Obesity and Lung Disease: A Guide to Pathophysiology, Evaluation, and Management (Respiratory Medicine)

Contents
Contributors
1: Effects of Obesity on Lung Function
	Introduction
	Adipose Tissue and Respiratory Mechanics
	Intra-abdominal and Intrathoracic Pressures
	Respiratory System Compliance
	Lung Volumes
		Relaxation Volume: FRC
		Total Lung Capacity
	Spirometry
	Breathing Pattern
	Peripheral Airway Function: Oscillometric Impedance and Nitrogen Washout
	Expiratory Flow Limitation During Tidal Breathing
	Intrinsic PEEP and Dynamic Hyperinflation
	Breathless During Exercise
	Ventilation Distribution
	Gas Exchange
	Effects of Obesity on Respiratory Function in Disease
	Interpretation of Lung Function
	References
2: Obesity-Mediated Alterations in Immune Function, Host Defense, and Lung Disease
	Introduction
		The Effects of Obesity on Innate Immune Responses and Their Impact on Pulmonary Disease
			Pulmonary Macrophages
			Other Innate Immune Cells: Dendritic Cells, Natural Killer Cells, and Innate Lymphoid Cells
		The Effects of Obesity on Adaptive Immune Responses and Their Impact on Pulmonary Disease
			T Cells
			B Cells
		Granulocytes: Neutrophils and Eosinophils
	Summary
	References
3: Obesity, the Microbiome, and Lung Disease
	Introduction
	Microbiome Terminology and Methods
	Overview of Obesity and the Microbiome
		Human Studies
		Obesity and the Microbiome in Animal Models
	Chronic Lung Disease
		Asthma
			Human Studies
			Animal Models
		Chronic Obstructive Pulmonary Disease (COPD)
			Human Studies
			Animal Models
		Pulmonary Fibrosis/Interstitial Lung Disease
			Human Studies
			Animal Models
		Pulmonary Hypertension
			Human Studies
			Animal Models
		Obstructive Sleep Apnea (OSA)
			Human Studies
			Animal Models
		Tuberculosis (TB)
			Human Studies
			Animal Models
	Acute Lung Disease
		Pneumonia, Acute Respiratory Distress Syndrome (ARDS)
			Human Studies
			Animal Models
		COVID-19
			Human Studies
			Animal Models
	Conclusion/Summary
	References
4: Genetics and Genomics of Obesity and Lung Diseases
	Introduction
	Nomenclature for the Chapter
	Genetics of Obesity and Asthma
	Mendelian Randomization Studies
	Genomics of Obesity and Asthma
	Genetics and Genomics of Obesity and Other Lung Diseases
	Conclusion and Future Directions
	References
5: The Western Dietary Pattern and Respiratory Health
	Introduction: Features of a Western Dietary Pattern
	Mechanisms by Which a Western Dietary Pattern Affects Respiratory Diseases
		Energy Surplus and Obesity Mechanisms in Respiratory Disease
			Energy Surplus, Obesity and Asthma
			Energy Surplus, Obesity and COPD
			Energy Surplus, Obesity and Respiratory Infections
		Fatty Acid Intake Mechanisms in Respiratory Disease
			Increased Saturated Fatty Acid Intake in Asthma
			Increased Saturated Fatty Acid Intake in COPD
			Increased Saturated Fatty Acid Intake in Respiratory Infections
			Omega-3 and Omega-6 Fatty Acid Intake in Asthma
			Omega-3 and Omega-6 Fatty Acid Intake in COPD
			Omega-3 and Omega-6 Fatty Acid Intake in Respiratory Infections
		Reduced Antioxidant Intake and Oxidative Stress in Respiratory Disease
			Antioxidant Intake and Oxidative Stress in Asthma
			Antioxidant Intake and Oxidative Stress in COPD
			Antioxidant Intake and Oxidative Stress in Respiratory Infections
		Dietary Advanced Glycation End Products (AGEs) and Respiratory Disease
			Advanced Glycation End Products (AGEs) in Asthma
			Advanced Glycation End Products (AGEs) in COPD
			Advanced Glycation End Products (AGEs) in Respiratory Infections
		Reduced Dietary Fibre Intake Mechanisms in Respiratory Disease
			Dietary Fibre Intake Mechanisms in Asthma
			Dietary Fibre Intake Mechanisms in COPD
			Dietary Fibre Intake Mechanisms in Respiratory Infections
	Evidence for the Effect of Western Dietary Patterns in Respiratory Disease
		Western Dietary Pattern and Asthma
			Association Between Western Dietary Pattern and Asthma in Adults
			Association Between Western Dietary Pattern and Asthma in Children and Adolescents
			Association Between Maternal Western Dietary Pattern Intake and Asthma in Offspring
			Associations Between Western Dietary Pattern, Obesity and Asthma
			Protective Dietary Patterns in Asthma
			Dietary Interventions Modifying Western Dietary Pattern to Improve Asthma
		Western Dietary Pattern and COPD
			Association Between Western Dietary Pattern and COPD Development
			Protective Dietary Patterns in COPD
			Dietary Interventions Modifying Western Dietary Pattern to Improve COPD
		Western Dietary Pattern and Respiratory Infections
			Associations Between Western Dietary Pattern and Respiratory Infections
			Association Between Western Dietary Pattern and Respiratory Infections in Adults
			Association Between Western Dietary Pattern and Respiratory Infections in Children
			Association Between Western Diet Pattern and Respiratory Infections in Pregnancy
			Dietary Interventions to Reduce Risk of Respiratory Infections
	Conclusion
	References
6: Pathogenesis of Obstructive Sleep Apnea in Obesity
	Introduction
	Obstructive Sleep Apnea: Diagnosis, Definitions, and Nomenclature
	Clinical Characteristics of Obstructive Sleep Apnea
	Epidemiology of Obesity and Obstructive Sleep Apnea
		Prevalence
		Risk Factors for OSA
		Hereditary and Genetic Factors
		Regional Fat Distribution
	Obstructive Sleep Apnea-Related Outcomes
		Cardiovascular Disease
		Metabolic Consequences
		Sleepiness, Neurocognitive Dysfunction, and Quality of Life
		Mortality
	Pathophysiology of Obstructive Sleep Apnea
		Upper Airway Imaging
		Regional Obesity and Upper Airway Function
		Nonmechanical Factors
		Neuroventilatory and Humoral Factors
		Pharyngeal Muscle Activity
	Treatment of Obstructive Sleep Apnea
		Weight Loss and Improved Upper Airway Function During Sleep
		Longitudinal Post-bariatric Surgery Weight Loss
	Conclusion
	References
7: Obesity Hypoventilation Syndrome
	Introduction
	Epidemiology
	Morbidity and Mortality
	Pathophysiology
		Altered Respiratory Mechanics
		Increased CO2 Production
		Sleep-Disordered Breathing
		Leptin
	Clinical Presentation and Diagnosis
	Predictors of Hypercapnia in Obese OSA Patients
	Treatment
		Positive Airway Pressure (PAP) Therapy
		CPAP Vs. NIV
		Gas Exchange: Hypoxia and Hypercapnia
		Sleepiness and Quality of Life
		Morbidity and Mortality
		In Summary
	PAP Vs. NIV in Specific OHS Subpopulations
		Comorbid COPD
		Obesity Hypoventilation Syndrome Without Severe OSA Phenotype
		The “Unstable OHS Patient”: Hospital Discharge After OHS Exacerbation
	Special Considerations
		The Role of Mask Selection
		Lack of Improvement in Hypoxemia/Hypercapnia After PAP Therapy
		CPAP Titration Failure
		PAP Treatment Failure
		Volume-Targeted Pressure Support Ventilation
		Is a Switch to CPAP Therapy Feasible?
	Oxygen Therapy
	Weight Loss Interventions and Weight-Reduction Surgery
		Pharmacotherapy for Obesity
	Tracheostomy
	Respiratory Stimulation
		Medroxyprogesterone
		Acetazolamide
	Summary
	References
8: Obesity and Asthma: Epidemiology and Clinical Presentation
	Introduction
	Epidemiological Evidence Linking Obesity and Asthma
		Epidemiological Studies in Adult Populations
		Epidemiological Studies in the Pediatric Age
		Potential Differences Throughout the Life Course
		Directionality, Causality, and Shared Risk Factors
		Beyond Body Mass Index
		The Role of Biological Sex
		Fat Composition and Distribution
		Asthma Leading to Obesity
		Summary
	Clinical Presentation of Obesity-Related Asthma
		Clinical Presentation of Obesity-Related Asthma in Children
		Clinical Presentation of Obesity-Related Asthma in Adults
		Lung Function in Adults with Obesity and Asthma
		Lung Function in Children with Obesity and Asthma
	References
9: Obesity and Asthma: Metabolic Dysregulation
	Introduction
	Metabolic Syndrome and Asthma Morbidity
	Insulin Resistance
	Dyslipidemia
	Mitochondrial Dysfunction: Glucose Metabolism
	Nitric Oxide Metabolism
	Untargeted Metabolomics
	Conclusion and Future Directions
	References
10: Obesity and Asthma: Endotypes and Mechanisms
	Introduction
	Pathophysiologic Mechanisms of Obesity and Asthma
		Metabolic Mechanisms Modulating Obese Asthma
		Alterations in Innate and Adaptive Immune Mechanisms
	Obese Asthma Phenotypes and Endotypes (Fig. 10.1)
		Defining Phenotypes and Endotypes
		Defining Current Key Cohorts
		Obese Endotypes and Phenotypes
		Performance of Biomarkers in Obese Asthma
	Clinical Considerations: The Obese Asthma Patient
		Symptom Burden and Exacerbations
		Diagnostic Challenges
		Varying Treatment Responses in Obese Asthma
	Conclusion
	References
11: Asthma Management in Obesity
	Diagnostic Testing
	Medications
		β-Agonists
		Inhaled Corticosteroid and Inhaled Corticosteroid/ Long-Acting Beta Agonists
		Long-Acting Muscarinic Antagonists
		Biologics
		Other Controller Therapy
		Role of Treating Insulin Resistance in Obese Asthma
		Targeting Oxidative Stress in Obese Asthma
	Management of Comorbidities
		Gastroesophageal Reflux Disease
		Depression
		Obstructive Sleep Apnea
	Infections and Exposures
		Susceptibility to Viral Infections
		Susceptibility to Air Pollution
	Weight Loss and Lifestyle Interventions
		Improving Dietary Quality
		Lifestyle Weight Loss Interventions
		Bariatric Surgery
	Summary/Conclusion
	References
12: Obesity and Chronic Obstructive Pulmonary Disease (COPD)
	Introduction
	Epidemiology
	Metabolic Syndrome in COPD
	Adipose Tissue Dysfunction in COPD?
	Effect of Obesity on Symptoms and Diagnosis
	Effect of Obesity on Lung Function in COPD
	Effect of Obesity on Exercise Performance in COPD
	Obesity and Exacerbations of COPD
	Sarcopenic Obesity in COPD
	Effect of Obesity on Prognosis in COPD
	Treatment of Obesity in COPD
	Summary
	References
13: Obesity, Metabolic Syndrome, and Pulmonary Hypertension
	Introduction
	Pulmonary Hypertension Classification
	Mechanisms of Obesity-Related Pulmonary Vascular Disease
		Pulmonary Arterial Hypertension
			Links between BMPR2 and Obesity
			Adipokines and PAH
			Dyslipidemia in PAH
			Insulin Resistance in PAH
			Oxidant Injury and PAH
			Human Data Linking PAH and Obesity
			Obesity, Estrogens, and PAH
		Postcapillary Hypertension
		Obesity Hypoventilation Syndrome (OHS)
			Hypercapnia
			Hypoxia
		Sleep-Disordered Breathing
	Implications of Obesity for the Diagnosis and Management of Pulmonary Hypertension
		Diagnostic Considerations
		Disease-Specific Recommendations
			Treatment Aimed Directly at PAH
			Treatment Aimed at Weight Loss
			Treatment of Metabolic Syndrome
			Treatment of OSA
			Assessment of Treatment
	Conclusions
	References
14: Association of Obesity and Thromboembolic Disease
	Epidemiology
	Pathophysiology
	Diagnostic Evaluation in Obese Patients with Suspected Pulmonary Embolism
	Treatment of Obese Patients with VTE: Initial Therapy
	Anticoagulant Choice in Bariatric Surgery Patients
	Treatment of Obese Patients with VTE: Extended Anticoagulant Therapy
	Interventional Therapies
	Chronic Thromboembolic Pulmonary Hypertension
	Conclusion
	References
15: Obesity and Respiratory Infections Including COVID-19
	Introduction
	Prevalence of Obesity and Overweight Continue to Rise in the US and Globally
	Obesity Increases the Severity of Illness from COVID-19
		Dysfunctional Immune Response Against Viral Infections in Obesity
		Effectiveness of COVID-19 Vaccination in People with Obesity
	Obesity Increases the Severity of Illness from Influenza
		Animal Models of Obesity and Influenza
		Reduced Effectiveness of Vaccination Against Influenza in Obesity
	Obesity and the Risk of Community-Acquired Bacterial Pneumonia
		Obesity and Risk of Nosocomial Pneumonia
		Obesity in Mice Impairs Host Defense Against Bacterial Pneumonia
	Comorbid Conditions Associated with Obesity Known to Affect Pulmonary Host Defense
	Knowledge Gaps and Future Directions
	References
16: Obesity and Lung Health in Children
	Introduction
	Obesity and Respiratory Function in Healthy Children
	Obesity and Asthma Risk in Children
	How Does Obesity Lead to Incident Asthma?
		Dietary Factors
		Sedentariness
		Shared Genetics
	Obesity and Asthma Phenotype in Children
		Severity
			Symptom Impairment
			Exacerbations
		Lung Function
			Airway Reactivity
		Atopy
		Airway Inflammation
		Systemic Inflammation
	The Child with Asthma and Obesity: Management Considerations
		Current Guidelines and Management Considerations
		Weight Loss Interventions
		Pharmacotherapy
	Sleep-Disordered Breathing and Obesity Hypoventilation Syndrome
	Obesity Hypoventilation Syndrome (OHS)
	Conclusions
	References
17: Obesity and Acute Respiratory Distress Syndrome
	Introduction
	Clinical Outcomes of ARDS in Patients with Obesity
		Studies in ARDS and General Critical Illness
		Limitations of Prior Investigations
		Possible Explanation of Findings
	Biologic Relationship of Obesity and ARDS
		Obesity and the Pathogenesis of ARDS
		Obesity, the Metabolic Syndrome, and the Inflammatory Response in ARDS
		Obese Pulmonary Mechanics: Is VILI Attenuated?
	Clinical Recommendations
	Conclusions
	References
18: Obesity and Mechanical Ventilation
	The Problem of Defining Obesity
	Key Features of Pressure Gradients Across the Respiratory Structures During Spontaneous Breathing in the Lean Person
	Key Features of Pressure Gradients Across the Respiratory Structures During Spontaneous Breathing in a Person with Obesity
	Respiratory Mechanics of the Patient with Obesity During Mechanical Ventilation
	Respiratory Mechanics of the Patient with Obesity and Inflammatory Lung Injury During Mechanical Ventilation
	Before and After Intubation: The Role of Pre-oxygenation and Non-invasive Ventilation
	Summary and Conclusions
	References
19: Obesity and COVID-19 in the Intensive Care Unit
	Introduction
	Epidemiology
	Pathophysiology
		Immune Response to COVID-19 in Obesity
		Acute Respiratory Distress Syndrome
	Management
		Prevention of Severe Infection
		Non-invasive Respiratory Support
		Invasive Mechanical Ventilation
		Mortality and Long-Term Outcomes
	Conclusions
	References
Index