Biomedical Engineering Reference
In-Depth Information
smoke-mediated redox cycling, has lead to concerns over its reproducibility
as a marker for oxidative stress in smokers and in patients with COPD (28).
The level of oxidative biomarkers in EBC can also be affected by diurnal
variation and age (25-27).
B. Reactive Nitrogen Species and Carbon Monoxide
Exhaled NO has been used as a marker of airway inflammation and indir-
ectly as a measure of oxidative stress. There have been some reports of
increased levels of NO in exhaled breath in patients with COPD, but not
to the extent reported in asthmatics (25,29). Although another study failed
to confirm this result (30), smoking increases NO levels in breath and the
reaction of NO with O
2
-
(which forms ONOO
) limits the usefulness of this
marker in COPD, except perhaps to differentiate from asthma.
Carbon monoxide (CO) is another biomarker of oxidative stress which
is generated by the induction of the stress responsive protein heme oxyge-
nase-1 (HO-1). HO-1 breaks heme to biliverdin which is converted into bilir-
ubin by biliverdin reductase with the release of CO and Fe. Bilirubin has
antioxidant properties whereas CO has been shown to be cytoprotective.
The release of CO can be measured in exhaled breath and has been shown
to be elevated in patients with COPD (31). Cigarette smoking increases the
formation of RNS and results in nitration and oxidation of plasma proteins.
The levels of nitrated proteins (fibrinogen, transferrin, plasminogen, and
ceruloplasmin) were higher in smokers (32) compared to non-smokers.
Nitric oxide and ONOO-mediated formation of 3-nitrotyrosine in plasma
and free catalytic iron (Fe
2
รพ
) levels in epithelial lining fluid (ELF) are ele-
vated in chronic smokers (33-35). Furthermore, the levels of nitrotyrosine
and inducible nitric oxide synthase (iNOS) were higher in airway inflamma-
tory cells obtained by induced sputum from patients with COPD, compared
to those with asthma (35). The levels of nitrotyrosine were negatively corre-
lated with the FEV
1
%. A recent study by Kanazawa et al. (34) has shown
that increased levels of nitrogen oxides and reduced peroxynitrite inhibitory
activity were present in induced sputum from patients with COPD. Simi-
larly, Ichinose et al. (33) have shown increased immunostaining of nitrotyr-
osine and iNOS in airway inflammatory cells obtained from induced sputum
in patients with COPD without any change in exhaled NO. They also
showed a significant negative correction between the FEV
1
and the amount
of nitrotyrosine formation in subjects with COPD. The increased level of
RNS was inhibited following steroid therapy in patients with COPD, and
the reduction in nitrotyrosine and iNOS immunoreactivity in sputum cells
was correlated with the improvement in FEV
1
and airway responsiveness
to histamine (35). These direct and indirect studies indicate that an increased
RNS- and ROS-mediated protein nitration and lipid peroxidation, respec-
tively, may play a role in the inflammatory response which occurs in COPD.
