Precision in Pulmonary, Critical Care, and Sleep Medicine: A Clinical and Research Guide (Respiratory Medicine)

Preface
Contents
Contributors
Part I: Introduction
	1: Introduction
		References
Part II: Genetics
	2: Differential Diagnosis of Diffuse Pulmonary Disorders Using Genetics
		Introduction
		Overview of Genetic Testing
		Neonatal Respiratory Distress Syndrome (RDS) and Diffuse Lung Disease in Childhood
		Pulmonary Alveolar Proteinosis (PAP)
		Pulmonary Vascular Disease
		Cystic Lung Disease and Spontaneous Pneumothorax
		Bronchiectasis and Obstructive Lung Disease
		Adult Interstitial Lung Disease
		Challenges and Future Directions
		References
	3: Genetics and Pharmacogenetics of Asthma
		Introduction
		Genetics of Asthma
		Genetics of Traits Related to Asthma
		Shared Genetics of Asthma and Allergic Diseases
		Genetics of Bronchodilator Response
		Genetics of Glucocorticoid Response
		Conclusion
		References
	4: Genetics and Pharmacogenetics of COPD
		The Era of Precision Medicine Needs in COPD
		The Evolving Genetic Map of COPD
		Overlapping Loci with Lung Function, COPD-Related Phenotypes, and Other Diseases
		Integrative Genomic Approaches
		Translating New COPD Genetics Knowledge into Clinical Applications
		COPD Pharmacogenetics
		Future Directions
		Conclusions
		References
	5: The Evolution of Precision Medicine in Cystic Fibrosis
		From Clinical Phenotyping to Personalized Molecular Diagnosis
			Standardized Approach to CF Diagnosis
			Diagnostic Approaches to CFTR Mutations
		From Disease Management to the Rise of Precision Medicine Therapies in CF
			Precision Medicine Approaches to CF Therapy
			Gene Therapy
			CFTR Modulators
		Evolving Concepts in CF Precision Medicine: Going Deeper and Beyond the CFTR Gene
		Future Directions
		Summary
		References
	6: Genetics of Idiopathic Pulmonary Fibrosis
		Introduction
		Clinical Presentation of IPF
		Clinical Evaluation, Diagnosis, and Treatment of IPF
		Rare Genetic Variants Associated with IPF
			Surfactant Proteins
			Telomerase Pathway Genes
		Common Genetic Variants and IPF
		Genetic Variants and Clinical Management of IPF
			Clinical Phenotypes
			Therapeutic Implications
		Early Detection of Pulmonary Fibrosis
		Conclusion
		References
	7: Genetics of Lung Cancer
		Introduction
		Role of Mutations in Lung Cancer
		Types of Genomic Alterations in Lung Cancer
		Causes of Somatic Mutations That Lead to Lung Cancer
		Genetics of Lung Cancer
			Candidate Gene Studies
			Genome-Wide Association Studies of Lung Cancer Risk
			Familial Lung Cancer Syndromes
			Genetics of Lung Cancer Survival
			Driver Mutations in NSCLC
			Epidermal Growth Factor Receptor (EGFR) Mutations
			Anaplastic Lymphoma Kinase (ALK) Fusion Mutation
			ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (ROS1) Mutations
			B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) Mutations
			Neurotrophic Receptor Tyrosine Kinase (NTRK) Gene Fusions
			MET Proto-Oncogene, Receptor Tyrosine Kinase (MET) Amplification and Mutation
			Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) Mutations
			Ret Proto-Oncogene (RET) Fusions
			KRAS Proto-Oncogene, GTPase (KRAS) Mutations
			Other NSCLC-Related Mutations
		Driver Mutations in SCLC
		Evolution of Lung Cancer
		Conclusion
		References
Part III: Biomarkers
	8: Chest Imaging for Precision Medicine
		Introduction
		Chest X-Ray
		Computed Tomography
		Magnetic Resonance Imaging
		Positron Emission Tomography
		Ultrasound
		Conclusion and Future Directions
		References
	9: Biobanking for Pulmonary, Critical Care, and Sleep Medicine
		Introduction
		Biobanking: History and Definitions
		Biobank Components
			Participants: Opt In, Opt Out, and Informed Consent
			Confidentiality, Privacy, and Data Protection
			Biobank Stakeholders and Governance
		Operations and Management
		Operational Aspects
		Types of Biobank Specimens in PCCSM Research
		Clinical Data Considerations in PCCSM Research
		Challenges
		Conclusion
		References
	10: Biomarkers in Obstructive Airway Diseases
		Introduction
		Asthma
			Asthma Endotypes
		COPD
			Genomic Biomarkers of COPD
			COPD Exacerbations
			Lung Function Decline in COPD
			Emphysema
			COPD Severity
			COPD Mortality
			Future Omics-Based COPD Biomarker Studies
		Asthma–COPD Overlap (ACO)
			Candidate ACO Biomarkers
			Lung Function Decline in ACO and Implications for Pharmacotherapy
		Future Directions
			Challenges for Precision Medicine in Obstructive Pulmonary Diseases
		Conclusion
		References
	11: Biomarkers in Interstitial Lung Diseases
		Introduction
		Epithelial Dysfunction Candidate Biomarkers
			Surfactant Proteins
			Krebs von den Lungen-6 (KL-6)
			Telomeres
			Other Proteins Reflecting Epithelial Damage
		ECM Remodeling and Fibropoliferation Candidate Biomarkers
			Matrix Metallopeptidase 7 (MMP7)
			Combined Protein Biomarkers
			ECM Neoepitopes
			Fibrocytes
		Immune Dysregulation Candidate Biomarkers
			Chitinase 3 Like 1 (CHI3L1)
			C-C Motif Chemokine Ligand 18 (CCL18)
			Immune-Related Gene Expression Signatures
		Conclusion
		References
	12: Molecular Diagnostics in Pulmonary Infections
		Molecular Diagnostics—Recognition and Identification of the Pathogen
			Illustrative Case (See Fig. 12.1)
			The Traditional Approach to Diagnosing Pneumonia: History, Physical Exam, and Basic Diagnostics
			Pathogen-Associated Biomarkers (See Table 12.1 for Summary)
			Genomic Profiling of Pathogen
				Multiplex PCR
				Quantitative PCR
				PCR for Recognition of Genes Mediating Resistance or Virulence
				PCR for Detection of Mycobacteria
			Mass Spectrometry for Proteomic Profiling
				MALDI-TOF MS
				Volatile Organic Compounds
			Metataxonomics and Metagenomics
		Molecular Diagnostics—Characterizing the Host Response
			Host Response Biomarkers (See Table 12.2 for Summary)
			C-reactive Protein
			Procalcitonin
			Cytokines
			Newer Biomarkers
			Genetics
			Transcriptomics
			Metabolomics and Lipidomics
			Sputum, Bronchoalveolar Lavage, and Exhaled Breath Sampling
		Conclusions
		References
	13: Biomarkers in Critical Care Illness: ARDS and Sepsis
		Introduction
			Identifying Biomarkers
		Defining Sepsis and Acute Respiratory Distress Syndrome
		Diagnostic Biomarkers in Sepsis
			Biomarkers in Existing Definitions of Sepsis
			Hypothesis-Based Candidates
			MicroRNAs
			Transcriptomics
			Metabolomics
		Prognostic Biomarkers in Sepsis and ARDS
			Survival Prognostication in Sepsis and ARDS
			Biomarkers in Survivors of Critical Illness
		Theranostic Biomarkers in Sepsis and ARDS
		Conclusions
		References
Part IV: Precise Phenotyping
	14: Lessons for Precision Medicine from Lung Cancer
		Introduction
		Lesson #1: Precision Medicine Is an Iterative Process: Better Disease Understanding Facilitates Better Individualized Assessment
			Lung Cancer Is a Heterogeneous Disease
			Determining the Extent of Disease Predicts Outcome
			A Patient’s Functional Status Influences Outcome
		Lesson #2: Tools for Individualized Assessments: Lung Cancer Risk, Diagnosis, and Staging
			Lung Cancer Screening
			Anatomic Staging
			Tumor Tissue Evaluation
		Lesson #3: From Individualization to Personalization – The Patient as Stakeholder
			A Precise Approach: From Individualized to Personalized
			Shared Decision-Making
		Conclusion
		References
	15: COPD Phenotyping
		General Considerations for Prevention, Diagnosis, and Treatment of Chronic Obstructive Pulmonary Disease
		Current COPD Management
		General Principles of Novel Concepts with Relevance for Precision Medicine
			Bronchial Hyper-responsiveness
			Exacerbations
			Comorbidities
			Research Approaches to COPD Phenotype Assessment
			Radiographic Phenotyping
			Biomarker Discovery
			Computational Approaches to Disease Classification
		Selection for Lung Volume Reduction: A Case of Precision Medicine in Clinical Practice #1
		Alpha-1 Antitrypsin Deficiency: A Case of Precision Medicine in Clinical Practice #2
		Future Directions
		References
	16: Precision Medicine in Pulmonary Hypertension
		Introduction
		Resting Hemodynamic Phenotyping
		Exercise Hemodynamic Phenotyping
		Phenotyping by Cardiopulmonary Imaging
		Molecular Phenotyping
			Genetics
			Omics
		Future Directions
		References
	17: Identifying Subtypes of Obstructive Sleep Apnea
		Studies Employing Cluster Analysis Using Data from Multiple Dimensions
		Using More Focused Approaches: Examining for Physiological Subtypes
		Clinical Subtypes Based on Symptoms
		Conclusions
		References
	18: Precision Medicine in Critical Illness: Sepsis and Acute Respiratory Distress Syndrome
		Introduction
		Targeted Proteomics: Laying the Foundation for Precision Medicine of Sepsis and ARDS
		What Can Be Learned from Genetic Approaches in Complex, Non-Mendelian Traits?
		Knowledge- and Discovery-Based Genomics Studies
		Unique Challenges to Achieving Precision Medicine in Critical Care
		Sepsis Genetics: Hints at Heterogeneous Treatment Effects
		ARDS Genetics and the Search for Causal Intermediates
		Sepsis Gene Expression Studies: Ready for Clinical Launch?
		Gene Expression Studies in ARDS
		Metabolomics Studies in Sepsis and ARDS
		Conclusion
		References
Part V: Mobile Health, Wearables, and Telemedicine
	19: Mobile Applications and Wearables for Chronic Respiratory Disease Monitoring
		Introduction
		mHealth from the Patient’s Perspective
			Usability and Engagement
			Perceived Benefits
			Parents’ Point of View
			Patients’ Concerns
			Summary
		mHealth from the Healthcare Provider’s Perspective
			mHealth Apps
			Wearables
		mHealth from the Healthcare System’s Perspective
			Cost-Effectiveness
			Privacy
			Widespread Diffusion of mHealth
		Conclusion
		References
	20: Personal Environmental Monitoring
		Introduction
		Air Pollution and Respiratory Health
		Regulatory Monitors
		Applications of Low-Cost Air Pollution Sensors
			Supplementing Traditional Air Monitoring Networks
			Evaluating Indoor Air Quality
			Measuring Personal Exposures Directly
		Considerations for Sensor Selection and Use
			Sensor Selection
			Sensor Calibration
			Practical Considerations for Sensor Deployment
		Advancing Respiratory Health Through Low-Cost Sensing: Applications and Future Directions
		Conclusion
		References
	21: Tele-ICU in Precision Medicine: It’s Not What You Do, But How You Do It
		Introduction
		Epidemiology
		Concepts/Models
		Data and Acuity Scoring Systems
		Outcomes
		Financial Considerations
			Direct Reimbursement/Revenue
			Indirect Revenue
		Conclusions/Future Challenges
		References
Part VI: Precision Therapeutics
	22: Lung Transplantation and Precision Medicine
		Introduction
		Surgical Issues
		Acute Lung Allograft Dysfunction
		Chronic Lung Allograft Dysfunction
		Conclusion
		References
	23: Precision in Mechanical Ventilation
		Ventilator-Induced Lung Injury
			Alveolar Overdistension
			Atelectrauma
			Biotrauma
		Restrictive Disorders of the Lung
			Low Tidal Volume Ventilation in ARDS
			Low Tidal Volume Ventilation in Non-ARDS
			Prone Positioning
			Plateau Pressure
			Protocolized PEEP
			Driving Pressure
			Recruitment Maneuvers, Best Respiratory System Compliance
			Esophageal Pressure
			Stress Index
			Pressure-Volume Curves
			Electrical Impedance Tomography
			Spontaneous Breathing
			Noninvasive Ventilation
		Obstructive Disorders of the Lung
			Auto-PEEP and Dynamic Overinflation
		Ventilator Asynchrony
			Breath Stacking
			Reverse Triggering
			Ineffective Triggering
			Auto-Cycling
			Inspiratory Flow Mismatching
			Conclusion
		References
	24: Precision Medicine for Cigarette Smoking Addiction
		General Considerations for Prevention, Diagnosis, and Treatment of Cigarette Smoking Addiction
			Prevention
			Diagnosis
			Treatment
			Follow Up
		General Principles of Novel Concepts with Relevance for Precision Medicine
			Sex Differences in Smoking Addiction
			Genetic Differences in Brain Nicotine Receptors
			Pharmacogenetic Differences in Nicotine Metabolism
			Comorbid Conditions Complicating Smoking
		Future Directions
			Tobacco Harm Reduction
		Summary
		References
	25: Implementing COPD Precision Medicine in Clinical Practice
		Introduction
		COPD as a Heterogeneous Disorder
		Precision Medicine in COPD
		Precision Medicine in the Use of Inhaled Corticosteroids
		Precision Medicine in the Use of Bronchodilators
		Precision Medicine in the Use of Antibiotic Prophylaxis
		Precision Medicine in the Use of Non-Pharmacologic Therapies
		Application of Precision Medicine in Drug Discovery
		Precision Medicine to Prevent Rapid Loss of Lung Function in COPD?
		Conclusion
		References
Part VII: Enabling Widespread Adoption of Precision Medicine
	26: Precision Medicine for All: Minority Health
		Introduction
		The US Population Is Increasingly Diverse and Multiethnic
		Lung Function: A Heritable Trait that Varies According to Genetic Ancestry
		Precision Medicine Approaches May Improve COPD Inequalities
		Precision Medicine Approaches May Improve Asthma Disparities
		Conclusions
		References
	27: Education for the Practice of Precision Medicine in PCCSM: Creating Tomorrow’s Workforce
		Introduction
			Undergraduate and Graduate Medical Education
			Competency Assessment Through Entrustable Professional Activities
			Ongoing Education for Practicing Providers
			Leveraging Characteristics of the Adult Learner
		What Are Specialty-Specific Genomic Opportunities in Pulmonary Medicine?
		Future of Pulmonary, Critical Care, and Sleep Medicine Training in Genomics and Personalized Medicine
		References
	28: Summary and Future Applications of Precision Medicine in Pulmonary, Critical Care, and Sleep Medicine
		Introduction
		Genetics and Pharmacogenetics in Pulmonary, Critical Care, and Sleep Medicine
		Biomarkers in Pulmonary, Critical Care, and Sleep Medicine
		Phenotyping in Pulmonary, Critical Care, and Sleep Medicine
		The Role of Sensors, Wearables and Health Information Technologies in Pulmonary, Critical Care, and Sleep Medicine
		Precision Therapies in Pulmonary, Critical Care, and Sleep Medicine
		Ongoing and Future Efforts in Pulmonary, Critical Care, and Sleep Precision Medicine
		Conclusion
		References
Index