Lung Injury Mechanisms, Pathophysiology, and Therapy

Introduction Claude Lenfant

Preface

Contributors

Introduction to Lung Injury

Overview

Acute LungInjury

Chronic Lung Injury

Therapeutic Approaches for Diseases Involving Lung Injury

Summary of Coverage and Chapter Organization

Overview

Introduction

Lung Organogenesis

Postnatal Development and Growth of the Lung

Postnatal Lung Disease and Injury

Repair in the Postnatal Lung

Summary

Overview

Introduction to Acute Lung Injury

Overview of the In£ammatory Response

Clinical ALI and ARDS

Summary

Overview

Introduction

Innate Host Defense

Early Response Cytokines

In£ammatory Cell Recruitment

Chemotactic Cytokines (Chemokines)

Summary

Overview

Introduction

Generalized Cellular Responses to Stress and Injury

Lung Injury and Its Mechanisms

Lung Defense Mechanisms

Fibroproliferation and Chronic Lung Disease

Summary

Overview

Introduction

Relevance of Tumor Necrosis Factor Alpha for Pulmonary Fibrosis

Platelet-Derived Growth Factor

Connective Tissue Growth Factor

Transforming Growth Factor Beta

Summary

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

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

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

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

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

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

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

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

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

Overview

Introduction

Rationale for Antioxidant Therapy: Role of Oxidative Stress in Lung Diseases

Antioxidant Therapy for Lung Injury

Limitations to Antioxidant Therapy

Summary

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

Overview

Introduction

Gene Transfer Approaches

Gene Therapy for Acute Lung Injury

Gene Therapy for Chronic Lung Injury

Summary

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

Overview

Current Research Perspectives on Pulmonary In£ammation and Lung Injury

Future Lung Injury Research

Summary

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