Asthma in the 21st Century: New Research Advances

Front cover
Half title
Full title
Copyright
Contents
Contributors
Foreword
Acknowledgments
Chapter 1 - Asthma: From one disease to endotypes
	1.1 Introduction
	1.2 History of “asthma”
		1.2.1 From antiquity to the 19th century
		1.2.2 The modern ERA: From the 20th century to the present time
	1.3 Clinical and epidemiological aspects of asthma
		1.3.1 Clinical aspects of asthma
		1.3.2 Epidemiological aspects of asthma
			1.3.2.1 Asthma definitions in epidemiology
			1.3.2.2 Respiratory symptoms and asthma prevalence rates
		1.3.3 From one disease to phenotypes
	1.4 Asthma phenotypes
		1.4.1 Phenotypes according to the age of onset of asthma
			1.4.1.1 Phenotypes in childhood
			1.4.1.2 Phenotypes in adulthood
		1.4.2 From phenotypes to endotypes
	1.5 Asthma endotypes
		1.5.1 Endotypes from inflammatory and severe asthma phenotypes
		1.5.2 Endotypes including omics-based approaches
		1.5.2 Endotypes identified by data-driven methods
			1.5.2.1 Among children
			1.5.2.2 Among adults
	1.6 Conclusion
	References
Chapter 2 - Eosinophilic and noneosinophilic asthma: Beyond severe asthma
	2.1 Introduction
	2.2 Eosinophilic asthma
		2.2.1 Defining eosinophilic asthma
		2.2.2 Clinical characteristics of eosinophilic asthma
			2.2.2.1 Allergic asthma
			2.2.2.2 Late-onset eosinophilic asthma
			2.2.2.3 Aspirin exacerbated respiratory disease
			2.2.2.4 Allergic bronchopulmonary aspergillosis and mycosis
		2.2.3 Mechanisms through which eosinophils contribute to disease
			2.2.3.1 Recruitment and activation of eosinophils
			2.2.3.2 Effector functions of eosinophils in asthma
			2.2.3.3 Impact of obesity on eosinophilic asthma
	2.2 Noneosinophilic asthma
		2.2.1 Defining noneosinophilic asthma
		2.2.2 Clinical characteristics of noneosinophilic asthma
		2.2.3 Mechanisms of noneosinophilic asthma
			2.2.3.1 Neutrophilic asthma
				2.2.3.1.1 Recruitment of neutrophils
				2.2.3.1.2 Functions of neutrophils
			2.2.3.2 Cigarette smoke-related asthma
			2.2.3.3 Obesity-related noneosinophilic asthma
			2.2.3.4 Paucigranulocytic asthma
	2.3 Implications for treatment of asthma
	2.4 Conclusion
	References
Chapter 3 - Airway microbiome and asthma
	3.1 Introduction
	3.2 Sampling and characterization of airway microbiome
		3.2.1 Sampling
		3.2.2 Marker gene analysis
		3.2.3 Metagenomic shotgun sequencing
		3.2.4 Statistical analysis
	3.3 Airway microbiota and asthma in adults
		3.3.1 Airway microbiota in patients with asthma versus healthy subjects
		3.3.2 Airway microbiota and asthma phenotypes
		3.3.3 Conclusion and discussion on airway microbiota in adults
	3.4 Airway microbiota, wheezing and asthma in children
		3.4.1 Wheezing illnesses
		3.4.2 Asthma
		3.4.3 Conclusion and discussion on airway microbiota in children
	3.5 Early life environment and airway microbiota
	3.6 Gut microbiota, airway microbiota and the gut–lung axis in asthma
	3.7 Conclusion and future directions
	References
Chapter 4 - Gender differences and sex-related hormonal factors in asthma
	4.1 Introduction
	4.2 Gender differences in asthma, findings from epidemiologic studies
		4.2.1 Asthma prevalence
		4.2.2 Incidence and remission
			4.2.2.1 Incidence and remission-findings from retrospective studies
			4.2.2.2 Incidence and remission-findings from prospective studies
			4.2.2.3 Incidence and remission-findings from prospective studies around puberty
		4.2.3 Diagnosis
		4.2.4 Severity and phenotypes
			4.2.4.1 Asthma emergency department visits, hospitalizations, and mortality
			4.2.4.2 Severity
			4.2.4.3 Phenotypes
	4.3 Hormonal factors: Events associated with changes in sex hormones among women
		4.3.1 Changes in respiratory outcomes with puberty and menarche
		4.3.2 Changes in respiratory outcomes with menstrual cycle
			4.3.2.1 Menstrual cycle phase
			4.3.2.2 Menstrual irregularity, long cycle, and polycystic ovary syndrome
		4.3.3 Changes in respiratory outcomes with oral contraceptive use
			4.3.3.1 Challenges when investigating association between hormonal treatment use and asthma
			4.3.3.2 Oral contraceptive
		4.3.4 Changes in respiratory outcomes with pregnancy
		4.3.5 Changes in respiratory outcomes with menopause
			4.3.5.1 Menopause and asthma
			4.3.5.2 Menopause and lung function
		4.3.6 Changes in respiratory outcomes with hormonal treatment for the menopause
	4.4 Hormones and respiratory health
		4.4.1 Overview of findings from experimental studies
			4.4.1.1 Lung physiology (Male>Female)
			4.4.1.2 Nonallergic inflammation/acute lung injury (Male>Female)
			4.4.1.3 Allergic lung inflammation (Female>Male)
			4.4.1.4 Lung fibrosis and chronic obstructive pulmonary disease (COPD) (Female>Male)
		4.4.2 Lung physiology, sex hormones, sex hormone-binding globulin and asthma: Findings from Epidemiologic studies and clin ...
			4.4.2.1 Childhood
			4.4.2.2 Adulthood
			4.4.2.3 Sex hormone-binding globulin
			4.4.2.4 Randomized clinical trials
	4.5 Gender specific determinants of asthma, beyond sex hormones
		4.5.1 Obesity
		4.5.2 Environment
		4.5.3 Gender and sex hormones
	4.6 Conclusion
	References
Chapter 5 - Diet and asthma
	5.1 Introduction
	5.2 Assessment of diet in epidemiological studies
		5.2.1 Tools to assess dietary intakes
		5.2.2 Approaches to analyzing dietary data
			5.2.2.1 Approach through foods and nutrients
			5.2.2.2 Approach through dietary patterns
				5.2.2.2.1 A priori approach–diet scores
					5.2.2.2.1.1 The Mediterranean diet score
					5.2.2.2.1.2 The alternate healthy eating index
					5.2.2.2.1.3 The dietary inflammatory index
				5.2.2.2.2 A posteriori approach–data-driven dietary patterns
					5.2.2.2.2.1 Principal component analysis (PCA)
					5.2.2.2.2.2 Cluster analysis
				5.2.2.2.3 Methods “in between”
	5.3 Windows of exposure and expression, and measurement error
	5.4 Diet and asthma: State of the art
		5.4.1 Dietary antioxidant intake
			5.4.1.1 Vitamin E
				5.4.1.1.1 Maternal diet during pregnancy
				5.4.1.1.2 Diet in childhood
				5.4.1.1.3 Diet in adulthood
			5.4.1.2 Vitamin C
				5.4.1.2.1 Maternal diet during pregnancy
				5.4.1.2.2 Diet in childhood
				5.4.1.2.3 Diet in adulthood
			5.4.1.3 Vitamin A
				5.4.1.3.1 Maternal diet during pregnancy
				5.4.1.3.2 Diet in childhood
				5.4.1.3.3 Diet in adulthood
			5.4.1.4 Selenium
				5.4.1.4.1 Maternal diet during pregnancy
				5.4.1.4.2 Diet in childhood
				5.4.1.4.3 Diet in adulthood
			5.4.1.5 Zinc
				5.4.1.5.1 Maternal diet during pregnancy
				5.4.1.5.2 Diet in childhood
				5.4.1.5.3 Diet in adulthood
			5.4.2 Dietary polyunsaturated fatty acid intake
				5.4.2.1 Maternal diet during pregnancy
				5.4.2.2 Diet in childhood
				5.4.2.3 Diet in adulthood
			5.4.3 Vitamin D
				5.4.3.1 Maternal diet during pregnancy
				5.4.3.2 Diet in childhood
				5.4.3.3 Diet in adulthood
			5.4.4 Folates
				5.4.4.1 Maternal diet during pregnancy
				5.4.4.2 Diet in childhood
				5.4.4.3 Diet in adulthood
			5.4.5 Fiber
				5.4.5.1 Maternal diet during pregnancy
				5.4.5.2 Diet in childhood
				5.4.5.3 Diet in adulthood
			5.4.6 Specific food or food groups
				5.4.6.1 Vegetables and fruits
			5.4.6.1.1 Maternal diet during pregnancy
				5.4.6.1.2 Diet in childhood
				5.4.6.1.3 Diet in adulthood
			5.4.6.2 Fish
				5.4.6.2.1 Maternal diet during pregnancy
				5.4.6.2.2 Diet in childhood
			5.4.6.2.3 Diet in adulthood
			5.4.6.3 Processed meat
				5.4.6.3.1 Maternal diet during pregnancy
				5.4.6.3.2 Diet in childhood
				5.4.6.3.3 Diet in adulthood
			5.4.6.4 Sugar sweetened beverages
				5.4.6.4.1 Maternal diet during pregnancy
				5.4.6.4.2 Diet in childhood
				5.4.6.4.3 Diet in adulthood
		5.4.7 Dietary patterns
			5.4.7.1 A priori approach–diet scores
				5.4.7.1.1 The Mediterranean diet score
			5.4.7.1.1.1 Maternal diet during pregnancy
			5.4.7.1.1.2 Diet in childhood
			5.4.7.1.1.3 Diet in adulthood
			5.4.7.1.2 The Alternate Healthy Eating Index-2010 (AHEI-2010)
				5.4.7.1.2.1 Maternal diet during pregnancy
				5.4.7.1.2.2 Diet in childhood
				5.4.7.1.2.3 Diet in adulthood
			5.4.7.1.3 The dietary inflammatory index
				5.4.7.1.3.1 Maternal diet during pregnancy
				5.4.7.1.3.2 Diet in childhood
				5.4.7.1.3.3 Diet in adulthood
			5.4.7.2 A posteriori approach–data-driven dietary patterns
				5.4.7.2.1 Maternal diet during pregnancy
				5.4.7.2.2 Diet in childhood
				5.4.7.2.3 Diet in adulthood
	5.5 Complex interrelations between diet, obesity, and physical activity in asthma prevention and management
		5.5.1 State of the art
		5.5.2 The issue of mediation by obesity in the diet-asthma association
		5.5.3 The issue of time-dependent confounding in the interrelations between nutritional factors and asthma
		5.5.4 Epiphenomenon
	5.6 Conclusion and future directions
	References
Chapter 6 - Indoor air and respiratory health: Volatile organic compounds and cleaning products
	6.1 Introduction
	6.2 Exposure assessment of indoor chemicals: VOCs, SVOCs, and cleaning products
		6.2.1 Exposure assessment of volatile organic compounds
		6.2.2 Exposure assessment of semivolatile organic compounds
		6.2.3 Cleaning products
	6.3 Respiratory health effects of residential exposure to VOCs, SVOCs, and cleaning products: Results from epidemiological ...
		6.3.1 Respiratory effects of volatile organic compounds
			6.3.1.1 Evidence in adults
			6.3.1.2 Evidence in children
			6.3.1.3 Conclusion on volatile organic compounds and asthma
		6.3.2 Respiratory effects of semivolatile organic compounds
			6.3.2.1 Conclusion on semivolatile organic compounds and asthma
		6.3.3 Cleaning products
			6.3.3.1 Evidence in adults
			6.3.3.2 Evidence in children
	6.4 Conclusions on respiratory health effects of cleaning products
	6.5 Conclusion and future directions
	References
Chapter 7 - Outdoor air pollution and asthma in a changing climate
	7.1 General introduction
	7.2 Air pollution and asthma
		7.2.1 Main air pollutants
		7.2.2 Short-term effect on asthma
		7.2.3 Long-term air pollution and asthma
			7.2.3.1 Long-term air pollution and asthma in children
			7.2.3.2 Long-term air pollution and asthma in adults
		7.2.4 Susceptibility factors
		7.2.5 Burden of air pollution exposure on asthma
		7.2.6 Possible mechanisms
		7.2.7 Causality
	7.3 Asthma and air pollution in the context of climate change
		7.3.1 Air pollution and climate change
		7.3.2 Climate change and asthma
		7.3.3 Interaction between climate change, air pollution, and asthma
	7.4 General conclusion
	References
Chapter 8 - Genetic and epigenetic links to asthma
	8.1 Introduction
	8.2 Asthma gene discovery through genome-wide association studies
		8.2.1 Beyond SNP associations
		8.2.2 Genetic associations of asthma subphenotypes
			8.2.2.1 Severe asthma
			8.2.2.2 Childhood- and adult-onset asthma
			8.2.2.3 Asthma with allergic diseases
			8.2.2.4 Gene-environment interactions in asthma
		8.2.3 Take-home messages from GWASs of asthma
	8.3 The role of rare and loss-of-function variants in asthma
		8.3.1 Rare LOF variants in the ADRB2 gene are associated with severe asthma
		8.3.2 A rare LOF variant in the IL33 gene is associated with eosinophilia and asthma
		8.3.3 Nonsense mutations in the FLG gene are associated with asthma
		8.3.4 A common LOF variant in GSDMB confers protection from asthma
		8.3.5 Take-home messages from rare variant and loss-of-function mutation studies
	8.4 Epigenomic studies of asthma
		8.4.1 Methods for studying DNAm
		8.4.2 Overview of DNAm studies in asthma
			8.4.2.1 Whole-genome DNAm studies of asthma in blood cells
			8.4.2.2 Whole-genome DNAm studies of asthma in airway epithelial cells
		8.4.3 Take-home messages from DNAm studies in asthma
	8.5 Conclusions and future directions
	References
Chapter 9 - Asthma and COPD: distinct diseases or components of a continuum?
	9.1 Introduction
	9.2 Asthma, COPD, overlap: definitions and basic epidemiology
		9.2.1 Definitions
		9.2.2 Burden
	9.3 Natural history of and risk factors for obstructive airways diseases, from childhood to advanced age
		9.3.1 From early life and childhood to adult asthma and COPD
		9.3.2 Common and specific risk factors
			9.3.2.1 Allergic sensitization
			9.3.2.2 Smoking and other environmental exposures
			9.3.2.3 Genetic factors
			9.3.2.4 Viral infections
		9.3.3 Asthma and COPD in adults
		9.3.4 Asthma and COPD in the elderly
	9.4 Shared and distinct underlying mechanisms
		9.4.1 Small airways obstruction
		9.4.2 Microbial environment
			9.4.3 Inflammatory pathways and their biomarkers
	9.5 Clinical presentations and diagnostic challenges
		9.5.1 Major clinical phenotypes
		9.5.2 Asthma-COPD overlap (ACO)
			9.5.2.1 Other diagnostic challenges
	9.6 Physiological similarities and differences between asthma and COPD
	9.7 The role of imaging in the assessment of chronic airways diseases
		9.7.1 Computed tomography (CT) signs of bronchial involvement
		9.7.2 Specific features of COPD
		9.7.3 Particular features of ACO
		9.7.4 Indications of imaging in clinical routine and research settings
	9.8 Therapeutic implications
		9.8.1 Inhaled corticosteroids and inhaled bronchodilators
		9.8.2 Biologics targeting type 2 inflammation
		9.8.3 Add-on, nonbiologic therapies
	9.9 Conclusions
	References
Chapter 10 - Asthma in an aging world
	10.1 Introduction
	10.2 Epidemiology of asthma in the elderly
		10.2.1 Epidemiology of elderly persons
		10.2.2 Epidemiology of asthma in the elderly
		10.2.3 Death from asthma in the elderly
	10.3 Physiological change in the airways due to aging
		10.3.1 Structural changes
		10.3.2 Changes in pulmonary function due to aging
		10.3.3 Immunosenescence
	10.4 Phenotype of asthma in the elderly
	10.5 Problems in diagnosing asthma in the elderly
		10.5.1 Airflow limitation
		10.5.2 Bronchial hyper-responsiveness
		10.5.3 Fraction of exhaled nitric oxide (FeNO)
		10.5.4 Underperception of dyspnea
		10.5.5 Problems in spirometry
		10.5.6 Comorbidities
	10.6 Treatment of asthma in the elderly
		10.6.1 Low peak inspiratory flow and difficulty in synchronization
		10.6.2 Inhaled corticosteroids
		10.6.3 Bronchodilators
		10.6.4 Combination agents comprising ICS, LABA, and LAMA
		10.6.5 Biologics
		10.6.6 Other agents
	10.7 Conclusion
	References
Chapter 11 - Asthma in the digital world
	11.1 Introduction
	11.2 Regulatory framework for data protection
	11.3 Electronic health records
	11.4 Registries in severe asthma
	11.5 Telehealth in asthma
	11.6 mHealth apps
	11.7 mHealth sensors
	11.8 Platforms
	11.9 Serious games
	11.10 Impact of digital health on asthma
		11.10.1 Phenotype discovery using digital health
		11.10.2 Diagnosis
		11.10.3 Management
		11.10.4 Adherence to treatment
	11.11 Conclusion
	References
Index
Back cover