Response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient's therapeutic CPAP requirement

Abstract

Background and objective: Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.

Methods: Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (P_crit ) and ventilation at CPAP level of 0 cmH₂ O (V_passive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHI<15 events/h on-therapy.

Results: Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH₂ O vs 8.9 (8.4-10.4) cmH₂ O, P = 0.007), consistent with their reduced collapsibility (lower P_crit , P = 0.017, higher V_passive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both P_crit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and V_passive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH₂ O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.

Conclusion: Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and eszopiclone) for OSA.

Trial registration: ClinicalTrials.gov NCT01633827.

Keywords: continuous positive airway pressure; obstructive sleep apnoea; personalized medicine; phenotyping; upper airway collapsibility.

Figure 1. Therapeutic CPAP levels are lower and predict response to the combination of oxygen and a hypnotic

(A) Individual therapeutic CPAP values for both groups. Responders (R, circles) had significantly lower CPAP requirements compared to Non-responders (Non-R, squares). (B) Receiver Operating Characteristic (ROC) curve indicates therapeutic CPAP level had ‘good’ predictive accuracy for determining responder status (AUC=0.86±0.9, 95%CI: 0.68–1.00, p=0.007).