Lung Injury: Mechanisms, Pathophysiology, and Therapy

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ISBN: 9780824757939 | 0824757939
Cover: Hardcover
Copyright: 4/20/2005

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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

iii

Preface

Contributors

vii

1. Introduction to Lung Injury

(18)

Robert H. Notter, Jacob N. Finkelstein, and Bruce A. Holm

Overview

(1)

Acute Lung Injury

(6)

Chronic Lung Injury

(4)

Therapeutic Approaches for Diseases Involving Lung Injury

(1)

Summary of Coverage and Chapter Organization

(7)

2. Principles of Lung Development, Growth, and Repair

(48)

Ian Copland, Keith Tanswell, and Martin Post

Overview

(1)

Introduction

(1)

Lung Organogenesis

(9)

Postnatal Development and Growth of the Lung

(8)

Postnatal Lung Disease and Injury

(5)

Repair in the Postnatal Lung

(3)

Summary

(21)

3. Acute Lung Injury: Etiologies and Basic Features

(44)

Paul R. Knight and Alexandre T. Rotta

Overview

(1)

Introduction to Acute Lung Injury

(1)

Overview of the Inflammatory Response

(13)

Clinical ALI and ARDS

(17)

Summary

(12)

4. Mediators and Inflammatory Cell Recruitment in Acute Lung Injury

111

(40)

Michael P. Keane, John A. Belperio, and Robert M. Strieter

Overview

111

(1)

Introduction

112

(2)

Innate Host Defense

114

(2)

Early Response Cytokines

116

(4)

Inflammatory Cell Recruitment

120

(2)

Chemotactic Cytokines (Chemokines)

122

(13)

Summary

135

(16)

5. Chronic Lung Injury: Basic Features and Clinical Relevance

151

(24)

David Perlman, Peter B. Bitterman, and Christine H. Wendt

Overview

151

(1)

Introduction

152

(1)

Generalized Cellular Responses to Stress and Injury

152

(3)

Lung Injury and Its Mechanisms

155

(5)

Lung Defense Mechanisms

160

(3)

Fibroproliferation and Chronic Lung Disease

163

(4)

Summary

167

(8)

6. Mediators and Mechanisms in Chronic Lung Injury and Fibrosis

175

(52)

Joseph A. Lasky, Luis A. Ortiz, and Arnold R. Brody

Overview

175

(1)

Introduction

176

(3)

Relevance of Tumor Necrosis Factor Alpha for Pulmonary Fibrosis

179

(10)

Platelet-Derived Growth Factor

189

(6)

Connective Tissue Growth Factor

195

(6)

Transforming Growth Factor Beta

201

(6)

Summary

207

(20)

7. Roles of Reactive Oxygen and Nitrogen Species in Lung Injury

227

(42)

Ian C. Davis, John D. Lang, and Sadis Matalon

Overview

227

(1)

Introduction

228

(1)

Chemistry and Biochemistry of Reactive Oxygen and Nitrogen Species

229

(4)

Biological Effects of Reactive Oxygen and Nitrogen Species

233

(12)

Reactive Species in Clinical ALI and ARDS

245

(6)

Summary

251

(18)

8. Vascular Dysfunction in Lung Injury

269

(28)

Stephen Wedgewood, Jeffrey R. Fineman, and Stephen M. Black

Overview

269

(1)

Normal Growth and Development of the Pulmonary Vascular Bed

270

(1)

Regulation of Neonatal Vascular Tone

270

(2)

Clinical Pulmunary Vascular Dysfunction

272

(3)

Animal Models

275

(2)

Mechanisms of Vascular Dysfunction

277

(4)

Therapies for Vascular Dysfunction

281

(2)

Summary

283

(14)

9. Surfactant Activity and Dysfunction in Lung Injury

297

(56)

Zhengdong Wang; Bruce A. Holm, Sadis Matalon, and Robert H. Notter

Overview

297

(1)

Endogenous Surfactant and Its Activity

298

(7)

Deficiency and Dysfunction of Lung Surfactant

305

(2)

Methods for Measuring Lung Surfactant Surface Activity and Dysfunction

307

(1)

Overview of Inhibitors and Mechanisms

308

(2)

Surfactant Inactivation by Blood Proteins

310

(3)

Surfactant Inactivation by Cell Membrane Lipids, Fluid Free Fatty Acids, and Lysophospholipids

313

(3)

Surfactant Dysfunction from Interactions with Reactive Oxygen or Nitrogen Species

316

(7)

Surfactant Dysfunction Involving Large Aggregates

323

(1)

Additivity of Lung Surfactant Inhibitors

324

(2)

Physiological Correlates of Lung Surfactant Dysfunction and Replacement in Animals

326

(7)

Summary

333

(20)

10. Cell and Animal Models of Lung Injury

353

(52)

Jacob N Finkelstein, Michael A. O'Reilly, Bruce A. Holm, Patricia R. Chess, and Robert H. Notter

Overview

353

(1)

General Concepts of Cell Models

354

(1)

Examples of Pulmonary Cells Studied in Vitro

355

(5)

Examples of Cultured Cell Lines

360

(2)

Exposures of Cells to Injury Stimuli

362

(1)

Animal Models of Lung Injury

363

(7)

Examples of Cell and Animal Assessments Involving Hyperoxia and Oxidative Stress

370

(9)

Summary

379

(26)

11. Genetically Modified Mouse Models of Lung Injury and Repair

405

(58)

Barry R. Stripp, Adam Giangreco, and Susan D. Reynolds

Overview

405

(1)

Basic Methodology for Modification of the Mouse Genome: Transgenic Mice

406

(15)

Basic Methodology for Modification of the Mouse Genome: Site-Specific Genetic Modification

421

(9)

Lung Injury Applications

430

(15)

Summary

445

(18)

12. Inhalation Toxicology: Methods and Models

463

(52)

Daniel L. Costa

Overview

463

(1)

Introduction

464

(1)

Structure/Function Relationships of the Respiratory System

465

(10)

Empirical Studies of Inhaled Toxicants

475

(4)

Inhalation Exposure Methods

479

(5)

Deposition and Clearance of Environmental Inhalants

484

(9)

Respiratory Tract Injury

493

(12)

Summary

505

(10)

13. Ventilation Therapies and Strategies for Acute Lung Injury

515

(58)

C.C. Dos Santos and A.S. Slutsky

Overview

515

(1)

Introduction

516

(4)

Background and Rationale Underlying Ventilatory Strategies in ARDS/ALI

520

(5)

Lung Protective Ventilatory Strategies

525

(18)

High Frequency Ventilation

543

(3)

Adjuncts to Mechanical Ventilation

546

(7)

Caveats: The Concept of Primary vs. Secondary ARDS

553

(2)

Summary

555

(18)

14. Anti-inflammatory Therapies for Lung Injury

573

(44)

Richard Phipps, William S. Beckett, Julia Kaufman, Christine Martey, P.J. Sime, and Thomas H. Thatcher

Overview

573

(1)

Introduction

574

(1)

Infectious Diseases of the Lung

575

(7)

Asthma

582

(6)

Acute and Chronic Bronchitis

588

(1)

Chronic Obstructive Pulmonary Disease (COPD)

589

(3)

Fibrosing Diseases of the Lung (Interstitial Lung Diseases)

592

(6)

Summary

598

(19)

15. Surfactant Replacement Therapy in Lung Injury

617

(48)

Patricia R. Chess, Jacob N. Finkelstein, Bruce A. Holm, and Robert H. Notter

Overview

617

(1)

Rationale for Surfactant Therapy in ALI/ARDS

618

(4)

Current Clinical Exogenous Surfactants

622

(2)

Experience with Surfactant Therapy in ALI/ARDS

624

(8)

Considerations Affecting the Efficacy of Exogenous Surfactant Therapy in ALI/ARDS

632

(5)

Examples of New Synthetic Surfactants for ALI/ARDS

637

(4)

Surfactant Therapy in Combinations with Other Agents in ALI/ARDS

641

(2)

Summary

643

(22)

16. Antioxidant Therapy for Lung Injury

665

(40)

Tiina M. Asikainen and Carl W. White

Overview

665

(1)

Introduction

666

(3)

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

669

(5)

Antioxidant Therapy for Lung Injury

674

(10)

Limitations to Antioxidant Therapy

684

(3)

Summary

687

(18)

17. Vascular Therapies in Lung Injury

705

(42)

Mahesh Bommaraju, Vasanth H. Kumar, Satyan Lakshminrusimha, Rita M Ryan, and Frederick C. Morin, III

Overview

705

(1)

Introduction

706

(4)

Disruption of Normal Pulmonary Vascular Regulation in Acute Injury

710

(1)

Vasodilator Therapy in Lung Injury

711

(11)

Anticoagulant Therapy

722

(1)

Combined Therapies for Vascular Dysfunction

723

(2)

Future Therapies

725

(4)

Summary

729

(18)

18. Gene Therapy for Lung Injury

747

(32)

P.J. Sime, M. Kolb, R.J. White, M. Hitt, and J. Gauldie

Overview

747

(1)

Introduction

748

(1)

Gene Transfer Approaches

748

(11)

Gene Therapy for Acute Lung Injury

759

(5)

Gene Therapy for Chronic Lung Injury

764

(4)

Summary

768

(11)

19. Combination Therapies for Lung Injury

779

(60)

Gloria S. Pryhuber, Carl T. D'Angio, Jacob N. Finkelstein, and Robert H. Notter

Overview

779

(1)

Concept of Combined-ModalityTherapy

780

(1)

Integration of Basic and Clinical Research on Combination Therapies for Lung Injury

780

(1)

Clinical Trials Studying Combination Therapies

781

(9)

Clinical ALI and ARDS

790

(3)

Potential Targets for Combination Therapies in the Acute Exudative Phase of ALI/ARDS

793

(1)

Therapies Targeting Ventilation/Perfusion Abnormalities in Acute Exudative ALI/ARDS

794

(9)

Agents Targeting Inflammation or Oxidant Injury in Early Phase ALI/ARDS

803

(5)

Agents Targeting the Fibroproliferative Phase of ALI/ARDS or Other Chronic Lung Diseases

808

(6)

Summary

814

(25)

20. Summary and Future Research Directions

839

(10)

Robert H. Notter, Jacob N. Finkelstein, and Bruce A. Holm

Overview

839

(1)

Current Research Perspectives on Pulmonary

Inflammation and Lung Injury

840

(2)

Future Lung Injury Research

842

(5)

Summary

847

(2)

Index

849

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Lung Injury: Mechanisms, Pathophysiology, and Therapy

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