Inflammation Patterns in CRS
10.5 Conclusion
References
11: Nasal Mucociliary Clearance
11.1 Introduction
11.2 Components of Mucociliary Clearance
11.3 Measurement of Mucociliary Clearance
11.4 Assessment of Ciliary Structure and Function
11.5 Mucociliary Clearance in Chronic Rhinosinusitis
11.6 Summary
References
12: Sinonasal Epithelium
12.1 Introduction
12.2 Multiple Epithelial Barrier Layers and Their Functions
12.2.1 The Supraepithelial Barrier
12.2.2 The Epithelial Cilia
12.2.3 Junctional Proteins and the Tightness of the Epithelial Cells
12.3 Interaction of the Epithelium and the Adaptive Immune System
12.3.1 Epithelial Cytokines
12.3.2 The Link Between Layers of Epithelial Barrier
12.3.3 Translation of the Mechanistic Knowledge into Daily Practice
References
13: Microbiology
13.1 Introduction
13.2 Bacterial Microbiota in CRS
13.3 Virome
13.4 Mycobiome
13.5 Interplay Between the Immune System and Microbes
13.6 Conclusions
13.7 Implications of Microbiome Equilibrium for Medical Practice
References
14: Staphylococcus aureus and Its Proteins
14.1 Interaction Between S. aureus and the Host
14.2 Colonization
14.3 Superantigens
14.4 S. aureus Proteases
14.5 δ-Toxin
14.6 Why Does S. aureus Drive Allergy?
14.7 Translation into Future Daily Practice
References
15: Viruses
15.1 Introduction
15.1.1 Epidemiology
15.2 Mechanisms
15.3 Antiviral Therapy
15.4 Translation into Future Daily Practice
References
16: Environmental and Allergic Triggers
16.1 Introduction
16.2 Environmental Triggers of CRS
16.3 Allergic Triggers of CRS
16.4 Conclusions
References
17: Dysfunctional Immune Regulatory System
17.1 Introduction
17.2 Immune Regulatory System
17.2.1 Congenital Immune System in Nasal Mucosa
17.2.2 Acquired Immune System in Nasal Mucosa
17.3 Dysfunctional Immune Regulation in Rhinosinusitis
17.3.1 Epithelial Dysfunction in CRS
17.3.2 Innate and Adaptive Inflammatory Responses Underlying the Pathogenesis of CRS
17.3.3 Eosinophilia and CRS
17.4 Restoration of Immune Regulation in Rhinosinusitis
17.4.1 The Regulatory Mechanism of Immune Dysregulation of CRS by Immunomodulators
17.4.2 The Regulatory Mechanism of Immune Dysregulation of CRS by Antibacterial Drugs
17.4.3 The Regulatory Mechanism of Antihistamine and Leukotriene Receptor Antagonism on Immune Dysregulation of CRS
17.4.4 The Regulatory Mechanism of Saline Irrigations on Immune Dysregulation of CRS
17.5 Conclusion
References
18: Chronic Rhinosinusitis with and Without Nasal Polyps
18.1 Introduction
18.2 Definition and Epidemiology
18.3 History and Physical Examination
18.3.1 History
18.3.2 Nasal Endoscopy
18.3.3 Imaging
18.4 Phenotypes of CRS
18.5 CRS Without Nasal Polyposis (CRSsNP)
18.6 CRS with Nasal Polyposis (CRSwNP)
18.7 Exogenous Factors in CRSwNP
18.7.1 Fungus
18.7.2 Bacteria and the Microbiome
18.7.3 Staphylococcus aureus Enterotoxin
18.7.4 Biofilms
18.7.5 Host Factors in CRSwNP
18.7.6 Immune Barrier Function
18.7.7 Eicosanoid Hypothesis
18.8 Comprehensive Overview of CRSwNP
18.9 Summary
References
19: Allergic Fungal Sinusitis
19.1 Introduction
19.2 Pathophysiology
19.3 Epidemiology and Microbiology
19.4 Clinical Presentation
19.5 Diagnostic Criteria
19.5.1 Eosinophilic Mucin
19.6 Radiologic Features
19.7 Treatment
19.8 Prognosis
19.9 Unanswered Questions About AFS
References
20: Type 2 Immune Reactions and Consequences
References
21: Regional Difference
References
22: Multimorbidities
22.1 Introduction
22.2 Allergic Rhinitis
22.3 Asthma
22.4 Non-Steroidal Anti-Inflammatory Drug (NSAID): Exacerbated Respiratory Disease
22.5 Gastroesophageal Reflux
22.6 Chronic Pulmonary Obstructive Disease
22.7 Bronchiectasis
22.8 Translation into Future Daily Practice
References
23: Clinical Diagnosis and Phenotypes
23.1 Aspirin-Exacerbated Respiratory Disease
23.1.1 Clinical Presentation and Diagnosis
23.2 Allergic Fungal Rhinosinusitis
23.2.1 Clinical Presentation and Diagnosis
23.3 Eosinophilic Granulomatosis with Polyangiitis
23.3.1 Clinical Presentation and Diagnosis
23.4 Cystic Fibrosis
23.4.1 Clinical Presentation and Diagnosis
23.5 Odontogenic Rhinosinusitis
23.5.1 Clinical Presentation and Diagnosis
23.6 Immunodeficiency
23.6.1 Clinical Presentation and Diagnosis
23.7 Primary Ciliary Dyskinesia
23.7.1 Clinical Presentation and Diagnosis
23.8 Conclusion
References
24: Imaging the Anatomic Landmarks for Safe FESS
24.1 Introduction
24.2 The Use of Imaging to Provide a “Roadmap” for FESS
24.3 CT Data Acquisition and Technique
24.4 The CT Evaluation of Nasal and Paranasal Sinus Anatomy for FESS, According to the Specific Surgical Plan, Which Follows the Four Lamellae Principle
24.5 Uncinectomy
24.6 Anterior Ethmoidectomy
24.7 Ethmoid Skull Base Height
24.8 Sphenoidotomy
24.9 Frontal Recess/Sinusotomy
24.10 Conclusion
References
25: Olfactory Function Assessment
25.1 Introduction
25.2 Subjective Smell Tests
25.2.1 Screening Tests
25.2.2 Smell Identification Tests
25.2.3 Smell Tests in Children
25.2.4 Threshold Tests
25.2.5 Objective Smell Tests
25.3 Translation into Future Daily Practice
References
26: Local and Systemic Biomarkers
26.1 Question-Based Selection of Nasal Biologic Samples and Its Optimal Collecting Techniques (Table 26.1)
26.2 Correlation Between Local and Systemic Biomarkers
26.3 Biomarkers for Endotype Identification
26.4 Biomarkers to Monitor Therapeutic Responses
26.5 Future Multi-omics Biomarkers in Precision Medicine
References
27: Benign Tumors of the Nose and Sinuses
27.1 Osteoma is the Most Common Benign Sinonasal Tumor
27.2 Juvenile Angiofibroma
27.3 Schwannomas
27.4 (Acquired) Lobular Capillary Hemangioma (Pyogenic Granuloma)
References
28: Sinonasal Inverted Papilloma
28.1 Introduction
28.2 Etiology
28.3 Clinical Features
28.4 Pathology
28.5 Imaging
28.6 Conclusions
References
29: Malignant Tumors of the Nose and Sinuses
References
30: Pediatric Chronic Rhinosinusitis: View from Europe
30.1 Prevalence of Pediatric Chronic Rhinosinusitis
30.2 Quality of Life
30.3 Development of the Sinuses
30.4 Clinical Diagnosis and Definition of PCRS
30.4.1 Definition
30.4.2 Diagnostic Tools
30.5 Predisposing Factors
30.5.1 Anatomical Factors in PCRS
30.5.2 Environmental Factors
30.5.3 Comorbid Diseases in PCRS
30.5.4 Cystic Fibrosis and PCD
30.6 Pathophysiology
30.6.1 Genetics
30.6.2 Inflammatory Mechanisms
30.6.3 Bacteriology
30.7 Medical Treatment
30.8 Surgery for PCRS
30.8.1 Adenoidectomy, Sinus Irrigation, and Balloon Sinuplasty
30.8.2 Functional Endoscopic Sinus Surgery
30.9 Translation into Future Daily Practice
References
31: Pediatric Chronic Sinusitis: View from China
31.1 Introduction
31.2 Clinical Characteristics in Children
31.2.1 Definition
31.2.2 Symptoms
31.2.3 Physical Examination
31.2.4 Diagnostic Tests
31.2.5 Imaging
31.3 Treatment (Essentials of Pediatric Endoscopic Surgery and Medicine) and Prognosis
31.3.1 Introduction
31.3.2 Medical Treatment of Chronic Rhinosinusitis in Children
31.3.3 Surgical Treatment
31.4 Prognosis
31.5 Conclusions
References
32: Wegener’s Granulomatosis
32.1 Introduction
32.2 Pathogenesis
32.3 Clinical Manifestations
32.4 Diagnosis
32.5 Treatment
32.6 Summary
References
33: IgG4-Related Disorders
33.1 Introduction
33.2 Pathogenesis
33.2.1 Genetic Phenotypes
33.2.2 Autoimmunity
33.2.3 Environment
33.2.4 Allergy
33.3 Clinical Features
33.3.1 Symptoms
33.3.2 Imaging Features
33.3.3 Laboratory Examinations
33.3.4 Histopathological Features
33.3.5 Diagnostic Criteria
33.4 Treatment
33.5 Translation into Future Daily Practice
References
34: Eosinophilic Granulomatosis with Polyangiitis
34.1 Pathogenesis
34.2 Pathology
34.3 Main Clinical Manifestations
34.4 Laboratory Findings
34.5 Diagnosis
34.6 Treatment
References
35: Oral Corticosteroids
35.1 Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
35.2 Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
35.3 The Dose of Oral Corticosteroid in Chronic Rhinosinusitis
35.4 Risks of Oral Corticosteroid
35.5 Bone Metabolism
35.6 Adrenal Suppression
35.7 Gastrointestinal
35.8 Others
35.9 Translation into the Future Daily Practice
References
36: Nasal Spray Corticosteroids
36.1 Mechanism
36.2 Efficacy
36.3 Safety
36.4 Limits
References
37: Nebulization Corticosteroids
37.1 History, Categories, and Principle of Nebulization
37.2 Mechanisms Underlying Efficacy of Steroid Nebulization in the Treatment of CRS
37.3 The Efficacy and Safety of Steroid Nebulization in CRS
37.4 Nebulization of Other Drugs in CRS
37.5 Translation into the Future Daily Practice
References
38: Steroid-Eluting Stent Placement
38.1 Introduction
38.2 Review of Steroid-Eluting Stents
38.3 Efficacy of Steroid-Eluting Stents
38.4 Safety of Steroid-Eluting Stents
38.5 Use of Stents in the Frontal Sinus Ostia
38.6 Conclusions and Future Perspectives
References
39: Steroid Infiltrated Packing Materials
39.1 Translation into Future Daily Practice
References
40: Corticosteroids Resistance
40.1 Introduction
40.2 Mechanism
40.3 Treatment
References
41: Leukotriene Receptor Antagonists
41.1 Translation into Practice
References
42: Antihistamine
42.1 Conclusions
References
43: Antibiotics
43.1 Introduction
43.2 Antibiotics Treatment Strategies for Patients with CRS
43.3 Elimination of Bacterial Infections During Acute Exacerbations of CRS with Antibiotics
43.4 Control of Persistent Inflammation During Chronic Phase of CRS with Antibiotics
43.5 Combination with Other Non-antibiotic Medical Treatment: Add Treatment Benefit or Similar Efficacy
43.6 Antibiotics, After Endoscopic Sinus Surgery: Achieve Long-Term Surgical Outcome
43.7 Side Effects of Antibiotics
43.8 Conclusions
43.9 Implications for Medical Practice
References
44: Decongestant and Nasal Irrigation
44.1 Decongestant
44.2 Nasal Irrigation
44.3 For Future Daily Practice
References
45: Probiotics, Bacterial Lysates, and Proton Pump Inhibitors
45.1 Introduction
45.2 Microbiota Dysbiosis in the Pathogenesis of CRS
45.3 Probiotics in the Treatment of CRS
45.4 Bacterial Lysates in the Treatment of CRS
45.5 Proton Pump Inhibitors (PPIs) in the Treatment of CRS
45.6 Conclusions
References
46: Impact of Endotyping on the Indication for Surgery
References
47: Surgical Procedures
47.1 Introduction
47.2 Preoperative Evaluation
47.3 Endoscopic Sinus Surgery: Surgical Approach
47.3.1 Initial Assessment and Exposure
47.3.1.1 Nasal Endoscopy
47.3.1.2 Septoplasty
47.3.1.3 Concha Bullosa Resection
47.3.2 Performing ESS
47.3.2.1 Uncinectomy
47.3.2.2 Maxillary Antrostomy
47.3.2.3 Ethmoidectomy
47.3.2.4 Sphenoid Sinusotomy
47.3.2.5 Frontal Sinusotomy
47.4 Conclusion
References
48: Reboot Surgery
References
49: Complications of Endoscopic Sinus Surgery
49.1 Causes of Complications in ESS
49.2 Classification of Complications in ESS
49.2.1 Orbital Complications
49.2.1.1 Lamina Papyracea Injury and Orbital Fat Exposure
49.2.1.2 Intraorbital Hematoma
49.2.1.3 Eye Muscle Injury
49.2.1.4 Optic Nerve Injury
49.2.2 Intracranial Complications
49.2.2.1 Cerebrospinal Fluid (CSF) Leakage
49.2.2.2 Carotid Injury
49.2.3 Postoperative Complications
49.2.3.1 Intracranial Infection
49.2.3.2 Epistaxis
49.2.3.3 Cavity Synechiae
49.2.3.4 Secondary Lacrimal Duct Obstruction
49.2.3.5 Secondary Sinusitis
49.2.3.6 Bone Remodeling
49.3 Conclusions
References
50: Peri-operative Management
50.1 Introduction
50.2 Preoperative Objective Assessment by Endoscopy and CT Scan
50.3 Preoperative Control of General Conditions Such as Hypertension, Diabetes, Coagulation Dysfunction, and Asthma
50.4 Bacteriology Before Surgery
50.5 Biopsy Before Surgery
50.6 Postoperative Management of Nasal Packs
50.7 Postoperative Douching
50.8 Follow-Up and Postoperative Endoscopic Reexamination
50.9 Follow-Up and Postoperative Evaluation
References
51: Surgery Outcome and Predictors
51.1 Symptoms and Quality of Life Improvement and Prediction
51.2 Polyp Recurrence and Revision Surgery and Prediction
51.3 Difficult-to-Treat CRS and Uncontrolled Disease and Prediction
References
52: Biologics in Chronic Rhinosinusitis with Nasal Polyps
52.1 Anti-IL5 Strategies
52.2 Anti-IgE
52.3 Anti-IL-4 Receptor Alpha Antagonism
52.4 Biologics in Clinical Practice
References
53: Integrated Care Pathways
53.1 Definitions: How to Define Uncontrolled Severe Type 2 CRSwNP with Comorbid Disease?
53.1.1 The EUFOREA Group Agreed on the Following Definitions
53.1.2 Endotyping in Uncontrolled Severe CRSwNP Based on Clinical Signs and Biomarkers
53.1.3 Sinus Surgery or a Biologic Approach, or a Combination of Both?
53.2 Evaluation of Efficacy vs. Adverse Events/Complications for Surgery and Biologics
53.2.1 Efficacy of Biologics in Phase 3 Trials
53.2.2 Efficacy of Surgery from Available Literature
53.2.3 AEs in Phase 3 Trials with Biologics
53.2.4 Complications of Sinus Surgery
53.2.5 The Patient Perspective on Biologics
53.3 Specific Considerations for Biologics
53.4 Limitations for the Selection of a Biologic Drug
53.5 Evaluation of the Clinical Response to a Biologic Within 6 Months of Treatment: “Continue or Stop” Rules
53.6 “Continue or Stop” Rules
53.7 The Treatment Response Has Been Verified Within 6 Months
53.8 Treatment Evaluation After 12 Months
53.9 Approach in Patients with CRSwNP and Asthma/N-ERD
References
54: Unmet Needs
Index