1st Edition
Lung Injury Mechanisms, Pathophysiology, and Therapy
Progressing from general scientific principles and concepts to in-depth topical discussions of current research and treatment methods, this comprehensive reference defines the cellular and molecular mechanisms contributing to inflammatory lung injury and repair. Extensive coverage is provided on key mediators and pathways important in acute and chronic pulmonary inflammation and lung injury, as well as the mechanistic pathophysiology of related diseases ranging from clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) to idiopathic pulmonary fibrosis (IPF) and other subacute and chronic conditions. Additional chapters also address vascular dysfunction, surfactant dysfunction, reactive oxygen/nitrogen species, and cell and animal models of acute and chronic lung injury.
Introduction Claude Lenfant
Preface
Contributors
Introduction to Lung Injury
Robert H. Notter, Jacob N. Finkelstein, and Bruce A. Holm
Overview
Acute LungInjury
Chronic Lung Injury
Therapeutic Approaches for Diseases Involving Lung Injury
Summary of Coverage and Chapter Organization
Principles of Lung Development, Growth, and Repair
Ian Copland, Keith Tanswell, and Martin Post
Overview
Introduction
Lung Organogenesis
Postnatal Development and Growth of the Lung
Postnatal Lung Disease and Injury
Repair in the Postnatal Lung
Summary
Acute Lung Injury: Etiologies and Basic Features
Paul R. Knight and Alexandre T. Rotta
Overview
Introduction to Acute Lung Injury
Overview of the In£ammatory Response
Clinical ALI and ARDS
Summary
Mediators and Inflammatory Cell Recruitment in Acute Lung Injury
Michael P. Keane, John A. Belperio, and Robert M. Strieter
Overview
Introduction
Innate Host Defense
Early Response Cytokines
In£ammatory Cell Recruitment
Chemotactic Cytokines (Chemokines)
Summary
Chronic Lung Injury: Basic Features and Clinical Relevance
David Perlman, Peter B. Bitterman, and Christine H. Wendt
Overview
Introduction
Generalized Cellular Responses to Stress and Injury
Lung Injury and Its Mechanisms
Lung Defense Mechanisms
Fibroproliferation and Chronic Lung Disease
Summary
Mediators and Mechanisms in Chronic Lung Injury and Fibrosis
Joseph A. Lasky, Luis A. Ortiz, and Arnold R. Brody
Overview
Introduction
Relevance of Tumor Necrosis Factor Alpha for Pulmonary Fibrosis
Platelet-Derived Growth Factor
Connective Tissue Growth Factor
Transforming Growth Factor Beta
Summary
Roles of Reactive Oxygen and Nitrogen Species in Lung Injury
Ian C. Davis, John D. Lang, and Sadis Matalon
Overview
Introduction
Chemistry and Biochemistry of Reactive Oxygen and Nitrogen Species
Biological E¡ects of Reactive Oxygen and
Nitrogen Species
Reactive Species in Clinical ALI and ARDS
Summary
Vascular Dysfunction in Lung Injury
Stephen Wedgewood, Jeffrey R. Fineman, and Stephen M. Black
Overview
Normal Growth and Development of the Pulmonary Vascular Bed
Regulation of Neonatal Vascular Tone
Clinical Pulmunary Vascular Dysfunction
Animal Models
Mechanisms of Vascular Dysfunction
Therapies for Vascular Dysfunction
Summary
Surfactant Activity and Dysfunction in Lung Injury
Zhengdong Wang, Bruce A. Holm, Sadis Matalon, and Robert H. Notter
Overview
Endogenous Surfactant and Its Activity
De¢ciency and Dysfunction of Lung Surfactant
Methods for Measuring Lung Surfactant Surface Activity and Dysfunction
Overview of Inhibitors and Mechanisms
Surfactant Inactivation by Blood Proteins
Surfactant Inactivation by Cell Membrane Lipids, Fluid Free Fatty Acids, and Lysophospholipids
Surfactant Dysfunction from Interactions with Reactive Oxygen or Nitrogen Species
Surfactant Dysfunction Involving Large Aggregates
Additivity of Lung Surfactant Inhibitors
Physiological Correlates of Lung Surfactant Dysfunction and Replacement in Animals
Summary
Cell and Animal Models of Lung Injury
Jacob N. Finkelstein, Michael A. O’Reilly,
Bruce A. Holm, Patricia R. Chess, and Robert H. Notter
Overview
General Concepts of Cell Models
Examples of Pulmonary Cells Studied in Vitro
Examples of Cultured Cell Lines
Exposures of Cells to Injury Stimuli
Animal Models of Lung Injury
Examples of Cell and Animal Assessments Involving Hyperoxia and Oxidative Stress
Summary
Genetically Modified Mouse Models of Lung Injury and Repair
Barry R. Stripp, Adam Giangreco, and Susan D. Reynolds
Overview
Basic Methodology for Modi¢cation of the Mouse Genome: Transgenic Mice
Basic Methodology for Modi¢cation of the Mouse Genome: Site- Speci¢c Genetic Modi¢cation
Lung Injury Applications
Summary
Inhalation Toxicology: Methods and Models
Daniel L. Costa
Overview
Introduction
Structure/Function Relationships of the Respiratory System
Empirical Studies of Inhaled Toxicants
Inhalation Exposure Methods
Deposition and Clearance of Environmental Inhalants
Respiratory Tract Injury
Summary
Ventilation Therapies and Strategies for Acute Lung Injury
C. C. Dos Santos and A. S. Slutsky
Overview
Introduction
Background and Rationale Underlying Ventilatory Strategies in ARDS/ALI
Lung Protective Ventilatory Strategies
High Frequency Ventilation
Adjuncts to Mechanical Ventilation
Caveats: The Concept of Primary vs. Secondary ARDS
Summary
Anti-inflammatory Therapies for Lung Injury
Richard Phipps, William S. Beckett, Julia Kaufman, Christine Martey, P. J. Sime, and Thomas H. Thatcher
Overview
Introduction
Infectious Diseases of the Lung
Asthma
Acute and Chronic Bronchitis
Chronic Obstructive Pulmonary Disease (COPD)
Fibrosing Diseases of the Lung (Interstitial Lung Diseases)
Summary
Surfactant Replacement Therapy in Lung Injury
Patricia R. Chess, Jacob N. Finkelstein, Bruce A. Holm, and Robert H. Notter
Overview
Rationale for Surfactant Therapy in ALI/ARDS
Current Clinical Exogenous Surfactants
Experience with Surfactant Therapy in ALI/ARDS
Considerations A¡ecting the E⁄cacy of Exogenous Surfactant Therapy in ALI/ARDS
Examples of New Synthetic Surfactants for ALI=ARDS
Surfactant Therapy in Combinations with Other Agents in ALI=ARDS
Summary
Antioxidant Therapy for Lung Injury
Tiina M. Asikainen and Carl W. White
Overview
Introduction
Rationale for Antioxidant Therapy: Role of Oxidative Stress in Lung Diseases
Antioxidant Therapy for Lung Injury
Limitations to Antioxidant Therapy
Summary
Vascular Therapies in Lung Injury
Mahesh Bommaraju, Vasanth H. Kumar, Satyan Lakshminrusimha, Rita M. Ryan, and Frederick C. Morin, III
Overview
Introduction
Disruption of Normal Pulmonary Vascular Regulation in Acute Injury
Vasodilator Therapy in Lung Injury
Anticoagulant Therapy
Combined Therapies for Vascular Dysfunction
Future Therapies
Summary
Gene Therapy for Lung Injury
P. J. Sime, M. Kolb, R. J. White, M. Hitt, and J. Gauldie
Overview
Introduction
Gene Transfer Approaches
Gene Therapy for Acute Lung Injury
Gene Therapy for Chronic Lung Injury
Summary
Combination Therapies for Lung Injury
Gloria S. Pryhuber, Carl T. D’Angio, Jacob N. Finkelstein, and Robert H. Notter
Overview
Concept of Combined-Modality Therapy
Integration of Basic and Clinical Research on Combination Therapies for Lung Injury
Clinical Trials Studying Combination Therapies
Clinical ALI and ARDS
Potential Targets for Combination Therapies in the Acute Exudative Phase of ALI=ARDS
Therapies Targeting Ventilation/Perfusion Abnormalities in Acute Exudative ALI/ARDS
Agents Targeting In £ammation or Oxidant Injury in Early Phase ALI/ARDS
Agents Targeting the Fibroproliferative Phase of ALI/ARDS or Other Chronic Lung Diseases
Summary
Summary and Future Research Directions
Robert H. Notter, Jacob N. Finkelstein, and Bruce A. Holm
Overview
Current Research Perspectives on Pulmonary In£ammation and Lung Injury
Future Lung Injury Research
Summary
Index
Biography
Robert H. Notter, Jacob Finkelstein, Bruce Holm
"…this book provides a current overview of acute and chronic lung injury….the book's extensive reference lists are a valuable resource for more in-depth information."
-Books, Films, Tapes, & Software
"…this is a unique book written and edited by the top authorities in the field. It will have great interest among basic scientists."
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