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. 1998 Aug;53(8):668–672. doi: 10.1136/thx.53.8.668

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

I Horvath 1, L Donnelly 1, A Kiss 1, P Paredi 1, S Kharitonov 1, P Barnes 1
PMCID: PMC1745300  PMID: 9828853

Abstract

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 2.80to 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.



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Selected References

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