1st Edition

Lung Injury Mechanisms, Pathophysiology, and Therapy

Edited By Robert H. Notter, Jacob Finkelstein, Bruce Holm Copyright 2005
    886 Pages 97 B/W Illustrations
    by CRC Press

    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."
    -Doody's Reviews