Biomedical Engineering Reference
In-Depth Information
XIV. OXIDATIVE STRESS AND THE DEVELOPMENT
OF AIRWAYS OBSTRUCTION
The neutrophil appears to be a critical cell in the pathogenesis of COPD.
Previous epidemiological studies have shown a relationship between circu-
lating neutrophil numbers and the FEV
1
(1,21). Moreover, a relationship
has also been shown between the change in peripheral blood neutrophil
count and the change in airflow limitation over time. A relationship between
peripheral blood neutrophil luminol enhanced chemiluminescence, as a
measure of the release of ROS and measurements of airflow limitation
has been shown in young cigarette smokers. Oxidative stress, measured as
lipid peroxidation products in plasma, has also been shown to correlate
inversely with the % predicted FEV
1
in a population study (74).
It is possible that inter-individual differences in antioxidant capacity
may contribute to the differences in the susceptibility against cigarette
smoke-induced COPD. In the general population, there is a positive associa-
tion between dietary intake of antioxidant vitamins and lung function. Epi-
demiological studies have demonstrated negative associations of dietary
antioxidant intake with pulmonary function and with obstructive airway
disease (75). Britton et al.(76), in a population of 2633 subjects, showed a
positive association between dietary intake of the antioxidant vitamin E
and lung function, supporting the hypothesis that this antioxidant may have
a role in protecting against the development of COPD. Another study has
suggested that antioxidant levels in the diet could be a possible explanation
for differences in COPD mortality in different populations (77). Dietary
polyunsaturated fatty acids may protect cigarette smokers against the devel-
opment of COPD (78). These studies support the concept that dietary anti-
oxidant supplementation including polyphenols may be a possible therapy
to prevent or inhibit the oxidative stress and inflammatory response which
are the key features in the development of COPD. Such interventional stu-
dies have been difficult to carry out but there is at least some evidence to
suggest that antioxidant vitamin supplementation reduces oxidant stress in
smokers, measured as a decrease in pentane levels in breath as an indication
of lipid peroxides in the airways (38).
XV. OXIDATIVE STRESS AND SUSCEPTIBILITY TO COPD
Only 15-20% of cigarette smokers appear to be susceptible to the effects of
cigarette smoke. These subjects show a rapid decline in FEV
1
and develop
COPD. There has been considerable interest in identifying those who are
susceptible and the mechanisms of that susceptibility (79), since this would
provide an important insight into the pathogenesis of COPD as did the
recognition of the association between
a
1
-antitrypsin and COPD.
