Restoring the Salivary Cortisol Awakening Response Through Nasal Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea

Abstract

Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.

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“…OS → Adrenal hormone alterations OS and resulting reduced cell energy can trigger stress hormone activation and altered regulation (cortisol supports glucose as a cell energy substrate) (Aschbacher et al, 2013;Ghiciuc et al, 2013;Joergensen et al, 2011;Kraemer et al, 2005;Schmoller et al, 2009). Brain cell death is amplified when cell energy depletion is coupled with glucocorticoids/ stress hormones (Sapolsky & Pulsinelli, 1985).…”

Salivary biomarkers of obstructive sleep apnea syndrome in children

“…We used salivary α‐amylase as a marker of ANS activity, and did not find evidence of autonomic dysregulation concomitant with HPA axis activation. However, it can be argued that the OSA children enrolled in this study were free of any of major adverse consequences of OSA .…”

“…Of note, salivary sampling strategies were stringently followed in the present study to prevent any of the typical confounders potentially associated salivary biomarker measurements . In addition, the HPA axis and ANS activities were studied by monitoring changes in the salivary biomarker daily trajectories and by calculating the AUC of their diurnal production, a more reliable approach than isolated single point sampling …”

“…Therefore, we did not find any evidence for perturbations in circadian clock or in circadian phenotype in children with OSA, as opposed to some reports in adults with OSA. 47,48 We used salivary a-amylase as a marker of ANS activity, 12,19,49 and did not find evidence of autonomic dysregulation concomitant with HPA axis activation. However, it can be argued that the OSA children enrolled in this study were free of any of major adverse consequences of OSA.…”

“…HPA axis activity dysregulation has been reported both in adults and children suffering from stress‐related illness: the sequential episodes of upper airway obstruction during sleep and the secondary arousals aiming to restore normal breathing could lead to alterations in the levels of cortisol, one of the major end products of the hypothalamus‐pituitary‐adrenal (HPA) axis . Although Malakasioti and cowokers in children and Karaka and coworkers in adults reported a reduction of morning serum cortisol in OSA syndrome, the available evidence to date does not provide clear indications as to whether severity‐dependent associations exist between OSA syndrome in children and HPA axis overall activity.…”