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

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 2.80 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. (Thorax 1998;53:668-672)

Regulation of IL-1β-induced GM-CSF production in human airway smooth muscle cells by carbon monoxide

“…Increased levels of CO have been detected in the breath of asthmatics (14). We previously reported that CO can markedly attenuate aeroallergen-induced airway inflammation (5).…”

“…Several laboratories also detected elevated levels of CO in the breath of patients with asthma (14). The physiological function of HO-1 and CO in the pathogenesis of asthma remains unknown.…”

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

“…This study has provided most direct in vivo evidence that PM induce ROS generation and cause oxidative tissue damage. In humans, experimental DEP exposures result in increased CO in exhaled air; CO is the catalytic product of HO-1, which acts as a sensitive marker for PM-induced oxidative stress [69][70][71][72].…”

Carbon monoxide in biological systems: an experimental and clinical study

“…Individuals with asthma have an increased level of CO in their exhaled air (Horvath et al, 1998). In a culture of human airway smooth muscle cells, addition of CO inhibited cell proliferation.…”