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  • Historical Perspective

  • Respiratory Tract Structure and Function

    • Oronasal Passages

      • Structure

      • Sensory Functions

      • Irritant, Thermosensory, and Mechanosensory Functions

    • Conducting Airways

      • Structure

      • Mucociliary Clearance and Antimicrobial Functions

    • Gas Exchange Region

      • Structure

      • Function

  • Biotransformation in the Respiratory Tract

  • General Principles in the Pathogenesis of Lung Damage Caused by Chemicals

    • Toxic Inhalants, Gases, and Dosimetry

    • Regional Particle Deposition

    • Deposition Mechanisms

    • Particle Clearance

      • Nasal Clearance

      • Tracheobronchial Clearance

      • Alveolar Clearance

  • Alveolar Macrophage Receptors

    • Alveolar Macrophage Receptors and Innate Immunity

    • Alveolar Macrophage Pattern-Recognition Receptors

  • Acute Responses of the Lung to Injury

    • Trigeminally Mediated Airway Reflexes

    • Bronchoconstriction, Airway Hyperreactivity, and Neurogenic Inflammation

    • Acute Lung Injury (Pulmonary Edema)

  • Chronic Responses of the Lung to Injury

    • Chronic Obstructive Pulmonary Disease

    • Lung Cancer

    • Asthma

    • Pulmonary Fibrosis

  • Agents Known to Produce Lung Injury in Humans

    • Inhalation Hazards

      • Acrolein

      • Asbestos

      • Silica

      • Naphthalene

    • Blood-Borne Agents That Cause Pulmonary Toxicity in Humans

      • Bleomycin

      • Cyclophosphamide and 1,3 Bis (2-Chloroethyl)-1-Nitrosourea (BCNU)

  • Evaluation of Toxic Lung Damage

    • Humans Studies

    • Animals Studies

      • Inhalation Exposure Systems

      • Pulmonary Function Tests in Experimental Animals

      • Morphological Techniques

      • Pulmonary Lavage and Pulmonary Edema

    • In Vitro Studies

      • Isolated Perfused Lung

      • Airway Microdissection and Organotypic Tissue Culture Systems

      • Lung Cell Culture

  • Acknowledgments

“Since the time of Hippocrates the growth of scientific medicine has in reality been based on the study of the manner in which what he called ‘Nature’ of the living body expresses itself in response to changes in the environment, and reasserts itself in face of disturbances and injury”

—John Scott Haldane (Haldane, 1922)

Historical Perspective

Toxic substances can disrupt the respiratory system and distant organs after chemicals enter the body by means of inhalation. Pathological changes in the respiratory tract also can be a target of blood-borne agents. Inhalation toxicology refers to the route of exposure, whereas respiratory toxicology refers to target organ toxicity. This chapter reviews the toxic responses of the respiratory system and is an update of the previous chapter (Witschi et al., 2008).

Historically, respiratory toxicology is a keystone of medicine, dating back to Hippocrates. In his medical thesis On Airs, Waters, and Places, Hippocrates recommended that physicians evaluate local atmospheres to discover the causes of diseases (Adams, 1849). In 1661, John Evelyn appealed to the English King and Parliament for relief from the poor air quality of London that was a result of the burning of “sea-coale” (a brown coal likely enriched in sulfur that washed up on the banks of the River Thames (Evelyn, 1661). This situation continued and became worse in the 19th century when the Industrial Revolution quickened awareness of respiratory toxicology due to air pollutions (see Chap. 29).

Later, Bernardino Ramazzini proposed that clinicians evaluate the relationships between occupational atmospheres and disease pathogenesis, starting a long history of respiratory toxicology role in occupational medicine. He observed that “corruption of the atmosphere” can be at the origin of many respiratory diseases. In his work De Morbis Artificum Diatriba (Diseases ...

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