Reviews and feature article
Oxidants and the pathogenesis of lung diseases

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The increasing number of population-based and epidemiologic associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways, which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid of the lung. Furthermore, it is clear that interindividual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (eg, asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome), and the potential risk factors (eg, age, genetics) for enhanced susceptibility to oxidant-induced disease.

Section snippets

Mechanisms of oxidant-induced toxicity

The mechanisms whereby oxidants exert their pathological effects on the lungs have been the focus of numerous studies and are still the subject of debate. Despite the diversity of these agents and the multitude of complex mechanisms that exist, several common themes have been identified that can serve as a platform for future research. Many ambient air pollutants may induce oxidative stress in the lung that arises when ROSs overwhelm antioxidant defenses (Fig 1). After this imbalance is

Oxidants and lung disease

Because the lung interfaces with the external environment, it is frequently exposed to airborne oxidant gases and particulates, and thus prone to oxidant-mediated cellular damage. Enhanced levels of oxidant production and cellular injury have been implicated in many pulmonary diseases including asthma and other allergic diseases, COPD, ARDS, and cystic fibrosis. In the following section, we briefly describe investigations on exacerbation of these important pulmonary diseases caused by ROS.

Susceptible populations

Interindividual differences in responses to air pollutant exposures have been well documented.117, 118, 119, 120 That is, in populations and clinical studies exposed similarly to air pollutants, pulmonary inflammatory and function responses are more severe in some individuals than in others. Importantly, investigators have also demonstrated high within-individual reproducibility of the responses to air pollutant exposures.120 The wide spectrum of adverse responses to the pollutants has been

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    (Supported by an educational grant from Merck & Co., Inc.)

    Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

    Supported by the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services.

    Terms in boldface and italics are defined in the glossary on page 457.

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