Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea

Abstract

Study objectives: Precision medicine for obstructive sleep apnea (OSA) requires noninvasive estimates of each patient's pathophysiological "traits." Here, we provide the first automated technique to quantify the respiratory arousal threshold-defined as the level of ventilatory drive triggering arousal from sleep-using diagnostic polysomnographic signals in patients with OSA.

Methods: Ventilatory drive preceding clinically scored arousals was estimated from polysomnographic studies by fitting a respiratory control model (Terrill et al.) to the pattern of ventilation during spontaneous respiratory events. Conceptually, the magnitude of the airflow signal immediately after arousal onset reveals information on the underlying ventilatory drive that triggered the arousal. Polysomnographic arousal threshold measures were compared with gold standard values taken from esophageal pressure and intraoesophageal diaphragm electromyography recorded simultaneously (N = 29). Comparisons were also made to arousal threshold measures using continuous positive airway pressure (CPAP) dial-downs (N = 28). The validity of using (linearized) nasal pressure rather than pneumotachograph ventilation was also assessed (N = 11).

Results: Polysomnographic arousal threshold values were correlated with those measured using esophageal pressure and diaphragm EMG (R = 0.79, p < .0001; R = 0.73, p = .0001), as well as CPAP manipulation (R = 0.73, p < .0001). Arousal threshold estimates were similar using nasal pressure and pneumotachograph ventilation (R = 0.96, p < .0001).

Conclusions: The arousal threshold in patients with OSA can be estimated using polysomnographic signals and may enable more personalized therapeutic interventions for patients with a low arousal threshold.

Keywords: arousability; endotype; pathophysiology; personalized medicine.

Figure 1

Example illustration of arousal threshold estimation in patients with (A) high and (B) low arousal thresholds. Green circles illustrate values of the arousal threshold, i.e., the value of ventilatory drive that precedes (triggers) EEG arousal. Staircase traces illustrate breath-by-breath values of ventilation (blue) and model-based estimation of ventilatory drive (black); the model is best fit to ventilation between events (shaded blue). Note that the time course of the estimated ventilatory drive trace matches that of esophageal pressure and diaphragm EMG. SpO₂ = pulse oxygen saturation. EMGdi = diaphragm EMG (integrated). Pes = Esophageal pressure. High frequency EEG power is shown to corroborate clinically scored EEG arousals (shaded green; sigmoid transformed, arbitrary units). Eupneic ventilation (dashed line) is estimated from the mean ventilation in the window. Both examples are from supine non-REM sleep.

Figure 2

Our novel measure of arousal threshold correlates favorably with measures using esophageal pressure (A) and intraoesophageal diaphragm EMG (B) (N = 29). Here, our polysomnographic method was implemented using pneumotach-measured ventilation. Blue shading shows the standard error (dark) and SD (light) of the regression. Note that y-axis scales are broader than the x-axis scales indicating that the polysomnographic values are smaller than the gold standards. The width of the prediction interval (1.96 × SD) indicates agreement (95% confidence); 1.96 × SD of the difference between the regression prediction and the gold standard is (A) ±89% eupnea and (B) ±86% eupnea.

Figure 3

Our novel measure of arousal threshold compares favorably with that estimated using the CPAP drop technique (N = 28). Here, our polysomnographic method was implemented using nasal pressure (linearized, see Methods). Blue shading shows the standard error (dark) and SD (light) of the regression. Agreement (1.96 × SD) is given by ±52% eupnea.

Figure 4

Comparisons of our novel measures of arousal threshold taken using nasal pressure—a clinical surrogate of ventilation—and gold standard oronasal ventilation measured via a pneumotachograph (N = 11). Note the excellent correlations observed. Blue shading shows the standard error (dark) and SD (light) of the regression. Grey line shows the line of identity. Agreement (1.96 × SD) is given by ±24% eupnea. Note that two patients have data at x = 100, y = 100.