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Historical Perspective
Respiratory Tract Structure and Function
Oronasal Passages
Conducting Airways
Gas Exchange Region
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
Alveolar Macrophage 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
Agents Known to Produce Lung Injury in Humans
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
Acknowledgments
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“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”
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—John Scott Haldane (Haldane, 1922)
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Historical Perspective
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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).
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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).
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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 of ...