Few smokers develop COPD. Why?
COPD is a common disease and its major risk factor, cigarette smoking, has been identified. However, only a minority of smokers develop clinically relevant disease. Although, the current understanding of the pathogenesis includes an "abnormal inflammation" as a response to various noxious agents, its various pathways are not clear. Oxidative stress, inflammation, tissue damage and tissue repair (remodeling) are parts of the complex procedure leading to COPD. This is a review of the available literature concerning the "susceptible" smoker. An epidemiological model is discussed, putting emphasis on the timing of the exposure to cigarette smoke. There are evidences that respiratory adenoviral infection in early life could be also an important factor. Differences in nutrition could also play a role in protecting against the oxidative stress. Airway hyperresponsiveness failed to clarify the whole picture and is still open for debate. Genetic differences are the most likely explanations to describe the "susceptible" smoker. However, the only well-established genetic risk factor is the alpha-l-antitrypsin. Other candidate genes were reviewed, alpha-l-antichymotrypsin, blood group antigens, vitamin-D binding protein, a2-macroglobulin, immunoglobulin deficiency, extracellular superoxide dismutase, secretory leukocyte proteinase inhibitor, cathepsin G, tumor necrosis factor-a gene and others. Microsatellite DNA instability in COPD could be a useful tool to identify the locus of genetic alterations leading to COPD. Thus, in addition to exposure to exogenous factors, host factors, most likely several genes, are involved and affect various pathways of the pathogenesis of COPD.
Department of Thoracic Medicine, University of Crete, Medical School, Heraklion, Crete, Greece. siafak@med.uoc.gr
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Siafakas
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Tzortzaki
D029481:Bronchitis, Chronic / Q000209:etiology; D004198:Disease Susceptibility; D006801:Humans; D009504:Neutrophils / Q000502:physiology; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000276:immunology; D011656:Pulmonary Emphysema / Q000209:etiology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology