Foreword
References
Preface
Acknowledgments
About This Book
Contents
About the Editors
Chapter 1: Sex Differences in Respiratory Physiology
1.1 Introduction
1.2 Historical Studies of Sex Differences
1.3 Definitions and Methods to Assess Respiratory Structure/Function
1.4 Sex Differences in the Developing Lung
1.5 Peri-Pubertal Sex Differences and Adulthood
1.6 Importance of Sex Differences in the Lung
References
Chapter 2: Sex Differences in the Anatomy of the Airways and the Lungs: Impact on Dysanapsis across the Lifespan
2.1 Introduction
2.1.1 Anatomical Overview of Airways and Lungs
2.1.1.1 Airways
2.1.1.2 Lung
2.2 Determinants of Sex Differences in the Airways, the Lungs, and dysanapsis
2.2.1 Dimensional Determinants
2.2.1.1 Nasopharynx
2.2.1.2 Pharynx
2.2.1.3 Glottis
2.2.1.4 Vocal Cords
2.2.1.5 Larynx
2.2.1.6 Trachea and Main Bronchi
2.2.2 Lung
2.3 Dysanapsis
2.4 Immunological Determinants
2.5 Hormonal Determinants
2.6 Conclusion
References
Chapter 3: Sex Steroids and Their Influence in Lung Diseases Across the Lifespan
3.1 Introduction
3.2 Biology of Sex Steroids
3.2.1 Estrogen
3.2.2 Progesterone
3.2.3 Testosterone
3.2.4 Other Regulators of Sex Steroids
3.3 Functions of Sex Steroids Across the Lifespan: An Emphasis on Lung Diseases
3.3.1 Effects of Sex Steroids in Prenatal Lungs
3.3.2 Effects of Sex Steroids in Early Childhood
3.3.3 Effects of Sex Steroids in Late Childhood/Puberty
3.3.4 Effects of Sex Steroids in Adult Lungs
3.3.5 Effects of Sex Steroids in Aging Lungs
3.4 Conclusion and Future Scope
References
Chapter 4: Sex Differences in the Developing Lung: Implications for Disease
4.1 Introduction
4.2 Neonatal Lung
4.2.1 Lung Development During Gestation and Infancy
4.2.2 Gender Disparities in Preterm Neonatal Outcomes
4.2.3 Gender and Respiratory Outcomes in Preterm Infants
4.2.3.1 Respiratory Distress Syndrome (RDS)
4.2.3.2 Bronchopulmonary Dysplasia (BPD)
4.2.3.3 Sex-specific Response to Environmental Smoking Exposures
4.2.3.4 Chronic Cough
4.2.3.5 Protracted (or Persistent) Bacterial Bronchitis (PBB)
4.2.3.6 Primary Ciliary Dyskinesia (PCD)
4.2.3.7 Non-cystic Fibrosis (Non-CF) Bronchiectasis
4.2.3.8 Cystic Fibrosis (CF)
4.3 Prepubertal Development of the Lung
4.3.1 Lung Development During Early Childhood
4.3.2 Pulmonary Function Testing in Infants and Preschool Children
4.3.2.1 Forced Deflation and the Rapid Thoracoabdominal Compression
4.3.2.2 Measures of Compliance and Resistance
4.3.2.3 Forced Oscillation Technique (FOT)
4.3.2.4 Inert Gas Washout (IGW)
4.3.2.5 Electrical Impedance Tomography (EIT)
4.3.2.6 Ventilator Graphics
4.3.3 Pulmonary Function Testing in Older Children
4.3.3.1 Spirometry
4.3.4 Sex Differences in Airway Obstruction and Lung Diseases
4.3.4.1 Respiratory Syncytial Virus Infection (RSV)
4.3.4.2 Asthma
4.4 Puberty and Postpubertal Lung Development
4.4.1 Lung Changes During Puberty
4.4.2 Sex-specific Differences in Late Childhood and Adulthood
4.4.3 Lung Changes and the Risk for Asthma
4.4.4 The Effect of Circadian Hormone Fluctuation on Lung Function and Asthma
4.4.5 The Effect of Sex Hormone Fluctuation Across the Menstrual Cycle on Lung Function, Asthma, and Obstructive Sleep Apnea
4.4.5.1 Asthma and the Menstrual Cycle in Older Girls
4.4.5.2 Obstructive Sleep Apnea (OSA)
4.5 Pregnancy
4.5.1 Societal and Health Burden of Adolescent (Teen) Pregnancy
4.5.2 Lung Function During Pregnancy
4.5.3 Asthma During Pregnancy
4.6 Summary
References
Chapter 5: Neonatal Lung Disease: Mechanisms Driving Sex Differences
5.1 Introduction
5.2 Sex-Specific Differences in Lung Development
5.2.1 Small Animal Models
5.2.2 Large Animal Models
5.2.3 Human Models
5.3 Sex-Specific Differences in Postnatal Lung Disease
5.3.1 Respiratory Distress Syndrome (RDS)
5.3.2 Bronchopulmonary Dysplasia (BPD)
5.3.3 LPS-Induced Neonatal Lung Injury
5.4 Mechanisms of Sex-Specific Differences in Neonatal Lung Injury
5.4.1 Hormone-Mediated Mechanisms
5.4.2 Hormone-Independent Mechanisms
5.4.2.1 Sex-Chromosome-Associated Genes
5.4.2.2 Sex-Based Differences in Pulmonary Gene Expression
5.4.2.3 Sex-Specific Differences in Anti-Oxidant and Inflammatory Pathway Mediators
5.4.2.4 MicroRNAs and Sex-Specific Differences
5.4.2.5 Role of Cellular Sex in Sex-Based Differences
5.5 Sex as a Crucial Biological Variable for Lung Protective Therapies
5.6 Conclusion
References
Chapter 6: Sex Differences in Cystic Fibrosis Across the Lifespan
6.1 Introduction
6.2 Diagnosis of CF
6.3 Timing and Impact of Puberty
6.4 Reproductive Years
6.4.1 Sex Disparities Observed in Respiratory Health
6.4.1.1 Lung Function
6.4.1.2 Bacterial Colonization
6.4.1.3 CF Exacerbations
6.4.1.4 Response to Therapies
6.4.2 Sex Disparities in Extrapulmonary Manifestations of CF
6.4.2.1 Nutrition
6.4.2.2 Cystic Fibrosis-Related Diabetes
6.4.2.3 Bone Disease/Osteoporosis
6.4.2.4 Fertility
6.5 Menopause
6.6 Sex Hormone Effects on CF
6.6.1 Estrogen
6.6.2 Progesterone
6.6.3 Testosterone
6.6.4 Dehydroepiandrosterone (DHEA)
6.7 Disease Perception, Medication Adherence, Activity
6.8 Survival
6.9 Lung Transplant
6.10 Conclusion
References
Chapter 7: Sex Differences in Chronic Obstructive Pulmonary Disease
7.1 Introduction
7.2 Epidemiology
7.3 Risk Factors
7.4 Pathophysiology
7.5 Clinical Features
7.6 Diagnosis
7.7 Treatment
7.8 Conclusion
References
Chapter 8: Sex Differences in Pulmonary Arterial Hypertension
8.1 Introduction
8.2 Pulmonary Arterial Hypertension
8.2.1 Clinical Definition
8.2.2 Pathobiology
8.2.3 Sex as a Risk Factor in PAH
8.3 Sex Hormones
8.4 Sex Differences in Preclinical Models of PAH
8.4.1 Sex Differences in Animal Physiology
8.4.1.1 Sex Differences Related to the Pulmonary Vasculature
8.4.1.2 Sex Differences and the Right Ventricle
8.4.1.3 Hormone Metabolites in Pulmonary Hypertension
8.4.1.4 The Role of Sex Chromosomes
8.4.2 Sex Differences in Ex Vivo and In Vitro Preclinical Models
8.4.2.1 Ex Vivo Studies
8.4.2.2 In Vitro Studies
8.4.3 Potential Mechanisms Underlying Sex-Related Differences in Preclinical Models of PAH
8.4.3.1 Hypoxia-Inducible Factors
8.4.3.2 Cellular Metabolism
8.4.3.3 Bone Morphogenetic Protein Signaling
8.5 Sex-Based Differences in Human PH
8.5.1 Clinical Data
8.5.2 Potential Mechanisms Underlying Sex-Related Differences in PAH Outcomes
8.5.2.1 Anatomical Factors
8.5.2.2 Sex Hormones
8.5.2.3 Genetics
8.6 Sex-Based Differences in Response to Treatments
8.6.1 Prostacyclin
8.6.2 Nitric Oxide Pathway
8.6.3 Endothelin Pathway
8.6.4 Mechanisms Underlying Sex-Related Differences in Therapy Response
8.7 Clinical Ramifications/Future Directions
References
Chapter 9: Sex and Gender Differences in the Susceptibility to Environmental Exposures
9.1 Introduction
9.2 Sex Differences in the Response to Ozone Exposure
9.2.1 Epidemiological Studies
9.2.2 Clinical Studies
9.2.3 Animal Models
9.3 Sex Differences in the Response to Air Particulate Matter Exposure
9.3.1 Epidemiological Studies
9.3.2 Animal Models
9.3.3 Cell Culture Models
9.4 Sex Differences in the Response to Carbon Monoxide Exposure
9.4.1 Human Studies
9.5 Sex Differences in the Response to Nitrogen Dioxide and Sulfur Dioxide Exposure
9.5.1 Epidemiological Studies
9.5.2 Clinical Studies
9.5.3 Cell Culture Models
9.5.4 Animal Models
9.6 Conclusion
References
Chapter 10: Respiratory Sex Differences in Response to Smoke Exposure
10.1 Introduction
10.2 Anatomy
10.3 Exposure
10.3.1 Tobacco Product Smoke
10.3.2 Wildfire, Wood, and Biomass Smoke
10.4 Exposure-Related Sex-Biased Respiratory Diseases
10.4.1 COPD
10.4.1.1 Mechanisms
10.4.2 Lung Cancer
10.4.2.1 Mechanisms
10.4.3 Asthma
10.4.3.1 Mechanisms
10.4.4 E-Cigarette- and Vaping-Associated Lung Injury (EVALI)
10.4.4.1 Mechanisms
10.4.5 Viral Infection
10.4.5.1 Mechanisms
10.4.6 Other Respiratory Effects
10.5 Conclusions
10.6 Future Directions
References
Chapter 11: Sex Differences in Adaptive Immunity in Chronic Lung Disease
11.1 Introduction
11.1.1 Sex Differences in Adaptive Immunity in Chronic Lung Diseases
11.2 Basics of Adaptive Immunity
11.2.1 Humoral Immunity
11.2.2 Cell-Mediated Immunity
11.2.3 CD4+ T Cell Subsets
11.3 Sex Bias in Adaptive Immunity
11.4 Sex Differences in Asthma
11.4.1 Epidemiological and Clinical Studies on Sex Differences in Asthma
11.4.1.1 Childhood Asthma
11.4.1.2 Onset of Puberty and Sex Differences in Asthma
11.4.1.3 Androgens and Asthma
11.4.1.4 Menstrual Cycles, Pregnancy, and Menopause and Asthma
11.4.2 Sex Differences in Adaptive Immune Pathways Important in Asthma
11.4.2.1 Adaptive Immune Responses in Allergic Asthma
11.4.2.2 Adaptive Immune Responses in Neutrophilic Airway Inflammation in Asthma
11.4.2.3 Tregs and Suppressive Immune Responses
11.4.3 Summary
11.5 Sex Differences in Fibrotic Lung Diseases
11.5.1 Adaptive Immune Responses in IPF
11.5.2 Adaptive Immune Responses in Sarcoidosis
11.6 Chapter Summary
References
Chapter 12: Network Medicine and Systems Biology Considerations to Understand Sex Differences in Lung Disease
12.1 Introduction
12.2 Sex Chromosomes in Lung Health and Disease
12.3 Single Omic Support for Molecular Sex Differences in Lung Disease
12.4 Genetics
12.5 Gene Expression
12.6 Epigenetics/DNA Methylation
12.7 Network Medicine Approaches to Sex Differences in Lung Disease
12.8 Validation of Human Disease Network Findings
12.9 Conclusions
References
Chapter 13: Sex Differences in Respiratory Infection
13.1 Introduction
13.2 Airway Anatomy, Physiology, and Host Genetics
13.3 The Influence of Sex Hormones on Lung Infection
13.4 Microbial Growth and Sex Hormones
13.4.1 Bacteria: Coxiella burnetii and Neisseria spp.
13.4.2 Mycobacterium Tuberculosis
13.4.3 Viral Infection: Influenza and SARS-CoV-2
13.4.4 Fungi: Coccidioidomycosis, Paracoccidioidomycosis, and Candida
13.5 Microbial Synthesis and Metabolism of Sex Steroids and ``Sex Steroid-Like Compounds´´
13.5.1 Sex Steroid-Induced Microbial Virulence: Pseudomonas and Candida
13.6 The Interaction of Sex Hormones, Host Immunity, and Respiratory Infection
13.6.1 Innate Immunity
13.6.2 Toll-Like Receptors (TLRs)
13.6.3 Neutrophils
13.6.4 Alveolar Macrophages
13.6.5 Monocytes and Monocyte-Derived Cells
13.6.6 Natural Killer Cells
13.6.7 Plasmacytoid Dendritic Cells (pDCs)
13.6.8 Adaptive Immunity
13.6.9 B Cells
13.6.10 T Cells
13.7 MicroRNAs (miRNAs)
13.8 Sociocultural and Behavioral Factors
13.9 Conclusion
References
Chapter 14: Androgen Excess in Women and the Respiratory System
14.1 Introduction
14.2 Hormonal Changes Associated with Menopause
14.2.1 Gonadotropin Releasing Hormones and Gonadotropins
14.2.2 Androgens
14.2.3 Estrogens
14.2.4 Anti-MΓΌllerian Hormone
14.3 Extragonadal Production of Sex Steroids: The Role of Adipose Tissue
14.4 Lung Function in Women: Changes after Menopause
14.4.1 Menopause and Asthma
14.4.2 Menopause and Obstructive Sleep Apnea
14.5 Cardiovascular Risk Factors that Could Affect Respiratory System after Menopause
14.5.1 Insulin Resistance
14.5.2 Smoking
14.5.3 Menopause and Obesity-Mediated Lung Injury
14.5.3.1 Pulmonary Mechanics
14.5.3.2 Inflammatory Mediators
14.5.3.3 Dyslipidemia
14.5.3.4 Effect of Weight Loss on Pulmonary Function
14.6 Effect of Menopausal Sarcopenia on Pulmonary Function
14.7 Effect of Hormone Replacement Therapy (HRT) on Pulmonary Function
14.8 Polycystic Ovary Syndrome
14.9 Possible Mechanisms Mediating Impairment in Lung Function in Hyperandrogenemic Conditions: Role of the Renin Angiotensin ...
14.10 Summary
References
Chapter 15: Sex Differences in Circadian Biology: Influences on Lung Health and Disease
15.1 Introduction
15.2 Circadian Rhythms
15.3 Sex Differences in Circadian Rhythms
15.4 Sexual Dimorphism in the Lungs
15.5 Sexual Dimorphism and Circadian Rhythms in Lung Immunity
15.6 Sex and Gender Differences in Lung Disease: Role of Circadian Rhythms
15.6.1 Sex and Gender Differences in Asthma
15.6.1.1 Circadian Rhythms and Asthma
15.6.2 Sex and Gender Differences in Chronic Obstructive Pulmonary Disease
15.6.2.1 Circadian Rhythms and Chronic Obstructive Pulmonary Disease
15.6.3 Sex and Gender Differences in Pulmonary Fibrosis
15.6.3.1 Circadian Rhythms and Pulmonary Fibrosis
15.6.4 Sex and Gender Differences in Infectious Respiratory Disease
15.6.4.1 Circadian Rhythms and Viral Infections
15.6.4.2 Circadian Rhythms and Bacterial Infections
15.7 Chronotherapeutics and Its Implications in Chronic Lung Disease
15.8 Conclusion and Future Directions
References
Chapter 16: Sex Differences in the Coronavirus Disease 2019
16.1 Introduction
16.2 Sex Chromosomes and COVID-19
16.3 The Roles of Estrogen and Progesterone in COVID-19
16.4 The Role of Androgens in COVID-19
16.5 Clinical Trials for COVID-19 Involving Sex Steroid Signaling
16.6 Gender Differences in COVID-19
16.7 Conclusion
References