Nasal Physiology and Pathophysiology of Nasal Disorders

Preface
Contents
1: Mucus, Goblet Cell, Submucosal Gland
1.1 Introduction
1.2 Mucus Composition
1.3 Mucin Genes
1.4 Goblet Cells and Submucosal Glands
1.5 Regulation of Mucin Secretion
1.5.1 Mucin Production
1.5.2 Mucin Exocytosis
1.5.3 Mucin Glycosylation
1.6 Pathophysiological Mucus Hypersecretion
1.6.1 Chronic Rhinosinusitis (CRS)
1.6.2 Allergic Rhinitis (AR)
1.7 Therapeutic Strategies to Inhibit Mucus Hypersecretion
1.7.1 Surgical Managements
1.7.2 Mucolytic and Mucokinetic Agents
1.7.3 Macrolide Antibiotics
1.7.4 Anti-inflammatory Agents
1.8 Conclusions
References
2: The Coagulation System and Rhinosinusitis
2.1 Introduction
2.2 The Coagulation System
2.2.1 The Coagulation Cascade
2.2.2 Regulators
2.2.3 Fibrinolysis
2.3 Activation of the Coagulation System in Rhinosinusitis
2.3.1 Tissue Factor (TF)
2.3.2 Thrombin
2.4 Coagulation Contributes to the Pathophysiology of Rhinosinusitis
2.4.1 Coagulation Factors and Protease-Activated Receptors (PARs)
2.4.2 Tissue Remodeling
2.4.3 Allergic Rhinitis (AR)
2.4.4 Excessive Fibrin Deposition
2.5 Anticoagulant Treatment of Rhinosinusitis
2.5.1 Heparin
2.5.2 Activated Protein C (APC)
2.6 Conclusions
References
3: Cilia, Ciliary Movement, and Mucociliary Transport
3.1 Cilia
3.1.1 General Description
3.1.1.1 Ciliated Cells
3.1.1.2 Cilia
3.1.2 Ciliary Structure
3.1.3 Structural Components: Dynein
3.1.4 Structural Abnormalities
3.1.5 Genetic Heterogeneity of PCD
3.2 Ciliary Movement
3.2.1 Ciliary Beat Cycle
3.2.2 Factors Influencing Ciliary Activity
3.2.3 Abnormal Beating Patterns in the Context of PCD
3.3 Mucociliary Transport
3.3.1 Structural and Functional Organization
3.3.2 Mucociliary Transport
3.4 Conclusion
References
4: Functional Defense Mechanisms of the Nasal Respiratory Epithelium
4.1 Overview
4.2 Anatomic Barrier
4.2.1 Epithelium Structure
4.2.2 Cilia and Mucus
4.2.3 Mucociliary Clearance
4.2.3.1 Diseases Affecting Mucociliary Clearance
4.2.4 Epithelial Integrity
4.2.4.1 Diseases Affecting Epithelial Integrity
4.3 Immunologic Barrier Function of the Sinonasal Epithelium
4.3.1 Receptor Molecules
4.3.2 Host Defense Molecules
4.3.3 Epithelial Chemokines and Cytokines
4.3.4 Epithelial Co-stimulatory Molecules and Inflammatory Enzymes
4.3.5 Cells of the Innate Immune System
4.3.6 Adaptive Immunity
4.3.7 T Cells and Cytokine Response
4.3.8 T Cell Response Modulation
4.3.9 NKT Cells, NK Cells, Cytotoxic T Cells, and Memory T Cells
4.4 Conclusion
References
5: Local B-Cell and T-Cell Populations in the Pathophysiology of Chronic Rhinosinusitis with Nasal Polyposis
5.1 Introduction
5.2 Role of T Cells in CRSwNP Pathophysiology
5.2.1 Th1/Th17 Immune Cells in Nasal Polyps
5.2.2 Th2 Immune Cells in Nasal Polyps
5.2.3 T Follicular Helper Cells in Nasal Polyps
5.2.4 Regulatory T Cells in Nasal Polyps
5.3 Role of B Cells in CRSwNP Pathophysiology
5.4 Summary and Conclusions
References
6: Mast Cells
6.1 Introduction
6.2 Origin and Distribution of MCs
6.3 Role of MCs in Acute Allergic Reactions
6.4 Role of MCs in Allergic Inflammation
6.5 Conclusion
References
7: Macrophage and Mast Cell
7.1 Part I: General Concept of Macrophage
7.1.1 Origin and Classification of Macrophages
7.1.2 Heterogeneity and Markers
7.1.3 Recruitment of Macrophages into Peripheral Mucosal Inflammatory Sites
7.1.4 Phagocytosis
7.1.5 Antigen Presentation by Macrophages and Dendritic Cells
7.1.6 Macrophage Activation
7.1.7 Role of Macrophages in Induction of Immune Tolerance
7.2 Part II: Distribution of Macrophages in Murine and Human Nasal Mucosa
7.3 Part III: Modification of Macrophages and Dendritic Cells and Its Clinical Impact on Inflammatory Disorders Such as Allergic Rhinitis
7.3.1 Endogenous IL-12 Induction from Macrophages by OK-432 and Its Effect on the Murine Allergic Rhinitis Model
7.3.2 Regulatory Role of Lymphoid Chemokines CCL19 and CCL21 in the Control of Allergic Rhinitis
References
8: The Neutrophil and Chronic Rhinosinusitis
8.1 Histologic Description
8.2 Hematologic Progenitors
8.3 Physiology and Function
8.4 Implication in Disease
8.5 Implications in Respiratory Disease
8.6 Implication in CRS
8.7 Therapeutic Implications
8.8 Summary
References
9: Eosinophils in Rhinologic Diseases
9.1 Introduction
9.2 Eosinophils at Baseline Condition
9.2.1 Eosinophils Are Resident in Several Tissues at Baseline Condition
9.3 Immunoregulatory Roles of Eosinophils
9.3.1 Eosinophils Present Antigens
9.3.2 Production of Cytokines and Other Immunomodulatory Molecules by Eosinophils
9.3.3 Immunoregulatory Functions of Eosinophils In Vivo
9.4 Effector Functions of Eosinophils
9.4.1 Granule Proteins
9.4.2 Activation of Human Eosinophils Takes Multiple Stages
9.4.3 Eosinophil Activation in Innate Immunity
9.5 Differences in the Eosinophilic Inflammation Between Allergic Rhinitis and Chronic Rhinosinusitis
9.6 What Are the Known Triggers for the Cytokine Response Leading to the Eosinophilic Inflammation?
9.7 Initiation of IgE Production
9.8 Aspirin-Exacerbated Respiratory Disease (AERD)
9.9 Eosinophil-Mediated Damage in CRS, But Not in Allergic Rhinitis
9.10 What Causes Eosinophil Degranulation?
9.11 Summary and Future Directions
References
10: Biologic Therapies for Chronic Rhinosinusitis
10.1 Pathophysiology
10.2 Current Therapies
10.3 Biologic Therapies
10.3.1 Anti-IgE Antibodies
10.3.2 Anti-IL-5 Antibodies
10.3.3 Anti-IL-4/Il-13 Antibodies
10.3.4 Future Therapeutic Targets
10.3.5 Biologic Therapy Guidelines
10.4 Conclusion
References
11: Nasal NO and Its Role in the Physiology of the Nose and Diagnosis
11.1 Introduction
11.2 Nitric Oxide (NO)
11.3 Nasal NO
11.4 Technique for Measuring nNO
11.5 Value of nNO Measurement in Clinical Practice
11.6 Diagnosis of Primary Ciliary Dyskinesia (PCD)
11.7 Concluding Remarks
References
12: Physiology and Pathophysiology of Sneezing and Itching: Mechanisms of the Symptoms
12.1 Historical Perspective
12.2 Physiology and Pathophysiology
12.3 Etiology
12.3.1 Rhinitis
12.3.1.1 Allergic Rhinitis
12.3.1.2 Infectious Rhinitis
12.3.1.3 Nonallergic Noninfectious Rhinitis
NARES (Nonallergic Rhinitis with Eosinophilia Syndrome)
Idiopathic (Vasomotor/Nonallergic and Non-eosinophilic) Rhinitis
12.3.1.4 Others Causes of Rhinitis
12.3.2 Photic Sneeze Reflex
12.3.3 Physical Stimulants of the Trigeminal Nerve
12.3.4 Central Nervous System Pathologies
12.3.5 Psychogenic (Intractable) Sneezing
12.3.6 Snatiation* Reflex
12.3.7 Sexual Ideation or Orgasm
12.4 Diagnosis, Differential Diagnosis, and Management of Rhinitis
12.5 Complications of Sneeze Reflex
12.6 Conclusion
References
13: The Dry Nose
13.1 Symptoms
13.2 Aetiology
13.2.1 Clinical Entities
13.2.1.1 Rhinitis Sicca Anterior
13.2.1.2 Primary Atrophic Rhinitis (PAR)
13.2.1.3 Secondary Atrophic Rhinitis (SAR)
13.3 Diagnosis
13.4 Treatment
13.4.1 Nasal Irrigation, Nasal Saline Spray and Inhalation
13.4.2 Nasal Ointments
13.4.3 Nasal Oils
13.4.4 Others
13.4.5 Treatment of Atrophic Rhinitis
13.5 Prophylaxis
13.6 Conclusions
References
14: Physiology of the Aging Nose and Geriatric Rhinitis
14.1 Importance of Aging in Rhinology
14.2 Anatomical Changes of the Aging Nose
14.2.1 Anatomy
14.3 Physiological Changes with Age
14.3.1 Alterations in Nasal Function
14.3.2 Olfaction and Nasal Sensitivity
14.3.3 Immunosenescence
14.4 Geriatric Rhinitis
14.4.1 Overview
14.4.2 Allergic Rhinitis
14.4.3 Nonallergic Rhinitis
14.4.4 Vasomotor Rhinitis
14.4.5 Drug-Induced Rhinitis
14.4.6 Atrophic Rhinitis
14.4.7 Gustatory Rhinitis
14.4.8 Hormonal Rhinitis
14.4.9 Chronic Rhinosinusitis
14.5 Treatment of the Geriatric Patient with Rhinitis
14.5.1 Overview
14.5.2 Medical Therapies
14.5.3 Avoidance
14.5.4 Increasing Nasal Moisture
14.5.5 Emollients
14.5.6 Oral and Intranasal Antihistamines
14.5.7 Intranasal Anticholinergics
14.5.8 Corticosteroids
14.5.9 Decongestants
14.5.10 Immunotherapy
14.6 Conclusions
References
15: Nutrition and the Upper Respiratory Tract
15.1 Introduction
15.2 Probiotics
15.3 Iron
15.4 Vitamin A
15.5 Omega-3
15.6 Zinc
15.7 Milk
15.8 Vitamin D
15.9 Type 2 Diabetes
15.10 Conclusions
References
16: Physiology of Lacrimal Drainage
16.1 Factors in Tear Flow
16.1.1 Evaporation
16.1.2 Capillarity
16.1.3 Krehbiel Flow
16.1.4 Siphon Effect
16.1.5 Microciliation and Reabsorption
16.1.6 Bernoulli’s Principle and Venturi Tube Effect
16.2 Tear Flow and Elimination
16.2.1 Flow from the Lacrimal Lake Through the Puncta
16.2.2 What Canalicular System Is more Important for Tear Elimination: Upper or Lower?
16.2.3 Flow Through the Canaliculi into the Sac
16.2.4 Lacrimal Pump
16.2.5 Flow from the Sac to the Nose
16.3 Other Factors on Tear Flow
16.3.1 Effect of Respiration
16.3.2 Valves
16.3.3 Clinical Principles Derived from the Physiologic Information
16.3.4 Role of Anatomic Vascular Organization and the Importance of Cavernous Body
16.4 Conclusions
References
17: Intranasal Trigeminal Perception
17.1 Introduction
17.2 The Nerves of the Nose
17.3 Consequences of Activation of Trigeminal Receptor and Nasal Reflexes
17.4 Neurogenic Inflammation
17.5 Psychophysical Testing of the Intranasal Trigeminal Function
17.6 Electrophysiology and Functional Imaging
17.7 Olfactory and Trigeminal Interaction
17.8 Conclusion
References
18: Sinus Pain
18.1 Introduction
18.2 Pain Pathophysiology
18.3 Migraine/Chronic Tension Headache
18.4 Medication Overuse Headache
18.5 Sinusitis
18.6 Contact Points and Nasal Obstruction
18.7 Temporomandibular Joint Disorders
18.8 Causes Removed from the Orofacial Area
18.9 Psychological Well-Being
18.10 History Taking
18.11 Examination
18.12 Investigations
18.12.1 Radiology
18.12.2 Blood Investigations
18.13 Management
18.14 Conclusions
References
19: Computational Fluid Dynamics of the Nasal Cavity
19.1 Current Applications of Computational Fluid Dynamics
19.1.1 Demonstration of Physiologic and Pathologic Flow Distributions in the Nose
19.1.2 Preoperative Planning and Postsurgical Outcome Assessment in Rhinosurgery
19.1.3 Recently Developed Applications of Computational Fluid Dynamics
19.2 Methodology
19.2.1 Imaging and Grid Generation
19.2.1.1 Using Computed Tomography
19.2.1.2 Using MRI
19.2.2 Method of Solution
19.2.3 Virtual Reality-Based Visualization of Flow Simulation Results
19.3 Application
19.3.1 Nasal Cavity 3D Imaging-Based Modeling: An Assessment Tool for the Anti-Obstructive Potency of Antiallergic Compounds
19.4 Conclusion
References
20: Physiology and Pathophysiology of Nasal Breathing
20.1 Preliminary Remarks
20.2 Nasal Airway Resistance
20.2.1 Physiological and Pathological Nasal Airflow Resistance
20.2.2 Short-Time Regulation of Nasal Airway Resistance
20.2.3 Long-Term Regulation of the Nasal Resistance
20.3 Nasal Functional Architecture: The Correlation of the Structure and Respiratory Function
20.3.1 Inflow Area
20.3.1.1 Nasal Vestibulum
20.3.1.2 Internal Nasal Ostium
20.3.1.3 Anterior Nasal Cavum
20.3.2 Functional Area
20.3.3 Outflow Area
20.3.3.1 Nasopharyngeal Meatus
20.3.3.2 Choana
20.3.3.3 Nasopharynx
20.4 Generation and Regulation of Turbulence in the Nose
20.5 The Nasal Cycle
20.6 Conclusions
References
21: Function of the Turbinates: Nasal Cycle
21.1 Definition of Nasal Cycle
21.2 Types of Nasal Cycles
21.2.1 Pearls
21.3 Origin, Function, and Regulation of the Nasal Cycle
21.4 Conclusion
References
22: Nasal Physiology and Pathophysiology and Their Relationship with Surgery: The Nasal Valves
22.1 Introduction
22.2 The Nasal Valves
22.2.1 Overview
22.2.1.1 The Internal Nasal Valve
22.2.1.2 The External Nasal Valve
22.2.1.3 Influences on Nasal Valve Strength
22.3 Nasal Physiology
22.3.1 The Nasal Cycle
22.3.2 Olfaction
22.3.3 Filtering Function
22.3.4 Humidifying Capacity
22.3.5 Airflow, Resistance, and Regulation
22.3.6 Immune Defense
22.4 Nasal Pathophysiology
22.4.1 Physics of Nasal Valve Pathophysiology
22.4.2 Nasal Valve Collapse
22.4.2.1 Internal Nasal Valve Collapse
22.4.2.2 External Nasal Valve Collapse
22.4.2.3 The Aging Nose
22.4.2.4 Paradoxical Obstruction
22.4.2.5 Chronic Rhinitis
22.4.2.6 Allergic Rhinitis
22.4.2.7 Nasal Polyposis
22.4.2.8 Epistaxis
22.5 Treatment
22.5.1 Surgical Techniques
22.5.2 Spreader Grafts
22.5.3 Alar Batten Grafts
22.5.4 Butterfly Graft
22.5.5 Nasal Valve Flaring Suture
22.5.6 Maxillary Expansion
22.5.7 Medical Treatment
22.5.7.1 Antihistamines
22.5.7.2 Intranasal Corticosteroids
22.5.7.3 Systemic Corticosteroids
22.6 Conclusion
References
23: Nose and Sleep Breathing Disorders
23.1 Introduction
23.2 Nose Anatomy and Physiology
23.3 Nose Pathologies
23.3.1 Nonreversible Factors
23.3.2 Reversible Factors
23.4 Physiopathology of Nose Obstruction and SDB
23.4.1 Starling Resistor Model
23.4.2 Oral Breathing
23.4.3 Nasal Receptors
23.4.4 Nitric Oxide
23.5 Craniofacial Development
23.5.1 Morphogenic Perspective
23.5.2 Phylogenic Perspective
23.6 Patient Evaluation
23.6.1 Clinical Examination
23.6.2 Investigations and Functional Testing
23.7 Patient Management
23.7.1 Rationale
23.7.2 Medical Treatment
23.7.2.1 General Treatment of Allergic Rhinitis
23.7.2.2 Management of SDB in Rhinitis Patients
23.7.2.3 Treatment of Nasal Valve Collapse with Nasal Dilators
23.7.3 Surgical Management
23.8 Conclusions
References
24: Pathophysiology of Obstructive Sleep Apnea
24.1 Pathophysiology of Obstructive Sleep Apnea
24.1.1 Obstructive Sleep Apnea
24.1.2 Influences of Wakefulness on Ventilatory Control
24.1.2.1 Anatomical Determinants of Upper Airway in OSA
Unique Anatomy of the Human Airway
Sites of Airway Collapse
Soft Tissue and Bony Structure Abnormalities
Obesity and Lung Volume
Airway Edema and Surface Tension
Obesity, Leptin, and Inflammation
24.1.2.2 Mechanical Determinants of Upper Airway Patency
24.1.2.3 Neuromuscular Control of Upper Airway Dynamics in Sleep
24.1.3 Measurements of Pharyngeal Collapsibility
24.1.4 Contribution of Anatomic Factors to OSA
24.1.5 Contribution of Neuromuscular Factors to OSA
24.1.6 Contribution of Neuroventilatory Factors to OSA
24.1.7 Interaction of Anatomic and Neuromuscular Factors on Pharyngeal Collapsibility
24.2 Conclusion
References
25: Rhinomanometry
25.1 Introduction
25.2 The Context of Rhinomanometry in Assessing Nasal Respiratory Function
25.2.1 What Are the Functions Associated with Nasal Respiration?
25.2.2 What Anatomic Elements are Encountered During Nasal Respiration?
25.2.3 Objective Measurement of Nasal Respiratory Function
25.2.3.1 Measurement of the Dimension of the Airway
25.2.3.2 Measurement of the Nasal Airflow Alone (Peak Flow Measurement)
25.2.3.3 Rhinomanometry: The Simultaneous Measurement of the Transnasal Pressure and Airflow
25.2.4 Rhinomanometry for Measurement of Nasal Respiratory Function
25.3 How Is the Measurement Done with Rhinomanometry?
25.3.1 Different Techniques: Most Common Method
25.3.2 Transnasal Flow Measurement: Anterior or Posterior Method
25.3.3 Transnasal Pressure Measurement for Posterior Rhinomanometry
25.3.4 Nasal Resistance or Conductance
25.4 Rhinomanometry Has Been Instrumental in Understanding Elements of Nasal Physiology
25.4.1 Measuring Changes That Occur in the Passage of Air Through the Nose with Growth and with Age
25.4.2 Measuring the Nasal Cycle
25.4.3 Discovering the Cause of Downside Obstruction When Lying on One’s Side (or with Pressure Application in Yoga)
25.4.4 Quantitating Airway Change with Recumbency
25.4.5 Assessing Nasal Airway Change with Exercise and CO2
25.4.6 Finding the Normal Range and Abnormal Range of Nasal Resistance Values
25.4.7 Measuring Disturbance in Nasal Respiratory Function
25.4.7.1 When Is Disturbance in the Nasal Airstream Significant?
25.4.7.2 Studying the Correlation of Elevated Resistance with the Symptom of Nasal Obstruction
25.4.7.3 Providing Objective Assessment When Crusting and Dysfunction of Nasal Lining Occur Due to Disturbance in the Airstream
25.4.8 Studying the Airflow in Conditions of Varying Temperature and Humidity
25.5 Clinical Applications of Rhinomanometry
25.5.1 When Things Do Not Add Up During Clinical Assessment
25.5.2 For Assessment of Surgical Candidate’s Chances of Optimal Outcome
25.5.3 To Analyze Changes in Patients Who Do Not Have Symptomatic Improvement with Surgery
25.5.4 Challenge Testing
25.6 Summary/Conclusion
References
26: Acoustic Rhinometry
26.1 Introduction
26.2 History
26.3 Theoretical Background and Criticism
26.4 Acoustic Rhinometry Equipment
26.5 Test Technique
26.6 Cross-Sectional Area–Distance Curve
26.6.1 Nasal Valve
26.6.2 Paranasal Sinuses
26.7 Applications of Acoustic Rhinometry
26.8 Conclusion
References
27: New Measurement Methods in the Diagnostic of Nasal Obstruction
27.1 Preliminary Remarks
27.2 New Techniques for the Diagnostic Evaluation of Nasal Obstruction
27.2.1 Rhinoresistometry (RRM)
27.2.1.1 Graphical Presentation
27.2.1.2 Numerical Evaluation
27.2.1.3 Objectification of Nasal Obstruction with RRM
27.2.2 Acoustic Rhinometry (ARM)
27.2.2.1 New Parameter in ARM
27.2.2.2 Objectification of Causes for Nasal Obstruction with ARM
27.2.3 Long-Term Rhinometry (LRM)
27.2.3.1 Upper Graph (Figs. 27.10 and 27.11)
27.2.3.2 Lower Graph (Figs. 27.10 and 27.11)
Heart Rate (Orange Curve)
Breathing Rate (Purple Curve)
Nasal Minute Volume (NMV) (Green Curve)
27.2.3.3 Indications for Long-Term Rhinometry
27.3 Diagnostic Procedures for Objectifying Nasal Obstruction and Its Causes
27.3.1 Combination of RRM, ARM and LRM
27.3.2 Examples
27.3.2.1 Example 1: No Nasal Complaints
Analysis of the Rhinometric Findings
Extent of Obstruction
Cause of the Obstruction
Assessment
27.3.2.2 Example 2: Severe Nasal Obstruction on the Right Due to a Septal Deviation
Rhinometric Findings: cf. Fig. 27.14a
Extent of Obstruction
Cause of the Obstruction on the Right
Assessment
Rhinosurgical Planning
Rhinosurgery
Analysis of Postoperative Rhinometric Findings
27.3.2.3 Example 3: Severe Nasal Obstruction on the Left Due to Septal Deviation
Extent of Obstruction
Cause of the Obstruction on the Right
Cause of the Obstruction on the Left
Assessment
Rhinosurgical Planning
Rhinosurgery
27.3.2.4 Example 4: Severe Nasal Obstruction on Both Sides Due to a Tension Nose
Extent of Obstruction
Cause of the Obstruction on Both Sides
Assessment
Rhinosurgical Planning
Surgery
27.3.2.5 Example 5: Severe Nasal Obstruction on Both Sides Due to Broad Columella
Extent of Obstruction
Cause of the Obstruction on Both Sides
Assessment
Rhinosurgical Planning
Surgery
27.3.2.6 Example 6: Subjective Nasal Obstruction Without Evident Aetiology
Extent of Obstruction
Cause of the Obstruction
Assessment
Assessment Together with Results of the LRM Examination
Rhinosurgical Planning
Surgery
Analysis of Postoperative Rhinometric Findings
27.4 Conclusions
References
28: Testing of Transport and Measurement of Ciliary Activity
28.1 Introduction
28.2 Testing of Transport
28.2.1 Testing of Transport In Vivo
28.2.1.1 Saccharine Test
28.2.1.2 Nuclear Testing
28.2.2 Testing of Transport In Vitro
28.3 Testing of Ciliary Activity
28.3.1 In Vivo
28.3.2 In Vitro
28.4 Additional Testing
28.4.1 Nasal Nitric Oxide
28.4.2 Genetic Analysis
28.4.3 Cell Culture
28.5 Conclusion
References
29: Nasal Defensive Proteins: Distribution and a Biological Function
29.1 General Concept of Nasal Defensive Proteins and Its Mechanism of Actions
29.1.1 Surfactants
29.1.2 Mucins
29.1.2.1 Classification
29.1.2.2 Mucin Genes
29.1.2.3 Mucin Gene Expression and Upregulation in Animal Model
29.1.2.4 Localization of Mucin Genes in Human Airways
29.1.3 Antimicrobial Peptides
29.1.3.1 Defensin
29.1.3.2 Defensin Synthesis and Its Regulation
29.2 Brief Introduction of Toll-Like Receptors in Nasal Epithelial Cells and Signaling Pathway
29.2.1 Distribution of TLRs in Nasopharyngeal Mucosae and Involvement of IL-15 in Inflammation
29.3 Conclusion
Appendix: Antiviral Proteins and Immunity for the Understanding of SARS-CoV-2 Virus Infection
Introduction
Defensins
Complement System
Interferons
Interferon Induction
Type I IFN Signaling
Direct and Indirect Antiviral Effects of Type I IFNs
Type II IFN
References
30: Olfaction
30.1 Introduction
30.2 Physiology
30.2.1 Embryology
30.2.2 Olfactory Pathways
30.2.2.1 The Olfactory Neuroepithelium
30.2.2.2 The First Olfactory Structure: The Olfactory Bulb
30.2.2.3 The Second Olfactory Structure: The Primary Olfactory Cortex
30.2.2.4 The Tertiary Olfactory Structures
30.2.2.5 Centrifugal Information
30.2.2.6 Properties of Olfactory Pathways
30.2.3 Orthonasal and Retronasal Olfaction
30.2.4 Olfactory and Trigeminal Interactions
30.2.5 Variability in Normal Olfactory Function
30.3 Pathology
30.3.1 Classification of Olfactory Disorders
30.3.1.1 Quantitative Olfactory Disorders
30.3.1.2 Qualitative Olfactory Disorders
30.3.2 Etiology of Olfactory Disorders
30.3.2.1 Chronic Rhinosinusitis
30.3.2.2 Post-Infectious Olfactory Loss
30.3.2.3 COVID-19-Related Olfactory Dysfunction
30.3.2.4 Post-traumatic Olfactory Loss
30.3.2.5 Congenital Anosmia
30.3.2.6 Neurological Disorders
30.3.2.7 Olfactory Cleft Disease
30.3.2.8 Miscellaneous
30.3.2.9 Idiopathic Olfactory Loss
30.3.2.10 Olfaction and Quality of Life
30.3.2.11 Counseling of the Patient
30.4 Conclusion
References
31: Olfactory Impairement in Disease and Aging
31.1 Introduction
31.2 Overview of the Olfactory System
31.2.1 Anatomy and Cellular Features
31.2.2 Regeneration of Olfactory Neurons
31.2.3 Human Olfactory Epithelium
31.2.4 Transduction Mechanisms
31.2.5 Diagnosis and Treatment of Olfactory Disorders
31.3 Common Causes of Olfactory Dysfunction
31.3.1 Age-Associated Olfactory Loss
31.3.2 Chronic Rhinosinusitis (CRS)
31.3.3 Neurodegenerative Diseases
31.3.4 Alzheimer’s Disease (AD)
31.3.5 Down’s Syndrome
31.3.6 Parkinson’s Disease (PD)
31.3.7 Huntington’s Disease
31.3.8 Multiple Sclerosis
31.3.9 Creutzfeldt–Jakob Disease (CJD)
31.3.10 Viral Infections
31.3.11 Human Immunodeficiency Virus (HIV) Infection and AIDS
31.3.12 Coronavirus-19 (SARS-CoV-19, COVID-19) Infection
31.3.13 Influenza Virus Infection
31.3.14 Medications and Olfactory Dysfunction
31.4 Summary and Future Directions
References
32: Electron Microscopy and the Nose
32.1 Electron Microscopy and the Nose
32.1.1 The Electron Microscope
32.1.2 Microscopic Anatomy of the Nose
32.1.2.1 Vestibule of the Nasal Cavity
32.1.2.2 Respiratory Region of the Nasal Cavity
32.1.2.3 Olfactory Region of the Nasal Cavity
32.1.3 Clinical Orientation of the Microscopic Anatomy of the Nose
32.2 Conclusion
References
33: Genetic Background of the Rhinologic Diseases
33.1 Introduction
33.2 Architecture and Function of the Sinuses
33.3 Histopathologic Features of the Nasal and Sinus Mucosa
33.4 Allergic Rhinitis and Its Genetic Background
33.4.1 Introduction
33.4.2 Allergic Rhinitis and Asthma
33.4.3 Allergic Rhinitis and Genetics
33.4.4 Molecular Targets for AR Therapy
33.4.5 Allergic Rhinitis and Epigenetics
33.5 Role of Genetics in Chronic Rhinosinusitis
33.5.1 Introduction
33.5.2 Chronic Sinusitis (CS)
33.5.3 Remodeling Theories
33.5.4 Chronic Infectious Sinusitis
33.5.5 Noneosinophilic Sinusitis (NES)
33.5.6 Molecular Basis of NES
33.5.7 Chronic Hyperplastic Eosinophilic Sinusitis (CHES)
33.5.8 Molecular Basis of CHES
33.5.9 Aspirin-Exacerbated Respiratory Disease (AERD)
33.5.10 Molecular Basis of AERD
33.5.11 Allergic Fungal Sinusitis (AFS)
33.5.12 Genetics of AFS
33.6 Genetics of Cystic Fibrosis and Pathophysiology in Airways
33.6.1 Introduction
33.6.2 Rationale for Cystic Fibrosis
33.6.3 Genetics and CF
33.6.4 Modifier Genes in CF
33.6.5 Cystic Fibrosis and Nasal Findings
33.6.6 CF and Nasal Polyposis
33.7 Role of Genetics in Nasal Polyposis
33.7.1 Introduction
33.7.2 Mucosal Irritation and the Role of Staphylococcal Exotoxin
33.7.3 Proinflammatory Cytokines Produced in Nasal Polyps
33.7.4 Eosinophils and Electrophysiology of Respiratory Surface Epithelium
33.7.5 Medical Treatment of Chronic Rhinosinusitis with Massive Nasal Polyposis Based on the Molecular Biology of Inflammation
33.8 Vasomotor Rhinitis and Its Genetic Background
33.8.1 Introduction
33.8.2 Epidemiology
33.8.3 Pathophysiology of VMR
33.8.3.1 Trauma
33.8.3.2 Autonomic Dysfunction
33.8.3.3 Cytokines and VMR
33.8.3.4 Light and Electron Microscopic Findings
33.8.3.5 Neuropeptides
33.8.3.6 Nitric Oxide
33.8.3.7 Nasal Secretory Proteins
33.8.3.8 Acid Reflux
33.9 Conclusions
References
34: Vomeronasal Organ
34.1 VNO Anatomy
34.2 VNO Histology
34.3 Genes Related to VNO
34.4 VNO Responses
34.5 VNO Function
References
35: Physiology of the Nasal Cartilages and Their Importance to Rhinosurgery
35.1 Part I: Anatomical Considerations
35.1.1 Nomenclature
35.1.2 Intrauterine Development
35.1.3 Postnatal Development
35.2 Part II: Functional Aspects
35.3 Part III: Alterations of Nasal Cartilages
35.3.1 Lacking Septodorsal Cartilage
35.3.2 Lacking Alar Cartilages
35.3.3 Physiological Septal Deviation
35.3.4 Congenital Nasal Deviations
35.3.5 Acromegaly
35.3.6 Damaged or Lacking Triangular Cartilage
35.3.7 Some Histological Aspects of Traumatised Nasal Cartilage
35.3.8 Transposition Technique
35.3.9 Frontal Nasal Trauma
35.3.10 Lateral Nasal Trauma
35.3.11 Scoring the Nasal Cartilages
35.3.12 Nasal Septal Abscess
35.4 Part IV: Remarks on Nasal Reconstruction
35.4.1 Anterior Nose and Nasal Cavities
35.4.2 One Option to Treat a Nasal Valve Stenosis
35.4.3 Back-to-Back Technique to Reconstruct the Anterior Septum
35.4.4 Closure of Septal Perforation in a Child
35.5 Conclusions
References
36: Physiology and Pathophysiology of the Growing Nasal Skeleton
36.1 Physiology of the Growing Nasal Skeleton
36.1.1 Introduction
36.1.2 The Facial Profile and Nasal Skeleton of the Newborn
36.1.3 Midfacial Development from Neonate to Adolescent
36.1.4 Postnatal Development of the Midfacial Skeleton in Mammals
36.1.5 Dimensional Growth of the Nose and Maturation
36.2 Pathophysiology of the Growing Nasal Skeleton
36.2.1 Congenital Anomalies
36.2.1.1 Midfacial Clefts and the Nasal Septum
36.2.1.2 Congenital Malformation of the Nose
36.2.2 Acquired Anomalies of the Nose
36.2.2.1 The Nose of the Neonate
36.2.2.2 Trauma at a Young Age: Bone and Cartilage Lesions
36.2.2.3 Fractures: Direct Effects and Follow-Up
Animal Experiments
36.2.2.4 Septum Haematoma and Abscess: Loss of Septum Cartilage
Animal Experiments
Role of Cartilaginous Septum in Midfacial Growth: Experimental Evidence
Upper Laterals
Mucosal Elevation
Release of Interlocked Stresses
Submucosal Resection of Parts of the Septum Cartilage: Effects on the Developing Nasal Skeleton
Histology
36.2.3 Repair and Reconstruction of the Nasal Septum
36.2.3.1 Wound Healing of Hyaline Cartilage and Perichondrium
In Vitro Experiments
Animal Experiments
Histology
36.2.3.2 Implantation of Grafts
Animal Experiments
Tissue Engineering
36.3 Conclusions and Clinical Epilogue
References
37: Physiologic Concerns During Rhinoplasty
37.1 Introduction
37.2 Anatomy of the Nasal Valve Area
37.2.1 Internal Nasal Valve
37.2.2 External Nasal Valve
37.3 Physiology of the Nasal Valve Area
37.4 Pathophysiology of the Nasal Valve Area
37.5 A Brief Word About the Preoperative Evaluation and Discussion
37.6 Prevention of Nasal Valve Area Breathing Complications During Rhinoplasty
37.6.1 Incisions
37.6.2 Approaches
37.6.3 Excisions
37.6.4 Hump Reduction
37.6.5 Osteotomies
37.6.6 Turbinates
37.7 Closing Thoughts
37.8 Conclusion
References
Further Reading
38: Nasal Pulmonary Interactions
38.1 Introduction
38.2 Physiological Interactions
38.3 Respiratory Inflammation
38.3.1 Inflammatory Interactions
38.3.2 Microbial and Inflammatory Mediator Transmission
38.3.3 Influence of Upper Respiratory Interventions on the Lower Respiratory Tract
38.4 Nasobronchial Reflexes
38.5 Olfaction and the Limbic System
38.6 Aerocrine Communication
38.6.1 Nitric Oxide
38.6.2 Carbon Dioxide
38.7 Conclusions
References
39: Physiologic and Dentofacial Effects of Mouth Breathing Compared to Nasal Breathing
39.1 Introduction
39.2 Respiratory Pattern
39.3 Physiologic and Dentofacial Effects
39.3.1 A Review of Early Literature
39.3.2 Current Perspective
39.3.3 Treatment
39.3.4 Conclusion
References
40: The Nose and the Eustachian Tube
40.1 Sniffing
40.2 Nose Blowing
40.3 Sneezing
40.4 Valsalva
40.5 Nasal Obstruction
40.6 Toynbee Test
40.7 Toynbee Phenomenon
40.7.1 Balloon Eustachian Tuboplasty
40.7.2 Technique
40.8 Otitic Barotrauma
40.9 Sinus Barotrauma
40.10 Conclusions
References
41: Nanomedicine and the Nose
41.1 Introduction
41.2 Clinical Nanomedicine Perspectives
41.3 Interdisciplinary Frameworks
41.4 Clinical Nanomedicine Applications
41.4.1 Regenerative Nanomedicine
41.4.1.1 Therapy
41.4.1.2 Design an Artificial Nose (Bioelectronic Nose)
41.4.2 Diagnosis and Imaging Methods Based on Nanomedicine
41.4.3 Targeting Delivery and Releasing
41.5 Conclusions
References