Ventilatory control sensitivity in patients with obstructive sleep apnea is sleep state dependent.

Abstract

Rationale: It is well known that changes in sleep-state influence the predisposition to obstructive sleep apnea (OSA). Specifically, the severity of OSA in many patients tends to worsen during rapid-eye movement (REM) sleep, whereas if patients can achieve slow wave sleep (i.e. non-rapid eye movement [NREM] sleep - stage N3) they typically demonstrate periods of prolonged stable breathing. Recent work has shown that several of the key pathological traits (upper airway collapsibility and muscle responsiveness, arousal threshold) known to cause OSA vary with sleep state. However, as yet no study has examined whether an individual's dynamic ventilatory control stability (i.e. loop gain) is altered by sleep state in patients with OSA. Method(s): To date, 32 OSA patients were studied with standard diagnostic polysomnogram. Loop gain was estimated from spontaneous breathing using 7 minute windows of NREM and REM sleep containing at least one respiratory event. Square root transformed nasal pressure airflow was used to provide a surrogate of ventilation. A standard model of ventilatory control (gain, time-constant, delay) that best matched ventilation data during periods of unobstructed breathing was used to estimate loop gain. NREM and REM loop gains were calculated as the mean loop gain for all windows that had spent >50% in NREM and REM sleep respectively. Paired comparisons were also performed to assess for differences within the different stages (N2 and N3) of NREM sleep. Result(s): Overall, loop gain was elevated in NREM compared to REM sleep (0.56+/-0.02 vs. 0.46+/-0.02; p<0.0001). When comparing REM with the sub-stages of NREM, loop gain was found to be higher in N2 versus REM (0.60+/-0.03 vs. 0.45+/-0.02, N=32, p<0.0001) whereas no statistical difference was observed between N3 and REM in the subset of 21 patients that had paired measurements in these states (0.60+/-0.03 vs. 0.45+/-0.02, N=21, p=0.09). When assessing the within NREM stage difference, we found that loop gain was higher in N2 versus N3 sleep (0.62+/-0.03 vs. 0.53+/-0.04; N=32, p=0.01). Conclusion(s): Our data demonstrate that ventilatory control stability varies with depth of sleep. Importantly, these data provide further evidence of mechanisms underlying the reduced OSA severity typically observed during slow wave sleep. Furthermore, the finding of a reduced loop gain in REM suggested that it is unlikely to contribute to the worsened OSA severity typically observed in REM sleep, but may in part, explain why respiratory events are typically of a longer duration in this state.