Proceedings of the American Thoracic Society
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There is growing evidence of higher prevalence of chronic obstructive pulmonary disease (COPD) in the elderly. Age-associated changes in the structure and function of the lung may increase a pathogenetic susceptibility to COPD. The lung may directly develop COPD in old age. ⋯ Tobacco smoke exposure resulted in the development of emphysema. These findings support the hypothesis that premature aging is not the direct cause of emphysema, but that premature aging enhances the susceptibility of the lung to extrinsic insults including tobacco smoke in these animal models. The mechanism of this enhancement needs further investigation and its elucidation should advance COPD management.
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This paper reviews the potential participation of novel pathogenic mechanisms in chronic obstructive pulmonary disease (COPD) relating to aging, including oxidative stress and enhanced expression of markers of senescence in emphysematous lungs and the potential enhanced tissue destruction involving alveolar apoptosis. These insights provide new beginnings for future investigations in the pathobiology of COPD which may lead to future therapies for this condition.
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The smaller airways, < 2 mm in diameter, offer little resistance in normal lungs, but become the major site of obstruction in chronic obstructive pulmonary disease (COPD). ⋯ The centrilobular emphysematous phenotype of COPD is associated with narrowing and obliteration of the terminal bronchioles that begins prior to the onset of emphysematous destruction.
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Review
Testing drugs in animal models of cigarette smoke-induced chronic obstructive pulmonary disease.
Animal models of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) provide potentially useful ways to test drug therapies, either by direct administration of the treatment of interest, or by use of genetically modified animals that mimic the actions of the drug of interest. Evaluation of the potential effects of a drug in animal models requires a long-term (generally 6-mo) smoke exposure to produce/prevent lesions because acute models do not completely predict chronic events. There are now more than 30 chronic studies in the literature which, in aggregate, show that antiproteolytic therapies, antiinflammatory therapies, and antioxidant therapies substantially or completely prevent emphysema, small airway remodeling, and pulmonary hypertension in laboratory animals. ⋯ New data from our laboratory indicates that, at least for murine emphysema, the development of disease goes through different phases, with early repair and late failure to repair smoke-induced damage. These observations suggest that the potential effects of drug treatment in humans may vary depending on the stage of the disease and that treatment may be more effective in relatively early disease. An additional complicating factor is that interventions that ameliorate emphysema may or may not prevent small airway remodeling and/or pulmonary hypertension, suggesting that different therapeutic approaches may be needed for the various different anatomic lesions of COPD.