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Difficult Asthma
Liam G Heaney, Andrew Menzies-Gow
CHAPTER 1:
Definition, Epidemiology, and Phenotypes of Severe Asthma
INTRODUCTION
DEFINING SEVERE ASTHMA
Distinguishing Severe Asthma from Difficult-to-treat Asthma
SEVERE ASTHMA PHENOTYPES AND THEIR EPIDEMIOLOGY
Phenotype Definition
Approaches to Phenotyping
SPECIFIC SEVERE ASTHMA PHENOTYPES
Allergic Severe Asthma
Late Onset Hypereosinophilic Severe Asthma (Including Aspirin Intolerant Asthma)
“Later” Onset Symptom-prone Severe Asthma
Additional Potential Severe Asthma Phenotypes
CONCLUSION
CHAPTER 2:
Economic Burden of Difficult Asthma
INTRODUCTION
METHODS OF ASCERTAINING ECONOMIC BURDEN
ECONOMIC BURDEN OF DIFFICULT ASTHMA
COST OF UNCONTROLLED ASTHMA
CONCLUSION
CHAPTER 3:
Clinical Assessment of Difficult Asthma
INTRODUCTION
SYSTEMATIC ASSESSMENT OF DIFFICULT ASTHMA
SYSTEMATIC ASSESSMENT PROTOCOL
HISTORY AND EXAMINATION
INVESTIGATIONS
Sputum Examination
Hematological Investigations
Pulmonary Function Tests
Imaging
Skin Prick Tests
Bone Densitometry
Overnight Sleep Studies
Esophageal pH Monitoring
MULTIDISCIPLINARY TEAM INVOLVEMENT IN THE SYSTEMATIC ASSESSMENT OF DIFFICULT ASTHMA
Ear, Nose, and Throat Specialist
Vocal Cord Dysfunction
Health Psychologist/Psychiatrist
Respiratory Physiotherapist
Asthma Clinical Nurse Specialist
SYSTEMATIC ASSESSMENT BY DIFFICULT ASTHMA SERVICES
CONCLUSION
CHAPTER 4:
Adherence in Difficult Asthma
INTRODUCTION
IMPLICATIONS OF NON-ADHERENCE IN DIFFICULT ASTHMA
IMPROVING ADHERENCE: THE NEED FOR MORE EFFECTIVE INTERVENTIONS
UNDERSTANDING THE REASONS FOR NON-ADHERENCE: THE KEY TO EFFECTIVE INTERVENTIONS
Dispelling Myths
A PERCEPTIONS AND PRACTICALITIES APPROACH
PATIENTS’ BELIEFS ABOUT MEDICINES: NECESSITY AND CONCERNS
THE COMMONSENSE ORIGINS OF PATIENTS’ BELIEFS ABOUT THEIR PERSONAL NEED FOR INHALED CORTICOSTEROIDS
Suspicion of Pharmaceuticals and Concerns about Inhaled Corticosteroids
MEMORY AND FORGETTING
OTHER FACTORS AND CHALLENGES
IMPLICATIONS FOR PRACTICE
IDENTIFYING NON-ADHERENCE: THE NEED FOR A “NO-BLAME” APPROACH
CONCLUSION
CHAPTER 5:
Psychological Morbidity in Difficult-to-treat Asthma
INTRODUCTION
HISTORICAL PERSPECTIVE (ASTHMA NERVOSA)
ASTHMA PSYCHOPATHOLOGY
IMPACT OF PSYCHOLOGICAL AND PSYCHIATRIC COMORBIDITY IN ASTHMA
Stress/Anxiety and Depression
Asthma Death/Near-fatal Asthma Studies
Studies in Severe Asthma
Personality Factors, Attitudes, Beliefs, and Coping Styles
Factitious Disease “Asthma”
Psychological Effects of Systemic Corticosteroids
TREATMENT OF MORBID PSYCHOLOGY IN DIFFICULT ASTHMA
Anxiety and Depression
Does the Treatment of Psychological Comorbidities Alter Asthma Outcomes?
ROLE OF A PSYCHOLOGIST IN A DIFFICULT ASTHMA CLINIC
FUTURE RESEARCH
CHAPTER 6:
Difficult Asthma in Children
INTRODUCTION
DIFFICULT-TO-TREAT SEVERE ASTHMA
Is the Asthma Diagnosis Correct?
Do the Child and Parents Understand the Written Asthma Management Plan?
Is the Medication Being Delivered?
Is the Child Adhering to Therapy?
Are there Ongoing Triggers Factors?
Is there a Concomitant Disease that might Be Affecting Asthma or Reducing the Quality of Life in Its Own Right?
Allergic Rhinitis and Rhinosinusitis
Obesity and Obstructive Sleep Apnea
Psychological and Mental Health Issues
Could the Current Treatment Be Making the Child Worse?
Are the Symptoms Being Overperceived or Being Exaggerated?
INVESTIGATION AND FILTERING OF CASES OF DIFFICULT-TO-TREAT ASTHMA
THERAPY-RESISTANT SEVERE ASTHMA
Pathology
Risk Factors for Near-fatal or Fatal Asthma Attacks
Phenotype Targeting of Therapy
OVERVIEW OF AVAILABLE TREATMENTS FOR THERAPY-RESISTANT SEVERE ASTHMA
Very High-dose Inhaled Corticosteroids
Fine Particle Inhaled Corticosteroids
Macrolide Antibiotics
Anti-IgE Therapy
Terbutaline Infusion
Immunotherapy
Other Treatments for True Steroid Resistant Severe Childhood Asthma
INTERMITTENT EPISODIC SEVERE VIRAL-TRIGGERED ASTHMA
CHAPTER 7:
Difficult Asthma—The Patient's Perspective
INTRODUCTION
IMPORTANCE OF SPECIALIST CARE
MANAGEMENT OF DIFFICULT ASTHMA
COMPLEX TREATMENT REGIMENS AND SIDE EFFECTS
IMPACT OF DIFFICULT ASTHMA ON QUALITY OF LIFE
EFFECTS ON FAMILY AND SOCIAL RELATIONSHIPS
EFFECTS ON EDUCATION AND ABILITY TO WORK
CONCLUSION
CHAPTER 8:
Comorbidity in Refractory Asthma
INTRODUCTION
REFLUX ESOPHAGITIS
DYSFUNCTIONAL BREATHING
HYPERVENTILATION
Acute (Exercise-induced) Hyperventilation
Diagnosing Hyperventilation
Chronic Hyperventilation
Overventilation
Treatment of Hyperventilation
OTHER FORMS OF DYSFUNCTIONAL BREATHING
Diagnosis of Vocal Cord Dysfunction
Treatment of Vocal Cord Dysfunction
OTHER PATTERNS OF DYSFUNCTIONAL BREATHING
SUMMARY OF DYSFUNCTIONAL BREATHING
OBESITY
OSTEOPOROSIS
DIABETES
EYE DISEASE
BRONCHIECTASIS
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS AND SEVERE ASTHMA WITH FUNGAL SENSITIZATION
RHINITIS/THE UPPER AIRWAY
CONCLUSION
CHAPTER 9:
Molecular and Immunological Basis for Severe Therapy-resistant Asthma
INTRODUCTION
MECHANISM OF CORTICOSTEROID ACTION
Gene Induction by Corticosteroids
Gene Repression by Corticosteroids
Type 2 T Helper Cell Mediators and Refractory Asthma
Interleukin-17 and Type 17 T Helper Cells in Refractory Asthma
Type 1 T Helper Cells in Refractory Asthma
Regulatory T Cells
Dendritic Cells
Superantigen
Reactive Oxygen Species/Reactive Nitrogen Species
Genetic Factors
CLINICAL IMPLICATIONS
CONCLUSION
Acknowledgments
CHAPTER 10:
Monitoring and Natural History of Refractory Asthma
INTRODUCTION
NATURAL HISTORY OF ASTHMA
Asthma in Children
Asthma in Adults
MONITORING SEVERE ASTHMA CONTROL AND RISK
Control
Risk
MONITORING INFLAMMATION IN SEVERE ASTHMA
Targeted Corticosteroid Therapy
Targeted Novel Anti-inflammatory Therapies
MONITORING ENVIRONMENTAL EXPOSURE IN SEVERE ASTHMA
Anti-IgE
Antifungal Therapy
Macrolide Antibiotics
MONITORING DISEASE PROGRESSION AND REMODELING IN SEVERE ASTHMA
PREDICTING THE FUTURE: DISEASE PROGRESSION AND RESPONSE TO THERAPY
Statistical Modeling of Airway Disease: Phenotyping the Heterogeneity
Patient-specific Multiscale Computational Models
CONCLUSION
CHAPTER 11:
Novel Treatment Strategies in Refractory Asthma
CURRENT MANAGEMENT OF REFRACTORY ASTHMA
NOVEL BRONCHODILATORS AND CORTICOSTEROIDS
Ultra-long-acting Bronchodilators
Dissociated Corticosteroids
BIOLOGICAL AGENTS
Tumor Necrosis Factor-α Blockers
Interleukin-5 Blockers
Interleukin-4 and Interleukin-13 Blockers
Other Interleukin Blockers
Anti-inflammatory Cytokines
ARACHIDONIC ACID PATHWAY BLOCKERS
Phospholipase Blockers
Leukotriene Modifiers
Prostaglandin D2 Blockers
OTHER DRUG THERAPIES
Macrolides
Antifungal Therapy
Phosphodiesterase-4 Inhibitors
Protein Kinase Inhibitors
Peroxisome Proliferator-activated Receptor-γ Agonists
Chemokine Antagonists
Endothelin Antagonists
Vitamin D
Statins
BRONCHIAL THERMOPLASTY
Efficacy of Bronchial Thermoplasty
Adverse Effects of Bronchial Thermoplasty
Place in Management of Refractory Asthma
IMMUNOTHERAPY
AVOIDANCE MEASURES
FACTORS INFLUENCING THE RESPONSE TO NOVEL THERAPIES
CONCLUSION
INDEX
TOC
Index
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