Low Plasma Orexin-A Levels Were Improved by Continuous Positive Airway Pressure Treatment in Patients With Severe Obstructive Sleep Apnea-Hypopnea Syndrome

Abstract

We have previously shown that plasma levels of orexin-A, a neuropeptide with an arousal-stimulating action, were decreased in parallel with the severity of the disease in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). To clarify the effects of nasal continuous positive airway pressure (nCPAP) treatment on plasma orexin-A levels in patients with this syndrome. Sleep tests and blood sample collections were conducted at the sleep-related respiratory disorders clinic and the sleep laboratory of the Iwate Medical University Hospital. We studied 27 patients with OSAHS (apnea-hypopnea index [AHI], >/= 20 by polysomnography) who were treated with nCPAP for 3 to 6 months. These patients were divided into the following two groups according to the arousal index (AI): group A (n = 11), >/= 60; group B (n = 16), < 60. Plasma samples were obtained before and after the nCPAP treatment for 3 to 6 months. Plasma immunoreactive (IR)-orexin-A concentrations were measured by radioimmunoassay after the extraction using cartridges. Plasma IR-orexin-A concentrations were inversely correlated with the AI (r = -0.807; p < 0.0001) and AHI (r = -0.661; p < 0.0001) in 27 patients before the nCPAP treatment. Mean (+/- SEM) plasma IR-orexin-A concentrations were significantly lower in group A (1.0 +/- 0.3 pmol/L) than in group B (4.6 +/- 0.4 pmol/L). Mean plasma IR-orexin-A concentrations were significantly increased after the nCPAP treatment in group A (to 3.4 +/- 1.2 pmol/L; p = 0.0069), whereas they were not significantly changed in group B. The increases in plasma IR-orexin-A concentrations after the nCPAP treatment were in parallel with the improvements in AI and Epworth sleepiness scale (a marker of severity of daytime excessive sleepiness) score in group A. The low plasma orexin-A levels were increased by the nCPAP treatment in patients with severe OSAHS, suggesting that orexin-A is a plasma marker that reflects the severity of OSAHS and the response to treatment.