Changes in exhaled carbon monoxide and nitric oxide levels following allergen challenge in patients with asthma

Carbon monoxide is a product of haem degradation by haem oxygenase (HO), activated by inflammatory cytokines and oxidants. This study examined whether allergen challenge can increase exhaled CO levels, as a reflection of HO activation. Exhaled CO and nitric oxide, an expired gas also thought to reflect cytokine-induced airway inflammation, were measured in 15 atopic steroid-naive nonsmoking patients with asthma (13 males, aged 30+/-2 yrs) before and for up to 20 h after allergen challenge. Baseline CO (4.4+/-0.3 parts per million (ppm)) and NO (20.6+/-1.2 parts per billion (ppb)) levels were elevated in asthmatic as compared with nonsmoking normal volunteers (n = 37, 2.1+/-0.2 ppm and 7.0+/-0.1 ppb, respectively, p<0.05). In 10 patients with a dual response in the forced expiratory volume in one second (FEV1) there was a maximal increase in exhaled CO at 1 h (343+/-7.1%) and at 6 h (69+/-12%, p<0.01), followed by a maximal fall in FEV1 (28+/-9%, p<0.05) at 9 h, whereas the maximal NO increase was observed at 10 h (50.2+/-11.8%). The maximal increase in exhaled CO in single response patients (n = 5) was 30+/-2% during the early asthmatic reaction and 46.3+/-9.2% between 4 and 10 h, followed by a fall in FEV1 (9+/-3%, p>0.05) at 9 h, whereas exhaled NO was not significantly changed. In five patients exhaled CO was not attenuated by inhalation of increasing concentrations of histamine causing a 20% fall in FEV1 (PC20) or its subsequent relief by beta2-agonists. In conclusion, exhaled carbon monoxide is increased during the early and late asthmatic reactions independently of the change in airway calibre, while exhaled nitric oxide is increased only during the late reaction and follows the increase in carbon monoxide and fall in the forced expiratory volume in one second in time.