Increased carbon monoxide in exhaled air of patients with cystic fibrosis

Background-Inflammation, oxidative stress, and recurrent pulmonary infectio ns are major aggravating factors in cystic fibrosis. Nitric oxide (NO), a m arker of inflammation, is not increased, however, probably because it is me tabolised to peroxynitrite. Exhaled carbon monoxide (CO), a product of heme degradation by heme oxygenase 1 (HO-1) which is induced by inflammatory cy tokines and oxidants, was therefore tested as a noninvasive marker of airwa y inflammation and oxidative stress. Methods-Exhaled CO and NO concentrations were measured in 29 patients (15 m en) with cystic fibrosis of mean (SD) age 25 (1) years, forced expiratory v olume in one second (FEV,) 43 (6)%, 14 of whom were receiving steroid treat ment. Results-The concentration of exhaled CO was higher in patients with cystic fibrosis (6.7 (0.6) ppm) than in 15 healthy subjects (eight men) aged 31 (3 ) years (2.4 (0.4) ppm, mean difference 4.3 (95% CI 2.3 to 6.1), p < 0.001) . Patients not receiving steroid treatment had higher CO levels (8.4 (1.0) ppm) than treated patients (5.1 (0.5) ppm, mean difference 3.3 (95% CI -5.7 to -0.9), p < 0.01). Normal subjects had higher NO levels (6.8 (0.4)ppb) t han patients with cystic fibrosis (3.2 (0.2) ppb, mean difference 3.8 (95% CI 2.6 to 4.9), p < 0.05) and were not influenced by steroid treatment (3.8 (0.4) ppb and 2.7 (0.3) ppb for treated and untreated patients, respective ly, mean difference 0.8 (95% CI -0.6 to 2.3), p > 0.05). Patients homozygou s for the Delta F508 CFTR mutation had higher CO and NO concentrations than heterozygous patients (CO: 7.7 (1.8)ppm and 4.0 (0.6) ppm, respectively, m ean difference 3.7 (95% CI -7.1 to -0.3), p < 0.05; NO: 4.1 (0.5) ppb and 1 .9 (0.7) ppb, respectively, mean difference 2.2 (95% CI -3.7 to -0.6), p < 0.05). Conclusions-High exhaled CO concentrations in patients with cystic fibrosis may reflect induction of HO-1. Measurement of exhaled CO concentrations ma y be clinically useful in the management and monitoring of oxidation and in flammatory mediated lung injury.