Biomedical Engineering Reference
In-Depth Information
as lipid proteins or DNA, or by measuring the stress responses to the
increased oxidant burden. Hydrogen peroxide in breath condensate is a
direct measurement of airspace oxidant burden, and is detected in higher
levels in patients with COPD than in normal subjects, and is present even
in higher levels during exacerbations of COPD (72).
Oxidative stress may exacerbate COPD through several mechanisms,
including the activation of the transcription factor, NF-
k
B, which switches
on the genes for TNF-
a
, interleukin-8, and other inflammatory proteins, and
oxidative damage of antiproteases, such as
a
1
-antitrypsin and secretory leu-
koprotease inhibitor, thus enhancing inflammation and proteolytic injury.
Smoking produces a fall in alveolar and lung glutathione (GSH) metabo-
lism, which are widely recognized as a central feature of COPD. It has been
demonstrated that the severity of airway obstruction, as measured by FEV
1
in smokers with COPD, correlated negatively with the concentration of
GSH in BALF: the higher the BALF GSH, the lower the FEV
1
(72).
Patients with acute exacerbations of COPD show increased production of
superoxide anion from their peripheral blood neutrophils compared with
the measurement in stable patients. Products of lipid peroxidation are signif-
icantly increased in plasma or BALF in healthy smokers and patients with
acute exacerbations of COPD, compared with healthy nonsmokers (72). It
has been demonstrated that the severity of airway obstruction, as measured
by FEV
1
in smokers with COPD, correlated negatively with the concentra-
tion of GSH in BALF: the higher the BALF GSH, the lower the FEV
1
(72).
The GSH concentration in BALF from patients with COPD was similar to
that in chronic smokers with no airflow obstruction. This emphasizes the
effects of smoking on GSH metabolism rather than reflecting the disease
severity in the COPD patients. The actual relevance of these studies in the
lungs of these patients is not known. It is possible that BALF GSH levels
are influenced by the recent smoking of these patients. Finally, the levels
of the antioxidant capacity in the plasma negatively correlate with the
increased release of oxygen radicals, from circulating neutrophils in patients
with exacerbations of COPD, suggesting, at least in part, that the systemic
oxidative stress in this condition derives from reactive oxygen species (73).
Exposure to cigarette smoke is reported to induce goblet cell metaplasia
and mucus production (74), but the mechanism is still unknown. Recently,
mucin synthesis in airways has been reported to be regulated by the epider-
mal growth factor receptor (EGFR) system. In particular, the exposure of
airway epithelial cells to cigarette smoke upregulates EGFR expression
and activates EGFR tyrosine phosphorylation, causing mucin synthesis in
epithelial cells (75). The mechanisms by which cigarette smoke induces
EGFR activation are not completely defined (75). However, it has been
recently observed that cigarette smoke is able to transactivate EGFR
stimulating the transmembrane metalloproteinase TNF
a
converting
enzyme (TACE) or a disintegrin and metalloproteinase (ADAM) -17. This
