ABSTRACT
Chronic obstructive pulmonary disease (COPD) is characterized and defined by limitation
of expiratory airflow. This can result from several types of anatomical lesions, including
loss of lung elastic recoil and fibrosis and narrowing of small airways. Inflammation,
edema, and secretions also contribute variably to airflow limitation. Smoking can
cause COPD through several mechanisms. First, smoke is a powerful inducer of an inflammatory
response. Inflammatory mediators, including oxidants and proteases, are believed to
play a major role in causing lung damage. Smoke can also alter lung repair responses
in several ways. Inhibition of repair may lead to tissue destruction that characterizes
emphysema, whereas abnormal repair can lead to the peribronchiolar fibrosis that causes
airflow limitation in small airways. Genetic factors likely play a major role and
probably account for much of the heterogeneity susceptibility to smoke and other factors.
Many factors may play a role, but to date, only α-1 protease inhibitor deficiency
has been unambiguously identified. Exposures other than cigarette smoke can contribute
to the development of COPD. Inflammation of the lower respiratory tract that results
from asthma or other chronic disorders may also contribute to the development of fixed
airway obstruction.
COPD is not only a disease of the lungs but is also a systemic inflammatory disorder.
Muscular weakness, increased risk for atherosclerotic vascular disease, depression,
osteoporosis, and abnormalities in fluids and electrolyte balance may all be consequences
of COPD.
Advances in understanding the pathogenesis of COPD have the potential for identifying
new therapeutic targets that could alter the natural history of this devastating disorder.
KEYWORDS
Bronchitis - emphysema - peribronchiolar fibrosis - cigarette smoking - protease -
antioxidant - repair
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John R SpurzemM.D.
University of Nebraska Medical Center, 985300 Nebraska Medical Center
Omaha, NE 68198-5300
Email: jspurzem@unmc.edu