Ventilatory Burden Predicts Change in Sleepiness Following Positive Airway Pressure in Sleep Apnea

Rationale Excessive daytime sleepiness, an important symptom of obstructive sleep apnea (OSA), is commonly quantified using the Epworth Sleepiness Scale score (ESS). Baseline OSA severity measures (ventilatory burden, flow limitation, and hypoxemia) provide insights into OSA pathophysiology and could predict changes in sleepiness (i.e. change-in-ESS) following continuous positive airway pressure (CPAP) treatment. Objectives We hypothesized that change-in-ESS following CPAP treatment can be predicted from baseline polysomnography. Methods Associations between OSA severity measures and ESS were evaluated in 2332 participants, adjusting for age, sex, BMI, and total sleep time. Change-in-ESS prediction was evaluated using 213 CPAP treatment studies (HomePAP, BestAIR, and ABC) in three steps: severity measures were compared (adjusted regression, n =64), a prediction model was developed using baseline ventilatory burden and baseline ESS ( n =139), and then evaluated in holdout participants ( n =74). Measurements and Main Results In cross-sectional analysis, ESS was associated with ventilatory burden (0.45 points/SD; 95% CI 0.23−0.67), hypoxic burden (0.39; 0.17−0.62), the apnea-hypopnea index (AHI) (0.36; 0.14−0.59), and flow limitation severity (0.22; 0.01−0.43). Comparison analysis revealed that change-in-ESS was most strongly associated with baseline ventilatory burden (-1.08 points/SD; -2.13 to -0.05) and baseline ESS (-2.75; -3.83 to -1.69); the AHI association was weaker (-0.97; -2.01−0.05). Predicted change-in-ESS and actual change-in-ESS were correlated in holdout participants (adjusted R² =0.313); median [IQR] actual change-in-ESS of predicted responders (≥2-point ESS improvement, n =54, 73.0%) was -5.0 [-10.0 to -2.0] and non-responders was 0.0 [-1.0−1.0] ( P <0.001). Conclusions Baseline ventilatory burden and baseline ESS were independently associated with change-in-ESS and could be used together to inform clinicians whether CPAP treatment will likely improve a patient’s sleepiness.