Both asthma and COPD are characterized by airflow obstruction and chronic persistent airway
inflammation, and many patients with asthma have characteristics of COPD, an overlap that often makes it difficult to establish an accurate diagnosis (Figure 2).
Indeed, the similarities betweenincluding tobacco smoke (either due to directly smoking or from second-hand smoke), or through occupational exposure to coal dust, asbestos, and chemicals.8,15 Because the majority of diagnosed COPD is related to tobacco exposure,
there has been considerable work to define the link between tobacco smoke and ongoing airway and parenchymal remodeling. Multiple pathogenic mechanisms likely contribute to the development of COPD (see below). In addition, since only 20% of smokers acquire COPD, genetic predisposition seems to play an important role in the pathogenesis of this disease.15 For example, patients with a genetic deficiency in alpha 1-antitrypsin are prone to
develop early-onset emphysema. Another important factor linking smoking to inflammation may be oxidative stress induced by oxidants found in cigarette smoke; reactive oxygen species such as superoxide anions and hydrogen peroxide generated as a consequence
of oxidative stress can propagate the inflammatory response by activating several redox-sensitive transcription factors (e.g., NF-kappa B and activated protein 1 [AP-1]) that can
upregulate expression of a number of proinflammatory cytokines.20,21 These cytokines
can trigger and propagate an inflammatory cascade as shown in Figure 3.22
Cigarette smoke
induces epithelial cells and alveolar macrophages to release tumor necrosis factor-a (TNFa),
which in turn, increases production of interleukin 8 (IL-8); both of these cytokines are potent
chemoattractants that cause an influx of monocytes, neutrophils and CD8 lymphocytes. These cells, when acted upon by proinflammatory cytokines, are stimulated to release proteinases that contribute to alveolar septal disruption, fibrosis, and mucus hypersecretion.13, 22-25 Thisadaptive immune response continues in the peripheral airways of patients with COPD even after smoking cessation.26 Genetic susceptibility to oxidative
stress induced by cigarette smoke may also explain why some smokers develop COPD and others do not. Smokers who develop COPD appear to have a higher degree of oxidative stress than those with a similar smoking history but no evidence of COPD.26
Although bronchial inflammation characterizes both COPD and asthma, the pathogenic inflammatory processes of these diseases differ significantly (Table 1).13 The characteristic physiologic abnormality in asthma is eosinophilic inflammation; indeed, an increase in activated and degranulating eosinophils has been demonstrated in bronchial biopsies and bronchoalveolar lavage of asthma patients.5,13 Unlike the neutrophil and CD8-
lymphocyte predominance in COPD, CD4+ lymphocytes orchestrate an eosinophilic inflammation and mast cell degranulation that characterize the bronchoconstrictor responses
in acute asthma. In addition, IgE antibodies have been linked to the initiation and persistence of airway responses to allergens.
inflammation, and many patients with asthma have characteristics of COPD, an overlap that often makes it difficult to establish an accurate diagnosis (Figure 2).
Indeed, the similarities betweenincluding tobacco smoke (either due to directly smoking or from second-hand smoke), or through occupational exposure to coal dust, asbestos, and chemicals.8,15 Because the majority of diagnosed COPD is related to tobacco exposure,
there has been considerable work to define the link between tobacco smoke and ongoing airway and parenchymal remodeling. Multiple pathogenic mechanisms likely contribute to the development of COPD (see below). In addition, since only 20% of smokers acquire COPD, genetic predisposition seems to play an important role in the pathogenesis of this disease.15 For example, patients with a genetic deficiency in alpha 1-antitrypsin are prone to
develop early-onset emphysema. Another important factor linking smoking to inflammation may be oxidative stress induced by oxidants found in cigarette smoke; reactive oxygen species such as superoxide anions and hydrogen peroxide generated as a consequence
of oxidative stress can propagate the inflammatory response by activating several redox-sensitive transcription factors (e.g., NF-kappa B and activated protein 1 [AP-1]) that can
upregulate expression of a number of proinflammatory cytokines.20,21 These cytokines
can trigger and propagate an inflammatory cascade as shown in Figure 3.22
Cigarette smoke
induces epithelial cells and alveolar macrophages to release tumor necrosis factor-a (TNFa),
which in turn, increases production of interleukin 8 (IL-8); both of these cytokines are potent
chemoattractants that cause an influx of monocytes, neutrophils and CD8 lymphocytes. These cells, when acted upon by proinflammatory cytokines, are stimulated to release proteinases that contribute to alveolar septal disruption, fibrosis, and mucus hypersecretion.13, 22-25 Thisadaptive immune response continues in the peripheral airways of patients with COPD even after smoking cessation.26 Genetic susceptibility to oxidative
stress induced by cigarette smoke may also explain why some smokers develop COPD and others do not. Smokers who develop COPD appear to have a higher degree of oxidative stress than those with a similar smoking history but no evidence of COPD.26
Although bronchial inflammation characterizes both COPD and asthma, the pathogenic inflammatory processes of these diseases differ significantly (Table 1).13 The characteristic physiologic abnormality in asthma is eosinophilic inflammation; indeed, an increase in activated and degranulating eosinophils has been demonstrated in bronchial biopsies and bronchoalveolar lavage of asthma patients.5,13 Unlike the neutrophil and CD8-
lymphocyte predominance in COPD, CD4+ lymphocytes orchestrate an eosinophilic inflammation and mast cell degranulation that characterize the bronchoconstrictor responses
in acute asthma. In addition, IgE antibodies have been linked to the initiation and persistence of airway responses to allergens.
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