Biomedical Engineering Reference
In-Depth Information
pulmonary microcirculation in smokers and in patients with COPD, since
neutrophils which are sequestered in the pulmonary microcirculation in
animal models of lung inflammation release more ROS than circulating
neutrophils (1).
Superoxide anion and H
2
O
2
can be generated by the xanthine
=
xanthine oxidase (XO) reaction. XO activity has been shown to be increased
in cell free BAL fluid and plasma from COPD patients, compared to normal
subjects; and this has been associated with increased O
2
-
and lipid peroxide
levels (24).
VIII. REACTIVE OXYGEN AND REACTIVE NITROGEN SPECIES
AS SURROGATE MARKERS IN PLASMA AND EXHALED
BREATH CONDENSATE
Interest is growing in identifying biomarkers for diseases in which oxidative
stress is involved. Direct measurements of oxidative stress are difficult since
ROS
=
free radicals are highly reactive and also short lived. An alternative has
been to measure markers of the effects of radicals on lung biomolecules such
as lipids, protein or DNA, or to measure the stress responses to an increased
oxidant burden. Various invasive and semi-invasive means of assessing these
oxidative biomarkers are available. Recent studies have focused on applying
non-invasive techniques to evaluate oxidative stress in COPD. Measure-
ments of these surrogate markers have been made in blood, urine, breath
or breath condensate or in induced or spontaneously produced sputum of
smokers and patients with COPD. The assessment of oxidative stress bio-
markers in exhaled breath condensate (EBC) is emerging as a promising area
of future research in COPD (25-27). The relative concentrations of various
oxidant
=
antioxidant biomarkers detected in EBC are listed in Table 2
(reviewed in Refs. 25-27). There is, however, a limitation of ROS
=
RNS bio-
markers at present due to the lack of correlation with disease severity or out-
come. Furthermore, the validity of EBC as a tool for the assessment of
airway oxidative stress is still questionable owing to limitations in the repro-
ducibility of analyzed oxidative biomarkers, with respect to intra- and inter-
individual variability, sampling time and variability in dilution of respiratory
droplets by water vapor, sensitivity, and specificity of the assays used. Other
confounding factors contributing to variation include smoking, consumption
of caffeine, alcohol, and intake of diet rich in antioxidants. Identification of
specific and reproducible biomarkers of oxidative stress and inflammation in
EBC would be of great value for non-invasive investigations of the natural
history and epidemiology of COPD, and for phenotyping in genetic studies.
A. ROS
Hydrogen peroxide, measured in exhaled breath condensate (EBC), is a
direct measurement of oxidant burden in the airspaces. The source of
