Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stress.
BACKGROUND
Chronic inflammatory diseases are associated with an increased production of oxidants. Induction of a stress protein, heme oxygenase (HO) HO-1, is a cytoprotective mechanism against oxidative cellular injury. HO-1 catabolises heme to bilirubin, free iron, and carbon monoxide (CO).


METHODS
Exhaled CO and sputum bilirubin levels were measured and HO-1 protein expression in airway macrophages was determined by Western blotting in asthmatic patients as levels of oxidants are raised in asthma and may induce HO-1.


RESULTS
Exhaled CO was significantly increased in 37 non-steroid treated asthmatic patients compared with 37 healthy subjects (5.8 (95% CI 5.20 to 6.39) ppm vs 2.9 (2.51 to 3.28) ppm; p < 0.0001) but was similar to normal in 25 patients who received corticosteroids (3.3 (95% CI 2.92 to 3.67) ppm; p > 0.05). In non-treated asthmatic patients more HO-1 protein was expressed in airway macrophages than in normal subjects. Bilirubin levels in induced sputum were also higher than in normal subjects. Inhalation of hemin, a substrate for HO, significantly increased exhaled CO from 3.8 (95% CI 2.80 to 4.87) ppm to 6.7 (95% CI 4.95 to 8.38 CI) ppm (p < 0.05) with a concomitant decrease in exhaled nitric oxide levels, suggesting an interaction between the two systems.


CONCLUSIONS
Increased exhaled CO levels and HO-1 expression may reflect induction of HO-1 which may be inhibited by steroids. Measurement of exhaled CO, an index of HO activity in non-smoking subjects, may therefore be clinically useful in the detection and management of asthma and possibly other chronic inflammatory lung disorders.
Horváth
I
I
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK.
Donnelly
L E
LE
Kiss
A
A
Paredi
P
P
Kharitonov
S A
SA
Barnes
P J
PJ
D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism*; D001663:Bilirubin / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D002248:Carbon Monoxide / Q000032:analysis*; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D018384:Oxidative Stress; D013183:Sputum / Q000737:chemistry
D015415:Biomarkers; D008565:Membrane Proteins; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001663:Bilirubin