Asthma is characterized by airway inflammation and shows a circadian variat
ion with nocturnal exacerbations. Because exhaled nitric oxide (ENO) measur
ement appears to be a noninvasive marker of airway inflammation, we examine
d the hypothesis that ENO would increase at night. In five nocturnal and fi
ve non-nocturnal asthmatics, ENO was measured at 4 P.M., 10 P.M., and 4 A.M
. before and after bronchodilator. Both pre- and post-bronchodilator ENO (m
ean pre- and post-bronchodilator +/- SEM, ppb) unexpectedly fell significan
tly in nocturnal asthma from 4 P.M. (77.2 +/- 8.2) compared to 10 P.M. (68.
4 +/- 8.7, p < 0.003) and 4 A.M. (66.0 +/- 8.5, p < 0.001) with no signific
ant difference between 10 P.M. and 4 A.M.. In contrast, there were no signi
ficant differences in mean ENO at 4 P.M., 10 P.M., and 4 A.M. in non-noctur
nal asthma. (51.3 +/- 10.8, 57.7 +/- 13.4, 53.8 +/- 12.5 ppb, respectively)
. Following bronchodilator, ENO rose significantly by 10.5 +/- 1.8 ppb in t
he nocturnal asthma group alone. The circadian rhythm of ENO differed great
ly between nocturnal and non-nocturnal asthma. The significant decrease in
ENO in nocturnal asthma may reflect an important chronobiological defect in
the endogenous production and/or increased disposition of nitric oxide, wh
ich in view of its bronchodilator action, could play a role in nocturnal ex
acerbations of asthma.