Endogenous nitric oxide in expired air: time-dependent effects of methylprednisolone in asthmatics

Expired nitric oxide (NO) is elevated in asthmatics, but the significance and clinical value of this phenomenon is unknown. We examined expired NO in 5 untreated mild asthmatics before and after the first and eighth daily systemic dose of methylprednisolone (MP, 20 mg). Plasma cortisol, blood CD4+ cells, and peak expired (low rates (PEFR) were also measured. A baseline phase showed that expired NO and total blood CD4+ cells were reproducible and stable over a 14 hr period, whereas plasma cortisol exhibited a normal circadian pattern. The first intravenous MP dose caused a transient elevation of expired NO concentrations, marked reductions in plasma cortisol and blood CD4+ cells, and slight improvement in PEFR. Before the 8th daily MP dose expired NO concentrations were reduced by 52 7% when compared ta the baseline phase and plasma cortisol was lowered by 91 ±5%; the responses in CD4+ cells and PEFR were unchanged. Expired NO did not temporally correspond with any other measured parameter and time-averaged changes (concentration or effect areas from 0-12 hr) were not statistically correlated. These findings suggest that expired NO is elevated in mild asthmatics and that inhibition by steroids is probably mediated via a slow (i.e., gene related) process, such as blocking induction of NO synthase. Changes in expired NO after steroid apparently do not reflect other systemic steroid actions, but may serve as a marker of local pulmonary events. Supported in part by NIH grant GM24211 and a Sandoz Pham Res Fellowship awarded to MAM.