D. Pratico et al., Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2 alpha III, an index of oxidant stress, AM J R CRIT, 158(6), 1998, pp. 1709-1714
Oxidative stress has been suggested as a potential mechanism in the pathoge
nesis of chronic obstructive pulmonary disease (COPD). It has been difficul
t to address this hypothesis because of the limitations of conventional ind
ices of lipid peroxidation in vivo. F-2-isoprostanes (iPs) are prostaglandi
n isomers formed by free radical dependent peroxidation of arachidonic acid
. Urinary iPF(2 alpha)-III is a relatively abundant iPs produced in humans.
In the present study, we investigated whether COPD is associated with enha
nced oxidative stress by measuring urinary levels of this compound. Urinary
excretion of iPF(2 alpha)-III was determined in 38 patients with COPD and
30 sex- and age-matched healthy control subjects. Levels of iPF(2 alpha)-II
I were significantly higher in patients with COPD (median, 84 pmol/mmol cre
atinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol/mmol
creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent
of age, sex, smoking history, or duration of the disease. An inverse relati
onship was observed with the level of PaO2 (r = -0.38, p = 0.019). Aspirin
treatment failed to decrease urinary levels of IPF2 alpha-III (102 +/- 8 ve
rsus 99.2 +/- 7.3 pmol/mmol creatinine), whereas Il-dehydro TxB(2) was sign
ificantly reduced (695 +/- 74 versus 95 +/- 10 pmol/mmol creatinine) (p < 0
.0001). Elevated levels of IPF2 alpha-III (median, 125 pmol/mmol creatinine
; range, 110 to 170) in five patients with COPD declined (median, 90 pmol/m
mol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in t
heir clinical condition resolved. increased urinary iPF(2 alpha)-III is con
sistent with the hypothesis that oxidative stress occurs in COPD. This prov
ides a basis for dose finding and evaluation of antioxidant therapy in the
treatment of this disease.