Murray & Nadel's Textbook of Respiratory Medicine

This document was uploaded by one of our users. The uploader already confirmed that they had the permission to publish it. If you are author/publisher or own the copyright of this documents, please report to us by using this DMCA report form.

Simply click on the Download Book button.

Yes, Book downloads on Ebookily are 100% Free.

Sometimes the book is free on Amazon As well, so go ahead and hit "Search on Amazon"

Author(s): V. Courtney Broaddus (Editor), Joel D Ernst (Editor), Jr Talmadge E King (Editor), Stephen C. Lazarus (Editor), Kathleen F. Sarmiento (Editor), Lynn M. Schnapp (Editor), Renee D Stapleton (Editor), Michael B. Gotway
Edition: 7
Publisher: ‎ Elsevier
Year: 2022

Language: English
Pages: 3317

Title
Front Matter.pdf
Murray & Nadel’s Textbook of Respiratory Medicine
Copyright.pdf
Copyright
Dedication.pdf
Dedication
Dedication 1.pdf
Dedication
Contributors.pdf
Contributors
Preface to the Seventh Edition.pdf
Preface to the Seventh Edition
1 Anatomy.pdf
1 -
Anatomy
Introduction
Gross and Subgross Organization
Airways
Bronchial Circulation
Pulmonary Circulation
Terminal Respiratory Units
Lymphatics
Innervation
Pleural Space and Pleural Membranes
Cellular Anatomy of the Lung
Airway Lining Cells
Alveolar Lining Cells
Mesenchymal Cells
Neural Cells
Hematopoietic and Lymphoid Cells
Pleural Cells
Molecular Anatomy of the Lung
Comparison of the Lung of Humans and Mice
Key Readings
Acknowledgments
eFIGURE IMAGE GALLERY
References
2 Lung Growth and Development.pdf
2 - Lung Growth and Development
Stages of Lung Development With Cellular and Molecular Mechanisms
Embryonic Stage
Pseudoglandular Stage
Canalicular Stage
Saccular Stage
Alveolar Stage
Developmental Insights Into Lung Repair and Regrowth
Emerging Technologies to Study Lung Development
Induced Pluripotent Stem Cell–Derived Lung Cells
Lung Organoids
CRISPR/Cas9 Genome Editing
Single-­Cell Sequencing
Representative Developmental Lung Diseases
Defects in Trachea/Esophagus Specification and Separation
Defects in Branching Morphogenesis
Lung Hypoplasia
Surfactant Protein Deficiencies
Preterm Birth and Bronchopulmonary Dysplasia
Childhood Interstitial Lung Diseases
Pulmonary Vascular Disease
Congenital or Lung Developmental Defects That Manifest Later in Life
Key Readings
References
3 Alveolar Compartment.pdf
3 - Alveolar Compartment
INTRODUCTION
Cellular Composition of the Alveolar Epithelium
Alveolar Type 1 Cells
Functional Roles of the Alveolar Unit
Surfactant Composition
Surfactant Protein A
Surfactant Protein B
Surfactant Protein C
Surfactant Protein D
Surfactant Secretion and Turnover
Alveolar Immune Defense and Inflammatory Modulation
Alveolar Epithelial Integrity and Barrier Function
Alveolar Fluid Clearance and Ion Transport
Developmental Ion and Fluid Management
Roles of Individual Ion Transporters
. The primary pathway for Na+ entry is via apical amiloride-­sensitive ENaC, with basolateral Na+,K+-­ATPase driving Na+ into th...
. Apically located amiloride-­insensitive CNG channels provide another Na+ entry pathway in the alveolar epithelium. CNG channel...
. Both AT1 and AT2 cells express a number of Cl− transport proteins, including CFTR, the CLC2 and CLC5 channels of the CLC famil...
. The activity of the Na+,K+-­ATPase pump provides the driving force for Na+ resorption by maintaining low intracellular levels ...
. A number of K+ channels are present on AECs and are important for maintaining membrane potential and the electrochemical gradi...
Physiologic Regulation of Ion and Fluid Transport
Impaired Fluid Clearance and Resolution of Alveolar Edema Under Pathologic Conditions
Alveolar Epithelial Repair
Diseases of the Distal Lung Epithelium
Key Readings
References
4 Airway Biology.pdf
4 - Airway Biology
INTRODUCTION
OVERVIEW
Airway Structure and Cellular Components
Upper Airway Structure and Function
Lower Airway Structure and Function
Microvasculature
Airflow
Upper Airways
Lower Airways
Airflow Resistance
Airway Lymphatic Vessels
Microvascular-­Related Inflammation
Extracellular Matrix and Fibroblasts
Anatomic Specificity of Extracellular Matrix
Smooth Muscle
Innervation
Afferent Autonomic Control of Airway Smooth Muscle
Efferent Autonomic Control of Airway Smooth Muscle
Other Neural Controls
Airway Epithelium
Morphology
Cell-­Cell Junctions
Airway Barrier Function
Tight Junction Proteins
Adherens Junction Proteins
Cell Populations
Upper Airway Epithelial Cells
Lower Airway Epithelial Cell Populations and Frequencies
Basal Cells
Intermediate Cells
. Ciliated cells are the most common type of differentiated cells lining the airway lumen of the bronchi and are present in high...
Secretory Cells
Mucous Cells
Pulmonary Neuroendocrine Cells
Ionocytes
Respiratory Brush (Tuft) Cells
Bronchoalveolar Stem Cells
Submucosal Glands
Progenitor Cells
Airway Epithelial Cell Life Span
Tissue-­Specific Stem Cells of the Airway
Facultative Progenitor Epithelial Cells
Airway Epithelial Cell Differentiation
Notch Signaling
Differentiation Pathways for Secretory and Ciliated Cells
Airway Surface Liquid
Composition
Airway Surface Liquid Layers
Water
Ions
Mucins and Other Macromolecules
Periciliary Layer Contribution to Airway Surface Liquid Hydration
Mucus Gel Layer
Integrated Effects of PCL and Mucus Gels on ASL Hydration
Secretion
Submucosal Gland Secretion
Surface Mucous Cell Secretion
Mucus and Mucociliary Interactions
Mucociliary Clearance
Establishment of Directional Mucociliary Clearance
Regulation of Cilia Beat Frequency and Motility
Periciliary Layer and Ciliary Beating
Purinergic Signals Integrate Mucociliary Functions
Mucociliary Transport
Cough Clearance of Mucus
Mucous Cell Metaplasia and Hyperplasia
Baseline Mucin Expression
Mucous Cell Metaplasia
Mucous Cell Hyperplasia
Mechanisms of Mucin Overproduction
Mechanisms of Regulated Mucin Secretion
Innate Defense Molecules and Microbiota
Integration of Barrier Function and Airway Defense
Soluble Pattern Recognition Receptor Proteins
Resident Immune Cells of the Airway Epithelium
Airway Immunoglobulin A
Nitric Oxide
Airway Microbiota
Key Readings
eFIGURE IMAGE GALLERY
References
5 Lung Mesenchyme.pdf
5 -
Lung Mesenchyme
INTRODUCTION
Dynamic Regulation of the Extracellular Matrix
Extracellular Matrix Degradation and Turnover
Extracellular Matrix Modification and Cross-­Linking
Cell–Extracellular Matrix Interactions via Integrins
Growth Factors Within the Lung Mesenchyme
The Lung Mesenchyme in Development
Branching Morphogenesis
Vascularization
Alveolarization
The Lung Mesenchyme in Aging
The Lung Mesenchyme in Disease
Obstructive Airway Diseases
Lung Fibrosis
Other Lung Disorders
Current Understanding and Gaps in Knowledge
Key Readings
References
6 Vascular Biology.pdf
6 - Vascular Biology
Overview of Development of the Pulmonary Circulation
Physiologic Control of the Pulmonary Circulation
Mechanical Factors or Passive Regulation
Gravity
Lung Volume
Shear Stress
Active Regulation
Hypoxic Pulmonary Vasoconstriction
Endothelium-­Derived Vasoactive Agents
Neural Control
Role of Pulmonary Veins
Communication Between Endothelial and Smooth Muscle Cells
Myoendothelial Junctions
Extracellular Vesicles
Nonrespiratory Functions of the Pulmonary Circulation
Pericytes, Adventitial Cells, and Other Cells
Pulmonary Vascular Endothelium and Control of Endothelial Permeability
Bronchial Circulation
Key Readings
eFigure Image Gallery
References
7 Lymphatic Biology.pdf
7 - Lymphatic Biology
INTRODUCTION
Anatomy of the Pulmonary Lymphatics
Pulmonary Lymphatic Markers
Role of Lymphatics in the Lung
Fluid Uptake and Prevention of Pulmonary Edema
Immune Cell Trafficking
Local Immunity and Inducible Bronchus-­Associated Lymphoid Tissue
Pulmonary Lymphatics in Lung Injury
Lymphatic Disorders During Lung Development
Asthma
Chronic Obstructive Pulmonary Disease
Interstitial Lung Disease
Lymphangioleiomyomatosis
Lung Transplantation
Tuberculosis
Sarcoidosis
Key Readings
References
8 Regeneration and Repair.pdf
8 -
Regeneration and Repair
Factors Mediating Acute Epithelial and Endothelial Cell Injury
Histopathology and Mechanisms That Constitute Alveolar Cell Injury
Endothelial Damage
Epithelial Damage
Lung Regeneration and Repair
Resolution of Inflammation
Resorption of Edema Fluid
Endothelial Repair
Epithelial Repair
Basic Principles in Epithelial Repair: Cell Spreading and Migration, Cell Proliferation, and Junctional Resealing
Stem and Progenitor Cells in the Lung
Stem/Progenitor Cells Involved in Lung Repair
Loss of Regenerative Potential: Depletion of the Facultative Progenitor Cell Pool
The Mesenchymal Niche in Epithelial Repair
Does Lung Repair Recapitulate Mechanisms of Lung Development
Key Readings
References
9 Genetics of Lung Disease.pdf
9 - Genetics of Lung Disease
INTRODUCTION
Human Genetics
Characterization of Genetic Variation
Linkage Disequilibrium
Public Databases
Genetic Epidemiology
Linkage Studies
Association Studies
Genome-­Wide Association Studies
Genetic Architecture and Rare Variants
Gene By Environment Interaction
Epigenetics
Fine Mapping and Functional Genetics
Integrative Genomics and Systems Genetics
Application to Pulmonary Diseases
Asthma
COPD and Lung Function
Acute Respiratory Distress Syndrome
Lung Cancer
Fibrosing Idiopathic Interstitial Pneumonia
Pulmonary Hypertension
Sarcoidosis
Rare Diseases
The Path Forward
Key Readings
eFIGURE IMAGE GALLERY
References
10 Ventilation, Blood Flow, and Gas Exchange.pdf
10 - Ventilation, Blood Flow, and Gas Exchange
Introduction
Ventilation
Total And Alveolar Ventilation
Total Ventilation
Alveolar Ventilation
Anatomic Dead Space
Physiologic Dead Space
INEQUALITY OF VENTILATION
Gravitational Influences on Inequality
Airway Closure
Nongravitational Influences on Inequality
Blood Flow
Pressures of the Pulmonary Circulation
Pressure Inside Blood Vessels
Pressures Outside Blood Vessels
Pulmonary Vascular Resistance
Pressure-­Flow Relations
Effect of Lung Volume
Other Factors Affecting Pulmonary Vascular Resistance
Distribution of Pulmonary Blood Flow
Normal Distribution
Three-­Zone Model for the Distribution of Blood Flow
The Effect of Lung Volume on the Distribution of Blood Flow—Zone 4
Other Factors Affecting the Distribution of Blood Flow
Abnormal Patterns of Blood Flow
Active Control of the Pulmonary Circulation
Hypoxic Pulmonary Vasoconstriction
Damage to Pulmonary Capillaries by High Wall Stresses
Blood-­Gas Transport
Oxygen
Carbon Dioxide
Gas Exchange
Causes of Hypoxemia (See Chapter 44)
Hypoventilation
Diffusion Limitation
. Figure 10.16 shows calculated changes in the Po2 of the blood along the pulmonary capillary as oxygen is taken up under normal...
Shunt
Ventilation-­Perfusion Relationships
Oxygen Sensing
Acknowledgment
Key Readings
eFigure Image Gallery
References
11 Respiratory System Mechanics and Energetics.pdf
11 - Respiratory System Mechanics and Energetics
Terminology
Flow
Volume
Pressure
Compliance, Resistance, and Time Constants
Respiratory Mechanics in Static Conditions
Elastic Recoil of the Lungs
Lung Connective Tissue
Alveolar Surface Forces and Surfactant
Hysteresis and Stress Adaptation
Elastic Recoil of the Chest Wall
Chest Wall Compliance
Integration of Lung and Chest Wall Mechanics
Calculation of Total Respiratory System Compliance from Lung and Chest Wall Compliance
Clinical Applications
Positive End-­Expiratory Pressure and its Impact on Pleural Pressure
Plateau Pressures in Patients Receiving Positive-­Pressure Mechanical Ventilation
Stress and Strain
The Respiratory System in Dynamic Conditions
Resistive Work Due to Gas Flow Through Airways
Laminar versus Turbulent Flow
Reynolds Number
Clinical Effects of Heliox
Flow Limitation
Other Resistive Work
Equation of Motion
Intrinsic Peep During Positive-­Pressure Ventilation of Copd
Measurement of Static Compliance and Resistance During Mechanical Ventilation
Respiratory Mechanics in ARDS
PEEP Optimization and Recruitment Maneuvers
Stress Index
Recruitment Maneuvers in ARDS
Ventilating ARDS Using Plateau Pressure, Tidal Volume, and Driving Pressure
Driving Pressure
Energetics and Work of Breathing
Measuring Work of Breathing Done by a Positive-­Pressure Ventilator in a Paralyzed Patient
Measuring Work of Breathing in a Spontaneously Breathing Patient
Oxygen Cost of Breathing
Key Readings
eFIGURE IMAGE GALLERY
References
12 Acid-Base Balance.pdf
12 - Acid-­Base Balance
FUNDAMENTAL CONCEPTS
Acid-­Base Chemistry
Carbon Dioxide and Bicarbonate
pH Versus H+, Conjugate Acids and Bases
Arterial and Venous Blood gas Analysis
Nomenclature of Acid-­Base Disorders
Role of Ventilation: Arterial Pco2
Role of the Kidneys
Metabolic Alkalosis
Metabolic Acidosis
Compensation
Respiratory Acidosis
Respiratory Alkalosis
Metabolic Acidosis
Strong Ion Difference
Metabolic Alkalosis
Metabolic Acidosis
Anion gap Concept
Causes of Anion gap Acidosis
Lactic Acidosis
Lactic Acidosis Biochemistry
Diabetic Ketoacidosis
Starvation Ketoacidosis
Uremic Acidosis
Toxic Forms of Anion Gap Acidosis
?Salicylates. Large ingestions of salicylates, such as aspirin, cause a mixed disorder with both an anion gap metabolic acidosis...
. Methanol, isopropyl ethanol, and ethylene glycol ingestions are frequent causes of anion gap metabolic acidoses. Methanol (rub...
Hyperchloremic Acidosis
Type 1 Renal Tubular Acidosis
Type 2 Renal Tubular Acidosis
Type 4 Renal Tubular Acidosis
Acidosis of Progressive Renal Failure
Gastrointestinal Causes of Hyperchloremic Acidosis
Miscellaneous Causes of Hyperchloremic Acidosis
Clinical Manifestations
Therapy
Metabolic Alkalosis
General Considerations
Chloride-­Responsive Alkalosis
Gastrointestinal Losses
Diuretics
Mechanisms of Hyperkalemia During Metabolic Acidosis
Sweat
Mechanical Ventilation
Chloride-­Resistant Alkalosis
Excessive Intake of Alkali
Extracellular Fluid Contraction
Clinical Manifestations
Therapy
Respiratory Acidosis
General Considerations
Causes
Clinical Manifestations
Therapy
Respiratory Alkalosis
General Considerations
Causes
Clinical Manifestations
Therapy
Key Readings
eFIGURE IMAGE GALLERY
References
13 Aerosols and Drug Delivery.pdf
13 - Aerosols and Drug Delivery
INTRODUCTION
Definition and Description of an Aerosol
Principles of Deposition
Measurements and Applications of Aerosol Particle Size
Generation of Therapeutic Aerosols
Dry Powder Devices
Pressurized Metered-­Dose Inhalers
Jet Nebulizers
Vibrating Mesh Nebulizers
Soft Mist Aerosols
Principles of Assessment of Delivery Systems
The Inhaled Mass
Deposition
Strategies to Optimize Deposition of Therapeutic Aerosols
Getting Particles Past the Oropharynx
Control of Breathing Pattern and Aerosol Deposition
Expiration and Problems With Aerosol Deposition
Additional Factors Influencing Development of Therapeutic Aerosols
Inhaled Proteins
Asthma
Cystic Fibrosis and Non–Cystic Fibrosis Bronchiectasis
Idiopathic Pulmonary Fibrosis
Pulmonary Mycobacterial Infections
Delivery of Inhaled Medications to Young Children
Delivery of Therapeutic Aerosols to the Nasal Mucosa
Aerosol Delivery During Mechanical Ventilation
Diagnostic Radioaerosols
Mucociliary Clearance and Disease
Alveolar Clearance
Key Readings
eFIGURE IMAGE GALLERY
References
14 Pleural Physiology and Pathophysiology.pdf
14 - Pleural Physiology and Pathophysiology
INTRODUCTION
Function
Anatomy
Pleural Membranes
Blood Supply
Lymphatics
Nerve Supply
Pleural Pressure
Physiology of the Pleural Space
Entry of Normal Pleural Liquid
A Systemic Microvascular Source
. The protein concentration of normal pleural liquid is low in sheep38 and probably in humans, which im­plies sieving of the pro...
. With increases in filtration rates across a semipermeable membrane, proteins are retarded relative to liquid and electrolytes,...
The Parietal Pleura Is the Major Source
Pleural Membranes Are Leaky
Entry From the Interstitium into the Pleural Space
The Pleural Space Is Vulnerable to Liquid Entry
Exit of Normal Pleural Liquid
Lymphatics Are the Major Exit Route
Lymphatics Have a Large Reserve Capacity
Pathophysiology of the Pleural Space
What Is Required to Produce a Pleural Effusion
What Diseases Could Account for This
Mechanisms of Increased Entry of Liquid
Increased Filtration Pressure
.An increase in microvascular pressure (i.e., capillary pressure) will increase the filtration across the microvascular barrier....
.A decrease in the osmotic pressure of the blood within microvessels would be expected to increase filtration. The osmotic press...
Increased Microvascular Permeability
.When the permeability of the microvascular barrier increases due to inflammation, infection, or malignancy, the resistance to t...
.As mentioned, the Starling factors discussed above are relevant to all the circulations of the body, systemic and pulmonary, an...
Mechanisms of Decreased Exit of Liquid
Categories of Pleural Effusions
Transudates
Exudates
Pseudoexudates
Indeterminate Effusions
Mechanisms by Which Specific Diseases Cause Pleural Effusions
Congestive Heart Failure
Malignancy
Pulmonary Embolism
Tuberculosis
Pleural Effusion Effects on Lung and Cardiac Function
Key Readings
References
15 Innate Immunit.pdf
15 - Innate Immunity
Introduction
Overview of the Components of Lung Innate Immunity
Innate Recognition in the Lung
Secreted Pattern Recognition Receptors
Collectins
Complement
Pentraxins and Other Secreted Pattern Recognition Receptors
Cellular Pattern Recognition Receptors
Plasma Membrane and Endosomal Pattern Recognition Receptors
. TLRs are expressed on airway and alveolar epithelial cells, macrophages, PMNs, and DCs.46–49 There are 10 TLRs in humans (TLR ...
. The first macrophage SR was described by Goldstein and colleagues and Brown and associates71,72 and was shown to bind and inte...
. C-­type lectin receptor (CLR) domains are also present in a family of cell surface receptors that plays an important role in t...
Cytoplasmic Pattern Recognition Receptors
. In humans, NLRs are a family of intracellular PRRs that have evolved to sense PAMPs in the cytoplasm of most cells. Cytoplasmi...
. The last group of cytoplasmic PAMP sensors is the RIG-­I–like receptors that have evolved to detect the presence of RNA from R...
Summary
Effector Mechanisms
Epithelium
Polymorphonuclear Leukocytes
Innate Lymphoid Cells
Mononuclear Phagocytes
Resident Macrophages
Alveolar Macrophages
Interstitial Macrophages
Monocytes
Functions of Recruited Monocytes and Macrophages
Resident and Recruited Dendritic Cells
System Integration
Key Readings
References
16 Adaptive Immunity.pdf
16 - Adaptive Immunity
INTRODUCTION
Components of the Immune System: Overview
Immune Recognition
B Cells and Antibodies
Structure of Immunoglobulin and the B Cell Receptor for Antigen
Formation of the B Cell Receptor Repertoire
Isotype Switching and Function of the Different Immunoglobulin Classes
B Cell Development
Immunoglobulin Interactions with Antigen
T Cells and Antigen-­Presenting Cells
T Cell Receptors
T Cell Receptor Structure and T Cell Receptor Repertoire Formation
Antigen-­Presenting Cells and the Major Histocompatibility Complex
Presentation and T Cell Recognition of Antigens
Development and Selection of the TCR Repertoire
T Cell Tolerance: Prevention of Self-­Reactivity
Generation of an Immune Response
T ­Cell Activation and Co-­stimulation
Subsets of T Helper Cells
CD4+ T Cell–B Cell Collaboration and Regulation of Antibody Production
Generation and Regulation of Cell-Mediated Immune Responses
Innate Lymphoid Cell Subsets and Function
Specific Immune Responses in the Lung
Lymphocyte Populations and Trafficking in the Lung
Antibody-­Mediated Immune Responses in the Lung
Immune Response to Extracellular Pathogens
Immune Response to Autoantigens
Immune Response in Allergic Disease
Cell-­Mediated Immune Responses in the Lung
Granulomatous Lung Disease
Cytotoxic T Cell Reactions in the Lung
Innate Lymphoid Cell Responses in the Lung
Key Readings
eFigure Image Gallery
References
17 Microbiome.pdf
17 - Microbiome
INTRODUCTION
The Genesis of the Lung Microbiome Field
Technologies for Microbiome Studies
Sequencing Data Analysis
Study Design Approaches for Microbiome Studies of the Respiratory Tract
Human Studies
Animal Model Studies
The Healthy Lung Microbiome
Derivation of the Lung Microbiome
The Early Life Origins of the Human Lung Microbiome
The Lung Microbiome in Disease
Obstructive Diseases
Asthma
Chronic Obstructive Pulmonary Disease
Cystic Fibrosis
Non–Cystic Fibrosis Bronchiectasis
Interstitial Lung Diseases
Idiopathic Pulmonary Fibrosis
Sarcoidosis
Infectious Diseases
Pneumonia
Nontuberculous Mycobacteria Infection
Tuberculosis
Human Immunodeficiency Virus Lung Disease
Lung Cancer
Lung Transplant
Acute Respiratory Distress Syndrome
Other Lung Diseases
Future Directions for Lung Microbiome Research
Key Readings
eFIGURE IMAGE GALLERY
References
18 History and Physical Examination.pdf
18 -
History and Physical Examination
Communication Skills
Clinical Reasoning
Clinical History
Chief Complaint and Present Illness
Major Pulmonary Symptoms
Dyspnea
. Patients with respiratory, cardiac, hematologic, metabolic, and neuromuscular disorders may all complain of dyspnea, which may...
Cough
. Most episodes of coughing are short lived, and patients, recognizing this, seldom visit their physicians for this type of coug...
Chest Pain
. Pleurisy, or acute inflammation of the pleural surfaces, has several distinctive features. Pleuritic pain is usually localized...
Family History and Social History
Medications and Allergies
Occupational History
Travel History
Past Medical History
Questionnaires, Computer-­Assisted and Nursing History
Physical Examination
Examination of the Chest
Inspection
Palpation
Percussion
Auscultation
Normal Lung Sounds
Adventitious (Abnormal) Lung Sounds
Fine and Coarse Crackles (Discontinuous Sounds)
Wheezes and Rhonchi (Continuous Sounds)
Voice-­Generated Sounds
Pleural Friction Rub
Extrapulmonary Sounds
Interpretation
Extrapulmonary Manifestations
Clubbing
Other Extrapulmonary Associations
Acknowledgment
Key Readings
Anchor 372
eFIGURE IMAGE GALLERY
References
19 Microbiologic Diagnosis of Lung Infection.pdf
19 - Microbiologic Diagnosis of Lung Infection
INTRODUCTION
Preanalytic Principles
Principles of Testing
Infection Prevention
Syndromic Order Sets
Specimen Selection, Collection, and Transport
Specimen Adequacy
Microbiologic Assays
Microscopy
Culture
Antimicrobial Susceptibility Testing
Nucleic Acid Tests
Antigen Testing
Serologic Testing and Interferon-­γ Release Assays
Acknowledgment
Key Readings
References
20 Thoracic Radiology Noninvasive Diagnostic Imaging.pdf
20 - Thoracic Radiology: Noninvasive Diagnostic Imaging
INTRODUCTION
Chest Radiography: Techniques
Radiographic Views and Techniques
Routine Examination
Expiratory Views
Major Factors Affecting Image Quality in Standard Film-­Screen Radiography and Digital Radiography
Radiographic Contrast
Spatial Resolution
Noise
American College of Radiology Standards
Portable Radiography
Digital Radiographic Techniques: Computed Radiography and Direct Radiography
Computed Radiography Storage Phosphor Systems
Direct Radiography
Clinical Efficacy
Medical Imaging and Radiation
Applications of Conventional Chest Radiography
Screening and “Routine” Chest Radiographs
Decubitus Views
Lordotic Views
Oblique Views
Fluoroscopy
Bronchography
Pulmonary Angiography (see Chapter 21)
Aortography and Bronchial Angiography (see Chapter 21)
Ultrasonography
Computed Tomography
Physical Principles
Image Display
Volumetric Imaging via Helical and Multislice Computed Tomography
Computed Tomography Scan Protocols
Scanning Range
Patient Position
Multislice Computed Tomography Detector Configuration and Scan Section Thickness
Contrast Enhancement
Radiation Exposure and Cancer Risk
Low-­Level Radiation-­Induced Malignancy: Evidence for and Against
Magnetic Resonance Imaging
Physical Principles
Techniques
Detection of Lung Cancer and Assessment of Solitary Pulmonary Nodules
Evaluation of Intensive Care Unit Patients
Indications in Acute Lung Disease
Dyspnea
Acute Respiratory Symptoms
Indications for Chest Radiography in the ICU
Acute Asthma
Exacerbation of COPD or Cystic Fibrosis
Applications of Cross-­Sectional Imaging Techniques
Solitary Pulmonary Nodules (see Chapter 41)
Multiple Pulmonary Nodules
Lung Cancer Staging
Computed Tomography
Positron Emission Tomography and Positron Emission Tomography–Computed Tomography
Magnetic Resonance Imaging
LUNG CANCER SCREENING
Hilar and Mediastinal Masses
Technical Aspects of Computed Tomography Performed for Lung Cancer Screening
Nodule Size
Nodule Attenuation
Nodule Morphology
Nodule Growth Rate
Diffuse Lung Disease
Increased Lung Opacity
. Thickening of the interstitial fiber network of lung by fluid, fibrous tissue, or interstitial infiltration by cells results i...
. Nodules can be classified as perilymphatic, random, or centrilobular, according to their distribution within the secondary pul...
Consolidation and Ground-1396983920Glass Opacity. Air space consolidation, by definition, is seen when alveolar air is replaced ...
Decreased Lung Opacity
. Emphysema is accurately diagnosed with HRCT, and HRCT is more sensitive for the detection of emphysema than is routine CT or c...
. Lymphangioleiomyomatosis (see images associated with Chapter 97, eFig. 97.2, and Fig. 20.25A–B) and PLCH (see Chapter 95) ofte...
Mosaic Perfusion. Decreased lung attenuation not reflecting the presence of cystic lesions or emphysema can sometimes be recogni...
Honeycombing
Diagnostic Utility
Intrathoracic Airway Disease
Central Airways
Bronchiectasis
Small Airway Disease
History of the Use of HRCT for DILD: Diagnosis, Assessing Activity and Directing Biopsy
. It is well documented that chest radiographs are limited in both their sensitivity and specificity in patients with DILD.203–2...
. Even in the presence of definite abnormalities, chest radiographs have limited diagnostic accuracy for patients with DILD.238 ...
. In addition to being more sensitive, specific, and accurate than chest radiographs, HRCT may also play a critical role in the ...
. Among the many indications for HRCT, an important one is as a potential guide for surgical lung biopsies. Many “diffuse” lung ...
Cardiovascular Disease
Pulmonary Thromboembolism
Evolution of Single-Slice CTPA to Multislice
Pleural Disease
CARDIOVASCULAR DISEASE AND THORACIC GREAT VESSELS
Acquired Cardiovascular Disease
Congenital Anomalies of the Thoracic Great Vessels
Type of Fluid
Pleural Versus Parenchymal Disease
Early Detection
Recent Advancements and Future Directions
Artificial Intelligence, Machine Learning, and Deep Learning
Functional Imaging and Quantification: COPD and Fibrotic Lung Disease
Dual-­Energy/Spectral Computed Tomography Imaging
Key Readings
eFIGURE IMAGE GALLERY
References
21 Thoracic Radiology Invasive Diagnostic Imaging and Image-Guided Interventions.pdf
21 - Thoracic Radiology: Invasive Diagnostic Imaging and Image-­Guided Interventions
INTRODUCTION
Transthoracic Needle Biopsy
Indications and Contraindications
Patient-­Lesion Selection and Preprocedure Clinical and Imaging Evaluation
Choice of Imaging Guidance
Procedure
Postprocedure Patient Management
Diagnostic Yield
Complications
Catheter Drainage of Intrathoracic Collections
Parapneumonic Effusions: Empyema
Malignant Pleural Effusions
Pneumothorax (See Chapter 110)
Lung Abscess (See Chapter 50)
Bronchial Arteriography
Indications and Contraindications
Pulmonary Arteriography
Indications and Contraindications
Thermal Ablation of Localized Lung Cancer and Pulmonary Metastatic Disease
Indications and Contraindications
Preoperative Computed Tomography–Guided Localization for Video-­Assisted Thoracic Surgery Nodule Resection
Indications and Contraindications
Key Readings
eFIGURE IMAGE GALLERY
References
22 Pathology Neoplastic and Non-neoplastic Lung Disease.pdf
22 - Pathology: Neoplastic and Non-­neoplastic Lung Disease
INTRODUCTION
Types of Lung Tissue Specimens
Tissue Processing and Histologic Evaluation
Cytology Specimens
Evaluation of Neoplastic Lung Lesions
Adenocarcinoma
Squamous Cell Carcinoma
Small Cell Carcinoma
Large Cell Neuroendocrine Carcinoma
Carcinoid Tumors
Other Less Common Tumor Types
Pathologic Staging
Evaluation of Non-­Neoplastic Lung Disease
Is There Acute Lung Injury
Diffuse Alveolar Damage
Organizing Pneumonia
Acute Fibrinous and Organizing Pneumonia
Is There Consolidation of Alveolar Spaces
Eosinophilic Pneumonia
Desquamative Interstitial Pneumonia
Pulmonary Alveolar Proteinosis
Is There Interstitial Fibrosis
Usual Interstitial Pneumonia
Nonspecific Interstitial Pneumonia
Is There Interstitial Inflammation
Cellular Nonspecific Interstitial Pneumonia Versus Lymphocytic Interstitial Pneumonia
Hypersensitivity Pneumonitis
Are There Nodules or Masses
Pulmonary Sarcoidosis
Infectious Granulomas
Pulmonary Langerhans Cell Histiocytosis
What if the Lung Parenchyma Looks Normal
Future Outlook
Key Readings
References
23 Ultrasonography Principles and Basic Thoracic and Vascular Imaging.pdf
23 - Ultrasonography: Principles and Basic Thoracic and Vascular Imaging
Physics of Ultrasound
Ultrasonography: Principles and Basic Thoracic and Vascular Imaging
Transducer Selection
Vascular Imaging
Thoracic Imaging
Abdominal Imaging
Ultrasound Modes
Two-­Dimensional Mode, or B-­Mode
M-­Mode
Doppler Imaging
Knobology
Imaging Planes and Transducer Movement
Depth
Gain
Orientation
Measurements
Ultrasound Artifacts
Acoustic Attenuation and Enhancement
Reverberation
Mirroring
Artifacts and Image Processing Features
Thoracic Ultrasound
Normal Pleura and Lung
Pneumothorax
Pleural Effusion and Thoracentesis
Pleura and Pleural Biopsy
Lung Parenchyma
B-­Lines
Consolidation
Diaphragm
Use of Ultrasound in the Clinical Evaluation of Acute Respiratory Failure
Vascular Imaging
Central Venous Catheter Placement
Technique
Peripheral Vascular Access
Deep Venous Thrombosis Assessment
Key Readings
eFigure Image Gallery
References
24 Ultrasonography Advanced Applications and Procedures.pdf
24 - Ultrasonography: Advanced Applications and Procedures
INTRODUCTION
Critical Care Echocardiography as a Diagnostic Tool for Intensivists
Impact of Critical Care Echocardiography on the Management of Critically ill Patients
Critical Care Echocardiography Training, Competency, and Certification
Image Acquisition and Interpretation of the Critical Care Echocardiogram
Data Quality, Confidence of Interpretation, and Responsibility for Unexpected Findings
Preparation for the Critical Care Echocardiogram
Probe Manipulation
Basic Critical Care Echocardiogram Views
Parasternal Long-­Axis View
Parasternal Short-­Axis View
Apical Four-­Chamber View
Subcostal View
Interpretation of Ultrasound Images
Left Ventricular Function
Right Ventricular Function
Right Atrial Pressure
Pericardial Effusion and Cardiac Tamponade
The UseS of Critical Care Ultrasound
Assessment of Volume Status
Inferior Vena Cava Diameter and Collapsibility and/or Distensibility
Inferior Vena Cava and Volume Status
Other Critical Care Ultrasound Examinations to Evaluate Shock and Assess Volume Status
Basic Critical Care Echocardiography
Advanced Critical Care Echocardiography
Pulmonary Ultrasound
Abdominal Ultrasound
Putting it all Together: a Systematic Approach
Key Readings
eFigure Image GalleRy
References
25 Positron Emission Tomography.pdf
25 - Positron Emission Tomography
Principles
Positron Emission Tomography Camera
Metabolic Tracer: 18f-­Fluorodeoxyglucose
Interpretation of Pet Images
Diagnosis
Staging
Influence on Treatment Choices and Planning With Curative Intent
Prognosis and Survival
Indications Beyond Initial Evaluation of Non–Small Cell Lung Cancer
Small Cell Lung Cancer
Mesothelioma
Neuroendocrine Tumors
Response to Therapy
Follow-­Up After Curative-­Intent Treatment
Health Economics
New Tracers
Key Readings
References
26 Diagnostic Bronchoscopy Basic Techniques.pdf
26 - Diagnostic Bronchoscopy: Basic Techniques
INTRODUCTION AND HISTORICAL BACKGROUND
Indications
Procedure
Sedation and Anesthesia
Local Anesthesia
Monitoring
Approach
Inspection
Basic Techniques
Bronchoalveolar Lavage
Bronchial Washings
Bronchial Brushings
Protected Specimen Brush
Endobronchial Biopsy
Transbronchial Biopsy
Conventional Transbronchial Needle Aspiration
Key Readings
References
27 Diagnostic Bronchoscopy Advanced Techniques (EBUS and Navigational).pdf
27 - Diagnostic Bronchoscopy: Advanced Techniques (EBUS and Navigational)
Endobronchial Ultrasound
Convex
Diagnostic Yield for Lung Cancer
Ultrasound Features That Predict Malignancy
Molecular Markers
Diagnostic Yield for Diagnoses Other Than Lung Cancer
. For diagnosing and subtyping lymphoma, the yield for EBUS has been around 70%, though with considerable variation reported.52–...
. The sensitivity of EBUS-­TBNA for pulmonary sarcoidosis is 85–90% as opposed to transbronchial biopsy and endobronchial biopsy...
. Although EBUS-­TBNA is suggested for evaluation of patients with mediastinal or hilar adenopathy concerning for tuberculosis o...
Rapid On-­Site Evaluation
Complication Rate and Safety
Cost
Education and Competency
Radial
Introduction
Imaging Techniques
Diagnostic Yield
Complications
Conclusion
Confocal Bronchoscopy
Elastography
Thin and Ultrathin Bronchoscopy
Virtual Bronchoscopy
Electromagnetic Navigation
Electromagnetic Navigational Transthoracic Needle Aspiration
Bronchoscopic Transparenchymal Nodule Access
Augmented Fluoroscopy Navigation
Cone Beam CT For Bronchoscopy
Robotic Bronchoscopy
Cryobiopsy
Key Readings
References
28 Therapeutic Bronchoscopy Interventional Techniques.pdf
28 - Therapeutic Bronchoscopy: Interventional Techniques
INTRODUCTION AND HISTORICAL BACKGROUND
Removing Foreign Bodies
Indications
Contraindications, Procedure, Results, and Complications
Managing Central Airway Disorders
Electrocautery
Indications and Contraindications
Results and Complications
Argon Plasma Coagulation
Indications and Contraindications
Results and Complications
Laser Photoresection
Indications
Contraindications
Results and Complications
Stent Placement
Indications and Contraindications
Results and Complications
Microdébrider
Cryotherapy
Indications and Contraindications
Results and Complications
Photodynamic Therapy
Indications and Contraindications
Results and Complications
Brachytherapy
Indications
Contraindications
Results and Complications
Managing Other Indications
Bronchoscopic Lung Volume Reduction
Indications and Contraindications
Endobronchial Valves
Bronchial Lung Volume-­Reduction Coils
Biologic Sealant
Bronchoscopic Thermal Vapor Ablation
Complications
Bronchial Thermoplasty for Severe Asthma
Indications and Contraindications
Results and Complications
Endobronchial Valve Placement for Persistent air Leaks
Key Readings
References
29 Thoracoscopy.pdf
29 - Thoracoscopy
INTRODUCTION
Thoracoscopy (Pleuroscopy/Medical Thoracoscopy)
Historical Context
Techniques
Equipment
Rigid
Semirigid
Environment
Indications
Contraindications
Complications
Patient Preparation
Anesthesia
Access to the Pleural Space
Position and Entry Site
Thoracoscopic Technique
Talc Poudrage Pleurodesis
Results
Pleural Effusions
Malignant Pleural Effusions
. Malignant pleural effusions are the leading diagnostic and therapeutic indication for thoracoscopy82 (Fig. 29.4A and eFig. 29....
. Thoracoscopy may be useful in staging lung cancer, diffuse malignant mesothelioma, and metastatic cancer. In lung cancer patie...
. The relative utility of thoracoscopic talc poudrage pleurodesis has been mentioned above. In summary, despite high success rat...
. Although the diagnostic yield of pleural fluid culture combined with closed-­needle biopsy for the diagnosis of TB is quite hi...
. For diagnosis in cases with effusions that are neither malignant nor tuberculous, thoracoscopy may give visual clues to the ca...
Empyema
Spontaneous Pneumothorax
Diffuse Pulmonary Diseases
Localized Diseases
Differences Between Thoracoscopy and Video-­Assisted Thoracic Surgery
Key Readings
efigure Image Gallery
References
30 Thoracic Surgery.pdf
30 -
Thoracic Surgery
Surgical Procedures on the Lung
Wedge
Segmentectomy
Lobectomy
Bilobectomy
Sleeve Resection
Pneumonectomy
Intubation at the Time of Surgery
Double-­Lumen Endotracheal Tube
Bronchial Blockers
Segmentectomy Versus Lobectomy
Minimally Invasive Surgery Versus Open Thoracotomy
Intraoperative Localization of Nodules
Wedge Resection for Interstitial Lung Disease
Postoperative Management
Chest Tube Management
Pneumonectomy Patients
Pain
Ventilator Management
Key Readings
References
31 Pulmonary Function Testing Physiologic and Technical Principles.pdf
31 - Pulmonary Function Testing: Physiologic and Technical Principles
Introduction
Mechanical Properties of the Respiratory System
Forced Spirometry
Maximal-­Effort Expiratory Vital Capacity
Forced Expiratory Volume Over Time
Forced Expiratory Volume Over Time as a Percentage of Forced Vital Capacity
Average Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity
Maximal Voluntary Ventilation
Flow-­Volume Relationships
Lung Volumes
Vital Capacity and Other Static Lung Volumes
Gas Dilution Methods
Peak Expiratory Flow Rate
Gas Density
. An advantage of the open-­circuit method is that it also permits an assessment of the uniformity of ventilation of the lungs b...
. An advantage of the open-­circuit method is that it also permits an assessment of the uniformity of ventilation of the lungs b...
. In a closed-­circuit method, a thermal-­conductivity meter measures the He concentration continuously, permitting return of th...
. Two other measurements of lung volume can be obtained from the dilution of gases used in standard tests of lung function. In t...
Radiographic Methods
Body Plethysmography
. This type of plethysmograph has a closed chamber with a fixed volume in which the subject breathes the gas in the plethysmogra...
. This type of plethysmograph (eFig. 31.2) has constant pressure and variable volume. When thoracic volume changes, gas is displ...
. This device (eFig. 31.3) combines features of both the closed and open types. As the subject breathes from the room, changes i...
. The thoracic gas volume (V, also often referred to as TGV) is the compressible gas in the thorax, whether or not it is in free...
Technical Issues
Underestimation of Mouth Pressure
Airway Resistance
General Principles
Forced Oscillation Methods
Lung Elastic Recoil
Expiratory Flow Limitation
Physiologic Factors
. Raw relates to a particular flow rate during continuous pressure-­flow curves, so the slope may be read at any desired airflow...
. Near TLC, resistance is small, but near RV, resistance is large. Lung volume may be changed voluntarily to evaluate Raw at lar...
. Raw is related directly to lung elastic recoil pressure at any lung volume. Subjects with increased lung elastic recoil have a...
. The airways are affected markedly by smooth muscle tone, depending on the state of inflation and the subject’s previous patter...
. Panting minimizes changes in the plethysmograph caused by thermal, water saturation, and carbon dioxide–oxygen exchange differ...
Protocol for Measurement of Lung Elastic Recoil
Analysis
. When the balloon is in place, the relationship between changes in lung volume and changes in Ppl can be measured
Expiratory Flow Limitation Assessed by Comparison of Tidal and Maximal Flow-­Volume Curves
Distribution of Ventilation
Measurements of Distribution Of Ventilation
Multiple-­Breath Nitrogen Washout
Resident Gas, Single-­Breath Test
. The subject inspires a single breath of pure oxygen from RV to TLC (inspiratory VC maneuver); nitrogen concentration at the mo...
. The slope of phase III (percentage of N2 per liter) is determined as the line of best fit (by least-­squares linear regression...
Diffusion
General Principles
Single-­Breath Method
Standardization of the Single-­Breath Methods
Technical and Physiologic FACTORS
Other Protocols for Measurement of Diffusing Capacity
?Steady-­State Method. In the steady-­state method, the patient breathes a mixture of 0.1% carbon monoxide in air for several mi...
. In the rebreathing method94 the patient rebreathes the test gas (air plus a low concentration of CO) from a reservoir, the vol...
. In the intrabreath (within-­breath or exhaled) DlCO method, DlCO is measured at increments of the exhaled volume using a metho...
. As originally described, the subject performs two VC maneuvers, then exhales to RV and rapidly inhales a mixture containing 0....
. Graham and associates106 have described a method of calculating DlCO that uses separate equations for the inhalation, breath-­...
. It is possible to separate the pulmonary diffusing capacity into its two components: the membrane diffusing capacity (Dm) and ...
Diffusing Capacity for Nitric Oxide
. Heavy smokers may have as much as 10–12% carboxyhemoglobin in their blood, and therefore the back-­pressure of carbon monoxide...
. As altitude increases and fractional concentration of inspired oxygen (Fio2) remains constant, pressure of inspired oxygen (Pi...
. Adjustment of the DlCO for lung volume is a controversial issue. A primary measurement from the single-­breath DlCO is KCO (th...
Regulation of Ventilation
Ventilation-­Perfusion Relationships
Measurements of Ventilation-­Perfusion Relationships
Body Size. Body size is one of the factors that probably affect normal values4; diffusing capacity has been found to vary with b...
. Maximal DlO2 (i.e., DlO2 during maximal exercise) has been found to decrease with increasing age according to the following eq...
. Despite the important effect of a noninstantaneous reaction rate between CO and hemoglobin, carbon monoxide transfer is surpri...
. DlCO is 15–20% greater in the supine than in the sitting position and 10% to 15% greater in the sitting than in the standing p...
. Alveolar Po2 affects DlCO because of the former’s effect on the carbon monoxide reaction with hemoglobin. For example, diffusi...
General and Specific Protocols for the Measurement of Regulation of Ventilation
Breath-­Holding Time
Hypercapnic Response
Hypoxic Response
Inspiratory Occlusion Pressure
Clinical Applications
. In general, there are three clinical conditions associated with abnormal carbon dioxide responses: decreased central chemorece...
. There are few clinical indications for evaluation of hypoxic responses. The response to alveolar hypoxia has been used in pati...
The Bohr Equation for Respiratory Dead Space
“Physiologic” Dead Space (Also Called Wasted Ventilation)
Alveolar Gas Equation
Calculation of Alveolar Ventilation
Relation of Alveolar Ventilation to Pulmonary Blood Flow
Calculation of Quantity of Venous-­to-­Arterial Shunt
Distribution of Ventilation-­Perfusion Ratios
Clinical Applications
Arterial Blood Gases
Other Pulmonary Function Tests
Bronchial Provocation
Tests of Nonspecific Airway Responsiveness
Respiratory Muscle Function Tests
Pulmonary Function Laboratory Management
General Structure: Personnel, Equipment, and Quality Control
Invasive Measurements
. The pH of blood is now measured almost entirely by the use of the pH electrode (eFig. 31.18). This device takes advantage of t...
. Early chemical methods for measuring gas concentrations in blood were laborious and demanding. They involved liberating chemic...
Anchor 768
Oxygen
. As with the measurement of Pco2, the development of an accurate, stable electrode has almost entirely supplanted the use of ol...
. Assessment of the adequacy of oxygen delivery requires not only measurement of the Po2 in plasma but also measurement of the o...
Noninvasive measurements
Oxygen
. It was recognized more than 50 years ago that the principles of spectrophotometry could be applied to transcutaneous measureme...
. The basic idea of the transcutaneous electrode is that a small polarographic electrode can measure the oxygen pressure in a bu...
Carbon Dioxide
. The noninvasive measurement of Pco2 is as important as the measurement of Po2, especially in critical care units and operating...
. In some centers, colorimetric measurement is used instead of capnography or other devices to monitor end-­tidal carbon dioxide...
. A device for transcutaneous measurement of Pco2 has been developed. It also involves trapping gas above the skin layer and mea...
. Although histamine and methacholine are well-­established agents for identifying airway hyperresponsiveness, the response to t...
Tests of Specific Airway Responsiveness
. Minimal inspiratory pressure (MIP) is measured during a maximal inspiratory effort against an occluded airway. In this test th...
. One of the limitations of measuring inspiratory muscle function by MIP is the need to provide a tight seal around the mouthpie...
. Although not a muscle pressure per se, peak cough flow is thought to reflect underlying expiratory muscle strength. It is the ...
. Maximum transdiaphragmatic pressure (Pdimax) is measured during the same maneuver as MIP by determining the difference between...
. MVV measurements can also be used to assess endurance. Endurance decreases as Ve/MVV increases in a pattern similar to that ob...
. This is another technique used to evaluate respiratory muscle strength and endurance. Changes in respiratory muscle electrical...
. Fluoroscopy may be used to evaluate diaphragmatic function. Decreased excursion should be evaluated with a lateral view using ...
Events Precipitating Respiratory Failure
. Higher airflow resistance or greater elastic recoil of lung or chest wall, or both, may increase the work of breathing and the...
. Reduction in the supply of vital metabolic substrates may limit the efficiency of respiratory muscles under certain circumstan...
. The number and distribution of fiber types determine inspiratory reserve. Disease processes and inactivity may alter the numbe...
Pediatric Testing
Special Tests and Considerations in Pediatric Pulmonary Function Testing
Safety and Contraindications To Testing
Infection Control
Key Readings
eFIGURE Image Gallery
References
32 Pulmonary Function Testing Interpretation and Applications.pdf
32 - Pulmonary Function Testing: Interpretation and Applications
INTRODUCTION
Major Patterns on Pulmonary Function Tests
Obstructive Ventilatory Defect
Restrictive Ventilatory Defect
Mixed Ventilatory Defects
Diffusing Capacity in Interstitial Lung Disease
Nonspecific Patterns
Pulmonary Vascular Disease
Respiratory Muscle Weakness
Changes in DlCO in Pulmonary Vascular Obstruction
Large Airway Obstruction: Stenosis and COLLAPSIBILITY (See Chapter 39)
Reference Values
General Approach to Interpretation
Additional Information on Reference Values
Statistical Considerations
Factors Affecting Pulmonary Function Testing And Interpretation: Caveats and Precautions
Test Performance Characteristics
Subject Characteristics
Medications
Obesity
Interpretation of Changes in Function Over Time
Variation Between Tests Within a Year
Aging Lung
Bronchodilator Responsiveness
Bronchodilator Responsiveness in Asthma
Bronchodilator Responsiveness in Copd
Bronchial Challenge Testing
Additional Information on Bronchodilator Responsiveness
Basis for the Definition of a Significant Bronchodilator Response
Limitations of the Fev1 In Assessing Responsiveness
Additional Application of Pulmonary Function Tests in Decision Making
Inhaler Selection
Asthma Control
Lung Volume Reduction
Lung Transplantation (See Chapter 140)
Rejection of Transplanted Lungs
Shunt
Lung Resection
Hypoxemia at Altitude (See Chapters 105 and 106)
Key Readings
eFigure Image Gallery
References
33 Exercise Testing.pdf
33 -
Exercise Testing
Physiologic Responses to Exercise
Exercise as a Multisystem Process
Healthy Individuals
Metabolic Activity
Oxygen Consumption. Oxygen consumption, denoted as , (a volume per time, e.g., mL/min) is the most useful parameter for assessin...
Carbon Dioxide Output. In early exercise, CO2 output () increases linearly relative to workload from resting values near 200 mL/...
Respiratory Exchange Ratio. Defined as CO2 elimination divided by oxygen uptake (), the respiratory exchange ratio (R) remains s...
Hemodynamic Responses
Cardiac Output. Cardiac output (mL/min) increases linearly with workload before plateauing near peak exercise; it can be estimat...
Heart Rate. Due initially to decreased vagal tone and later to increases in sympathetic activity, heart rate (beats/min) increas...
. PA pressure rises only modestly with progressive exercise in healthy individuals due to recruitment and distention of the pulm...
. Characterized during CPET by the O2 pulse, stroke volume increases in early exercise before leveling off in late exercise.18 I...
. Due to increases in cardiac output and vascular resistance in the skin, renal, and splanchnic circulations, systemic blood pre...
Ventilatory Responses
Minute Ventilation. Due to an increase in respiratory rate and tidal volume, minute ventilation (, mL/min) rises throughout exer...
Ventilatory Equivalents for Oxygen and Carbon Dioxide. The ventilatory response can be expressed as a function of the amount of ...
. Due to increased tidal volume and recruitment of the pulmonary vasculature resulting from increased pulmonary blood flow, the ...
Gas Exchange
Arterial and End-­Tidal Partial Pressures of Carbon Dioxide. Despite the increasing , the arterial Pco2 (mm Hg) and end-­tidal P...
Arterial and End-­Tidal Partial Pressures of Oxygen and the Alveolar-­Arterial Oxygen Difference. Below the ventilatory threshol...
Changes With Age
Sex Differences
Obesity
Individuals With Underlying Cardiopulmonary Disease
Heart Failure
Pulmonary Vascular Disease
Interstitial Lung Diseases
Adult Congenital Heart Disease
Chronic Obstructive Pulmonary Disease
Cardiopulmonary Exercise Testing
Indications and Contraindications
Determining the Etiology of Dyspnea and Exercise Limitation
. When the cause of dyspnea is not apparent from history, physical examination, laboratory testing (including a hemoglobin and r...
. Patients presenting with exercise limitation rather than dyspnea state that they just are not able to perform the amount of wo...
. When individuals have disease in more than one system, CPET can determine which system is primarily responsible for their exer...
. CPET can be used to diagnose exercise-­induced bronchoconstriction, a transient bronchoconstriction that develops during or af...
Assessing Functional Status and Degree of Impairment
Risk Stratification
Risk Assessment for Thoracic Surgery. Multiple studies have looked at preoperative CPET to determine if patient outcomes can be ...
. The landmark National Emphysema Therapy Trial150 demonstrated that LVRS was of benefit but only to the subset of patients defi...
Risk Assessment for Extrathoracic Surgery. A number of studies have investigated the utility of CPET for risk stratification or ...
Prognosticating Clinical Outcomes
Heart Failure. is the most objective data available for assessing exercise capacity in individuals with heart failure. Both the ...
Adult Congenital Heart Disease. CPET has become a valuable tool in the management of patients with congenital heart disease beca...
Pulmonary Arterial Hypertension. Assessment of exercise capacity can also be used to assess prognosis and response to treatment ...
Exercise Prescriptions for Cardiac and Pulmonary Rehabilitation Programs
Safety Considerations and Contraindications to Cardiopulmonary Exercise Testing
Conducting Exercise Tests
Exercise Equipment
Exercise Modalities and Protocols
Cycle Ergometer Versus Treadmill
Invasive Cardiopulmonary Exercise Testing
Noninvasive Estimates of Cardiac Output During Cardiopulmonary Exercise Tests
Indications for Arterial Blood Gases
Interpreting Cardiopulmonary Exercise Tests
Reference Values
Identifying the Ventilatory Threshold
Identifying the Primary System Limiting Exercise: Algorithmic Versus Pattern Recognition Approaches
Alternative Methods of Assessing Exercise Tolerance
Exercise Treadmill Testing
Key Readings
eFIGURE IMAGE GALLERY
References
34 Preoperative Evaluation.pdf
34 -
Preoperative Evaluation
INTRODUCTION
Patient-­Related Risk Factors
Procedure-­Related Risk Factors
Pulmonary Risk Prediction Tools
Role of Pulmonary Diagnostic Testing
Chest Radiography
Pulmonary Function Testing
Other Laboratory Testing
Preoperative Risk Reduction Strategies
Smoking Cessation
Prehabilitation
Oral Hygiene
Intraoperative Risk Reduction Strategies
Anesthesia
Neuromuscular Blockade
Mechanical Ventilation
Postoperative Risk Reduction Strategies
Perioperative Risk Reduction Protocols
Sleep-­Disordered Breathing Considerations
Airway Management Considerations
Key Readings
References
35 Evaluation of Respiratory Impairment and Disability.pdf
35 - Evaluation of Respiratory Impairment and Disability
INTRODUCTION
Definitions
Impairment
Disability
Additional Terms
Clinical Approach to Impairment Evaluations
History
Physical Examination
Diagnosis, Causation, and Maximum Medical Improvement
Guides to Respiratory Impairment Ratings
American Thoracic Society Guidelines for Evaluation of Impairment or Disability
American Medical Association Guides to the Evaluation of Permanent Impairment
Classification of Impairment Resulting From Specific Pulmonary Diseases
Asthma
Bronchiectasis (See Chapter 69)
Sleep Disorders (See Chapters 117–122)
Lung Cancer (See Chapters 76 and 77Chapter 76Chapter 77)
Diseases of the Pulmonary Arteries
Conditions of the Upper and Lower Airways (See Chapters 70 and 71Chapter 70Chapter 71)
Role of Diagnostic Test Results in Impairment Ratings
Radiographic Data
Pulmonary Function Testing (See Chapters 31 and 32)
Cardiopulmonary Exercise Testing (See Chapter 33)
Blood Gas Analysis
Addressing Discrepancies Between Objective and Subjective Data
Apportionment and Future Medical Treatment
Apportionment
Expected Future Medical Treatment
Major State and Federal Benefit and Compensation Programs
Workplace Protections
Respiratory Protection
Work Restrictions
Americans With Disabilities Act Amendments Act
Future Directions
An Updated Framework of Disability
Programs in Which Physicians Primarily Determine Disability
Federal Black Lung Program
Social Security Disability
Programs in Which Physicians Primarily Determine Impairment
Workers’ Compensation
Veterans Administration
Energy Employees Occupational Illness Compensation Program
Family and Medical Leave Act
Key Readings
References
36 Dyspnea.pdf
36 -
Dyspnea
Definition of Dyspnea
Language of Dyspnea
Qualitative Phrases—The Descriptive Dimension of Dyspnea
Emotional Phrases—The Affective Dimension of Dyspnea
Mechanisms of Dyspnea
Assessment of dyspnea
Psychometric measurement of dyspnea intensity
Multidimensional Assessment of Dyspnea
Exercise Performance as an Indication of Dyspnea
Reported Exercise Limitation Due to Dyspnea
Quality of Life and Dyspnea
Diagnostic Approach to the Patient with Dyspnea
Physiologic Categories of Dyspnea in the Context of the Respiratory System
History
Language
Timing
Position
Associated Symptoms
Intensity
Physical Examination
Laboratory Assessment
Pulmonary Function Testing
Special Studies
Treatment of Dyspnea
Decreasing Respiratory Drive
Reducing Respiratory Effort and Improving Respiratory Muscle Function
Role of Exercise Training in Relieving Dyspnea
Altering Central Perception
Relief of Dyspnea in End-­Stage Lung Disease
Key Readings
References
37 Cough.pdf
37 - Cough
INTRODUCTION
Definition of Cough
Physiology and Neurobiology
Mechanics of Coughing
Cough Motor Controls
Sensory Receptors for the Cough Reflex
Membrane Receptors/Channels for Cough Transduction
Central Nervous System Control
Mechanisms of Cough Hypersensitivity
Approach to the Patient With Cough
Measuring Cough Severity and Frequency
Measuring Cough Reflex
Acute, Subacute, and Chronic Cough
Postnasal Drip (Rhinosinusitis, Upper Airway Cough Syndrome)
Asthma and Associated Eosinophilic Conditions
Gastroesophageal Reflux Disease
Chronic Bronchitis/COPD
Bronchiectasis
Angiotensin-­Converting Enzyme Inhibitors
Postinfectious
Idiopathic Pulmonary Fibrosis
Other Conditions
Chronic Cough of Unknown Cause (Idiopathic Cough)
Cough Suppression Therapies
Nonpharmacologic Approach: Speech Pathology Management
Pharmacologic Approach: Antitussive Therapies
Narcotic and Non-­Narcotic Antitussives
Neuromodulators
Expectorants and Mucolytics
Potential Neuromodulators
Key Readings
Complete reference list available at ExpertConsult.com
eFIGURE IMAGE GALLERY
References
38 Chest Pain.pdf
38 - Chest Pain
INTRODUCTION
Epidemiology
Neurobiology Of Pain
Somatic Pain
Visceral Pain
Hyperalgesia
Measuring Pain
Chest Pain Syndromes
Pleuropulmonary Disorders
Pleurisy
Pulmonary Hypertension
Tracheobronchitis
Inflammation or Trauma of the Chest Wall
Cardiovascular Disorders
Acute Coronary Syndrome
Valvular Heart Disease
Pericarditis
Cocaine Toxicity
Disorders of the Aorta
Noncardiac Chest Pain
Musculoskeletal Disorders
Gastrointestinal Disorders
Psychological Factors
Mediastinitis
Thoracic Outlet Syndrome
Miscellaneous Causes
Evaluation of Chest Pain
Cardiac Ischemia
Pulmonary Embolism
Pericardial Disease
Cardiac Tamponade
Pulmonary Hypertension
Thoracic Aortic Dissection
Pneumothorax
Thoracic Outlet Syndrome
Chest Trauma
Gastroesophageal Reflux
Pancreatitis
Key Readings
References
39 Wheezing And Stridor.pdf
39 -
Wheezing And Stridor
Evaluation
Approach
Stridor
Definition
Evaluation
Approach
The Future Of Lung Sound Analysis
Key Readings
References
40 Hemoptysis.pdf
40 - Hemoptysis
INTRODUCTION
Definition Of Severity Of Bleeding
Epidemiology and Outcome
Vascular Origin of Hemoptysis
Prognostic Indicators
Diagnosis
Initial Evaluation
Radiology
Diagnostic Bronchoscopy
Treatment
General Considerations
Airway Management
Endovascular Approach
Endoscopic Approach
Surgical Approach
Preventive Strategies For Bleeding During Lung Biopsy
Key Readings
References
41 Pulmonary Nodule.pdf
41 - Pulmonary Nodule
INTRODUCTION
Epidemiology
Evaluation and Management
Guidelines for Nodule Management
Communication
Solid Versus Subsolid Nodules
Future of Pulmonary Nodule Management
Molecular Biomarkers
Imaging Biomarkers and Deep Machine Learning
Bronchoscopy
Exhaled Breath Analysis
Key Readings
References
42 Positive Screening Test for Tuberculosis.pdf
42 - Positive Screening Test for Tuberculosis
INTRODUCTION
Indications for Tuberculin Skin Test and/or Interferon Gamma Release Assays
Screening for Latent Tuberculosis Infection
Target Populations for Screening
Screening Individuals With Increased Risk of Mycobacterium tuberculosis Infection
Screening Tests for Latent Tuberculosis Infection
Tuberculin Skin Test
Tuberculin Skin Test Placement and Interpretation
Interferon-­Gamma Release Assays
Current Interferon-­Gamma Release Assay Platforms
Interferon-­Gamma Release Assay Interpretation
Selection of Tuberculosis Skin Test or Interferon-­Gamma Release Assays for Latent Tuberculosis Infection Screening
Situations in Which Tuberculosis Skin Test is Preferred
Children Younger Than 5 Years
Situations in Which Interferon-­Gamma Release Assay Is Preferred
Individuals With Prior Bacillus Calmette-­Guérin
Individuals at Risk of Being Lost to Follow-­up
Situations in Which Dual Testing May Be Considered
Clinical Evaluation
Approach to Tuberculosis Skin Test– or Interferon-­Gamma Release Assay–Positive Individuals
Approach to Tuberculosis Skin Test–Positive Individuals with Prior Bacillus Calmette-­Guérin
Other Causes of False-­Positive Tuberculosis Skin Testing Reactions
Nontuberculous Mycobacterial Infection
Allergic Reaction to Tuberculin
Tuberculin Skin Test Boosting
Causes of False-­Positive Interferon-­Gamma Release Assays Testing Results
Interferon-­Gamma Release Assay Boosting
False Interferon-­Gamma Release Assay Conversions
Technical Causes of False-­Positive Interferon-­Gamma Release Assay Results
Technical Causes of False-­Negative Tuberculosis Skin Test or Interferon-­Gamma Release Assays
Treatment for Latent Tuberculosis Infection
Key Readings
References
43 Aspiration.pdf
43 -
Aspiration
Presenting Conditions
Vocal Cord Dysfunction/Paradoxical Vocal Fold Motion Disorder
Foreign Body Aspiration
Airways Disease
Asthma
Bronchiolitis And Bronchiectasis
Pneumonitis: Aspiration Versus Chemical
Exogenous Lipoid Pneumonia
Interstitial Lung Disease
Nontuberculous Mycobacterial Infection
Clinical Presentation
Evaluation and Testing
Treatment
Nil Per OS Status
Compensatory Strategies
Swallowing Therapy
Medical Treatment
Surgery
Key Readings
References
44 Hypoxemia.pdf
44 - Hypoxemia
Definition
Measurements
Consequences
Response
Detection
Arterial Blood Gas
Noninvasive Pulse Oximeter
Mechanisms of HYPOXEMIA
Low Ventilation-­Perfusion
Shunt
Diffusion Limitation
Mixed Venous Oxygen
Mechanisms With Normal Alveolar-­Arterial Partial Pressure of Oxygen Difference
Hypoventilation (see Chapters 45 and 132)
Low Inspired Partial Pressure of Oxygen
Mechanisms Accounting OF Hypoxemia in Respiratory Diseases and Conditions
Pneumonia
Pleural Effusion
Pulmonary Embolism
Pneumothorax
Asthma or COPD
Interstitial Lung Disease or Idiopathic Pulmonary Fibrosis
Acute Respiratory Distress Syndrome
Obesity
Hepatopulmonary Syndrome
Coronavirus Disease 2019
Approaches to Hypoxemia
Increased Inspired Oxygen
LATERAL Positioning
Proning
Improving Mixed Venous Partial Pressure of Oxygen
Positive End-­Expiratory Pressure
Clinical Tests
Exercise
Contrast Echocardiography
Breathing 100% Oxygen
Sleep
Acknowledgment
Key Readings
References
45 Hypercapnia.pdf
45 - Hypercapnia
INTRODUCTION
Normal Carbon Dioxide Homeostasis
Mechanisms and Etiologies
Increased CO2 Production
Decreased Minute Ventilation
Increased Dead Space
Ventilatory Supply and Demand
Specific Diseases
Consequences
Clinical Manifestations and Evaluation
Diagnostic Evaluation
Arterial Blood Gas
Surrogate Arterial Pco2 Estimates
Sleep Studies
End-­Tidal CO2 Monitoring
Transcutaneous CO2 Monitoring
Diagnostic Testing for Causes of Hypercapnia
Management
Key Readings
References
46 Community-Acquired Pneumonia.pdf
46 - Community-­Acquired Pneumonia
INTRODUCTION
Pathophysiology and Pathogenesis
Epidemiology
Age-­Related Factors
Personal Habits
Comorbidities
Viral CAP in Immunocompromised Hosts
Geographic and Occupational Considerations
Clinical Presentation
Typical Versus Atypical Pneumonia
Patient Evaluation
Clinical Evaluation
Laboratory Evaluation
Radiologic Evaluation
Microbiologic Evaluation
Sputum Examination
Blood and Pleural Fluid Cultures
Antigen Detection
Nucleic Acid Amplification Tests
Metagenomic Sequencing
Serologic Evaluation
Invasive Diagnostic Techniques
Lower Airway Samples
Transthoracic Lung Aspiration
Differential Diagnosis
Therapeutic Approach to Pneumonia
Assessment of Severity
Correction of Host Abnormalities
Selection of Antimicrobial Agents
Adjustments in Antimicrobial Therapy in Patients Who Are Stable or Improving
Adjustments in Antimicrobial Therapy in Patients Who Are Deteriorating or Not Improving
Common Causes of Pneumonia
Major Causes of Pneumonia
Streptococcus pneumoniae (Pneumococcal Pneumonia)
. S. pneumoniae is the most frequent cause of CAP among patients who require hospitalization.40,41 The overall incidence of pneu...
. pneumoniae. S. pneumoniae contains a core genome and a large number of noncore genes, promoting diversity.186 The polysacchari...
. The classic presentation of pneumococcal pneumonia consists of a rigor followed by sustained fever, cough, dyspnea, and produc...
. A Gram stain of purulent sputum revealing numerous characteristic lancet-­shaped diplococci with blunted ends (commonly seen i...
. With an appropriate antibiotic, a clinical response is expected within 24 to 48 hours. The onset of suppurative complications,...
. Antimicrobial resistance complicates treatment for S. pneumoniae in much of the world, including in the United States, with in...
Legionella
. L. pneumophila causes outbreaks and sporadic infections; both patterns may be seen either in the community or in hospitals, an...
. Unlike S. pneumoniae, legionellae are facultative intracellular pathogens and have evolved strategies to survive and replicate...
. The usual incubation period for Legionella pneumonia is 2 to 10 days but can be longer.214 Lethargy, headache, fever, recurrin...
. Legionella are obligatory aerobic, fastidious, gram-­negative bacilli that stain poorly with Gram stain (see Chapter 19, Fig. ...
. A clinical response to appropriate antibiotic therapy is usually observed within 48 hours. In contrast, radiographic findings ...
. Azithromycin and fluoroquinolones are both superior to erythromycin or clarithromycin for treatment of Legionella infections a...
Common Viral Causes of Pneumonia
Influenza Virus
. The most common of influenza-­associated complications, influenza pneumonia can be categorized into primary viral pneumonia, s...
. The CDC and IDSA recommend antiviral treatment for individuals at risk for more severe influenza or in individuals requiring h...
Other Common Causes of Pneumonia
Haemophilus influenzae
. H. influenzae is a gram-­negative coccobacillus and an obligate human pathogen. With the routine vaccination of children again...
. Haemophilus species are a part of the respiratory microbiome, and H. influenzae quantity increases in patients with chronic lu...
. Haemophilus pneumonia is clinically indistinguishable from other bacterial pneumonias.269 Leukocytosis and CRP greater than 10...
. Diagnosing H. influenzae pneumonia by a Gram stain of sputum is difficult because the small, pleomorphic coccobacilli are easi...
. The overall mortality rate of H. influenzae pneumonia is 2–7%, lower than for CAP in general, and ICU admission is also less f...
. H. influenzae isolates produce β-­lactamase in 20–50% of cases and are therefore often resistant to ampicillin. β-­lactamase–n...
Nonresponding Pneumonia/Treatment Failure
Infectious Causes
Noninfectious Causes
Diagnostic Evaluation
Mycoplasma pneumoniae
. Mycoplasma pneumoniae is a tiny gram-­negative pleomorphic bacterium that grows by parasitizing mammalian cells. Older studies...
. M. pneumoniae lacks a rigid peptidoglycan-­containing cell wall. It contains a polar attachment organelle responsible for adhe...
. The incubation period may be as long as 3 weeks. The prodrome can involve fever, myalgia, and dry cough.284 Many infections ar...
. When obtained, sputum generally displays moderate numbers of PMNs without a predominant organism. Gram staining does not detec...
. Mycoplasma pneumonia is usually a benign, often self-­limited infection with an excellent prognosis for complete recovery. ARD...
. Antimicrobial therapy with a tetracycline, macrolide, or fluoroquinolone shortens the course of clinical symptoms and hastens ...
Staphylococcus aureus
. S. aureus, a large gram-­positive bacterium with a coccal shape and a tendency to cluster, has emerged as an important cause o...
. S. aureus contains a range of genes encoding virulence factors regulated by the accessory gene regulator, which links quorum s...
. S. aureus CAP presents with similar signs and symptoms to pneumococcal CAP.301 At the time of presentation, MRSA-CAP is associ...
. Purulent sputum with multiple clusters of large gram-­positive cocci, particularly if intracellular, is strong evidence of S. ...
. Even with appropriate antibiotics, the duration of fever and need for ICU care are often prolonged for S. aureus pneumonia, pa...
. The treatment of choice for MSSA CAP is a penicillinase-­resistant penicillin (e.g., oxacillin 8 to 12 g/day) or a first-­gene...
Gram-­Negative Bacillary Pneumonia
Enterobacteriaceae
. Enterobacteriaceae normally colonize the digestive tract; oropharyngeal colonization is associated with hospitalization and an...
Pathogenesis. A major virulence factor for K. pneumoniae infection is the capsule, and hypervirulent strains have higher capsule...
Clinical Manifestations. In Klebsiella CAP, a syndrome of pleuritic chest pain, hemoptysis, and bloody sputum (occasionally with...
Microbiologic Diagnosis. Enterobacteriaceae pneumonia should be suspected when sputum Gram stain reveals large numbers of unifor...
Clinical Course. Enterobacteriaceae pneumonia fatality rates are 25–50%.46 Bacteremia, neutropenia, and advanced age contribute ...
Treatment. Treatment of serious infections due to Enterobacteriaceae is complicated by widespread antimicrobial resistance. Incr...
Pseudomonas aeruginosa and Related Organisms
. P. aeruginosa is an uncommon cause of CAP and accounts for approximately 1–2% of CAP cases.354,355 Higher rates are found in p...
. P. aeruginosa has a large genome containing several pathogenicity islands.369 Type 4 pili and flagella aid attachment to the r...
. The clinical and radiologic picture of pneumonia due to P. aeruginosa (eFig. 46.26) is indistinguishable from that of the Ente...
. Gram-­stained sputum from patients with Pseudomonas pneumonia typically shows many slender, gram-­negative bacilli (eFig. 46.2...
. Even in otherwise healthy individuals, P. aeruginosa CAP mortality is 30%,46 and median survival of less than 12 hours after a...
. The decision to include empirical therapy for P. aeruginosa pneumonia in CAP is based on identification of risk factors such a...
Other Viral Pneumonias
. RSV is a pleomorphic (150 to 300 nm), enveloped virus with a single-­stranded, nonsegmented RNA genome. Two surface proteins, ...
. RSV is worldwide in distribution. In temperate climates, annual outbreaks of RSV infection are most common in winter months389...
. Viral replication generally begins in the nasopharynx, then moves to the bronchiolar epithelium, and gradually progresses (1 t...
. The incubation period is usually 4 to 6 days. The clinical manifestations of infection depend on both the age and immunologic ...
. RSV infection can be diagnosed by rapid antigen detection, PCR-­based assays, or viral culture. Rapid antigen tests can be per...
. Correction of hypoxemia is the most important aspect of managing RSV LRT infection.424 There are currently two licensed drugs ...
Less Common Causes of Pneumonia
Acinetobacter baumannii
. A. baumannii, a gram-­negative bacteria, is a rare cause of CAP and more commonly associated with HAP/VAP.443 Acinetobacter ca...
. Patients with Acinetobacter CAP often present acutely with shock, ARDS, and disseminated intravascular coagulation.443,445,446...
. Examination of expectorated sputum, which is usually purulent, may reveal a predominance of paired gram-­negative coccobacilli...
. The mortality rate of community-­acquired Acinetobacter pneumonia is often over 50%.445,446 Patients at greatest risk of death...
. Community isolates of A. baumannii can be susceptible to β-­lactam/β-­lactam inhibitor combinations, carbapenems, fluoroquinol...
Anaerobic Bacteria
. Anaerobic bacteria usually cause pneumonia in association with aspiration. Risk factors for aspiration are reduced cough and i...
. Anaerobic infections are associated with three different syndromes associated with aspiration pneumonia: chemical pneumonitis,...
. Gram stain of sputum or BAL fluid of a patient with anaerobic pneumonia reveals PMNs with an abundance of intracellular and ex...
Clinical Course. Uncomplicated aspiration pneumonia generally responds promptly to appropriate antibiotics. Fatality rates are l...
. β-­Lactamase–mediated resistance is common among anaerobes. Empirical treatment for serious anaerobic pneumonia requires the u...
Bordetella pertussis
Chlamydophila pneumoniae (Formerly Chlamydia pneumoniae)
. C. pneumoniae is a gram-­negative coccobacillus. Older serologic studies suggested C. pneumoniae caused up to 15% of cases of ...
. The pathogen is an obligate intracellular bacterium. The infective elementary bodies are taken up into cells via the interacti...
. Primary infection by C. pneumoniae is usually asymptomatic: an acute, mild respiratory tract infection is observed in up to 20...
. C. pneumoniae cannot be visualized by Gram stain, and tissue culture is required to grow the pathogen. Although direct fluores...
. Complete recovery following C. pneumoniae infection is the rule; fatalities are principally seen in patients with mixed infect...
Chlamydia psittaci (Formerly Chlamydophila psittaci): Psittacosis
Coxiella burnetii: Q Fever
Melioidosis (Burkholderia pseudomallei)
Moraxella catarrhalis
Neisseria meningitidis
Pasteurella multocida
Plague Pneumonia (Yersinia pestis)
Pulmonary Anthrax (Bacillus anthracis)
Streptococci Other Than Pneumococci
Tularemia (Francisella tularensis)
Chronic Pneumonias
. Actinomyces, which are gram-­positive non–spore-­forming, branching filamentous bacilli, cause human disease, of which A. isra...
. Nocardia species, gram-­positive bacilli that appear as beaded, branching filaments, can cause pulmonary nocardiosis. N. aster...
. R. equi, an intracellular gram-­positive bacillus, is a veterinary pathogen that may cause lung abscess and pneumonia.86 Infec...
Less-­Common Viral Pathogens
Adenovirus
. Human AdV respiratory infections are predominantly caused by species B (including types 3, 7, 11, 14, 21, and 55), C (types 1,...
. Most adenoviruses, as well as coxsackie B viruses, bind to the coxsackie virus and AdV receptor, whose usual function is to me...
. The incubation period for AdV infection ranges from 2 to 14 days. Typical presentations include pharyngitis, rhinitis, conjunc...
. Diagnosis of AdV infections was previously achieved by virus culture or antigen detection by immunofluorescence staining. Howe...
. Antiviral treatment of AdV infection is controversial because no randomized trials have been conducted. Cidofovir, a cytosine ...
Coronaviruses
. Human coronaviruses OC43 and 229E, first discovered in the 1960s, have been recognized as causes of the common cold. HCoV-­NL6...
. Knowledge of the pathogenesis of conventional human coronaviruses, as well as SARS-­CoV and MERS-­CoV, is limited. HCoV-­NL63 ...
. Conventional human coronaviruses produce a typical coryzal illness indistinguishable from colds due to other viruses, and are ...
. Diagnosis of SARS-­CoV and MERS-­CoV is based on a comprehensive contact and travel history and confirmed by laboratory tests....
. At present, there are no CoV-­specific antiviral treatments available. A number of agents have shown activity against coronavi...
Cytomegalovirus
. The major reservoir for CMV is asymptomatic infected persons because CMV infection in healthy individuals is followed by prolo...
. In human fibroblast cell cultures, CMV produces a slowly progressive lytic infection. Infected cells contain large irregular b...
. In immunocompetent persons, most CMV infections are asymptomatic or may present as an acute pharyngitis, with features similar...
. CMV pneumonia should be in the differential diagnosis for any immunocompromised patient with unexplained lower respiratory sym...
. The treatment of choice for CMV pneumonitis is ganciclovir, a nucleoside analogue that competitively inhibits CMV DNA synthesi...
Hantaviruses
. The hantavirus pulmonary syndrome (HPS) is a rodent-­born zoonosis in which humans experience severe, often fatal disease. Eac...
. Hantaviruses use cell surface beta-­3 integrins to enter endothelial cells, resulting in aberrant endothelial cell adhesion an...
. The typical incubation period of HPS is 2 to 3 weeks (range, 1 to 51 days). Presentation of HPS begins with a prodrome of feve...
. Serology is the mainstay of diagnosis. In the absence of immunodeficiency, patients universally have detectable serum IgM and ...
. Treatment is supportive and requires careful management of fluid status to maintain perfusion without exacerbating pulmonary e...
Herpes Simplex Virus
. Humans are the reservoir for HSV-­1 and HSV-­2 viruses. With primary infection, infectious virus is produced in the skin and m...
. Primary HSV infection begins at a local site, with rapid viral replication in parabasal and intermediate epithelial cells and ...
. HSV-­1 pneumonia is very uncommon and is predominantly seen in immunocompromised patients, such as those with malignancy,659 b...
. The diagnosis of HSV pneumonia should be suspected in any immunocompromised patient with unexplained pulmonary opacities, espe...
. Antiviral susceptibility testing should be considered in patients with severe HSV infection who do not respond to initial trea...
Measles Virus
. Measles is found worldwide, but epidemic patterns vary depending on population density and levels of acquired immunity. Before...
. Measles virus is acquired through respiratory droplets or aerosolized particles, initially infecting lymphocytes, dendritic ce...
. The median incubation period is around 10 to 12 days but may be longer in adults. Measles typically presents with a prodrome o...
. The most common laboratory method for confirming measles virus infection is by detecting measles virus–specific IgM from sera ...
. The treatment of measles involves supportive care and prompt recognition and treatment of secondary bacterial infections. No s...
Metapneumoviruses
. hMPV was first identified by Dutch researchers in 2001 from archived pediatric respiratory specimens in which no pathogen had ...
. Incubation period is thought to be 5 to 9 days.706 hMPV predominantly causes mild self-­limited respiratory infections. In chi...
. Relatively little is known regarding the pathogenesis of this disease. Alpha-­v beta-­1 integrin has been identified as a func...
. Most hMPV infections are detected by nucleic acid amplification techniques such as RT-­PCR. Numerous commercial molecular pane...
. Treatment is supportive. No antiviral agents or vaccines are currently licensed for treatment or prevention of hMPV infections...
Parainfluenza Viruses
. Parainfluenza viruses have a worldwide distribution, and almost all persons are infected during childhood. By adulthood, over ...
. Replication of parainfluenza viruses is generally restricted to the respiratory tract epithelium, initially infecting nasal an...
. PIV infection in adults predominantly manifests as a common cold, including cough, rhinorrhea, and sore throat.736 PIV-­associ...
. Rapid diagnosis of parainfluenza infection can be made by detection of viral antigen or RNA in respiratory secretions obtained...
. There are currently no available antiviral agents of proven effectiveness against PIV. Ribavirin, intravenous immunoglobulin, ...
Rhinovirus
. RVs are worldwide in distribution. RV infections happen year-­round, with peak circulation in early fall and a smaller peak in...
. Previously, the majority of RV types were known to bind the intercellular adhesion molecule-­1, while a minority utilized the ...
. RVs are the commonest cause of upper respiratory tract infections in adults and children. The incubation period of RV is usual...
. Detection of RV nucleic acid in multiplexed PCR-­based assays (see Chapter 19) is now commonly used to diagnose RV infection, ...
. There are currently no approved antiviral therapies for RV. Treatment is largely supportive, including analgesics, antihistami...
Varicella-­Zoster Virus
. Primary VZV infection is predominantly a childhood disease in unvaccinated populations. In temperate settings, greater than 90...
. The incubation period of varicella averages 2 weeks, and almost all cases of varicella develop within 10 to 21 days after expo...
Clinical Manifestations
. Varicella usually begins with a fever and a self-­limited, pruritic vesicular rash that affects most of the body and occasiona...
Herpes Zoster. Herpes zoster represents reactivation of latent VZV along one to three dermatomes and, in adults, is usually asso...
. Real-­time PCR assays are now commonly used to confirm VZV infection from skin lesions as well as from BAL or cerebrospinal fl...
. First-­line treatment for varicella pneumonia or other VZV complication is intravenous acyclovir (10 mg/kg every 8 hours) for ...
Microbiologic Studies
Imaging Studies
Prevention of Pneumonia
Vaccines
Smoking Cessation
Key Readings
eFIGURE IMAGE GALLERY
References
46a COVID-19.pdf
46a - COVID-­19
INTRODUCTION
VIROLOGY
TRANSMISSION
EPIDEMIOLOGY
CLINICAL PRESENTATION
SYSTEMIC MANIFESTATIONS
RESPIRATORY MANIFESTATIONS
GASTROINTESTINAL MANIFESTATIONS
CARDIAC MANIFESTATIONS
EAR, NOSE, AND THROAT MANIFESTATIONS
OCULAR MANIFESTATIONS
NEUROLOGIC MANIFESTATIONS
HEMATOLOGIC MANIFESTATIONS
DERMATOLOGIC MANIFESTATIONS
INFLAMMATORY SYNDROMES
IMMUNOCOMPROMISED PATIENTS
CLINICAL COURSE
LABORATORY FINDINGS
IMAGING
DIAGNOSIS
SARS-­COV-­2 NUCLEIC ACID TESTING
SARS-­COV-­2 SEROLOGY TESTING
OTHER TESTS
PATHOLOGY AND PATHOMECHANISMS
PATHOLOGY OF COVID-­19 PNEUMONIA
IMMUNOPATHOLOGIC OBSERVATIONS IN COVID-­19 PNEUMONIA
PATHOMECHANISMS OF COVID-­19
TREATMENT
RESPIRATORY CARE
ANTIVIRAL AND ANTI-­INFLAMMATORY THERAPIES
ANTICOAGULANT AND ANTITHROMBOTIC THERAPY
FUTURE DEVELOPMENTS
Key Readings
eFIGURE Image GalleRy
References
47 Influenza.pdf
47 - Influenza
Characteristics of Influenza Viruses
Epidemiology
Infection Control
Pathogenesis
Copathogenesis of Influenza with Bacteria
Vaccines
Patient Management
Clinical Presentation
Diagnostic Testing
Specimens
Rapid Antigen Detection Tests
Immunofluorescence Assay
Molecular Diagnostics
Culture
Serology
Summary
Radiographic Findings
Antiviral Therapies
Adamantanes
Neuraminidase Inhibitors
Cap-­Dependent Endonuclease Inhibitor
Antiviral Resistance
Antiviral Treatment Decisions
Patients with Pneumonia
Critically Ill Patients
Other Therapies
Human Infection with Novel Influenza Viruses
A/H5N1
A/H7N9
Key Readings
Acknowledgments
eFIGURE IMAGE GALLERY
References
48 Hospital-Acquired Pneumonia.pdf
48 - Hospital-­Acquired Pneumonia
INTRODUCTION
Pathogenesis
Epidemiology
Incidence
Impact on Outcomes
Etiologic Agents
Diagnosis
Establishing a Clinical Diagnosis
Determining the Etiologic Agent
Treatment
Empirical Treatment Approach
Targeted Treatment Approach
Pharmacokinetic/Pharmacodynamic Antibiotic Dosing
Inhaled Antibiotics
Antibiotic De-­Escalation and Duration of Treatment
Prevention
Minimizing Oropharyngeal Colonization
Preventing Aspiration
Airway Clearance, Early Mobilization, Pain Control
Prophylactic Antibiotics
Multipronged Interventions
Key Readings
References
49 Ventilator-Associated Pneumonia.pdf
49 - Ventilator-­Associated Pneumonia
INTRODUCTION
Pathogenesis
Epidemiology
Incidence
Attributable Mortality, Morbidity, and Costs
Etiologic Agents
Diagnosis
The Clinical Diagnostic Strategy
The Invasive Diagnostic Strategy
Summary of the Evidence
Treatment
Initial Treatment
Avoiding Overuse of Antibiotics
Aerosolized Therapy
Prevention
Conventional Infection Control Approaches
Specific Prophylaxis Against Ventilator-­Associated Pneumonia
Implementing a Structured Prevention Policy
Key Readings
References
50 Lung Abscess.pdf
50 - Lung Abscess
INTRODUCTION
Definition
Pathophysiology
Clinical Manifestations
Differential Diagnosis
Radiographic Features
Diagnostic Studies
Microbiology5,11–13
Complications
Treatment
Antimicrobial Therapy
Surgical Intervention
Percutaneous Tube Drainage
Endoscopic Drainage
Key Readings
References
51 Tuberculosis Epidemiology and Prevention.pdf
51 - Tuberculosis: Epidemiology and Prevention
INTRODUCTION
Epidemiology of Tuberculosis
Transmission of M. Tuberculosis
Source Case
Environmental Factors
Circumstances of Exposure
Host Factors
Lessons from genotyping M. Tuberculosis
Risk Factors for Disease
Prevention of Tuberculosis
Prompt Diagnosis and Effective Treatment
Infection Control Measures to Reduce Transmission of M. Tuberculosis
Clinician Awareness
Administrative Controls (Policies)
Environmental Controls
Personal Respiratory Protection
Treatment of Latent Tuberculosis Infection
Indications for Treating Latent TB Infection
. The rates of TB among persons who are infected with both M. tuberculosis and HIV are extremely high, ranging from 3–16% per ye...
. Two percent to 4% of persons in close contact with a person with infectious TB develop TB in the year after exposure.128-­130 ...
. Because the risk of developing TB is greatest during the initial 1 to 2 years after acquisition of the infection, any person w...
. This group includes persons with a history of TB who never received anti-­TB chemotherapy or who were not treated adequately, ...
. Although the risk of TB is not always quantifiable, there is sufficient evidence to warrant preventive therapy in certain situ...
Current Treatment Regimens
Preferred Regimens
. The alternative regimen is 6 or 9 months of daily isoniazid. The 6-month regimen is strongly recommended for HIV-negative adul...
Management of Exposure to Drug-­Resistant Organisms
Monitoring for Adverse Reactions
Immunization with Bacille Calmette-­Guérin
New Tuberculosis Vaccines
Key Readings
References
52 Tuberculosis Pathogenesis and Immunity.pdf
52 - Tuberculosis: Pathogenesis and Immunity
INTRODUCTION
M. Tuberculosis and the M. Tuberculosis Complex
Innate Immunity
Cellular Niches and Granulomas
Macrophage Subcellular Niches
Cytokine Responses
Vitamin D
Cell Death Pathways
Adaptive Immunity
Classical T Cells
Nonclassical T Cells
Other Mechanisms of Immunity
Evasion of Adaptive Immunity
Latency/Dormancy and Reactivation
New Tuberculosis Vaccines
Key Readings
References
53 Tuberculosis Clinical Manifestations and Diagnosis.pdf
53 - Tuberculosis: Clinical Manifestations and Diagnosis
INTRODUCTION
Diagnosis of Pulmonary Tuberculosis
Diagnostic Evaluation
Patient History
Physical Examination
Radiographic Features
Laboratory Diagnostic Evaluation
Testing for Suspected Pulmonary Tuberculosis
Specimen Collection
Acid-­Fast Staining
Mycobacterial Culture
. tuberculosis Identification. The methods to identify M. tuberculosis can be classified as (1) phenotypic methods including bio...
Phenotype-­Based Identification Methods. The classical phenotype-­based methods to identify M. tuberculosis complex require a po...
Molecular Identification Methods. Several molecular methods are available to identify M. tuberculosis directly on the specimen o...
Non–Sputum-­Based Tests
. Recently, tests based on the detection of lipoarabinomannan (LAM) antigen in urine have emerged as novel tests for TB diagnosi...
. Several antigens, including highly purified and recombinant antigens specific for M. tuberculosis complex, have been used in s...
. Clinicians caring for suspected TB cases with negative smear and NAAT results are often faced with the dilemma of whether to i...
Drug Susceptibility Testing
Extrapulmonary Tuberculosis
Pleural Tuberculosis
Disseminated Tuberculosis
Lymphatic Tuberculosis
Genitourinary Tuberculosis
Bone and Joint Tuberculosis
Central Nervous System Tuberculosis
Intestinal Tuberculosis
Peritoneal Tuberculosis
Pericardial Tuberculosis
Key Readings
eFIGURE IMAGE GALLERY
References
54 Tuberculosis Treatment of Drug-Susceptible and Drug-Resistant.pdf
54 - Tuberculosis: Treatment of Drug-­Susceptible and Drug-­Resistant
INTRODUCTION
Background
Principles of Treatment
Treatment
Treatment Initiation
Recommended Treatment Regimens for Drug-­Susceptible Tuberculosis
Dosing Frequency and Treatment Adherence
Patient-­Centered Care
Directly Observed Therapy
Patient Evaluation
Patient Response to Treatment
Background
Identifying Patients at Risk for Poor Outcomes
Poor Treatment Response and Treatment Failure
Case Management
Adverse Effects
Hepatotoxicity
Gastrointestinal Symptoms
Rash
Neurotoxicity
Optic Neuritis
Therapeutic Drug Monitoring
Interruptions in Therapy
Culture-­Negative Tuberculosis
Extrapulmonary Tuberculosis
Central Nervous System
Bone and Joint
Pericardial
Lymph Node
Special Populations
People Living With Human Immunodeficiency Virus
Hepatic Disease
Kidney Disease
Older Patients
Children
Pregnancy and Breastfeeding
DRUG-RESISTANT TUBERCULOSIS
Initiating Empirical Treatment for Drug-­Resistant Tuberculosis
Key Principles of Treating Drug-­Resistant Tuberculosis
Mechanisms and Pharmacology of Drugs Used to Treat Drug-­Resistant Tuberculosis
Empirical Expanded Regimens
Empirical Regimens for Multidrug-­Resistant Tuberculosis
Treatment Duration
New Regimen for Extensively Drug-­Resistant Tuberculosis or Treatment-­Intolerant or Nonresponsive Multidrug-­Resistant Tubercul...
Isoniazid Monoresistance
Surgery
Key Readings
eFIGURE IMAGE GALLERY
References
Appendix: Essentials Of Chemotherapy
Introduction
Beginnings
Drugs in Current Use
First-­Line Drugs
Second-­Line Drugs
References: Appendix
55 Nontuberculous Mycobacterial Infections.pdf
55 -
Nontuberculous Mycobacterial Infections
Epidemiology
Incidence and Prevalence
Geographic Distribution and Variation
Transmission and Pathogenesis
Transmission
Factors Associated With Infection
Factors Associated with Disease
Diagnosis and Management of Specific Pathogens
Laboratory Diagnosis
Slowly Growing Mycobacteria
Mycobacterium avium Complex
. Several aspects of treatment for MAC pulmonary disease are difficult to explain and are even counterintuitive. The greatest mi...
. Successful treatment of disseminated MAC in persons with AIDS is based on treatment of both the mycobacterial and HIV infectio...
. The treatment of choice for MAC lymphadenopathy and localized lymphadenopathy due to most NTM pathogens is complete surgical r...
Mycobacterium kansasii
. M. kansasii is susceptible to a broad array of antimicrobial agents, including rifamycins, macrolides, fluoro­quinolones, clof...
. The treatment regimen for disseminated disease, as usually observed in patients with AIDS, should be the same as for pulmonary...
Mycobacterium xenopi
Mycobacterium malmoense
Mycobacterium simiae
Mycobacterium szulgai
Rapidly Growing Mycobacteria
Mycobacterium abscessus
. M. abscessus is typically resistant in vitro to most of the medications used to treat TB and has demonstrated in vitro activit...
. Serious infections should be treated with a regimen similar to that used for pulmonary disease. Skin and soft tissue infection...
Mycobacterium chelonae
Mycobacterium fortuitum Complex
CYSTIC FIBROSIS AND NONTUBERCULOUS MYCOBACTERIA
Surgical Resection
Therapeutic Drug Monitoring
Hypersensitivity Pneumonitis–­Like Nontuberculous Mycobacteria Pulmonary Disease
Prevention of Nontuberculous Mycobacteria Infections
Health Care–Associated Nontuberculous Mycobacteria Disease
Key Readings
eFigure Image Gallery
References
56 Fungal Infections Endemic.pdf
56 - FUNGAL Infections: Endemic
INTRODUCTION
Histoplasma
History and Epidemiology
Pathogenesis
Clinical Manifestations
Acute Histoplasmosis
Disseminated Histoplasmosis
Chronic Pulmonary Histoplasmosis
Transmissibility
Diagnosis
Treatment
Mild to Moderate Acute Pulmonary Histoplasmosis
Moderately Severe to Severe Acute Pulmonary Histoplasmosis
Chronic Cavitary Histoplasmosis
Disseminated Histoplasmosis
Immunocompromised Patients
Drug Monitoring
Management of Complications
Coccidioides
History and Epidemiology
Pathogenesis
Clinical Manifestations
Pulmonary Coccidioidomycosis (Valley Fever or Primary Coccidioidal Infection)
Acute Respiratory Failure and Acute Respiratory Distress Syndrome
Disseminated Coccidioidomycosis
Pulmonary Nodule (Coccidioidoma)
Cavitary Coccidioides
Transmissibility
Diagnosis
Treatment
Uncomplicated Acute Pneumonia
Complicated Pneumonia With or Without Dissemination
Pulmonary Nodule
Pulmonary Cavity
Blastomyces
History and Epidemiology
Pathogenesis
Clinical Manifestations
Acute Pulmonary Blastomycosis
Chronic Pulmonary Blastomycosis
Extrapulmonary Disease
Transmissibility
Diagnosis
Treatment
Mild to Moderate Blastomycosis
Moderately Severe to Severe Blastomycosis
Paracoccidioides
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Treatment
Sporothrix
Talaromyces
Emergomyces
Key Readings
eFIGURE IMAGE GALLERY
References
57 Fungal Infections Opportunistic.pdf
57 - Fungal Infections: Opportunistic
INTRODUCTION
Antifungal Therapy
Polyenes
Azoles
Echinocandins
Flucytosine
Terbinafine
Cryptococcosis
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Treatment
Candidiasis
Aspergillosis
Introduction and Epidemiology
Pathogenesis
Infection Types
Mucormycosis
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Treatment
Non-­Aspergillus Hyaline Hyphomycetes
Epidemiology and Pathogenesis
Clinical Presentation and Diagnosis
Treatment
Dematiaceous (Melanized) Hyphomycetes
Key Readings
eFIGURE IMAGE GALLERY
References
58 Parasitic Infections.pdf
58 -
Parasitic Infections
INTRODUCTION
Initial Evaluation of a Patient With Possible Parasitic Infection of the Lungs
Helminths
Nematodes
Ascariasis
Hookworm Disease
Strongyloidiasis
Tropical Pulmonary Eosinophilia
Visceral Larva Migrans
Dirofilariasis
Trichinosis
Gnathostomiasis
Trematodes
Paragonimiasis
Schistosomiasis
Cestodes
Echinococcosis
Echinococcus multilocularis
Protozoa
Amebiasis
Malaria
Toxoplasmosis
Other Protozoa
Babesiosis
Cryptosporidiosis
Free-­Living Ameba
Leishmaniasis
Microsporidiosis
Trypanosomiasis
In Memoriam
Key Readings
eFIGURE IMAGE GALLERY
References
59 Outbreaks, Pandemics, and Bioterrorism.pdf
59 -
Outbreaks, Pandemics, and Bioterrorism
INTRODUCTION
Clinical Presentations
Awareness and Recognition
Classical Syndromes and High-­Consequence Pathogens
Dermatologic Syndromes
Pulmonary Syndromes
Hemorrhagic Fevers
Other Syndromes
Management
Infection Prevention and Control
Reporting
Supportive Care
Diagnostics
Therapeutics
Coordination
Leadership
Communication
Preparedness
Key Readings
References
60 Asthma Pathogenesis and Phenotypes.pdf
60 -
Asthma: Pathogenesis and Phenotypes
Introduction
Epidemiology
Prevalence
Mortality
Risk Factors
Allergy
The Hygiene Hypothesis
The Human Microbiome
Respiratory Viral Infections
Atypical Bacterial Infections
Air Pollution
Other Early Life Factors
Occupational Exposures
Natural History
Neonatal Period
Childhood
Atopic or Allergic March
Teenage Years
Remission
Progressive Airflow Obstruction
Adulthood
Asthma in the Elderly
Genetics of Asthma
Early Evidence That Asthma is Heritable
Candidate Gene Association Studies
Genome-­Wide Association Studies
Asthma in Diverse Ethnic Groups
Severe Asthma and Disease Severity
Lessons Learned
Epigenetic Studies for Asthma Susceptibility and Severity
Molecular and Cellular Basis of Asthma
Histopathology of Asthma
Nerves and Nerve Receptors in Asthma
Overview of Molecular Immunology of Asthma
Molecular Immunology of T2-­High Asthma
Molecular Aspects of T2-­Low Forms of Asthma
Paucigranulocytic Asthma
Type 1 Immunity in Asthma
Type 3 Immunity in Asthma
Neutrophils and Asthma
Systemic Inflammation and Metabolic Dysfunction
Lipid Mediators
Asthma Exacerbations and Interferon Biology in the Airway
Phenotyping
Asthma Heterogeneity
Cellular Phenotypes
Molecular Phenotypes (Endotypes)
T2-­High Endotype
T2-­Low Asthma
Key Readings
References
61 Asthma and Obesity.pdf
61 -
Asthma and Obesity
INTRODUCTION
Pathophysiology
Obesity and Inhibition of Type 2 Inflammation
Obesity and Non–Type 2 Mechanisms of Asthma
Impact of Obesity on Pulmonary and Asthma Physiology
Clinical Features
Diagnostic Evaluation
Pharmaceutical Interventions
Medication Response to Conventional Asthma Medications in Obese Asthma Patients
Medication Response to Asthma Biologics in Obese Asthma Patients
Comorbidities
Diet, Exercise, and Weight Loss Interventions
Key Readings
eFigure Image GalleRy
References
63 COPD Pathogenesis and Natural History.pdf
63 -
Copd: Pathogenesis and Natural History
Pathologic Changes in Established Copd
Small Airway Disease
Chronic Bronchitis and Mucus Hypersecretion
Emphysema
Pulmonary and Systemic Vascular Dysfunction
Epidemiology
Copd as A Worldwide Disease
Prevalence and Incidence
Smoking and Other Environmental Factors
Genetics of Copd
Methods of Determining Susceptibility
Confirmed Genetic Risk Factors
Pathogenesis
Mechanisms of Oxidant Injury and Antioxidants
Smoking-­Induced Epigenetic Reprogramming of the Airway Epithelium
Small Airway Remodeling and Matrix Damage
Proteases/Antiproteases
Innate Cellular Responses
Mediators of Inflammation and of its Resolution
Pulmonary Microvascular Changes Induced by Oxidant Injury
Copd as a Disease of Accelerated Aging
Primary Hallmarks
Antagonistic Hallmarks
Integrative Hallmarks
Adaptive Immune Inflammation and Autoimmunity
Phenotypic Heterogeneity and Natural History
Sex as A Factor in Copd Heterogeneity
Aat Deficiency
Preserved Ratio Impaired Spirometry
Progression and Mortality
Key Readings
References
64 Asthma Diagnosis and Management.pdf
62 -
Asthma: Diagnosis and Management
INTRODUCTION
Definition
Clinical Diagnosis
Personal History
Work History
Physical Examination
Physiology of AIRFLOW Limitation
Pulmonary Function Testing
Spirometry
Provocative Challenges and Airway Hyperresponsiveness
Evaluation and Treatment of Asthma
Introduction
Assessment
Asthma Impairment and Risk
Lung Function
Imaging
Asthma Phenotypes, Endotypes, and Biomarkers
. The emergence of an increased body of literature to support the presence of asthma phenotypes and endotypes has made it impera...
. Eosinophils may be detected in one or multiple compartments, including the peripheral blood, the airway submucosa, and the air...
. Nitric oxide (NO) and related compounds are generated by various resident and inflammatory airway cells and have a broad varie...
. IgE is an important marker of airway inflammation and may play a key role in allergic asthma. The presence of allergen-­specif...
. A significant proportion of patients with severe asthma will have airway granulocytes, including neutrophils and eosinophils.8...
. There is increased interest in using quantitative computed tomography to evaluate disease severity in asthma.90 In 123 subject...
Asthma Treatment Approaches
Overview
Specific Pharmacologic Agents
. Anticholinergic agents act as bronchodilators by competing with acetylcholine at neuromuscular junctions, thereby blocking tra...
. With recognition of the central role of inflammation in the pathophysiology of asthma, contemporary treatment strategies empha...
. Leukotrienes (LTs) are derived from cell membrane arachidonic acid metabolism. LT receptors on airway smooth muscle and macrop...
. Theophylline is a well-­established phosphodiesterase inhibitor that has mild anti-­inflammatory properties. Because of its na...
. Macrolides were initially shown to be effective in a subset of asthma patients who had evidence of mycoplasma in their airways...
. Over the past 5 years, there has been a significant increase in the number of biologics approved for the treatment of asthma. ...
Immunoglobulin E Targeted Therapies. Omalizumab was the first FDA-­approved monoclonal antibody for asthma and is now also indic...
Interleukin-­5 Targeted Therapies. There are currently two anti–IL-­5 antibodies (mepolizumab and reslizumab) and one anti–IL-­5...
IL-­4 Targeted Therapies. Dupilumab is a fully human monoclonal IgG4 antibody to the α-­subunit of the IL-­4 receptor. The IL-­4...
Biologic Therapy: Patient Selection, Response, and Switching. The increased availability of biologic therapies for asthma has le...
Bronchial Thermoplasty
Additional Management Strategies
Medication Adjustment Based on Asthma Control
Difficult-­to-­Treat and Severe Asthma
Control of Triggers
Assessment and Management of Concomitant Diagnoses
. Vocal cord dysfunction (VCD), also referred to as paroxysmal vocal fold motion, was first described as a separate clinical ent...
Management of Acute Asthma
Clinician-­Patient Partnership
Key Readings
References
64 COPD Diagnosis and Management.pdf
64 -
COPD: Diagnosis and Management
Clinical features
Symptoms
Physical Examination
Pulmonary Function Testing and Diagnosis
Spirometry
Lung Volumes
Diffusing Capacity
Exercise Testing
Imaging
Laboratory Testing
Arterial Blood Gases
Erythrocytosis
Serum Bicarbonate
Alpha1-­Antitrypsin Serum Levels
Blood Eosinophils
Sputum
Complications
Pneumothorax
Giant Bullae
Pneumonia
Right Ventricular Dysfunction
Sleep Disorders
Systemic Manifestations and Comorbidities
Cardiovascular Disease
Osteoporosis
Diabetes
Gastroesophageal Reflux Disease
Depression and Anxiety
Differential Diagnosis
Chronic Obstructive Asthma
Chronic Bronchitis Without Airflow Obstruction
Bronchiectasis
Bronchiolitis Obliterans
Diffuse Panbronchiolitis
Lymphangioleiomyomatosis
Treatment
General Principles of Treatment
Reduction of Risk Factors
Smoking Cessation. Throughout the developed world, cigarette smoking is the most important risk factor for the development of CO...
. In the developing world, cigarette smoke is less of an issue than is exposure to smoke from biomass fuel, used for cooking and...
. In addition to active and secondary smoke exposure, allergens and air pollutants may have an impact on COPD. Catastrophic air ...
. A significant proportion of COPD exacerbations are triggered by respiratory infections. Although there are data to suggest tha...
. Exacerbations of COPD are sentinel events and are closely associated with disease progression. Increasing severity of COPD is ...
Pharmacotherapy
Bronchodilators
β-­Adrenergic Agonists
Muscarinic Antagonists
Methylxanthines
Phosphodiesterase-­4 Inhibitors
Corticosteroids
. Airway and systemic inflammation are critical components of the pathogenesis of COPD.233–235 Therefore corticosteroids, with t...
. With rare exceptions, the use of systemic corticosteroids should be reserved for the treatment of exacerbations; in patients w...
Combination Therapy
Stepwise Pharmacologic Management
Antioxidants and Mucolytics
Leukotriene Modifiers
Nonpharmacologic Treatment
Mucus Clearance
Oxygen
. Based on these data, guidelines recommend long-­term administration of oxygen (>15 h/day) to patients with COPD with resting h...
. Patients whose arterial Po2 or Spo2 are borderline at rest may develop worsening hypoxemia with exercise. This is especially t...
. Just as they do with exercise, patients with COPD may experience a significant drop in arterial oxygen tension during sleep, d...
. When flying at altitudes higher than 12,000 feet, aircraft are pressurized to protect passengers and crew from hypoxemia, baro...
. Most patients receive oxygen via a nasal cannula. Flow rates should be adjusted to achieve an Spo2 greater than 90% (arterial ...
Noninvasive Ventilation
Pulmonary Rehabilitation
Surgical Treatment of Emphysema
Treatment of Emphysema With Endobronchial Valves
Acute Exacerbations
Definition
Triggers
Treatment
. During an acute exacerbation, SABAs should be used aggressively, alone or in combination with muscarinic antagonists. Although...
. Substantial data support the use of systemic corticosteroids for treatment of exacerbations of COPD. Their use is associated w...
. The use of antibiotics for exacerbations of COPD is somewhat controversial, largely because of the paucity of data documenting...
Development of New Treatments
Key Readings
eFIGURE IMAGE GALLERY
References
65 Smoking Hazards Cigarettes, Vaping, Marijuana.pdf
65 -
Smoking Hazards: Cigarettes, Vaping, Marijuana
Cigarette Smoking
Epidemiology of Cigarette Smoking
Toxicology of Cigarette Smoke
Smoking-­Related Diseases
Cancer
Chronic Lung Disease
Infection
Cardiovascular Disease
Wound Healing/Postoperative Complications
Other Complications of Cigarette Smoking
Health Hazards of Secondhand Smoke
Electronic Cigarettes
Pulmonary Toxicity
e-­Cigarettes and Smoking Cessation
Other Potential Toxicities of e-­Cigarettes
Cannabis
Pulmonary Toxicity
Cardiovascular Toxicity
Cocaine and Methamphetamine
Key Readings
References
66 Smoking Cessation.pdf
66 -
Smoking Cessation
Nicotine Addiction
Neurobiologic Mechanisms of Addiction
Smoking Cessation
Guidelines
Smoking Cessation Counseling
Motivating Smokers to Quit
Pharmacotherapy for Smoking Cessation
Nicotine Replacement Therapy
Bupropion
Varenicline
Combination Therapy
Electronic Nicotine Delivery Systems and E-­Cigarettes
Benefits of Quitting
Resources for Health Care Providers
Acknowledgment
Key Readings
References
67 Cystic Fibrosis Pathogenesis and Epidemiology.pdf
67 -
Cystic Fibrosis: Pathogenesis and Epidemiology
Historical Perspective
Epidemiology
Genetic Basis
Pathophysiology
CFTR as an ABC Gene
Structure/Activity and Cftr Gating Mechanism
Biogenesis and Processing of Native CFTR
Cellular Defects Attributable to F508del CFTR
Overview of Lung Pathophysiology
Cellular Functions of The CFTR Gene Product
Regulation of Sweat Chloride by Cftr
Regulation of Airway Surface Liquid Homeostasis
Mucus Biogenesis, Adhesion, and Transport
Cystic Fibrosis Exocrine Glandular Epithelium
Host Defense and Infection
Animal Models of Cystic Fibrosis
Cftr And Pulmonary Remodeling
Key Readings
References
68 Cystic Fibrosis Diagnosis and Management.pdf
68 -
Cystic Fibrosis: Diagnosis and Management
Diagnosis
Overview
Clinical Manifestations
Lower Respiratory Tract Disease
Microbiology
Imaging
Lung Function
Upper Respiratory Tract Disease
Complications of Respiratory Tract Disease
Gastrointestinal Manifestations
Pancreatic Disease
Hepatobiliary Disease
Genitourinary Tract Abnormalities
Sweat Gland Dysfunction
Treatment
Overview
Monitoring and Aggressive Approach
Cystic Fibrosis Transmembrane Conductance Regulator Potentiators, Correctors, and Other Treatments for the Basic Defect
. CFTR potentiators activate mutant CFTR localized to the cell surface by potentiating channel gating stimulated by physiologic ...
. Significant efforts toward the goal of correcting the folding of F508del CFTR, thus restoring ion channel activity to the misf...
. Readthrough of premature termination codons (PTCs) represents a potential approach to address CF caused by nonsense mutations,...
Gene Therapy
mRNA Replacement and Other Nucleotide Repair Strategies
Respiratory Therapies
Physical Airway Clearance
Airway Rehydration Therapy
Dornase Alfa
Inhaled Antibiotics
Bacterial Eradication
. Although macrolide antibiotics do not exhibit significant antipseudomonal properties, the utility of these agents in diffuse p...
Anti-­inflammatory Therapy
Other Supportive Care
Pulmonary Exacerbations
Treatment of Lung Complications
Treatment of Gastrointestinal Complications
Surgical Therapy
Lung Transplantation
Nutrition
Psychosocial Factors
Key Readings
efigure Image GalleRy
References
69 Bronchiectasis.pdf
69 -
Bronchiectasis
INTRODUCTION
Classification Schema
Epidemiology
PATHOPHYSIOLOGY
“Vicious Cycle” and Microbiology
Biofilms
Associated Disease States and Etiologic Considerations for Bronchiectasis
Approach to Diagnosis of Bronchiectasis Etiology
Lung Injury Due to Acute Infection
Bronchiectasis Associated with Nontuberculous Mycobacteria
Cystic Fibrosis
Disorders of Immunity
Alpha1-­Antitrypsin Anomalies
COPD
Primary Ciliary Dyskinesia
Bronchial Cartilage or Elastic Fiber Defects
Connective Tissue Disorders
Congenital and Developmental Anomalies
Idiopathic Inflammatory Disorders
Aspiration/Inhalation Accidents (See Also Chapter 43)
Postobstructive Disorders
Allergic Bronchopulmonary Aspergillosis (See also Chapter 96)
Idiopathic Bronchiectasis
Miscellaneous
Management
Airway Hygiene and Hyperosmotic Agents
Antimicrobial Therapy
Anti-­Inflammatory Therapy
Nonsteroidal Anti-­inflammatory Drugs
Inhaled Corticosteroids
Therapies for Treatment of Frequent Exacerbations
Intermittent Macrolide Therapy
Inhibition of Neutrophil Elastase
Surgery
Miscellaneous
Overall Approach to Management
Prognosis
Key Readings
eFigure Image Gallery
References
70 Upper Airway Disorders.pdf
70 -
Upper Airway Disorders
The Nose
Anatomy, Histology, and Physiology
Pathologic Conditions of the Nasal Cavity
Rhinitis
Allergic Rhinitis
Immunotherapy
Nonallergic Chronic Rhinitis
The Paranasal Sinuses
Anatomy, Histology, and Physiology
Paranasal Sinus Disease
Acute Rhinosinusitis
Epidemiology
Treatment
Chronic Rhinosinusitis
Epidemiology
Pathophysiology
Association With Allergy and Asthma
Chronic Rhinosinusitis with Nasal Polyposis
Treatment
The Oral Cavity, Oropharynx, Hypopharynx, and Larynx
Anatomy, Histology, and Physiology
Oral Cavity
Oropharynx
Hypopharynx
Larynx
. The structural bone and cartilages of the larynx include the hyoid bone, paired thyroid lamina, and cricoid ring. These struct...
. The arytenoid cartilage is attached to the cricoid ring through a series of anterior and posterior ligaments that form the cap...
. The epiglottis has ligamentous attachments to the hyoid bone (hyoepiglottic ligament) and thyroid cartilage (thyroepiglottic l...
. The mucosal and fibromuscular structures include the aryepiglottic folds, false vocal folds, and true folds. As stated previou...
. The pharynx and larynx have prominent and complex functions in the upper airway to separate the alimentary tract from the resp...
Disorders of Swallowing
Epidemiology
Symptoms of Disorders of Swallowing
Evaluation of Dysphagia
Treatment
Gastroesophageal and Laryngopharyngeal Reflux Disease
Association with Asthma and COPD
Evaluation of Gastroesophageal Reflux Disease and Laryngopharyngeal Reflux Disease
Treatment of Gastroesophageal Reflux Disease
Paradoxical Vocal Fold Motion Disorder and Laryngospasm
Definition and Diagnosis
Etiology
Treatment
Vocal Fold Paralysis
Unilateral
Bilateral
Laryngeal Stenosis
Upper Aerodigestive Tract Malignancies
Subglottis and Cervical Trachea
Anatomy, Histology, and Physiology
Subglottic and Cervical Tracheal Stenosis
Pathophysiology
Diagnosis
Treatment
Acknowledgment
Key Readings
efigure Image Gallery
References
71 Large Airway Disorders.pdf
71 -
Large Airway Disorders
INTRODUCTION
Clinical Features
Diagnostic Approach
Spirometry and Flow-­Volume Loops
Chest Imaging
Bronchoscopy
Management
Stenosis and Malacia
Stenosis
Malacia
Intrinsic Disorders
Benign Tracheal Stenosis
Malignant Large Airway Disease
TRACHEOBRONCHOPATHIA OSTEOCHONDROPLASTICA
Tracheobronchial Amyloidosis
Infections
Tuberculosis
Fungal Infections
Bacterial Infections
Respiratory Papillomatosis
Inflammatory
Relapsing Polychondritis
Sarcoidosis
Granulomatosis with Polyangiitis
Inflammatory Bowel Disease
Broncholithiasis
Vascular Malformations
Tracheobronchomalacia and Excessive Dynamic Airway Collapse
Extrinsic Disorders
Fibrosing Mediastinitis
Fistulas
Emerging Therapies
Three-­Dimensional Printed Airway Stents
Tracheal Replacement
Key Readings
References
72 Bronchiolitis.pdf
72 -
Bronchiolitis
Anatomic and Physiologic Features
Inflammatory and Infectious Bronchiolitis
Inflammatory Bronchiolitis
Infectious Bronchiolitis
Respiratory Bronchiolitis
Diffuse Panbronchiolitis
Follicular Bronchiolitis
Bronchiolitis Obliterans
Constrictive Bronchiolitis After Lung Transplantation (See Chapter 140)
Chronic Lung Allograft Dysfunction
. Constrictive bronchiolitis is likely a final histologic lesion resulting from a failure in epithelial cell regeneration in the...
. Among injury responses, alloimmune injury appears most important to CLAD pathogenesis. CLAD risk is linked to acute cellular r...
. Lung transplant recipients may develop antibodies to donor HLA antigens. The de novo development of donor-­specific antibodies...
. Autoimmune responses may also contribute to the development of CLAD. Lung injury may expose self-­antigens that would otherwis...
Bronchiolitis Obliterans Syndrome After Allogeneic Stem Cell Transplantation
Bronchiolitis Obliterans and Connective Tissue Diseases
Bronchiolitis Obliterans After Infection
Bronchiolitis From Inhaled or Ingested Toxins
Treatment of Constrictive and Proliferative Bronchiolitis
Bronchopulmonary Dysplasia
Key Readings
References
73 Lung Cancer Molecular Biology and Targets.pdf
73 -
Lung Cancer: Molecular Biology and Targets
INTRODUCTION
Molecular Biology
Carcinogens
Metabolic Reprogramming
Genomic Instability
DNA Damage Response
Host Tumor Interaction and Inflammation
Cell of Origin
Field of Cancerization
Tumor Heterogeneity
Tumor Invasion
Clinically Relevant Molecular Targets in Lung Carcinoma
EGFR/HER2 Pathway
Targeted Agents and Clinical Concerns
Prognosis and Outcomes
KRAS Pathway
Targeted Agents and Clinical Considerations
Prognosis and Outcomes
ALK/ROS1/NTRK Gene Fusions
Targeted Agents and Clinical Considerations
BRAF
MET/PIK3CA
Immunotherapy as Targeted Molecular Therapy
Future Challenges in Targeted Therapy in Lung Carcinoma
Acknowledgments
Key Readings
References
74 Lung Cancer Epidemiology.pdf
74 -
Lung Cancer: Epidemiology
Geographic, Gender, and Ethnic Variability
Smoking
Smoking Behavior and Risk for Lung Cancer
Occupational and Environmental Factors
Occupational Exposures
Asbestos
Diesel Exhaust
Other Occupational Exposures
Radiation
High-­LET Radiation: Radon
Low-­LET Radiation: X-­Rays and γ-­Rays
Air Pollution
Atmospheric Air Pollution
Indoor Air Pollution
Diet and Obesity
Other Causative Associations
Genetic Susceptibility to Lung Cancer
High-­Risk Syndromes Conferring an Increased Risk of Lung Cancer
Common Low-­Penetrance Genes: Genome-­Wide Association Studies
Acknowledgments
Key Readings
eFIGURE IMAGE GALLERY
References
75 Lung Cancer Screening.pdf
75 -
Lung Cancer: Screening
Generalizability
Components for Effective Lung Cancer Screening
Patient Eligibility
Patient Education and Shared Decision-Making
Nodule Management
Management of Other Screening-­Detected Findings
SMOKING Cessation (see Chapter 66)
Implementation
Types of Screening Programs
A Framework for Implementation of Lung Cancer Screening
Identification and Engagement of Individuals Eligible for Screening
Resources for Ensuring Consistency of the Screening Test
Communication Across the Screening Process
Future Advances
Implementation
Screening Eligibility
Molecular and Imaging Biomarkers
Key Readings
References
76 Lung Cancer Diagnosis and Staging.pdf
76 -
Lung Cancer: Diagnosis and Staging
Presentation/Initial Evaluation
Tumor-­Node-­Metastasis Staging of Lung Cancer
Eighth Edition Lung Cancer Stage Classification
Staging of Small Cell Lung Cancer
Quality Gaps in Lung Cancer Diagnosis and Staging
Histology and Prognosis
Approach to Staging
Suspected Metastatic Disease
Locally Advanced Disease/Suspected Mediastinal Involvement
Noninvasive Staging
Invasive Staging: Mediastinoscopy
Key Readings
Special Considerations in Lung Cancer
Superior Vena Cava Syndrome
Oligometastatic Non–Small Cell Lung Cancer
Paraneoplastic Syndromes
Musculoskeletal Effects
Hematologic Effects
Hypercalcemia
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Ectopic Corticotropin Syndrome
Neurologic Effects
eFIGURE IMAGE GALLERY
References
77 Lung Cancer Treatment.pdf
77 -
Lung Cancer: Treatment
INTRODUCTION
Prognostic and Predictive Factors in Lung Cancer
Treatment of Non–Small Cell Lung Cancer by Stage
Stage I Non–Small Cell Lung Cancer
Stage II Non–Small Cell Lung Cancer
Stage III Non–Small Cell Lung Cancer
Stage IIIA
Stage IIIB and Stage IIIC
Stage IV Non–Small Cell Lung Cancer
First-­Line Chemotherapy
Maintenance Chemotherapy
Second-­Line Chemotherapy
Targeted Therapy
. Activating mutations in the tyrosine kinase domain of EGFR include exon 19 deletions and exon 21 (L858R) substitutions and wer...
. The ALK-­fusion gene is found in about 8% of NSCLC79 and is the second most common driver mutation for which there is an effec...
. ROS1 gene rearrangements are observed in approximately 2% of patients with adenocarcinoma of the lung.4 Many TKIs approved for...
. The most common mutation in v-­raf murine sarcoma viral oncogene homolog B1 (BRAF) is the V600E mutation, which is observed in...
. Additional mutations include RET fusions (2% of NSCLC),118 MET exon 14 skipping mutation (3–4%), HER2 dysregulation (2%),4 and...
Immunotherapy
. Second-­line therapy is given when first-­line therapy either fails or stops working. In two large phase III trials of patient...
. Immune-­related adverse events may develop anywhere throughout the body (colitis, thyroiditis, diabetes, neuropathy, myositis,...
Oligometastatic Disease
Treatment of Small Cell Lung Cancer
Palliative Care
Special Considerations in Lung Cancer
Superior Sulcus Tumors and Pancoast Syndrome
Superior Vena Cava Syndrome
Key Readings
eFIGURE IMAGE GALLERY
References
78 Rare Primary Lung Tumors.pdf
78 -
Rare Primary Lung Tumors
Definition of Rare Pulmonary Tumors
Rare Malignant Primary Pulmonary Epithelial Tumors
Sarcomatoid Carcinomas
Pneumoblastoma
Mucoepidermoid Carcinoma
Carcinoids and Large Cell Neuroendocrine Carcinoma
Pathologic Features
Carcinoid Tumors
Large Cell Neuroendocrine Carcinoma
Primary Pulmonary Lymphomas
Mucosa-­Associated Lymphoid Tissue–Type Lymphoma
Lymphomatoid Granulomatosis
Other Lymphomas and Lymphoproliferative Diseases
Primary Pulmonary Sarcomas
Parenchymal Sarcomas
Vascular Sarcomas
Pseudotumors and Borderline Entities
Inflammatory Myofibroblastic Tumor
Respiratory Tract Papillomatosis
Pulmonary Langerhans Cell Histiocytosis (See Chapter 95)
Lessons Learned for the Management of Rare Primary Pulmonary Tumors
Clinical Strategy
Distinguishing Primary Tumors From Metastases
Molecular Profiling
Treatment Principles
Networks
Key Readings
efigure Image Galley
References
79 Metastatic Malignant Tumors.pdf
79 -
Metastatic Malignant Tumors
Epidemiology
Clinical History
Mechanism of Metastasis to the Lung
Diagnosis
Differential Diagnosis
Distinguishing Metastasis From Primary Lung Tumors
Pathology
Molecular Classification
Options for Obtaining a Tissue Diagnosis
Bronchoscopy
Computed Tomography–Guided Biopsy (see Chapter 21)
Surgery
Treatment
Multimodality Therapy of Potentially Curable Disease
Stereotactic Radiotherapy
Radiofrequency Ablation
Surgical Resection of Metastases
Palliative Care
Special Cases
Airway Metastasis
Vascular Embolic Metastasis
Pleural Metastases
Key Readings
efigure Image Gallery
References
80 Benign Lung Tumors.pdf
80 - BENIGN LUNG TUMORS
INTRODUCTION
CLINICAL MANIFESTATIONS
BENIGN EPITHELIAL LESIONS
PAPILLOMAS
ADENOMAS
MICRONODULAR PNEUMOCYTE HYPERPLASIA
BENIGN NONEPITHELIAL LESIONS
HAMARTOMA AND RELATED LESIONS
INFLAMMATORY MYOFIBROBLASTIC TUMOR
SOLITARY FIBROUS TUMOR
MENINGOTHELIAL-­LIKE NODULES AND INTRAPULMONARY MENINGIOMA
OTHER RARE ENTITIES
Key Readings
EFIGURE IMAGE GALLERY
References
81 Pulmonary Thromboembolism Presentation and Diagnosis.pdf
81 -
Pulmonary Thromboembolism: Presentation and Diagnosis
Introduction
Pathogenesis and Risk Factors
Natural History: Deep Venous Thrombosis
Natural History: Pulmonary Embolism
Clinical Presentation
Diagnosis of Venous Thrombosis
Clinical Prediction Rules
D-­Dimer Assays
Combination of Prediction Rules for DVT and D-­Dimer Results
Contrast Venography
Duplex Ultrasonography
Magnetic Resonance Imaging
Computed Tomography
Diagnosis of Pulmonary Embolism
Clinical Prediction Rules
D-­Dimer Testing
Standard Laboratory Evaluation
Ventilation-­Perfusion Scanning
Ventilation-­Perfusion Scanning With Spect
Computed Tomography Pulmonary Angiography (See Also Chapter 20)
Echocardiography
Concurrent Lower Extremity Venous Evaluation
Pulmonary Angiography
Diagnostic Approach to Pulmonary Embolism: Summary
Massive Pulmonary Embolism
Risk Stratification
Other Predictors of Mortality
Pulmonary Embolism During Pregnancy
Recurrent Pulmonary Embolism and Deep Venous Thrombosis
Long-­Term Consequences of Pulmonary Embolism
Key Readings
Other Forms of Embolism
Schistosomiasis
Air Embolism
Fat Embolism
Amniotic Fluid Embolism (See Chapter 129)
Septic Embolism
Other Emboli
efigure Image Gallery
References
82 Pulmonary Thromboembolism Prophylaxis and Treatment.pdf
82 -
Pulmonary Thromboembolism: Prophylaxis and Treatment
Prophylaxis
Bioavailability of Subcutaneous Anticoagulants
Differing Philosophies of Venous Thromboembolism Prophylaxis
Venous Thromboembolism Prophylactic Drugs
Unfractionated Heparin
Low-­Molecular-­Weight Heparins
Fondaparinux
Oral Anticoagulants
. Vitamin K antagonists, or warfarin in the United States and several other countries, was originally used for inpatient, and la...
. Dabigatran is a direct inhibitor of thrombin. It is U.S. Food and Drug Administration (FDA) approved for prophylaxis solely in...
. Riva­roxaban is a direct inhibitor of factor Xa. It is FDA approved for VTE prophylaxis in patients with hip (dosed for 35 day...
Joint Replacement. In clinical trials, rivaroxaban 10 mg/day was superior to the European enoxaparin regimen, 40 mg once daily s...
Internal Medicine. Rivaroxaban prophylaxis for 45 days was compared with placebo in approximately 12,000 discharged internal med...
Cancer. Prophylaxis with rivaroxaban 10 mg/day for 6 months was compared with placebo in high–VTE risk ambulatory patients with ...
. Another anti–factor Xa drug, apixaban, is begun 12 to 24 hours after hip or knee replacement surgery at 2.5 mg every 12 hours ...
Joint Replacement. Approximately 1% of hip and knee replacement patients had symptomatic VTE during the trials’ observation peri...
. Betrixaban is a longer-­acting anti–factor Xa drug that is FDA approved for internal medicine patients for VTE prophylaxis of ...
. Aspirin, long-­recognized for its antiplatelet arterial antithrombotic properties through cyclooxygenase-­1 inhibition of thro...
Mechanical Prophylaxis
Vena Cava Interruption
Management of Prophylaxis
Prophylaxis in COVID-­19 Patients and Suspects
Treatment of Pulmonary Embolism
Overview
Pathophysiology (See Chapter 81)
Circulatory Compromise
Respiratory Compromise
Initial Management of Suspected Pulmonary Embolism
Pulmonary Embolism Suspected in a Patient With Hypotension, Shock, or Cardiac Arrest
Pulmonary Embolism Suspected in a Patient Without Hypotension, Shock, or Cardiac Arrest
Initial Management of Confirmed Pulmonary Embolism
Assessment of Pulmonary Embolism Mortality Risk
Assessment of Bleeding Risk
Assessment of Risk for Heparin-­Induced Thrombocytopenia
Assessment to Determine the Site of Pulmonary Embolism Treatment
Telemedicine and Pulmonary Embolism Response Teams
Initial Treatment of the Patient With Confirmed Pulmonary Embolism and Hypotension, Shock, or Cardiac Arrest
. Systemic thrombolysis is indicated for patients with hypotension, shock, or cardiac arrest resulting from acute PE, provided t...
. Low-­dose thrombolysis represents an approach to maintain efficacy and reduce the rate of major bleeding complications observe...
. Catheter-­directed therapies aim to establish reperfusion in the setting of life-­threatening PE while avoiding the major blee...
. Surgical embolectomy is an option for patients with hypotension, shock, or cardiac arrest resulting from acute PE who are not ...
. Extracorporeal membrane oxygenation and percutaneous RV assist have been reported as life-­sustaining treatments that may lead...
Initial Treatment of the Patient With Confirmed Pulmonary Embolism Without Hypotension, Shock, or Cardiac Arrest
. Anticoagulants provide effective initial (day 1 to day 7), long-­term (day 7 to 3 months), and extended (beyond 3 months) trea...
Unfractionated Heparin. Continuous intravenous UFH provides highly effective treatment of acute VTE.42 However, proper dosing an...
Low-Molecular-Weight Heparins. LMWHs are at least as effective and safe as UFH for the initial treatment of most patients with a...
Fondaparinux. Fondaparinux is effective and safe to treat acute PE initially.166 The therapeutic dose depends on the patient’s w...
Direct Inhibitors of Factor XA or Thrombin. DOACs are as effective as vitamin K antagonists for long-­term treatment of VTE and ...
. Current guidelines and treatment algorithms consistently recommend the insertion of vena cava filters to treat acute PE when a...
. Recommendations regarding the duration of anticoagulant therapy have changed over time. There is general agreement that an acu...
Special Problems
Isolated Subsegmental Pulmonary Embolism
Incidental Pulmonary Embolism
Hemoptysis
Pulmonary Embolism in Transit
Paradoxical Embolism
Cancer
Pregnancy
Recurrent Thromboembolism During Anticoagulant Therapy
Key Readings
References
83 Pulmonary Hypertension General Approach.pdf
83 -
Pulmonary Hypertension: General Approach
Definition of Pulmonary Hypertension
Epidemiology
Diagnostic Approach
Populations at Risk FOR Pulmonary Arterial Hypertension
Schistomiasis
Scleroderma
Other Connective Tissue Diseases
Other at-­Risk Cohorts
Heritable Pulmonary Arterial Hypertension
Exposures
Diagnosis
Clinical Presentation
Diagnostic Testing
Blood Testing
Pulmonary Function Testing
Six-­Minute Walk Testing
Nocturnal Oximetry and Sleep Testing
Cardiopulmonary Exercise Testing
Electrocardiography
Transthoracic Echocardiography
Cardiac Magnetic Resonance Imaging
Computed Tomography
Ventilation-­Perfusion Scanning
Right Heart Catheterization
Performance
Provocative Maneuvers
. Vasoreactivity testing during RHC to determine acute responsiveness to a pulmonary vasodilator is not recommended in all types...
. Exercise can be used during RHC to provoke changes in patients with normal resting hemodynamics, assess for occult left heart ...
. Another provocative maneuver that can be used to unmask occult LHD (i.e., a PCWP of 15 mm Hg or less with an intermediate or h...
Testing to Determine Prognosis
Biomarkers
Imaging
Exercise Testing
Group 2: Pulmonary Hypertension
Treatment Considerations for Group 2 Pulmonary Hypertension
Group 5: Pulmonary Hypertension
Hematologic Disorders (See Chapter 127)
Systemic and Metabolic Disorders
Others
Complex Congenital Heart Disease
Treatment Considerations for Group 5 Pulmonary Hypertension
Key Readings
efigure Image Gallery
References
84 Pulmonary Arterial Hypertension Group 1.pdf
84 - Pulmonary Arterial Hypertension: Group 1
Pathobiology
Pulmonary Arterial Hypertension: Group 1
Pulmonary Arterial Hypertension Subgroups
Idiopathic
Heritable
Drugs and Toxins
Pulmonary Veno-­Occlusive Disease/Pulmonary Capillary Hemangiomatosis
Connective Tissue Disease
Congenital Heart Disease
Portal Hypertension
Human Immunodeficiency Virus
Supportive Therapies
Exercise and Physical Activity
Hypoxia and High Altitude
Pregnancy and Birth Control
Oral Anticoagulants
Diuretics
Calcium Channel Blockers
Targeted Therapies
Endothelin Receptor Antagonists
Phosphodiesterase Type 5 Inhibitors
Soluble Guanylyl Cyclase Activators
Prostacyclin Analogues
Epoprostenol
Subcutaneous and Intravenous Treprostinil Sodium
Epoprostenol and Treprostinil Dosing
Inhaled Iloprost and Treprostinil
Oral Treprostinil and Selexipag
Combination Therapy
Atrial Septostomy and Potts Shunt
Mechanical Support
Lung Transplantation
Risk Assessment
Approach to Therapy
Acknowledgement
Key Readings
eFIGURE IMAGE GALLERY
References
85 Pulmonary Hypertension Due to Lung Disease Group 3.pdf
85 -
Pulmonary Hypertension Due to Lung Disease: Group 3
COPD
Idiopathic Pulmonary Fibrosis
Sleep-­Disordered Breathing, Obesity Hypoventilation, and High Altitude
Scleroderma Interstitial Lung Disease
Other Lung Diseases
Pathologic Changes and Pathogenesis
Pulmonary Vascular Remodeling
Pathogenesis
Hypoxic Pulmonary Vasoconstriction
Neurohormones
. Angiotensin II is a potent vasoconstrictor of the pulmonary vascular bed. The pulmonary vasculature appears to be more sensiti...
. Endothelin-­1 (ET-­1) is a 21–amino acid peptide secreted by vascular endothelial cells in response to stimuli, including puls...
Inflammation
Right Ventricle
Lung Mechanics
Clinical Presentation
Symptoms and Signs
B-­Type Natriuretic Peptides
Electrocardiography
Chest Radiography
Echocardiography
Computed Tomography
Cardiac Magnetic Resonance Imaging
Right Heart Catheterization
Summary
Treatment
Treatments Useful in all Patients With Pulmonary Hypertension Due to Chronic Lung Disease
Lifestyle Modifications
Oxygen
Diuretics
Treatment of Sleep-­Disordered Breathing
Lung Transplantation
Treatments That May Be Considered in Selected Patients
Lung Volume Reduction Surgery
Phlebotomy for Polycythemia
Iron Supplementation
Pulmonary Arterial Hypertension–Specific Therapies
Treatment of Decompensated Right Ventricular Failure
. Calcium channel blockers are not useful in the treatment of CLD-­PH. In a study of 53 patients with COPD and PH, treatment wit...
. Three ERAs are approved by the Food and Drug Administration for the treatment of PAH. Bosentan and macitentan are dual ETA and...
. Prostanoids such as epoprostenol are potent pulmonary vasodilators normally synthesized by the pulmonary vascular endothelium,...
. NO is produced by the enzyme NO synthase within endothelial cells and activates guanylate cyclase, increasing smooth muscle ce...
. Sildenafil and tadalafil are selective inhibitors of cyclic guanosine monophosphate–specific phosphodiesterase type 5 and caus...
. Riociguat is a soluble guanylate cyclase agonist approved by the Food and Drug Administration in 2013 for the treatment of PAH...
Key Readings
eFIGURE IMAGE GALLERY
References
86 Pulmonary Hypertension Due to Chronic Thromboembolic Disease Group 4.pdf
86 -
Pulmonary Hypertension Due to Chronic Thromboembolic Disease: Group 4
INTRODUCTION
Epidemiology and Risk Factors
Pathogenesis
Diagnostic Evaluation
Ventilation-­Perfusion Scanning, Echocardiography, and Exercise Testing
Radiologic Imaging
Determining Operability
Pulmonary Thromboendarterectomy
Inoperable Disease
Medical Therapy
Balloon Pulmonary Angioplasty
Key Readings
Key Points
References
87 Pulmonary Vasculitis.pdf
87 -
Pulmonary Vasculitis
Classification
Epidemiology
Normal Vascular Anatomy and Histology
Histopathology of Vasculitis
Pathogenesis
Initial Diagnosis
Clinical Scenarios Suggestive of Vasculitis
Chronic and/or Destructive Upper Airway Lesions
Chest Imaging Findings of Cavitary or Nodular Disease
Diffuse Alveolar Hemorrhage (See Chapter 94)
Acute Glomerulonephritis
Pulmonary-­Renal Syndrome
Palpable Purpura
Mononeuritis Multiplex
Eye Findings
Multisystem Disease
Specific Testing
Antineutrophil Cytoplasmic Antibodies
Other Laboratory Studies
Chest Imaging
Other Imaging Studies
Bronchoscopy
. Whereas a confident diagnosis may occasionally be made without tissue, diagnostic tissue biopsy remains necessary for a defini...
Anchor 442
Specific Clinical Disorders
Granulomatosis With Polyangiitis
Eosinophilic Granulomatosis With Polyangiitis (see Chapter 96)
Microscopic Polyangiitis
Small Vessel Vasculitis Related to Immune Complexes
Treatment
General Principles
Induction OF REMISSION
In Non–Organ-Threatening Disease
In Organ-­Threatening or Life-­Threatening Disease
In Rapidly Progressive Renal Failure, DAH
After Relapse of Organ-­ or Life-­Threatening Disease
In Refractory Disease
Maintenance
Specific Treatment Issues in EGPA
Monitoring for Complications
Key Readings
eFigure Image GalleRy
References
88 Pulmonary Vascular Anomalies.pdf
88 -
Pulmonary Vascular Anomalies
Pulmonary Arteriovenous Malformations
Definition and Epidemiology
Hereditary Hemorrhagic Telangiectasia
Clinical Presentation
Screening and Diagnosis
Treatment
Pulmonary Sequestration
Intralobar
Imaging
Extralobar
Imaging
Treatment
Pulmonary Vein Varix
Clinical Presentation
Imaging
Treatment
Pulmonary Artery Aneurysm
Clinical Presentation
Imaging
Treatment
Anomalies of Systemic Arterial Supply
Clinical Presentation
Imaging
Treatment
Key Readings
eFIGURE IMAGE GALLERY
References
89 Idiopathic Pulmonary Fibrosis.pdf
89 -
Idiopathic Pulmonary Fibrosis
Introduction
Approach to Patients With Suspected Interstitial Lung Disease
Clinical Assessment
Chest Imaging
Pulmonary Function Testing
Laboratory Tests
Bronchoalveolar Lavage
Lung Biopsy
Idiopathic Pulmonary Fibrosis
Epidemiology
Gross Appearance And Histopathology
Etiologic Factors and Pathogenic Mechanisms
Familial Pulmonary Fibrosis
Clinical Features
Blood and Serologic Studies
Chest Imaging
Chest Radiography
High-­Resolution Computed Tomography
Other Imaging Techniques
Pulmonary Function Tests
Diagnosis
Therapeutic Approach
Era Before Antifibrotic Therapy
Current Era
. Pirfenidone (5-­methyl-­1-­phenyl-­2-­[1H]-­pyridone) is a novel antifibrotic agent that inhibits the progression of fibrosis ...
. Nintedanib (BIBF-­1120) is a tyrosine kinase inhibitor that targets the platelet-­derived growth factor receptor, vascular end...
Lung Transplantation (see Chapter 140)
Management of Comorbidities and Palliative Care
Gastroesophageal Reflux
Pulmonary Hypertension
Sleep-­Related Issues
Lung Cancer
Other Comorbidities
Rehabilitative and Palliative Care
Prognosis
Staging of IPF and Predicting Outcome
Acute Exacerbations of Idiopathic Pulmonary Fibrosis
Key Readings
eFIGURE IMAGE GALLERY
References
90 Nonspecific Interstitial Pneumonitis and Other Idiopathic Interstitial Pneumonias.pdf
90 -
Nonspecific Interstitial Pneumonitis and Other Idiopathic Interstitial Pneumonias
Major Idiopathic Interstitial Pneumonias
Nonspecific Interstitial Pneumonia
Clinical Features
Laboratory Features
Radiologic Features
Histopathologic Features
Differential Diagnosis
Clinical Course and Outcome
Cryptogenic Organizing Pneumonia
Clinical Features
Laboratory Features
Radiologic Features
Histopathologic Features
Clinical Course and Outcome
Acute Interstitial Pneumonia
Clinical Features
Radiologic Features
.Diffuse, bilateral, air space opacification is seen on the chest radiograph (eFig. 90.9). 61-­63
.The typical high-­resolution CT (HRCT) features of AIP are bilateral, multifocal, or diffuse areas of ground-­glass opacity and...
Histopathologic Features
Clinical Course and Outcome
Respiratory Bronchiolitis–Associated Interstitial Lung Disease and Desquamative Interstitial Pneumonia
Clinical Features
Laboratory Features
Radiographic Features
.The chest radiograph is insensitive for detection of RB-­ILD and is often normal. Sometimes, bronchial wall thickening or retic...
.The key HRCT features of RB-­ILD include central bronchial wall thickening proximal to segmental bronchi, peripheral bronchial ...
Histopathologic Features
Clinical Course and Outcome
Rare Idiopathic Interstitial Pneumonias
Idiopathic Lymphocytic Interstitial Pneumonia
Clinical Features
Laboratory Features
Radiologic Features
.The chest radiograph is nonspecific, with reticular opacities (eFig. 90.16) the most frequent abnormality. A mixed alveolar-­in...
.The main parenchymal abnormalities on CT scan consist of ground-­glass opacities (eFig. 90.17), thickening of interlobular sept...
Histopathologic Features
Clinical Course and Outcome
Idiopathic Pleuroparenchymal Fibroelastosis
Clinical Features
Laboratory Features
Radiologic Features
.In patients with early PPFE, chest radiography may be normal. With disease progression, bilateral, irregular pleural thickening...
.The characteristic CT scan findings are dense, subpleural consolidations with associated traction bronchiectasis and architectu...
Histopathologic Features
Clinical Course and Outcomes
Acknowledgment
Key Readings
eFIGURE IMAGE GALLERY
Anchor 386
Anchor 387
Anchor 388
Anchor 389
Anchor 390
Anchor 391
References
91 Hypersensitivity Pneumonitis.pdf
91 -
Hypersensitivity Pneumonitis
Classification
Epidemiology
Etiology
MICROBES
Animal Proteins
Chemical Sensitizers
Immunopathogenesis
Host Factors and Genetics
Tobacco Use
Viral Infections
Pathogen Virulence
Histopathology
Diagnosis
Exposure Assessment
History
Antibody Testing
Inhalational Challenge
Clinical Features
Signs and Symptoms
Lung Function
Bronchoalveolar Lavage
Chest Imaging
Lung Biopsy
Multidisciplinary Discussion
Prognosis and Disease Behavior
Management
Antigen Avoidance
Pharmacologic Therapy
Lung Transplantation
Prevention and Outbreak Identification
Key Readings
eFIGURE IMAGE GALLERY
References
92 Connective Tissue Diseases.pdf
92 -
Connective Tissue Diseases
Approach to Diagnosing and Treating Connective Tissue Disease–Interstitial Lung Disease
Clinical Features
Radiologic Features
Histopathologic Features
Role of Autoantibodies in the Diagnosis of CTD-­ILD
Approach to Treatment of CTD-­ILD
Systemic Sclerosis (Scleroderma)
Epidemiology and Risk Factors
Chemically Induced Scleroderma-­Like Disorders
Pulmonary Manifestations
Interstitial Lung Disease
Pathogenesis
. Individuals may be predisposed genetically to develop SSc, and there are emerging markers that define risks for diffuse lung d...
Inflammation Amplification. A wide variety of cytokines identified in bronchoalveolar lavage (BAL) fluid clearly contribute to t...
Fibrogenetic Factors. The hallmark of SSc in both lung and skin is the accumulation of connective tissue matrix cells and protei...
Epithelial Damage. Although a key pathogenic event in idiopathic ILD, epithelial damage has been relatively underemphasized in d...
Clinical Features
Imaging
Pulmonary Function Tests
Bronchoalveolar Lavage
Biopsy
Serologic Investigations
Prognosis
Treatment
Pulmonary Vascular Disease
Other Pulmonary Complications
Rheumatoid Arthritis
Epidemiology and Risk Factors
Pulmonary Manifestations
Interstitial Lung Disease
Organizing Pneumonia
Bronchiolitis Obliterans
Follicular Bronchiolitis
Bronchiectasis
Pulmonary Vasculitis
Pulmonary Rheumatoid Nodules
Pleural Disease
Other Pulmonary Complications
Drug-­Induced Pulmonary Disease
Acute Exacerbations of Interstitial Lung Disease
Pulmonary Function Tests
Radiologic Features
Treatment of Pulmonary Complications
Systemic Lupus Erythematosus
Epidemiology and Risk Factors
Pulmonary Manifestations
Diffuse Lung Disease
. ILD is uncommon in SLE, affecting only 1–15% of patients. It is usually mild, with slow progression or stability over time. IL...
. Although seen in approximately 1–4% of SLE patients, acute lupus pneumonitis is often life-threatening, with a mortality rate ...
Shrinking Lung Syndrome
Diffuse Alveolar Hemorrhage (see Chapter 94)
Pulmonary Arterial Hypertension
Pleural Disease
Sjögren Syndrome
Epidemiology and Risk Factors
Pulmonary Manifestations
Interstitial Lung Disease
Tracheobronchial Disease
Polymyositis and Dermatomyositis
Epidemiology and Risk Factors
Pulmonary Manifestations
Interstitial Lung Disease
. The clinical features of diffuse lung disease in PM and DM depend on the nature of the lung process. Dyspnea and nonproductive...
. Chronic diffuse lung disease is associated with peripheral reticular opacities, particularly in the lung bases. Acute pneumoni...
. Lung function tests show a restrictive ventilatory defect with reduced DlCO. With recent hemorrhage or marked myopathy, there ...
. BAL lymphocytosis and neutrophilia have been described in diffuse lung disease associated with PM/DM. The significance of BAL ...
. Several studies have reported no association between creatine kinase levels and respiratory disease. In fact, the presence of ...
Other Pulmonary Manifestations
Treatment of Pulmonary Complications
Mixed Connective Tissue Disease
Idiopathic Pneumonia with Autoimmune Features
Relapsing Polychondritis
Behçet Syndrome
Ankylosing Spondylitis
Marfan Syndrome
Key Readings
eFIGURE IMAGE GALLERY
References
93 Sarcoidosis.pdf
93 -
Sarcoidosis
Epidemiology
Etiology, Immunology, and Genetics
Etiology
Diagnostic Approach
General Considerations
Extrapulmonary Involvement
Radiographic Findings
Serum Markers
Histologic Examination
Diagnosis of Sarcoidosis Without Confirmatory Biopsy
Controversies Concerning the Number of Organs to Sample by Biopsy
Evaluation of Pulmonary Disease
Importance of Symptoms and Quality of Life
Pulmonary Function Testing
Lung Imaging
Health-­Related Quality of Life
Sarcoidosis-­Associated Pulmonary Hypertension
Evaluation for Extrapulmonary Disease
General Considerations
Eye
Skin
Nervous System
Heart
Liver
Vitamin D Dysregulation
Parasarcoidosis Syndromes
Treatment
General Considerations
Anti-­Inflammatory Agents
General Comments
Corticosteroids
Rationale for Corticosteroid-­Sparing Agents
Antimalarial Agents
Antimetabolites
Tumor Necrosis Factor Antagonists
Approach to Extrapulmonary Disease
Fibrotic Sarcoidosis
Lung Transplantation
Pulmonary Hypertension
Fatigue
Small Fiber Neuropathy
Mycetoma
Bone Health
Key Readings
eFIGURE IMAGE GALLERY
References
94 Diffuse Alveolar Hemorrhage.pdf
94 -
Diffuse Alveolar Hemorrhage
INTRODUCTION
Classification
Clinical Presentation
Laboratory Findings
Radiologic Features
Physiologic Features
Histopathologic Features
Diagnosis of Diffuse Alveolar Hemorrhage
Diagnosis of Underlying Etiology
Role of Surgical Lung Biopsy and Renal Biopsy
Therapeutic Approach
Specific Causes
VASCULITIS (See Chapter 87)
Granulomatosis With Polyangiitis
Microscopic Polyangiitis
Isolated Pulmonary Capillaritis
Mixed Cryoglobulinemia
Behçet Syndrome
Henoch-­Schönlein Purpura
Pauci-Immune Glomerulonephritis
Immunologic Disorders
Anti–Glomerular Basement Membrane Disease (Goodpasture Syndrome)
Connective Tissue Disease
. Among the connective tissue diseases, SLE is the most common cause of DAH (eFig. 94.4).43,119–121 It is unusual for DAH to be ...
. Antiphospholipid syndrome (APS) can manifest as a primary disorder; however, it is commonly seen in the setting of other under...
. Other connective tissue diseases such as rheumatoid arthritis, polymyositis, dermatomyositis, scleroderma, and mixed connectiv...
Immune Complex–Related Crescentic Glomerulonephritis
Acute Pulmonary Allograft Rejection
Coagulation Disorders
Idiopathic Pulmonary Hemosiderosis
Miscellaneous Causes
Drugs and Toxins
Diffuse Alveolar Damage
Mitral Stenosis
Pulmonary Veno-­occlusive Disease
Pulmonary Capillary Hemangiomatosis
Lymphangioleiomyomatosis and Tuberous Sclerosis
Key Readings
efigure Image Gallery
References
95 Pulmonary Langerhans Cell Histiocytosis and Other Rare Diffuse Infiltrative Lung Diseases.pdf
95 -
Pulmonary Langerhans Cell Histiocytosis and Other Rare Diffuse Infiltrative Lung Diseases
Pulmonary Langerhans Cell Histiocytosis
Epidemiology
Pathology
Pathogenesis
Radiographic Findings
Pulmonary Function Testing
Clinical Features and Diagnostic Evaluation
Management
Outcomes and Prognosis
Rare Infiltrative Disorders of the Lung
Neurofibromatosis
Hermansky-­Pudlak Syndrome
Dyskeratosis Congenita
Niemann-­Pick and Gaucher Diseases
Pulmonary Alveolar Microlithiasis
Key Readings
Complete reference list available at ExpertConsult.com
eFIGURE IMAGE GALLERY
References
96 Eosinophilic Lung Diseases.pdf
96 -
Eosinophilic Lung Diseases
Eosinophil Biology
Physiologic Role of Eosinophils
Differentiation and Recruitment of Eosinophils to the Lung
Release of Preformed Proteins
Targeting the Eosinophil Cell Lineage
General Features of Eosinophilic Pneumonias
Historical Perspective
Clinical Presentation
Pathology
Diagnosis
Idiopathic Chronic Eosinophilic Pneumonia
Clinical Features
Imaging
Laboratory Studies
Bronchoalveolar Lavage
Differential Diagnosis
Pulmonary Function Tests
Treatment and Prognosis
Idiopathic and Smoking-­Related Acute Eosinophilic Pneumonia
Clinical Features
Exposure and Triggers
Imaging
Laboratory Studies
Bronchoalveolar Lavage
Pulmonary Function Tests
Lung Biopsy
Treatment and Prognosis
Eosinophilic Granulomatosis With Polyangiitis
History and Nomenclature
Pathology
Clinical Features
Imaging
Laboratory Studies and Bronchoalveolar Lavage
Antineutrophil Cytoplasmic Antibodies
Pathogenesis
Diagnosis
Treatment and Prognosis
Allergic Bronchopulmonary Aspergillosis and Related Syndromes
Pathogenesis
Clinical Features and Diagnosis
Laboratory Studies
Imaging
Treatment
Other Allergic Bronchopulmonary Mycoses
Bronchocentric Granulomatosis
Hypereosinophilic Syndromes
Definition and Classification
Pathogenenesis
Clinical and Imaging Features
Treatment and Prognosis
Idiopathic Hypereosinophilic Obliterative Bronchiolitis
Eosinophilic Pneumonias of Parasitic and Infectious Origin (See Also Chapter 58)
Tropical Pulmonary Eosinophilia
Ascaris Pneumonia
Eosinophilic Pneumonia in Larva Migrans Syndrome
Strongyloides Stercoralis Infection
Eosinophilic Pneumonias in Other Parasitic Infections
Eosinophilic Pneumonias of Other Infectious Causes
Drug-­, Toxic Agent-­, And Radiation-­Induced Eosinophilic Pneumonias
Medications and Illicit Drugs (see also Chapter 99)
Radiation Therapy
Eosinophilic Bronchitis
Key Readings
Hypereosinophilic Asthma
Idiopathic Interstitial Pneumonias
Pulmonary Langerhans Cell Histiocytosis
Other Conditions
eFigure Image Gallery
References
97 Lymphangioleiomyomatosis.pdf
97 -
Lymphangioleiomyomatosis
Epidemiology
Genetic and Molecular Basis of Tuberous Sclerosis Complex and Lymphangioleiomyomatosis
Inheritance
Molecular Pathogenesis
Tumor Suppressor Proteins Control Cell Growth
Tuberous Sclerosis Complex Proteins Regulate Signaling Through the Akt Pathway
Tuberous Sclerosis Complex Mutations Are Found in the Lung and Kidney Lesions of Patients With Sporadic Lymphangioleiomyomatosis...
Genetic Evidence Suggests that Lymphangioleiomyomatosis is a Metastatic Neoplasm
Role of Lymphangiogenesis and Lymphatic Spread in Dissemination of Lymphangioleiomyomatosis
Role of Estrogen in the Pathogenesis of Lymphangioleiomyomatosis
Immune Evasion as a Mechanism for Lymphangioleiomyomatosis Cell Proliferation
Mechanisms of Matrix Remodeling in Lymphangioleiomyomatosis
Clinical Features
Physical Examination
Imaging Studies
Pulmonary Function Testing
Pathology
Diagnosis
Management
Pharmacologic treatment
Hormonal Agents
Doxycycline
Sirolimus
Other Therapeutic Considerations
General recommendations
Screening
Sporadic Lymphangioleiomyomatosis
Tuberous Sclerosis–Associated Lymphangioleiomyomatosis
Pregnancy
Air Travel (see Chapter 106)
Pleural Disease (see Chapters 110 and 111)
LUNG Transplantation (see Chapter 140)
Angiomyolipomas
Disease Progression
Prognosis
Future Clinical Trials
Key Readings
Sirolimus Prescribing Guide
Initiation
Maintenance
Other Useful Tips
Other Advice
Vaccinations in Patients With Lymphangioleiomyomatosis
General Comments
Pleural Disease in Lymphangioleiomyomatosis
Spontaneous Pneumothorax
Chylous Pleural Effusions or Chylothorax
efigure Image Gallery
References
98 Pulmonary Alveolar Proteinosis Syndrome.pdf
98 -
Pulmonary Alveolar Proteinosis Syndrome
Pathogenesis
Granulocyte-­Macrophage Colony-­Stimulating Factor
Murine Models of Disordered Surfactant Homeostasis
Abnormal Surfactant Clearance
Abnormal Surfactant Production
Role of GM-­CSF Autoantibodies
Genetic Factors
Hereditary PAP
Pulmonary Surfactant Metabolic Dysfunction Disorders
Disease Associations
Environmental Factors
Mechanisms of Disruption of Surfactant Homeostasis
Primary Pulmonary Alveolar Proteinosis
Secondary Pulmonary Alveolar Proteinosis
Pulmonary Surfactant Metabolic Dysfunction
Nomenclature and Classification
Epidemiology
Clinical Presentation
Pulmonary Alveolar Proteinosis
Pulmonary Surfactant Metabolic Dysfunction
Evaluation and Differential Diagnosis
Radiographic Appearance
Pulmonary Function Testing
Bronchoscopy, Bronchoalveolar Lavage
Lung Biopsy
Laboratory Studies
Approach to Diagnosis
Natural History
Secondary Infections
Pulmonary Fibrosis
Spontaneous Resolution
Treatment
Autoimmune Pulmonary Alveolar Proteinosis
Whole-­Lung Lavage
Granulocyte-­Macrophage Colony-­Stimulating Factor
Targeting GM-­CSF Autoantibodies
Targeting Cholesterol Homeostasis
Hereditary Pulmonary Alveolar Proteinosis
Secondary PAP
Surfactant Metabolic Dysfunction Disorders
Key Readings
eFIGURE IMAGE GALLERY
References
99 Drug-Induced Pulmonary Disease.pdf
99 -
Drug-­Induced Pulmonary Disease
Oncology Agents
Antibiotic-­Derived Agents
Bleomycin
Mitomycin C
Alkylating Agents
Busulfan
Cyclophosphamide
Chlorambucil
Melphalan
Other Alkylating Agents
Antimetabolites
Methotrexate
Azathioprine and 6-­Mercaptopurine
Cytosine Arabinoside
Gemcitabine
Fludarabine
Nitrosoureas
Podophyllotoxins
Etoposide and Teniposide
Paclitaxel
Docetaxel
All-­Trans Retinoic Acid and Differentiation Syndrome
Molecularly Targeted Therapy
Monoclonal Antibodies
. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is designed to inhibit tumoral neoangiogenesi...
. Cetuximab and panitumumab are two monoclonal antibodies directed against the epidermal growth factor receptor (EGFR). Both hav...
. Trastuzumab selectively binds the human epidermal growth factor receptor-­2 (HER-­2) protein and is an adjuvant treatment for ...
. Rituximab is an anti-­CD20 chimeric monoclonal. The most common side effect of rituximab is an infusion reaction in more than ...
Tyrosine Kinase Inhibitors
. Gefitinib is a selective EGFR tyrosine kinase inhibitor. Acute interstitial pneumonia has been associated with this drug, and ...
. Erlotinib is another EGFR antagonist. Erlotinib has also been rarely associated with pulmonary toxicity, including fatalities....
. Imatinib is an inhibitor of the BCR-ABL, KIT, and platelet-­derived growth factor receptor (PDGFR) tyrosine kinases.84 Fluid r...
. Dasatinib is another BCR-ABL tyrosine kinase inhibitor. Dasatinib is associated with pleural effusions, pulmonary hypertension...
. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that block the intracellular domain of the vascular endo...
. Ceritinib, alectinib, crizotinib, and brigatinib are inhibitors of anaplastic lymphoma kinase (ALK) and are used for treatment...
Immunomodulatory Agents
Interferons
Rapamycin Analogues
Immune Checkpoint Inhibitors
Antimicrobial Agents
Nitrofurantoin
Acute Reaction
Chronic Reaction
Sulfasalazine
Illicit drugs
Heroin AND METHADONE
Methylphenidate
Cocaine
Talc Granulomatosis
Cardiovascular Drugs
Angiotensin-­Converting Enzyme Inhibitors
Amiodarone
β-­Adrenergic Antagonists
Tocainide and Flecainide
Anti-­Inflammatory Agents
Aspirin
Other Nonsteroidal Anti-­Inflammatory Drugs
Penicillamine
Leflunomide
Biologic Agents
Leukotriene Antagonists
Corticosteroids
Drug-­Induced Systemic Lupus Erythematosus
Oxygen
Miscellaneous Drugs and Agents
Tocolytic-­Induced Pulmonary Edema
Hydrochlorothiazide
Methysergide, Bromocriptine, and Cabergoline
Amphetaminergic Agents
Key Readings
eFIGURE IMAGE GALLERY
References
100 Asthma in the Workplace.pdf
100 -
Asthma in the Workplace
Introduction
Definitions of Asthma in the Workplace
Sensitizer-­Induced Occupational Asthma
Epidemiologic Aspects
Causal Agents
Pathophysiology
Immunologic, Immunoglobulin E–Mediated Occupational Asthma
Immunologic, Non–Immunoglobulin E–Mediated Occupational Asthma
Risk Factors
Environmental Factors
Host-­Related Factors
Diagnosis
Noninvasive Measures of Airway Inflammation
Outcome And Management
Prevention
Socioeconomic Impact
Irritant-­Induced Asthma
Epidemiologic Aspects
Pathophysiology
Risk Factors
Diagnosis
Outcome And Treatment
Prevention
Work-­Exacerbated Asthma
Epidemiologic Aspects
Pathophysiology
Work Exposures Associated With Work-­Exacerbated Asthma
Diagnosis
Differentiating Work-­Exacerbated Asthma From Non–Work-­Related Asthma or Occupational Asthma
Socioeconomic Impact
Key Readings
References
101 Pneumoconioses.pdf
101 -
Pneumoconioses
Pathogenesis and Exposure-­Response Relationships
Chest Imaging
Silicosis
Definition
Industries and Occupations at Risk
Pathology
Pathogenesis
Airflow Obstruction, Chronic Bronchitis, and Emphysema
Connective Tissue Diseases, Renal Disease, and Cardiovascular Disease
Lung Cancer
Tuberculosis
Clinical Features
Radiographic Features
Lung Function
Diagnosis and Complications
Management and Control
Coal mine dust lung disease
Definition
Composition of Coal Mine Dust
Pathology
Epidemiology and Natural History
Disease Phenotypes
Classic Coal Workers’ Pneumoconiosis
Rapidly Progressive Pneumoconiosis
Dust-­Related Diffuse Fibrosis
Chronic Bronchitis, Emphysema, and Lung Function Impairment
Rheumatoid Pneumoconiosis
Lung Cancer
Clinical Features
Chest Imaging
Lung Function
Diagnosis
Management
Asbestos-­Related Fibrosis of the Lungs (Asbestosis) and Pleura
Industries and Occupations at Risk
Pathogenesis
Asbestosis (Pulmonary Parenchymal Fibrosis)
Pathology
Epidemiology and Natural History
Clinical Features
Radiographic Features
Lung Function
Diagnosis
Pleural Plaques, Pleural Fibrosis, and Visceroparietal Reactions
Pathology and Pathogenesis
Epidemiology
Clinical Features and Diagnosis
Benign Asbestos-­Related Pleural Effusions
Management, Prevention, and Health Monitoring
Beryllium lung disease
Beryllium: Uses, Human Toxicity, and Exposures
Pathology and Immune Pathogenesis
Clinical Features
Diagnosis and Management
Acknowledgments
Key Readings
eFIGURE IMAGE GALLERY
References
102 Indoor and Outdoor Air Pollution.pdf
102 -
Indoor and Outdoor Air Pollution
Air Pollutants
Pollutants: What They Are and Why They Matter
Mechanisms of Defense Against Air Pollution–Related Respiratory Effects
Deposition of and Clearance of Particles (see Chapter 13)
Gases: Deposition and Damage are Functions of Solubility
Oxidative Stress
Methods of Studying the Health Effects of Air Pollution
Epidemiologic Studies
Controlled Human Exposure Research
Animal Research
In Vitro Research
Outdoor air Pollution: Standards and Adverse Respiratory Effects of Specific Pollutants
Particulate Matter
Sulfur Dioxide
Nitrogen Dioxide
Ozone
Indoor air Pollution
Sources of Indoor Pollution
Indoor Combustion: Major Source of Indoor Air Pollution
Secondhand Smoke and Obstructive Lung Disease
Gas Stove Exposure: Cause of Asthma Exacerbation
Wood Smoke Exposure: Respiratory Health Effects
Respiratory Effects of Kerosene Heater Use
Other Indoor Pollutants: “Toxic” Indoor Environment
Key Readings
References
103 Acute Responses to Toxic Exposures.pdf
103 -
Acute Responses to Toxic Exposures
INTRODUCTION
Pathogenesis of Lung Injury From Inhaled Toxicants
Patterns of Response to Irritant Inhalation
General Management Principles
Chronic Sequelae and Residual Effects
Specific Exposures
Chlorine, Chloramines, Hydrochloric Acid, and Related Chemicals
Oxides of Nitrogen, Ozone, Sulfur Dioxide, and Acid Aerosols
Military and Crowd-­Control Agents
Sulfur Mustard
Phosgene
Chloropicrin
Neurotoxicants
Chloroacetophenone (Mace), Other Tear Gas Agents, and Zinc Chloride
Toxic Metals
Cadmium, Mercury, and Nickel
Other Metals
Metal Fume Fever, Polymer Fume Fever, Organic Dust Toxic Syndrome, and Other Inhalation Fevers
Fluorocarbon Aerosol Spray Pneumonitis
Hydrocarbon Pneumonitis and Fire-­Eater’s Lung
Paraquat
Smoke Inhalation
Pharmacologic Syndromes
Other Inhalant Exposures
Ammonia
Bromine and Methyl Bromide
Hydrogen Sulfide
Methyl Isocyanate and Methyl Isothiocyanate
Miscellaneous Exposures
Key Readings
References
104 Trauma and Blast Injuries.pdf
104 -
Trauma and Blast Injuries
Introduction
Resuscitative Thoracotomy
Urgent Thoracotomy
Delayed Thoracotomy
Thoracic Cage Injuries
Rib Fractures
Lung Parenchyma Injuries
Pulmonary Contusion
Pulmonary Laceration
Bronchopleural Fistula
Pneumothorax
Hemothorax (See Chapter 113)
Chylothorax (see Chapter 111)
Pneumatocele or Intraparenchymal Hematoma
Tracheobronchial Injuries
Diaphragm Injuries
Blast Lung Injury
Introduction
Primary Blast Injuries
Secondary Blast Injuries
Tertiary Blast Injuries
Quaternary Blast Injuries
Physics Of The Blast Wave
Spalling Forces
Implosion Forces
Inertia Forces
Results of Blast Injury
Management
Key Readings
eFIGURE IMAGE GALLERY
References
105 High Altitude.pdf
105 -
High Altitude
INTRODUCTION
ACCLIMATIZATION to High Altitude
Pulmonary ACCLIMATIZATION
Control of Ventilation
Changes in Common Sea-­Level Activities at High Altitude
Sleep
Exercise
Maximal Work
Ventilation
Gas Exchange
Cardiovascular Response
Exercise Performance at High Altitude
Training at High Altitude
Maladaptation
Problems of Lowlanders on Ascent to High Altitude
Susceptibility to Altitude Illness
Acute Mountain Sickness
. AMS is marked by the presence of headache in addition to one or more other symptoms, including lassitude, anorexia, nausea, di...
. Symptoms develop after 6 to 10 hours at a given elevation, not immediately. In a study of a general tourist population traveli...
. Despite a considerable amount of research in this area, there is no coherent, unified explanation for why individuals develop ...
. The pharmacologic and nonpharmacologic approaches to prevention and amelioration of AMS have been described in published guide...
. Descent leads to resolution of all forms of altitude illness, but patients with mild AMS usually recover by simply resting at ...
High-­Altitude Cerebral Edema
High-­Altitude Pulmonary Edema
. Typically manifesting within 2 to 4 days of ascent to altitudes higher than 2400 m, persons with HAPE usually present in the e...
. HAPE is a form of noncardiogenic pulmonary edema marked by normal left ventricular function. Unlike the situation with AMS and...
. The nonpharmacologic preventive measures previously described for AMS also apply to HAPE, with a slow ascent being the most im...
. Proper treatment depends on the severity of the illness and the clinical setting. In remote locations with limited access to c...
Problems of High-­Altitude Residents
Chronic Mountain Sickness
. Symptoms of CMS resemble those found in persons with polycythemia at low altitude: headache, dizziness, lethargy, impaired mem...
. The likely initiating factors for CMS are a blunted HVR and relative hypoventilation. Hypoventilation increases alveolar hypox...
. The keys to treating CMS are to reduce the hypoxic stimulus for RBC production and to decrease RBC mass. Although relocation t...
High-­Altitude Pulmonary Hypertension
Reentry and Resident Pulmonary Edema
Preexisting Illness and High Altitude
Respiratory Diseases
Chronic Obstructive Pulmonary Disease
Interstitial Lung Disease
Asthma
Pulmonary Vascular Disease
Sleep Apnea
Thromboembolic Disease
Underlying Medical Problems and Altitude Illness Medications
Key Readings
eFIGURE IMAGE GALLERY
References
106 Air Travel.pdf
106 - AIR TRAVEL
INTRODUCTION
EPIDEMIOLOGY AND GENERAL RISKS OF AIR TRAVEL
PHYSIOLOGIC IMPACT OF COMMERCIAL AIR TRAVEL
PREFLIGHT ASSESSMENT OF FITNESS TO FLY
ASSESSING FOR IN-­FLIGHT HYPOXEMIA IN PATIENTS WITH RESPIRATORY DISEASE
ASSESSING FOR IN-­FLIGHT HYPOXEMIA IN PATIENTS NOT USING SUPPLEMENTAL OXYGEN AT SEA LEVEL
PRESCRIBING SUPPLEMENTAL IN-­FLIGHT OXYGEN IN PATIENTS ALREADY USING SUPPLEMENTAL OXYGEN AT SEA LEVEL
PROVIDING SUPPLEMENTAL IN-­FLIGHT OXYGEN
CONSIDERATIONS REGARDING SPECIFIC LUNG DISEASES AND AIR TRAVEL
PNEUMOTHORAX
LYMPHANGIOLEIOMYOMATOSIS
BIRT-­HOGG-­DUBÉ SYNDROME
PULMONARY HYPERTENSION
SICKLE CELL DISEASE AND TRAIT
RESTRICTIVE LUNG DISEASE DUE TO CHEST WALL DEFORMITY, NEUROMUSCULAR DISEASE, OR INTERSTITIAL LUNG DISEASE
CYSTIC FIBROSIS
TRANSMISSION OF RESPIRATORY INFECTIONS DURING AIR TRAVEL
RISK OF VENOUS THROMBOEMBOLISM DURING AIR TRAVEL
PRACTICAL ASPECTS OF ASSESSING THE PATIENT WITH PULMONARY SYMPTOMS IN FLIGHT
SUMMARY
Key Readings
References
107 Diving Medicine.pdf
107 -
Diving Medicine
Adaptation to Diving
Equipment and Techniques
Breath-­Hold Diving
Open-­Circuit Scuba
Rebreather Diving
Surface-­Supplied Equipment
Saturation Diving
Disorders Related to Diving: Nomenclature
Pressure Effects and Boyle’s Law
Relation of Gas Volume to Depth
Barotrauma
Barotrauma of Descent
Barotrauma of Ascent
Dissolved Inert Gas effects and Henry’s Law
Inert Gas Kinetics
Inert Gas Supersaturation in Tissues
Decompression Sickness
Risk Factors
Clinical Manifestations
Diagnostic Testing
Treatment
Hyperbaric Therapy
Inert Gas Narcosis
Other Physiologic and Pathophysiologic Considerations for Diving
Oxygen Toxicity
Thermal Exposure
High-­Pressure Nervous Syndrome
Water Immersion
Immersion Pulmonary Edema
Medical Clearance to Dive
General Fitness for Diving
Pulmonary Disorders
Primary Spontaneous Pneumothorax (see Chapter 110)
Asthma and COPD
Energy Needs
Bullous Lung Disease
Cardiac Disorders
Coronary Artery Disease
Atrial Septal Defect
Patent Foramen Ovale
Dysrhythmias
Neurologic Disorders
Diabetes
DROWNING
Key Readings
Drowning
Pathophysiology
Clinical Presentation
Cardiovascular System
Pulmonary System
Central Nervous System
Treatment
Prognosis
efigure Image Gallery
References
108 Pleural Effusion.pdf
108 - PLEURAL EFFUSION
INTRODUCTION
APPROACH TO PATIENTS WITH PLEURAL EFFUSION
DIFFERENTIAL DIAGNOSIS OF PLEURAL EFFUSION
SEPARATION OF EXUDATES FROM TRANSUDATES
DIFFERENTIATING EXUDATIVE PLEURAL EFFUSIONS
Appearance of Pleural Fluid
Pleural Fluid Protein
Pleural Fluid Lactate Dehydrogenase
Pleural Fluid Glucose
Pleural Fluid White Cell Count and Differential
Pleural Fluid Cytology
Other Diagnostic Tests for Malignancy
Culture and Bacteriologic Stains
OTHER DIAGNOSTIC TESTS FOR PLEURAL FLUID
N-­Terminal Pro–Brain Natriuretic Hormone
Pleural Fluid pH
Pleural Fluid Amylase or Lipase
Tests for Collagen Vascular Diseases
Adenosine Deaminase
PLEURAL MANOMETRY
USEFUL RADIOGRAPHIC TESTS IN PATIENTS WITH SUSPECTED PLEURAL DISEASE
Ultrasound
Interferon Gamma
Molecular Techniques for Diagnosis of Mycobacteria tuberculosis
Computed Tomography
Magnetic Resonance Imaging
Positron Emission Tomography and Computed Tomography
INVASIVE TESTS IN PATIENTS WITH UNDIAGNOSED EXUDATIVE PLEURAL EFFUSIONS
Nonspecific Findings on Invasive Testing
Needle Biopsy of the Pleura
Image-­Guided Pleural Biopsy
Bronchoscopy
Thoracoscopy or Video-­Assisted Thoracic Surgery
TRANSUDATIVE PLEURAL EFFUSIONS
CONGESTIVE HEART FAILURE
Pathophysiology (See Chapter 14)
Clinical Manifestations
Diagnosis and Management
HEPATIC HYDROTHORAX (SEE CHAPTER 126)
Pathophysiology
Clinical Manifestations
Diagnosis and Treatment
Spontaneous Bacterial Pleuritis
NEPHROTIC SYNDROME
PERITONEAL DIALYSIS
MYXEDEMA
PERICARDIAL DISEASE
CENTRAL VENOUS OBSTRUCTION
VERY LOW PROTEIN TRANSUDATES
Urinothorax
Subarachnoid-­Pleural Fistula
Iatrogenic
OTHER CAUSES OF TRANSUDATIVE PLEURAL EFFUSIONS
EXUDATIVE PLEURAL EFFUSIONS
PULMONARY EMBOLISM
Clinical Manifestations
Diagnosis
Treatment
ABDOMINAL DISEASES
Esophageal Perforation
. The symptoms associated with esophageal perforation result from the acute mediastinitis produced by contamination of the media...
. The diagnosis of esophageal rupture should be considered in all acutely ill patients with an exudative pleural effusion. The b...
. The treatment of the esophageal rupture may range from nonoperative stenting to primary repair to esophagectomy depending on t...
Pancreatic Disease
. In two prospective reports a decade apart, exactly 50% of the nearly 200 patients admitted with acute pancreatitis had a pleur...
. Patients with chronic pancreatic disease often have a large chronic pleural effusion. When the pancreatic ductal system is dis...
. Some patients with pancreatic disease develop ascites characterized by high amylase and protein levels. If these patients shou...
Intra-­abdominal Abscesses
. Subphrenic abscess most commonly develops as a postoperative complication 1 to 3 weeks after intra-­abdominal surgery.241 Sple...
?Diagnosis and Treatment. The diagnosis of intra-­abdominal abscess is best established with an abdominal CT scan (eFig. 108.7 a...
Post-abdominal Surgery
Liver Transplantation
Bilious Pleural Effusion
INFLAMMATORY DISEASES
Rheumatoid Pleuritis
. Almost all patients with rheumatoid pleural effusions are older than 35 years. Approximately 80% are men, and approximately 80...
. The diagnosis is suggested by the clinical picture of rheumatoid arthritis in the presence of a pleural effusion. The pleural ...
. The natural history of rheumatoid pleuritis varies. Most patients experience a spontaneous resolution within 3 months, but the...
Lupus Pleuritis
. Most patients with lupus pleuritis have arthritis or arthralgias before the development of a pleural effusion. Almost all pati...
. The possibility of lupus pleuritis should be considered in any patient with an exudative pleural effusion of unknown cause. Th...
. The pleuritis with systemic lupus responds to corticosteroid administration. It is recommended that patients with lupus pleuri...
Immunoglobulin G4–Related Pleuritis
Sarcoidosis
Asbestos-Related Disease
. Patients with pleural effusion secondary to asbestos exposure have surprisingly few symptoms. In the series of Epler and cowor...
. The diagnosis of benign asbestos effusion is one of exclusion. It requires the following criteria: history of direct or indire...
. The natural history of the patient with an asbestos pleural effusion is one of chronicity, with frequent recurrences and somet...
Uremia
Post–Cardiac Injury Syndrome
. The syndrome typically develops about 3 weeks after the injury, but it can happen any time between 3 days and 1 year. The two ...
. The diagnosis of PCIS should be considered in any patient who develops a pleural effusion after injury to the heart. The diagn...
. PCIS usually responds to treatment with anti-­inflammatory agents, such as aspirin, colchicine or indomethacin. Corticosteroid...
Post–Coronary Artery Bypass Surgery
Drug-Induced Pleural Disease
Other Inflammatory Diseases
Miscellaneous
Lung Transplantation
Meigs Syndrome
. Pleuropulmonary reactions occasionally result from the administration of nitrofurantoin. Such reactions can have an acute or a...
. Dantrolene sodium is a long-­acting skeletal muscle relaxant with a chemical structure similar to that of nitrofurantoin. Its ...
. The administration of methysergide can lead to a pleuropulmonary disease similar to that seen with nitrofurantoin.301 Symptoms...
. The administration of ergot alkaloid drugs, such as bromocriptine, ergotamine, dihydroergotamine, nicergoline, pergolide, and ...
. There have been two detailed case reports of pleuropulmonary reactions consisting of chills, cough, dyspnea, and bilateral pul...
. Amiodarone is an antiarrhythmic that may produce severe pulmonary toxicity. Pleural effusions are seen as a manifestation of a...
. Recombinant IL-­2 is sometimes used in the treatment of malignancies, especially melanoma or renal cell carcinoma. One of the ...
. Dasatinib, an inhibitor of multiple tyrosine kinase inhibitors, is used primarily for treating adults with chronic myeloid leu...
Endometriosis
Ovarian Hyperstimulation Syndrome
Trapped Lung (See Chapter 112)
Yellow Nail Syndrome
Misplaced Catheters
Key Readings
EFIGURE IMAGE GALLERY
References
109 Pleural Infections.pdf
109 -
Pleural Infections
Bacterial Pleural Empyema
Historical Perspective
Incidence
Epidemiology
Pathogenesis
Clinical Presentation
Pleural Fluid Sampling
Biochemistry
Microbiology
Antibiotic Selection and Duration
Nutrition
Early Risk Stratification
Investigative Techniques for Pleural Infection
Radiology
Bronchoscopy
Chest Tube Drainage
Fibrinolytic Therapy
Monitoring Response to Medical Management
Surgical Options
Pleural Tuberculosis
Pathogenesis
Clinical Manifestations
Pleural Fluid
Diagnosis
Treatment
Actinomycosis
Nocardiosis
Fungal Infections
Aspergillosis
Blastomycosis
Coccidioidomycosis
Primary Coccidioidomycosis
Rupture of Coccidioidal Cavity
Cryptococcosis
Histoplasmosis
Pneumocystis Jirovecii
Viral Infections
Primary Atypical Pneumonia
Other Viruses
Acquired Immunodeficiency Syndrome
Parasitic Diseases
Amebiasis
Echinococcosis
Paragonimiasis
Key Readings
eFIGURE IMAGE GALLERY
References
110 Pneumothorax.pdf
110 -
Pneumothorax
SPONTANEOUS PNEUMOTHORAX
Epidemiology
Etiology
Primary Spontaneous Pneumothorax
Ectomorphic Body Shape
Abnormal Lung Parenchyma and Smoking
Traumatic Pneumothorax
Diagnosis
Treatment
Iatrogenic Pneumothorax
Diagnosis
Treatment
Catamenial Pneumothorax
Pathogenesis
Treatment
Key Readings
eFIGURE IMAGE GALLERY
References
111 Chylothorax.pdf
111 -
Chylothorax
Overview of the Lymphatic System and Drainage of the Thoracic Duct
Anatomy
Components of Chyle
Etiology and Clinical Manifestations of Chylothorax
Etiology of Chylothorax
Traumatic Chylothorax
Nontraumatic Chylothorax
Clinical Manifestations
Specific Syndromes/Conditions Related to Chylothorax
. LAM is a multisystem disease of women characterized by proliferation of abnormal smooth muscle–like LAM cells leading to cysti...
. Chylothorax and chyloascites can present in patients with liver cirrhosis. High portal venous pressure can increase thoracic d...
. Fetal chylothorax, sometimes termed primary fetal pleural effusion or congenital chylothorax, is rare with an incidence of 0.0...
Diagnosis
Fluid Appearance
Biochemical Analysis
Imaging
Treatment
General Approaches
DRAIN THE PLEURAL FLUID
Reduce the Flow of Chyle and Close the Defect
Dietary Management
Drugs
Minimally Invasive Treatments: Lymphangiography, Embolization, and Disruption
Surgery: Thoracic Duct Ligation
REPLACE Chyle Components and Nutrients
Treat the Underlying Disease
Mediastinal Lymphadenopathy (Especially Lymphoma) and Obstructive Mediastinal Structures
Lymphangioleiomyomatosis
Hepatic Cirrhosis
OBLITERATE the Pleural Space
Pseudochylothorax
Pathophysiology
Clinical Manifestation
Diagnosis
Treatment
Acknowledgment
Prevention of Chylothorax During Surgery
Prognosis
Key Readings
eFIGURE IMAGE GALLERY
References
112 Pleural Fibrosis and Unexpandable Lung.pdf
112 - PLEURAL FIBROSIS AND UNEXPANDABLE LUNG
INTRODUCTION
DIAGNOSIS OF PLEURAL FIBROSIS AND OF UNEXPANDABLE LUNG
GENERAL MANAGEMENT PRINCIPLES
CAUSES OF PLEURAL FIBROSIS
ASBESTOS-­RELATED PLEURAL FIBROSIS
RHEUMATOLOGIC DISEASES
MALIGNANCY (SEE CHAPTER 114)
UREMIA
TUBERCULOSIS
IMMUNOGLOBULIN G4–RELATED DISEASE
AMYLOID
MEDICATIONS AND IATROGENIC CAUSES
PLEUROPARENCHYMAL FIBROELASTOSIS (SEE CHAPTER 90)
PLEURAL INFECTION
Anchor 248
POST–CORONARY ARTERY BYPASS GRAFT SURGERY
HEMOTHORAX (SEE CHAPTER 113)
Key Readings
References
113 Hemothorax.pdf
113 -
Hemothorax
INTRODUCTION
Diagnosis
Etiology
Traumatic Hemothorax
Nontraumatic Hemothorax
Iatrogenic HEMOTHORAX
Management
Complications of Hemothorax
Surgical Intervention
Key Readings
References
114 Pleural Malignancy.pdf
114 -
Pleural Malignancy
Metastatic Pleural Disease
Types Of Tumor
Clinical Features
Malignant Pleural Effusions
Pleural Fluid Analysis
Radiographic Evaluation
Diagnosis
Therapy and Palliation
Prognosis
Mesothelioma
Incidence and Etiology
Demographics
Clinical Features
Subtypes
Diagnosis
Radiographic Evaluation
Pathologic Features
Staging
Prognosis
Approach to Therapy
Surgical Therapy
Chemotherapy
Immunotherapy
Radiation Therapy
Palliative Therapy
Screening and Chemoprevention
Solitary Fibrous Tumor of the Pleura
Clinical Features
Radiologic Features
Pathologic Features
Staging
Primary Pleural Lymphoma
Immune Checkpoint Inhibitor–Related Pleural Effusion
efigure Image GalleRy
References
115 Mediastinal Tumors and Cysts.pdf
115 -
Mediastinal Tumors and Cysts
Introduction
Normal Anatomy of the Mediastinum
Clinical Presentations of Mediastinal Disease
Imaging the Mediastinum
Conventional Radiographic Techniques
Computed Tomography
Magnetic Resonance Imaging
Ultrasonography
Nuclear Imaging
Techniques for Obtaining Mediastinal Tissue
Image-­Guided Biopsy
Endobronchial and Endoscopic Ultrasound-­Guided Aspiration
Transthoracic Needle Aspiration and Biopsy
Surgical Biopsy
Mediastinoscopy
Video-­Assisted Thoracoscopic Surgery
Mediastinal Mass
Classification
Incidence
Specific Mediastinal Tumors And Cysts
Lesions of the Anterior Mediastinum
Thymic Neoplasms
Germ Cell Tumors
Lymphoma
Thyroid Lesions
Parathyroid Lesions
Mesenchymal Tumors
NUT Carcinoma
Lesions of the Middle Mediastinum
Enlargement of Lymph Nodes
Developmental Cysts
Lesions of the Posterior Mediastinum
Neurogenic Tumors
Miscellaneous Mediastinal Masses
Benign Lesions
Vascular Masses and Enlargements
Diaphragmatic Hernia
General Approach to a Mediastinal Mass
Initial Evaluation
Surgical Management
Acknowledgments
Key Readings
eFIGURE IMAGE GALLERY
References
116 Mediastinitis and Fibrosing Mediastinitis.pdf
116 -
Mediastinitis and FIBROSING MEDIASTINITIS
INTRODUCTION
Acute Mediastinitis
Anatomic Considerations
Clinical Presentation
Evaluation and Useful Studies
Mediastinitis Resulting From Visceral Perforation
Spontaneous Esophageal Rupture (Boerhaave Syndrome)
Iatrogenic Injuries
Other Visceral Insults
Mediastinitis Secondary to Extension From Outside the Mediastinum
Descending Necrotizing Mediastinitis
Ascending and Other Uncommon Causes of Mediastinitis From Direct Extension
Mediastinitis Following Cardiac Surgery
“Spontaneous” OR “Primary” Mediastinitis
Spontaneous Mediastinitis
Hemorrhagic Mediastinitis Secondary to Inhalational Anthrax
Management of Acute Mediastinitis
Microbiology and Antimicrobial Selection
Mechanical Débridement: Operative, Percutaneous, and Endoscopic Interventions
FIBROSING MEDIASTINITIS and Mediastinal Granuloma
FIBROSING MEDIASTINITIS
Clinical Features
Diagnosis
Treatment
Idiopathic Fibrosing Mediastinitis and Fibrosing Mediastinitis From Other Causes
Mediastinal Granuloma
Clinical Features
Diagnosis
Treatment
Mediastinal Adenitis
Clinical Features
Diagnosis
Treatment
Acknowledgments
Key Readings
eFIGURE IMAGE GALLERY
References
117 Control of Breathing and Upper Airways During Sleep.pdf
117 -
Control of Breathing and Upper Airways During Sleep
INTRODUCTION
Generation of Wakefulness and Sleep
Wakefulness
Non-­REM Sleep
The “Sleep Switch”
Effects of Common Neurodepressive Drugs on Brain Arousal State
Application to Sleep and Drug-­Induced Respiratory Depression
Breathing and its Control
Respiratory Neurons
Organization
Respiratory Rhythm and Motor Activation
. The pre-­Bötzinger complex is often emphasized given its role in respiratory rhythm generation. The pre-­Bötzinger complex is ...
. In expiration, the expiratory neurons of the Bötzinger complex inhibit inspiratory pre-­motoneurons and motoneurons. Caudal VR...
Respiratory Rhythm Generation and Central Apnea
Respiratory Motor Pools and Muscle Activity
Respiratory Muscles Vary in the Degree of Their Relationship to Breathing
Effects of Sleep
Chemosensors and Chemoreflexes
Location and State Dependence of Responses
Integrative Physiologic Mechanisms Underpinning Respiratory Dysfunction and Instability During Sleep
Breathing is Dependent on Feedback Regulation in Sleep
Principle
Application
Loop Gain and its Importance
Principle
Application
Arousal from Sleep: A Consequence and Cause of Respiratory Disturbance
Principle
Application
Principle
Application
Overarching Principle: Various Trajectories can Lead to a Sleep-­Disordered Phenotype
Clinically Relevant Concepts in Respiratory Control
Obesity
Principle
Application
Heart Failure
Principle
Application
Aging
Principle
Application
Other Clinical Conditions
Principles
Application
. Patients with baseline hypercapnia often experience worsening hypercapnia during non-­REM sleep. The effect of REM sleep is qu...
. Patients with neuromuscular disease also experience deterioration of gas exchange during non-­REM sleep with further worsening...
Parenchymal Lung Disease. In patients with parenchymal lung disease, such as emphysema or pulmonary fibrosis, similar mechanisms...
Individualized Therapy Targeting Underlying Mechanisms
Key Readings
eFIGURE IMAGE GALLERY
References
118 Consequences of Sleep Disruption.pdf
118 -
Consequences of Sleep Disruption
Effects of Sleep Disruption on Acute and Chronic Disease
Neurocognitive Changes
Acute Effects
Chronic Implications
Psychiatric Disorders
Pain Perception
Acute Effects
Chronic Implications
Cardiovascular Disease
Immune Function
Endocrine and Metabolic Dysfunction
Acute Effects
Chronic Implications
Cancer Risk
Special Patient Populations
Maternal-­Fetal Health
Critically Ill Patients
Maternal Health
Fetal Development
Treatment of Sleep Disruption
Sleep Hygiene
Primary Sleep Disorders
Comorbid Illnesses
Acknowledgments
Key Readings
References
119 Sleep-Disordered Breathing A General Approach.pdf
119 -
Sleep-­Disordered Breathing: A General Approach
Thinking Like a Sleep Pulmonologist
The Golden 8 Hours
Ventilation, Oxygenation, and Mechanics During Sleep
Identifying Pulmonary Patients at Risk for Comorbid Sleep Disorders
Taking a Relevant Sleep History
Questionnaires
Diagnostic Sleep Testing
Navigating Devices and Technologies
Common Clinical Scenarios to Consider Sleep-­Disordered Breathing
Arrhythmias
Prevalence of Arrhythmias in Obstructive Sleep Apnea
Contributing Mechanisms
Impact of Obstructive Sleep Apnea Treatment on Arrhythmia
Stroke
Epidemiology of Obstructive Sleep Apnea and Central Sleep Apnea in Stroke
Contributing Mechanisms
Impact of Continuous Positive Airway Pressure on Stroke Risk
Impact of Continuous Positive Airway Pressure on Neurologic Outcomes After Stroke
Pulmonary Hypertension
Inpatient and Intensive Care Unit Patients
Perioperative Evaluation
Chronic Obstructive Pulmonary Disease
Asthma
Key Readings
eFIGURE IMAGE GALLERY
References
120 Obstructive Sleep Apnea.pdf
120 -
Obstructive Sleep Apnea
Pathogenesis
Upper Airway Dimensions
Upper Airway Collapsibility
Neuromuscular Factors
Upper Airway Inflammation
Fluid Shift
Predisposing Factors
Obesity
Upper Airway Anatomic Abnormalities
Gravity/Body Position
Genetic Factors
Endocrine Disturbances
Smoking
Alcohol, Drugs
Epidemiology
Prevalence
Sex Differences
Ethnicity
Aging
Pregnancy
Clinical Evaluation
Clinical Presentation
Elements of a Complete Sleep History
Measurement of Sleepiness
Diagnosis
Questionnaires/Prediction Equations
Laboratory Polysomnography
Unattended Sleep Studies
In-­Hospital Diagnosis
Differential Diagnosis
Periodic Hypersomnia
Idiopathic Hypersomnia
Movement Disorders During Sleep
Circadian Rhythm Disorders
Parasomnias
Pathophysiology of Consequences
Neurocognitive Sequelae
Cardiometabolic Sequelae
Consequences/Complications of OSA
Neurobehavioral Complications of OSA
Excessive Sleepiness and Motor Vehicle Operation
Fatigue
Mood Disturbances: Depression, Anxiety
Quality of Life
Cognitive Impairment
Neurodegenerative Disease and Dementia
Cardiometabolic Complications
Hypertension
Arrhythmias
Myocardial Infarction
Cerebrovascular Events
Congestive Heart Failure
Pulmonary Hypertension
Renal Perfusion/Dysfunction
Metabolic Disturbances: Insulin Resistance, Dyslipidemia
Hepatic Sequelae/Steatohepatitis
Mortality
Other Complications
Disease Management Strategies
OSA and Ocular Disease
Erectile Dysfunction
OSA and Cancer
Key Readings
efigure Image Gallery
References
121 Central Sleep Apnea.pdf
121 -
Central Sleep Apnea
Hypercapnic Central Sleep Apnea
Secondary Forms of Hypercapnic Central Sleep Apnea
Developmental and Degenerative Diseases
Brainstem Tumors
Cerebrovascular Disease
Neuromuscular Diseases
Primary Hypercapnic Central Sleep Apnea
Central Alveolar Hypoventilation Syndrome
Treatment
Nonhypercapnic Central Sleep Apnea
Secondary Forms of Nonhypercapnic Central Sleep Apnea
Central Sleep Apnea in Association With Heart Failure: Cheyne-­Stokes Respiration
. Although symptoms of heart failure, including orthopnea, paroxysmal nocturnal dyspnea, witnessed apnea, fatigue, and insomnia ...
. Because few symptoms have been attributed to CSR-­CSA, symptomatic targets for therapy are difficult to identify. However, bec...
. Because CSR-­CSA arises as a consequence of heart failure, it would be reasonable to optimize pharmacologic and device treatme...
Positive Airway Pressure
Continuous Positive Airway Pressure. The effects of Continuous positive airway pressure (CPAP) have been studied extensively in ...
Adaptive Servoventilation. Adaptive servoventilation (ASV) is a form of positive airway pressure specifically designed to allevi...
Central Sleep Apnea Associated With Cerebrovascular Disease
Central Sleep Apnea Associated With Atrial Fibrillation
Central Sleep Apnea Associated With Renal Failure
Central Sleep Apnea Associated With Acromegaly
Central Sleep Apnea Associated With High Altitude (See Chapter 105)
Central Sleep Apnea Associated With Opioid Use
Complex Sleep Apnea
Primary Nonhypercapnic Central Sleep Apnea
Idiopathic Central Sleep Apnea
Key Readings
eFigure Image Gallery
References
122 Sleep-Disordered Breathing Treatment.pdf
122 -
Sleep-­Disordered Breathing: Treatment
Obstructive Sleep Apnea
Nonsurgical Options
Weight Loss
Positional Therapy
Positive Airway Pressure
Adherence to Therapy
Negative External Pressure Therapy
Nasal Therapies
Oral Appliances
Nocturnal Supplemental Oxygen
Pharmacologic Therapy
Surgical Options: Anatomic Targets (See Chapter 70)
How to Think About Upper Airway Surgery for Obstructive Sleep Apnea
Nasal Procedures
Soft Palate Procedures
Tongue Muscle Strengthening: Genioglossus Advancement
Tongue Volume Reduction: Lingual Tonsillectomy
Hypoglossal Nerve Stimulation
Maxillomandibular Advancement
Applying These Concepts: an Algorithm Incorporating Surgical and Nonsurgical Treatments
Sleep-­Related Hypoventilation Syndromes
Obesity Hypoventilation Syndrome
Central Sleep Apnea
Continuous Positive Airway Pressure
Bilevel Positive Airway Pressure With Backup Rate
Adaptive Servoventilation
Supplemental Oxygen
Compression Stockings
Phrenic Nerve Stimulation
Neuromuscular Disease
COPD
Key Readings
eFigure Image Gallery
References
123 Pulmonary Complications of HIV Infection.pdf
123 -
Pulmonary Complications of HIV Infection
Introduction
Epidemiology
Immunologic Abnormalities
Diagnostic Approach
CD4+ Lymphocyte Count
Fiberoptic Bronchoscopy
Infectious Complications
Bacteria
Other Bacteria
Mycobacteria
Mycobacterium tuberculosis
Mycobacterium avium Complex
Mycobacterium kansasii
Other Mycobacteria
Fungi
Pneumocystis jirovecii
Cryptococcus Species
Histoplasma capsulatum
Coccidioides immitis
. The clinical presentation is often nonspecific; fever and chills (68%), night sweats (36%), and weight loss (50%) are all comm...
. The risk of symptomatic disease is highest if CD4+ counts are less than 250 cells/μL.27 Most cases of disseminated coccidioido...
. In a series of 91 HIV-­infected patients with coccidioidomycosis, diffuse reticulonodular opacities (see Fig. 56.5) were seen ...
. Serologic tests are useful in the evaluation of suspected coccidioidomycosis. Several studies have found an 80–90% sensitivity...
. Either amphotericin B or a lipid formulation of amphotericin B is the treatment of choice for HIV-­infected patients with seve...
Aspergillus Species
. The entire spectrum of Aspergillus-­related lung disease (see Chapter 57) has been observed in HIV-­infected persons, from col...
. The definitive diagnosis of aspergillosis requires demonstration of tissue invasion and isolation of the organism by culture. ...
. Compared with the fungi previously discussed, there is less experience treating aspergillosis in HIV-­infected patients.223 Vo...
Blastomyces dermatitidis
. The largest case series reported 15 cases of HIV-­associated blastomycosis; all but one patient had a CD4+ lymphocyte count le...
. Intravenous amphotericin B is the treatment of choice for HIV-­infected patients with severe disease.233,234 Treatment with am...
Talaromyces marneffei
. Most cases of talaromycosis are seen in patients with a CD4+ lymphocyte count less than 100 cells/μL. The clinical presentatio...
. T. marneffei is most commonly a disseminated disease in HIV-­infected patients, and the diagnosis is usually made by isolation...
. Amphotericin B, followed by itraconazole, is the standard treatment for P. marneffei.27 Mild forms of disease can be treated i...
Viruses
Cytomegalovirus
. Retinitis and gastrointestinal disease are the two most common forms of HIV-­associated CMV disease. CMV is a frequent isolate...
. The imaging findings of CMV pneumonia vary and include reticular or ground-­glass, alveolar, and nodular opacities (eFig. 123....
. When CMV pulmonary disease is suspected in conjunction with other end-­organ disease (e.g., retinitis), CMV therapy must be in...
. Data for treatment of CMV pneumonia in HIV-­infected patients are limited. Intravenous ganciclovir or foscarnet is recommended...
Other Herpesviruses
Influenza
Coronavirus Disease 2019
Parasites
Toxoplasma gondii
. Central nervous system complications of T. gondii are well recognized in HIV disease and include encephalitis and focal brain ...
. The chest radiograph usually reveals bilateral opacities, either in a fine reticulonodular pattern indistinguishable from PCP ...
. The diagnosis of pulmonary toxoplasmosis is usually established by bronchoscopy and study of BAL fluid.254 T. gondii can be de...
. The treatment for pulmonary toxoplasmosis is identical to that for central nervous system toxoplasmosis. First-­line treatment...
Other Parasites
Noninfectious Disorders
Malignancies
Kaposi Sarcoma
. Pulmonary KS is detected clinically in approximately one-­third of patients with known KS, with the proportion detected at aut...
. Pulmonary KS characteristically presents with bilateral opacities in a central or perihilar distribution, as shown in Figure 1...
. The diagnosis of pulmonary KS is usually established by bronchoscopy. The observation of characteristic endobronchial, red or ...
. Tumors can regress in size and number in response to ART, and therefore combination ART is recommended for all patients with K...
Non-­Hodgkin Lymphoma
. Most HIV-­infected patients with NHL present with disseminated disease and extranodal involvement.282 Frequent extranodal site...
. The most common chest radiograph findings include single (Fig. 123.9; eFig. 123.32) or multiple parenchymal nodules (eFig. 123...
. The diagnosis of NHL requires demonstration of malignant lymphocytes on cytology or biopsy specimens. Most often the diagnosis...
. Pulmonary involvement in NHL is treated as part of systemic disease. Median survival from AIDS-­related NHL has greatly improv...
Primary Effusion Lymphoma
Multicentric Castleman Disease
Non–Small Cell Lung Cancer
. HIV-­infected patients develop lung cancer at slightly younger ages than do non–HIV-­infected patients, after controlling for ...
. Diagnosis and treatment of lung cancer in an HIV-­infected patient is similar to that in a non–HIV-­infected individual. Ongoi...
Pulmonary Arterial Hypertension
. In a review of 131 cases of PAH in HIV-­infected patients,320 the presenting symptoms and radiographic, pulmonary function, el...
. As with idiopathic PAH, the diagnosis of HIV-­associated PAH requires confirmation of elevated pulmonary arterial pressures an...
. The optimal treatment of HIV-­associated PAH is unclear.322 In general, patients should receive antiretroviral therapy because...
Obstructive Lung Disease
COPD
Asthma
Treatment of COPD and Asthma
Interstitial Pneumonitides
Lymphocytic Interstitial Pneumonitis
. The most striking feature of HIV-­associated LIP is the effect of age on its incidence. Early in the AIDS epidemic, one-­third...
. The definitive diagnosis of LIP requires histologic confirmation by biopsy. There are so few studies of LIP among HIV-­infecte...
Nonspecific Interstitial Pneumonitis
. The clinical features of NSIP are indistinguishable from those of PCP; however, NSIP may present at CD4+ lymphocyte counts gre...
. The diagnosis of NSIP requires both histologic confirmation and the exclusion of other etiologies. The natural history of HIV-...
Sarcoidosis
Immune Reconstitution Inflammatory Syndrome
. Numerous disease processes have been associated with IRIS. These include many infections, sarcoidosis, autoimmune conditions, ...
. The diagnosis of IRIS requires compatible clinical features and exclusion of alternative causes for worsening clinical status....
Key Readings
eFIGURE IMAGE GALLERY
References
124 Pulmonary Complications of Primary Immunodeficiencies.pdf
124 -
Pulmonary Complications of Primary Immunodeficiencies
Diagnostic Workup
Antibody Deficiencies
Cellular Immunodeficiency
Phagocyte Deficiencies
Complement Deficiencies
Anatomic Defects
Genetic Testing
Antibody Deficiencies
X-­Linked Agammaglobulinemia
Common Variable Immunodeficiency
Immunoglobulin A Deficiency
Specific Antibody Deficiency
Immunoglobulin G Subclass Deficiency
Hyper–Immunoglobulin M Syndrome (B Cell Intrinsic)
Mutations in AICD or UNG
Deficiency in Both Cellular Immunity and Antibody Production (Combined Immunodeficiencies)
Hyper–Immunoglobulin M Syndrome (Combined)
X-­Linked Hyper-­IgM Syndrome
Mutations of NF-­κB Essential Modifier
Combined Hyper-­IgM Syndrome Caused by Other Mutations
Severe Combined Immunodeficiency
Combined Immunodeficiencies or Syndromic Immunodeficiencies
Digeorge Syndrome
Wiskott-­Aldrich Syndrome
Ataxia-­Telangiectasia
Hyper–Immunoglobulin E Syndrome
Phagocyte Disorders
Developmental Defects In Neutrophils
Leukocyte Adhesion Deficiency
Chronic Granulomatous Disease
Gata-­2 Deficiency
Mendelian Susceptibility to Mycobacterial Disease
Disorders in Innate Immunity
Myd88 and Irak-­4 Deficiencies
Complement Deficiencies
Key Readings
References
125 Pulmonary Complications of Stem Cell and Solid Organ Transplantation.pdf
125 -
Pulmonary Complications of Stem Cell and Solid Organ Transplantation
Infectious Complications
Bacterial Pneumonia
Mycobacterial Infections
Fungal Infections (See Chapter 57)
Epidemiology and Clinical Characteristics
Diagnostic Testing
Treatment
Pneumocystis jirovecii Pneumonia
Viral Infections
Herpesviruses
Community-­Acquired Respiratory Viruses
Noninfectous Complications of Hematopoietic Cell Transplantation
Early-­Onset Complications
Idiopathic Pneumonia Syndrome
Pulmonary Alveolar Proteinosis
Pulmonary Vascular Disease
Late-­Onset Complications
Bronchiolitis Obliterans Syndrome
Restrictive Lung Dysfunction and Interstitial Lung Disease
Organizing Pneumonia
Pleuropulmonary Fibroelastosis
Noninfectious Complications in Solid Organ Transplantation
Postoperative Respiratory Failure
Pleural Effusions
Diaphragmatic Dysfunction
Metastatic Pulmonary Calcification
Drug-­Induced Pneumonitis
Malignancy After Transplantation
Acknowledgment
Key Readings
eFIGURE IMAGE GALLERY
References
126 Pulmonary Complications of Abdominal Diseases.pdf
126 -
Pulmonary Complications of Abdominal Diseases
Gastroesophageal and Gastrointestinal Disorders
Gastroesophageal Reflux Disease
Pathophysiology
Asthma
Chronic Cough
Other Lung Diseases
Diagnosis and Treatment
Inflammatory Bowel Disease
Pulmonary Function Disturbances
Intrinsic Pulmonary Complications
Iatrogenic Pulmonary Complications
Hepatic Diseases
Pleural Effusion
Pulmonary Function Disturbances
Hepatopulmonary Syndrome
Definition and Diagnosis
Epidemiology
Pathogenesis
Clinical Manifestations
Treatment
Prognosis
Portopulmonary Hypertension
Definition and Diagnosis
Epidemiology
Pathogenesis
Clinical Manifestations
Treatment
Prognosis
Primary Biliary Cirrhosis
Chronic Hepatitis C
Sclerosing Cholangitis
Alpha1-­Antitrypsin Deficiency
Pancreatic Diseases
Acute Pancreatitis
Early Respiratory Insufficiency and Imaging Abnormalities
Acute Respiratory Distress Syndrome
Delayed Complications of Acute Pancreatitis
Autoimmune Pancreatitis
Kidney Diseases
Pulmonary Edema
Pulmonary Hypertension
Pleural Disease
Pulmonary Calcification
Sleep Disorders
Hemodialysis-­Induced Hypoxemia
Key Readings
eFIGURE IMAGE GALLERY
References
127 Pulmonary Complications of Hematologic Diseases.pdf
127 -
Pulmonary Complications of Hematologic Diseases
Red Blood Cell Disorders
Anemia
Polycythemia
Hemoglobinopathies
Sickle Cell Disease
Acute Chest Syndrome
Activation of Inflammatory Pathways in Patients With Sickle Cell Disease
Pulmonary Hypertension
Pathogenesis
Chronic Lung Disease
Thalassemia
Other Hemoglobin Disorders
White Blood Cell Disorders
Leukemias
Plasma Cell Disorders
Thrombosis and Disorders of Coagulation
Inherited Thrombophilia
Coagulopathies and Platelet Disorders
Complications of Transfusion
Transfusion-­Associated Acute Lung Injury
Epidemiology
Pathogenesis
Clinical Features and Evaluation
Treatment
Transfusion-­Associated Circulatory Overload
Key Readings
eFIGURE IMAGE GALLERY
References
128 Pulmonary Complications of Endocrine Diseases.pdf
128 -
Pulmonary Complications of Endocrine Diseases
Diabetes
Ventilatory Impairment
Lung And Chest Wall Restriction
Loss of Alveolar Microvascular Reserves
Respiratory Muscle Dysfunction
Impaired Immune Defenses
Comorbidities
Role of Adipocyte-­Derived Mediators
Pulmonary Response to Glycemic Control
Thyroid Disorders
The Hypothalamic-­Pituitary-­Thyroid Axis
Hypothyroidism
Airway Obstruction or Laryngeal Dysfunction
Pulmonary Dysfunction
Alveolar Hypoventilation
Sleep-­Disordered Breathing
Respiratory Muscle Dysfunction
Pleural Effusion
Hyperthyroidism
Pulmonary Hypertension
Thyrotoxicosis
Lung Cancers
Growth Hormone Disorders
Acromegaly
Anatomy and Respiratory Physiology
Obstructive Sleep Apnea
Association with Neoplasm
Treatment
Growth Hormone Deficiency
Calcium Dysregulation and Pulmonary Calcification
Parathyroid Hormone
Pulmonary Causes of Hypercalcemia
Dystrophic and Metastatic Pulmonary Calcification
Radiographic Features
Treatment
Adrenal Disorders
Adrenocortical Hormones and Lung Development
Adrenal Insufficiency
Cushing Syndrome
Immune Checkpoint Inhibitors
Key Readings
efigure Image GalleRy
References
129 The Lungs in Obstetric and Gynecologic Diseases.pdf
129 -
The Lungs in Obstetric and Gynecologic Diseases
INTRODUCTION
Physiologic Alterations During Normal Pregnancy
Alterations in Respiratory Physiology
Upper Airway
Chest Wall
Lung Function
Ventilation
Alterations in Cardiovascular Physiology
Lung Disorders in Obstetrics
Obstructive Airway Disease
Asthma
Cystic Fibrosis
Infectious Diseases
Bacterial Pneumonia
Viral Pneumonia
Fungal Pneumonias
Tuberculosis
Pulmonary Edema and Pulmonary Vascular Disease
Increased Pressure (Cardiogenic) Pulmonary Edema
Tocolysis-­Associated Pulmonary Edema
Pulmonary Edema Associated with Preeclampsia
Pulmonary Embolism
Amniotic Fluid Embolism
Arteriovenous Malformations
Air Embolism
Acute Lung Injury in Pregnancy
Aspiration Pneumonitis
Acute Respiratory Distress Syndrome
Other Respiratory Diseases in Pregnancy
Obstructive Sleep Apnea
Interstitial Lung Disease
Pleural Disease
Lung Transplantation
Lung Disorders in Gynecology
Catamenial Pneumothorax
Endometriosis
Lymphangioleiomyomatosis
Gestational Trophoblastic Disease
Ovarian Hyperstimulation Syndrome
Key Readings
References
130 The Respiratory System and Neuromuscular Diseases.pdf
130 -
The Respiratory System and Neuromuscular Diseases
INTRODUCTION
Functional Anatomy of the Respiratory System
Central Nervous System
Voluntary Breathing Controllers
Automatic Breathing Controllers
Spinal Cord
Peripheral Nervous System
Lower Motor Neurons
Total Lung Capacity
Controller Feedback
Diseases Affecting the Respiratory System
Central Nervous System Diseases
Cortical and Brainstem Disorders
. The pathways that connect the voluntary respiratory centers of the cortex with spinal motor neurons (corticospinal tracts) can...
. Automatic breathing but not voluntary breathing is classically disrupted in central alveolar hypoventilation, otherwise known ...
Diseases of the Spinal Cord
. Spinal cord injury (SCI) is most commonly due to traumatic injury caused by motor vehicle accidents, falls, sports accidents, ...
. For unknown reasons, the frequency of sleep apnea appears to be increased by as much as fourfold in patients with SCI compared...
Peripheral Nervous System Diseases
Diseases of Motor Nerves or Anterior Horn Cells and Diseases of the Neuromuscular Junction
Acute Diseases Affecting Motor Nerves
. Acute immune-­mediated polyneuropathy, also referred to as Guillain-­Barré syndrome, is a heterogeneous group of diseases now ...
. Poliomyelitis is a viral disease affecting the anterior horn cell and motor nerve caused by a human enterovirus. Significant e...
Chronic Diseases Affecting Motor Nerves
. ALS is a progressive neurodegenerative disease with no known cure. The usual clinical presentation is that of an individual wi...
Neuromuscular Junction Diseases
. Myasthenia gravis is the most common disease affecting neuromuscular transmission. It is an autoimmune disease characterized b...
. Botulism is a neuroparalytic syndrome caused by a toxin produced by the gram-­positive bacterium Clostridium botulinum, which ...
Other Neuromuscular Junction Toxins. A number of other toxins can affect the NMJ. The insecticides organophosphates and carbamat...
Diseases of the Respiratory Muscles
. Duchenne muscular dystrophy and Becker muscular dystrophy are the most common inherited muscle diseases found in childhood, af...
. Dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM) are systemic inflammatory diseases of unknown etiol...
Metabolic Myopathies
. A number of enzyme deficiencies can lead to glycogen storage diseases characterized by the accumulation of glycogen in tissue,...
. Disorders of lipid metabolism or defects directly involving the mitochondria can result in myopathy. Disorders of lipid metabo...
Critical Illness Neuropathy and Myopathy
Ventilator-­Induced Diaphragm Dysfunction
Unilateral Diaphragmatic Paralysis
Bilateral Diaphragmatic Paralysis
Approach to the Individual with Neuromuscular Disease
Evaluation
Background
Clinical Assessment
. Effective cough requires a coordinated maneuver starting with adequate inspiration to high volumes, followed by glottic closur...
. Patients with neuromuscular diseases such as ALS frequently develop bulbar muscle dysfunction due to motor neuron involvement ...
. Tests of pulmonary function are useful for initial assessment of and, often more important, follow-­up of patients over time.1...
. Carbon dioxide can be measured as arterial Pco2, the traditional measure of adequate ventilation, or as exhaled or end-­tidal ...
. Sleep-­disordered breathing in neuromuscular disease is common, precedes diurnal hypoventilation, and predicts the onset of di...
Diaphragm Imaging. Chest radiography may show unilateral or bilateral diaphragm elevation suggesting diaphragmatic paralysis. Th...
. The gold standard diagnostic test is measurement of transdiaphragmatic pressure (Pdi) using thin balloon-­tipped polyethylene ...
Management
Ventilatory Support
Data Supporting Noninvasive Positive-­Pressure Ventilation in Neuromuscular Disease
. The use of nocturnal ventilation in patients with neuromuscular disease with sleep-­disordered breathing has been shown to hav...
Full-­Time Ventilatory Support
Cough Support
Key Readings
References
131 The Respiratory System and Chest Wall Diseases.pdf
131 -
The Respiratory System and Chest Wall Diseases
INTRODUCTION
Kyphoscoliosis
Diagnosis and Etiology
Pathophysiology
Pulmonary Function and Respiratory Mechanics
Exercise Capacity
Clinical Course
Treatment
Medical Treatment
Surgical Treatment
Thoracoplasty
Pectus Excavatum
Diagnosis and Etiology
Pathophysiology
Respiratory Mechanics and Exercise Capacity
Treatment
Flail Chest
Diagnosis and Etiology
Trauma and Flail Chest
Pathophysiology
Respiratory Mechanics
Respiratory Failure
Pulmonary Function Tests
Treatment
General Aspects
Ankylosing Spondylitis
Diagnosis and Etiology
Pathophysiology
Respiratory Mechanics
Pulmonary and Respiratory Muscle Function
Gas Exchange and Exercise Capacity
Interstitial Lung Disease
Treatment
Obesity
Diagnosis and Etiology
Pathophysiology
Pulmonary Function
Respiratory Mechanics
Gas Exchange
Control and Pattern of Breathing
Respiratory Muscle Function
Exercise Capacity
Treatment
Pathogenic Aspects of Respiratory Failure in Chest Wall Diseases
Key Readings
eFIGURE IMAGE GALLERY
Anchor 2555
eFigure 131.3Oleothorax seen on frontal chest radiograph.A homogeneous right upper thoracic opacity (arrowheads) represents extr...
References
132 Acute Ventilatory Failure.pdf
132 -
Acute Ventilatory Failure
Introduction
Pathophysiology
Insufficient Ventilatory Drive
Congenital Causes
Acquired Causes
Pharmacologic Causes
Other Acquired Causes
Principles of Management
Neural Transmission Impairment (see Chapter 130)
Cervical Spinal Cord Injury
Motor Neuron Disease
Injury or Disease Affecting the Phrenic Nerve
Immunologic Neuropathies
Neuromuscular Junction Impairment
Immunologic Disease
Infectious Disease
Myopathies
Pharmacologic Causes
Neuromuscular Weakness Associated With Critical Illness
Intensive Care Unit–Acquired Weakness
Ventilator-­Induced Diaphragmatic Dysfunction
Assessment of Need for Mechanical Ventilation in Neuromuscular Weakness
Principles of Ventilator Management
Chest Wall Defects (see Chapter 131)
Chest Wall Skeletal Abnormalities
Pleural Disease
Principles of Management
Parenchymal Lung Disease
Principles of Ventilator Management
Airway Obstruction
Upper Airway Obstruction
COPD
Pathophysiology
Clinical Assessment
Medical Therapy
Noninvasive Ventilation (see Chapter 136)
High Flow Nasal Cannula Oxygen
Practical Application of Noninvasive Ventilation
. Selection of appropriate patients is key to the successful application of NIV. The selection process should take into account ...
. Tolerance of the mask is key to the success of NIV. Thus, the mask must fit well and be strapped on sufficiently to control ai...
. In the acute setting, both “critical care” and “bilevel” ventilators (pressure-­limited devices designed especially for the ad...
. Initial ventilator pressures are usually set low to enhance patient comfort and acceptance but must often be adjusted upward a...
. Most patients with COPD exacerbations do not have severe oxygenation defects and can be managed successfully with pressure-­li...
. Coaching and encouragement, especially during the first few hours, are critically important in achieving adaptation. Judicious...
. Noninvasive ventilation is safe and well tolerated in most properly selected patients. The most commonly encountered problems ...
Increasing Use of NIV and HFNC for COPD
Invasive Mechanical Ventilation
. Although invasive mechanical ventilation is being used less often for acute exacerbations, it still has an important role in s...
. Volume-­limited or pressure-­limited modes can be used, but volume-­limited assist-­control is the most frequent choice initia...
Asthma
Medical Management of Acute Asthma
Ventilatory Management
. In patients with acute asthma exacerbations, ventilatory failure is unusual, but signs of severe respiratory distress, such as...
. CPAP alone or NIV may ameliorate respiratory distress in asthmatics by reducing the work of breathing via a direct bronchodila...
. The role of NIV in the management of asthma exacerbations has not been clearly defined.201 An early cohort study observed subs...
. Invasive mechanical ventilation in patients with acute ventilatory failure due to asthma should be used as a last resort but i...
. Extracorporeal membrane oxygenation has been used successfully to support patients with very severe asthma attacks when mechan...
Vascular Impairment
Key Readings
References
133 Pulmonary Edema.pdf
133 - PULMONARY EDEMA
INTRODUCTION
PATHOPHYSIOLOGY
INCREASED PRESSURE EDEMA
Pathophysiology
Mechanisms
. Congestive heart failure is the most common cause of increased pressure edema. That is why increased pressure edema is often c...
. The sum of driving pressures favoring flow out of the vasculature would increase if perimicrovascular hydrostatic pressure was...
. Increased pressure pulmonary edema may also result from decreases in the protein osmotic pressure difference opposing the hydr...
. Although the preceding section has focused mainly on driving pressures from the microvascular (endothelial) space to the inter...
INCREASED PERMEABILITY EDEMA
Pathophysiology
Mechanisms
CLINICAL ASSESSMENT
SYMPTOMS AND SIGNS
DIAGNOSTIC STUDIES
CHEST IMAGING
ARTERIAL BLOOD GAS STUDIES
Measurement of Pulmonary Edema Fluid Protein Concentration
MEASUREMENT OF LUNG WATER AND BARRIER FUNCTION
Barrier Function
Acute Decompensated Heart Failure: History and Biologic Markers
Biologic Markers of Lung Injury
TREATMENT
EMERGENCY THERAPY
INCREASED PRESSURE EDEMA
General Principles
Ventilatory Strategies
Right Heart Catheterization
Specific Pharmacologic Therapy
. Depending on their specific therapeutic indications, vasodilators are used for hypertension, congestive heart failure, and ang...
. Patients with symptoms of pulmonary edema, especially from increased vascular pressure, usually benefit from administration of...
. Patients with cardiogenic shock and other cardiac catastrophes that lower systemic blood pressure often require inotropic agen...
. Narcotics, and particularly morphine sulfate 2 to 4 mg or its equivalent, given intravenously over several minutes, has long b...
INCREASED PERMEABILITY EDEMA
General Principles
Lung-­Protective Ventilator Strategies
. In tandem with lung-­protective ventilation, a strategy of placing the patient in the prone position for at least 16 hours a d...
Specific Pharmacologic Therapies
OUTCOME
RESOLUTION OF PULMONARY EDEMA
. Of all the possible pharmacologic agents used to treat critical lung injuries, corticosteroids have the longest history. Despi...
. When oxygen saturation is critically low, reducing oxygen consumption to the minimum is advised to reduce oxygen consumption, ...
Extracorporeal Membrane Oxygenation
Increased Pressure Edema
Increased Permeability Edema
Key Readings
References
134 Acute Respiratory Distress Syndrome.pdf
134 -
Acute Respiratory Distress Syndrome
Incidence
Pediatric Diagnostic Criteria
Risk Factors
Etiology and Pathogenesis of Ards
Overview of Pathophysiology
Pathology
The Alveolar-­Capillary Membrane
Surfactant
Neutrophils and Other Inflammatory Mediators
Inflammation and Coagulation
Na+ and Water
Angiopoietins
Ventilator-­Induced Lung Injury
Genetic Determinants of Acute Lung Injury
Subphenotypes of ARDS
Mortality and Complications of ARDS
Mortality
Predictors of Poor Prognosis
Complications of ARDS
Treatment
Supportive Care
Hemodynamic Management
Nutrition
Pharmacotherapy
Corticosteroids
Vasodilators
Surfactant
Antioxidants and Anti-­Inflammatory Agents Other Than Steroids
Catecholamines
Mesenchymal Stem Cell Therapy
Discrepancies Between Studies in Animals and Humans
Mechanical Ventilation in ARDS
Pressure and Volume Limitation
Neuromuscular Blockade
The Role of Peep and Recruitment Maneuvers
Permissive Hypercapnia
Mechanical Ventilation of Patients in the Prone Position (Proning)
Volume-­Control Versus Pressure-­Control Ventilation
High-­Frequency Jet Ventilation and High-­Frequency Oscillation
Liquid Ventilation
Summary
Extracorporeal Membrane Oxygenation
Long-­Term Outcomes
Physical Outcomes
Psychological Outcomes
Key Readings
eFIGURE IMAGE GALLERY
References
135 Mechanical Ventilation.pdf
135 - MECHANICAL VENTILATION
INTRODUCTION
POSITIVE-­PRESSURE MECHANICAL VENTILATOR FUNCTION
BASIC FEATURES OF A POSITIVE-­PRESSURE BREATH
DELIVERING VENTILATION: FLOW-­TARGETED VERSUS PRESSURE-­TARGETED BREATHS
MODES OF VENTILATION
OTHER ASPECTS OF VENTILATOR FUNCTION
PHYSIOLOGIC EFFECTS OF POSITIVE-­PRESSURE MECHANICAL VENTILATION
VENTILATION AND RESPIRATORY SYSTEM MECHANICS
CO2 Clearance: Alveolar Ventilation and the Equation of Motion
ALVEOLAR RECRUITMENT AND GAS EXCHANGE
PEEPi and the Ventilatory Pattern
PATIENT-­VENTILATOR INTERACTIONS
POSITIVE-­PRESSURE VENTILATION AND CARDIAC FUNCTION
COMPLICATIONS OF POSITIVE-­PRESSURE MECHANICAL VENTILATION
VENTILATOR-­INDUCED LUNG INJURY
VENTILATOR-­INDUCED DIAPHRAGM DYSFUNCTION
Disuse Atrophy (Over-­assistance Myotrauma)
Load-­Induced Diaphragm Injury (Under-­assistance and Eccentric Myotrauma)
OXYGEN TOXICITY
PATIENT-­VENTILATOR INTERFACE COMPLICATIONS
PATIENT-­VENTILATOR DYS-­SYNCHRONY
Breath Triggering Dys-­synchrony
Flow Pattern Dys-­synchrony
Breath Cycling Dys-­synchrony
Clinical Implications
Managing Dys-­synchronies
APPLYING MECHANICAL VENTILATORY SUPPORT
MECHANICAL VENTILATORY SUPPORT INVOLVES TRADEOFFS
CONSIDERATIONS IN CHOOSING VENTILATOR SETTINGS FOR DIFFERENT FORMS OF RESPIRATORY FAILURE
Parenchymal Lung Injury
Obstructive Airway Disease
Neuromuscular Respiratory Failure
Resolving Respiratory Failure: Liberation from Mechanical Ventilation
INNOVATIONS IN MECHANICAL VENTILATORY SUPPORT
ALTERNATIVE STRATEGIES FOR “LUNG PROTECTION”
Positive-­Pressure Ventilation in the Prone Position
Airway Pressure Release Ventilation and High-­Frequency Oscillatory Ventilation
AUTOMATED WEANING STRATEGIES
OPTIMIZING SYNCHRONY DURING ASSISTED MECHANICAL VENTILATION
Proportional Assist Ventilation
Neurally Adjusted Ventilatory Assist
BEDSIDE IMAGING DURING MECHANICAL VENTILATION
ACKNOWLEDGMENT
Key Readings
References
136 Noninvasive Support of Ventilation.pdf
136 -
Noninvasive Support of Ventilation
Pathophysiology, Rationale, and Expected Benefits
COPD Exacerbation
Cardiogenic Pulmonary Edema
Hypoxemic Acute Respiratory Failure
Practical and Technical Aspects
Modes of Ventilation and Settings
Continuous Positive Airway Pressure and Bilevel Positive Airway Pressure
Asynchrony under BPAP
Other Modalities
Ventilators
Interfaces
Indications
Exacerbation of COPD
Asthma
Exacerbation of Other Chronic Lung Diseases
Cardiogenic Pulmonary Edema
HYPOXEMIC RESPIRATORY FAILURE
NIV to Prevent Intubation in de Novo Respiratory Failure
NIV for Pneumonia
NIV for ARDS
NIV in Immunocompromised Patients
Prevention of Postoperative Complications
Pathophysiology of Postoperative Respiratory Complications
Prophylactic NIV in the Postoperative Period
Therapeutic NIV in the Postoperative Period
Chest Trauma
Do-­Not-­Intubate Patients
During the Weaning Process and Post-­extubation
Weaning
Post-­extubation
Preventive Use During Procedures
Endoscopic Procedures
Endotracheal Intubation
Epidemiology of Noninvasive Ventilation in Acute Care
Home Noninvasive Ventilation
Epidemiology
Pathophysiology
Indications for Home NIV
Special Features in NMD
Special Features of OHS
Home NIV for Chronic Hypercapnic COPD
Importance of Monitoring Home NIV
Key Readings
References
137 Noninvasive Support of Oxygenation.pdf
137 -
Noninvasive Support of Oxygenation
Indications for Oxygen Therapy
Devices and Interfaces
Low-­Flow Systems
Nasal Cannula
Simple Face Mask or Hudson Mask
Reservoir Systems
Partial-­Rebreathing Mask
Non-­rebreathing Mask
High-­Flow Systems
Venturi Mask
Continuous Positive Airway Pressure
High-­Flow Nasal Cannula
Indications FOR High-­Flow Nasal Cannulas
Acute Hypoxemic Respiratory Failure
Pediatric Populations
Pneumonia
Acute Respiratory Distress Syndrome
Immunocompromise
Cardiogenic Pulmonary Edema
Other Hypoxemic Lung Diseases
Hypercarbic Hypoxemic Respiratory Failure
Post-­Extubation SUPPORT
Preoxygenation for Intubation
Perioperative Period and During Procedures
Patients Near the End of Life or Not Wishing to be Intubated
Key Readings
References
138 Extracorporeal Support of Gas Exchange.pdf
138 -
Extracorporeal Support of Gas Exchange
Principles of Extracorporeal Membrane Oxygenation
Historical Perspective
Veno-­Venous Extracorporeal Membrane Oxygenation
Indications
Components
Oxygenators
Pumps
Cannulas
Tubing
Cannulation
Patient-­Machine Interaction
Effect on Oxygenation
Membrane Lung
Native Lung
O2 Transfer by the Membrane Lung. depends on three main factors (see Fig. 138.3)
Mixed Venous Blood Oxygenation. During VV-­ECMO, the main determinants of mixed venous So2 are the oxygen saturation of the bloo...
Oxygen Uptake from the Native Lung. The NL will contribute to arterial oxygenation by adding oxygen to the mixed venous blood ac...
Effect on CO2 Removal
Management of the Membrane Lung
Ventilatory Management of the Native Lung
Anticoagulation and Hematologic Monitoring
Complications
Weaning From Veno-­Venous Extracorporeal Membrane Oxygenation
Low-­Flow Co2 Removal
Indications
Co2 Removal for Ultraprotective Ventilation in Acute Respiratory Distress Syndrome
CO2 Removal for COPD
Extracorporeal Membrane Oxygenation as Bridge to TRANSPLANTATION
Key Readings
eFigure Image Gallery
References
139 Pulmonary Rehabilitation.pdf
139 -
Pulmonary Rehabilitation
Indications and Candidacy
Components
Exercise Training
Education
Psychosocial Support
Nutritional Support
Inspiratory Muscle Training, Breathing Training, and Chest Physical Therapy
Promoting Physical Activity
Long-­Term Outcomes and Maintenance of Benefits
Obstacles to Patient Participation and Adherence
Comorbidities
Program Organization
Outcome Assessment and Measurement
Novel Models
Pulmonary Rehabilitation Following Copd Exacerbation
Pulmonary Rehabilitation for Disorders Other than COPD
Policy and Access Issues
Acknowledgements
Key Readings
The Future of Pulmonary Rehabilitation
References
140 Lung Transplantation.pdf
140 - LUNG TRANSPLANTATION
INTRODUCTION
INDICATIONS AND CANDIDATE SELECTION
TIMING OF REFERRAL AND LISTING
ALLOCATION SYSTEM
BRIDGING TO TRANSPLANTATION: ARTIFICIAL LUNG TECHNOLOGIES
DONOR SELECTION AND MANAGEMENT
LUNG PRESERVATION
AVAILABLE SURGICAL TECHNIQUES
SINGLE ­LUNG TRANSPLANTATION
BILATERAL LUNG TRANSPLANTATION
HEART-­LUNG TRANSPLANTATION
BILATERAL LOBAR TRANSPLANTATION
ROUTINE POSTTRANSPLANTATION MANAGEMENT
OUTCOMES
SURVIVAL
PULMONARY FUNCTION
EXERCISE CAPACITY
HEMODYNAMICS
QUALITY OF LIFE
COMPLICATIONS
PRIMARY GRAFT DYSFUNCTION
AIRWAY COMPLICATIONS
PHRENIC NERVE INJURY
NATIVE LUNG HYPERINFLATION
INFECTION
Bacteria
Cytomegalovirus
Aspergillus
REJECTION AND CHRONIC LUNG ALLOGRAFT DYSFUNCTION
Hyperacute Rejection
Acute Cellular Rejection
Acute Antibody-­Mediated Rejection
Bronchiolitis Obliterans Syndrome (See Chapter 72)
Restrictive Allograft Syndrome
POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER
LUNG CANCER
RECURRENCE OF PRIMARY DISEASE
RETRANSPLANTATION
KEY READINGS
FUTURE DIRECTIONS
EFIGURE IMAGE GALLERY
References
141 End-of-Life Care in Respiratory Failure.pdf
141 - END-­OF-­LIFE CARE IN RESPIRATORY FAILURE
INTRODUCTION
PREDICTING THE OUTCOME OF RESPIRATORY FAILURE
TREATMENT GOALS AT THE END OF LIFE
WHERE AND HOW PATIENTS DIE
ETHICAL AND LEGAL JUSTIFICATION FOR END-­OF-­LIFE CARE
JUSTIFICATION FOR WITHHOLDING AND WITHDRAWING LIFE-­SUSTAINING THERAPY: A HISTORY
REQUESTS FOR NONBENEFICIAL TREATMENTS
JUSTIFICATION FOR ADMINISTERING PALLIATIVE CARE
Administering Medications for Symptom Relief During the Dying Process
Physician-­Assisted Dying
MEDICAL DECISION MAKING AT THE END OF LIFE
IMPORTANCE OF PHYSICIAN, PATIENT, AND FAMILY COMMUNICATION
IMPROVING COMMUNICATION AND THE QUALITY OF CARE AT THE END OF LIFE
UNDERSTANDING WHAT PATIENTS, FAMILIES, AND CLINICIANS NEED AT THE END OF LIFE
PROVIDING APPROPRIATE SETTINGS FOR DYING PATIENTS
EMOTIONAL AND SPIRITUAL SUPPORT
SYMPTOM MANAGEMENT
WHY SYMPTOMS MAY BE POORLY MANAGED
MANAGEMENT OF PAIN
MANAGEMENT OF ANXIETY
MANAGEMENT OF DELIRIUM
MANAGEMENT OF DYSPNEA
MANAGEMENT OF NAUSEA AND VOMITING
MANAGEMENT OF HUNGER AND THIRST
WITHHOLDING AND WITHDRAWAL OF LIFE-­SUSTAINING THERAPY
WHAT THERAPIES ARE WITHHELD AND WITHDRAWN
WITHHOLDING AND WITHDRAWAL OF INTUBATION AND MECHANICAL VENTILATION
Key Readings
eFigure Image Gallery
References
Appendix A Glossary of Terms and Standard Symbols.pdf
Glossary of Terms and Standard Symbols