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

This new edition provides a fully updated guide to obesity’s relation to lung disease. Over forty percent of the U.S. population is obese, and obesity is increasing in much of the world. Obesity has a major impact on health conditions such as diabetes and cardiovascular disease. The effects of obesity on lung disease have drawn increasing attention in recent years. Furthermore, the COVID pandemic has dramatically illustrated how obesity affects respiratory disease, constitutes a major risk factor for COVID-19, and presents challenges to pulmonary care in the ICU. Obesity changes physiology, immune and metabolic function, and is associated with changes in diet and the microbiome, all of which combine to have a major impact on the pathogenesis of respiratory diseases. Obesity is thus a risk factor for many respiratory diseases such as asthma, pulmonary hypertension, thromboembolic disease, obstructive sleep apnea and ARDS. Obesity also complicates the management of manyother respiratory diseases and conditions such as COPD, thromboembolic disease, and the care of the critically ill patient. The objectives of this book are three-fold: To review how physiological, immune and metabolic factors might contribute to lung disease. To discuss the impact of obesity on common lung diseases To outline important considerations in the management of critically ill obese patients. There have been major advances in our understanding of the relationship between obesity and lung disease since the first edition in 2013, in addition to the major lessons learned about the importance of obesity during the COVID-19 pandemic. This has led to the addition of eight new chapters on topics such as, the microbiome, lung transplant, and COVID-19 in the ICU. This is an ideal guide for all clinicians taking care of patients with pulmonary and critical care diseases, as well as basic and translational scientists interested in how obesity affects respiratory health. 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 As a result of the rapidly growing rate of obesity worldwide, clinicians are struggling to provide the best strategies for treating obese patients with concomitant pulmonary conditions. Obesity does not simply change the epidemiology of pulmonary disease; obesity has a profound impact on the pathophysiology of common pulmonary diseases. Obesity affects the severity of asthma, response to treatment, and is likely a major modifier of the phenotype of asthma. Obesity also appears to affect response to pathogens, and as such has a major influence on response to pneumonia, and has a significant impact on outcomes pertaining to acute lung injury in the intensive care unit. Obesity and Lung Disease: A Guide to Management is the first text in the field to cover the full range of issues related to managing obese patients with pulmonary problems.