Biologic Markers in Pulmonary Toxicology (1989) / Chapter Skim
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Executive Summary
Executive Summary
Pages 1-10
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Sobered by such episodes, the United States developed an aggressive program for reducing air pollutants. Still, subtle differences in pulmonary performance can occur and chronic pulmonary problems afflict one of every five persons; exposure even of healthy persons to environmental pollutants, even at their current magnitudes, plays a role.
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Even before exposure occurs, biologic differences among humans might cause some to be more suscep AL4RKERS IN PULMONARY TOXICOLOGY tible to environmentally induced disease. Thus, biologic markers are tools that can be used to clarify the relationship, if any, between exposure to a xenobiotic compound and health impairment.
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Such markers include inborn differences in metabolism, variations in immunoglobulin concentrations, low organ reserve capacity, or other identifiable genetically determined or environmentally induced variations in absorption, metabolism, and response to environmental agents. Other factors that can affect individual susceptibilities include nutritional status of the organism, the role of the target site in controlling overall body function, the condition of the target tissue (whether disease is or was present)
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And techniques for analyzing markers are well advanced; e.g., new techniques allow analysis of exhaled air, sputum, nasal ravage fluid, and bronchoalveolar ravage fluid for chemical evidence of exposure to specific pollutants. The field of mathematical modeling has advanced to the point where models now include physiologic measurements, such as blood flow rates, ventilation rates, metabolic rates, and both blood-air and blood-tissue partition coefficients.
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MARKERS OF PHYSIOLOGIC EFFECTS IN INTACT ORGANISMS Chapter 3 describes the role of physiologic measurements of the functional status of the respiratory tract, which are s applicable for use in intact humans and animals. These measurements range from commonly used clinical tests of respiratory function to currently developing assays of the integrity of tissue barriers.
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Increases in proteins and other products in biologic fluids, such as bronchoalveolar ravage fluid, can serve as sensitive markers of the inflammatory response. The human respiratory tract contains a complex array of host defenses-anatomic barriers, mucociliary clearance, phagocytic cells, and various components of cellular and humoral immunity-that collectively cleanse inhaled air and inactivate infectious and other injurious agents that are inhaled.
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Molecular markers have proved useful in the detection and diagnosis of some infectious diseases and in sickle-cell anemia and alpha- and beta-thalassemia, and they are being developed for other diseases, such as Duchenne muscular dystrophy, cystic fibrosis, Lesch-Nyhan syndrome, phenylketonuria, antithrombin III deficiency, and alpha,-antitrypsin deficiency. The development and use of molecular markers to identify cellular responses to environmental toxicants will be important in increasing understanding of the mechanisms involved in pulmonary disease.
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Further research is required on the role ~ · · · ~. ~ OI lIlCreaSeS In llOIlSpeC11 1C airway reactivity in identifying persons susceptible to environmental agents and on the role of increases in airway reactivity in the natural history of chronic obstructive pulmonary disease (COPD)
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Cell and mediator changes found in bronchoalveolar and nasal-ravage fluid need to be related to physiologic and pathologic changes to assess their utility as biologic markers. Nasal ravage needs to be investigated as a means of evaluating pollutant exposure and as an epidemiologic tool.
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