Circadian Variation in Exhaled Nitric Oxide in Nocturnal Asthma

Abstract

Asthma is characterized by airway inflammation and shows a circadian variation with nocturnal exacerbations. Because exhaled nitric oxide (ENO) measurement appears to be a noninvasive marker of airway inflammation, we examined the hypothesis that ENO would increase at night. In five nocturnal and five 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 (mean pre- and post-bronchodilator +/- SEM, ppb) unexpectedly fell significantly 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 significant difference between 10 P.M. and 4 A.M.. In contrast, there were no significant differences in mean ENO at 4 P.M., 10 P.M., and 4 A.M. in non-nocturnal 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 the nocturnal asthma group alone. The circadian rhythm of ENO differed greatly 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, which in view of its bronchodilator action, could play a role in nocturnal exacerbations of asthma.

Across-shift changes of exhaled nitric oxide and spirometric indices among cotton textile workers

“…Some studies have shown these circadian changes [39], although some others, such as Antosova et al, have shown that FeNO levels are similar at 6 a.m. and 2 p.m. So this circadian rhythm seems to have had a minimal effect in our study [40][41][42]. We didn't assess the history of atopy in our subjects.…”

Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms

“…TEN HACKEN et al [24] found a higher exhaled NO level in nocturnal asthmatics than in non-nocturnal asthmatics at a single higher exhalation flow rate (167 mL?s -1 ), whereas GEORGES et al [25] did not find a significant difference in exhaled NO between such groups by using a lower exhalation flow rate (80 mL?s -1 ). Exhaled NO concentration at a single exhalation flow rate is a sum of both alveolar and bronchial NO sources, where bronchial NO predominates at lower flow rates while the contribution of alveolar NO increases with increasing flow rates [12].…”

Nocturnal asthma: underlying mechanisms and treatment

“…Although eNO levels were higher at 4 AM than at 4 PM, the authors were unable to demonstrate a true circadian rhythm in eNO levels in nocturnal asthmatics [11]. A subsequent study by Georges et al [12], however, found a circadian variation in eNO in subjects with nocturnal asthma, with nocturnal asthmatics demonstrating a significant circadian decrease in levels, which were 77.2 ± 8.2 ppb at 4 PM, 68.4 ± 8.7 ppb at 10 PM (P < 0.003), and 66.0 ± 8.5 ppb at 4 AM (P < 0.001) [12]. Previous studies had demonstrated that eNO could decrease in the setting of bronchoconstriction [13], but when the authors adjusted for changes in FEV 1 in a mixed-model analysis, only a portion of the decrease in eNO could be attributed to bronchoconstriction.…”