Estimating Apnea Phenotypes From Polysomnography: Oxygen

Not Applicable

Completed

Brief Summary: This study seeks to employ advanced methods to estimate the individual factors contributing to sleep apnea from standard recordings made during routine clinical sleep studies. This study focuses on breathing control or "loop gain" as one of the factors contributing to sleep apnea. Increased levels of oxygen in the air is known to make breathing more stable by lowering "loop gain". Here, our goal is to use a new method capable of detecting a reduction in loop gain with oxygen. The investigators also aim to test whether a high loop gain measured at baseline/placebo predicts a greater improvement in sleep apnea with oxygen therapy.

Detailed Description: In a single-blinded randomized crossover study, inspired oxygen/air (40%/21%) is delivered on two separate nights. Loop gain is measured from routine polysomnography using a novel mathematical method. A value of loop gain \>1 reflects unstable breathing, and a value less than but approaching 1 denotes a system more prone to oscillate. Loop gain is measured as the changes in ventilatory drive/effort that arises subsequent to changes in ventilation (e.g. due to obstructive apnea). A simple chemoreflex model (gain, time constant, delay) is fit to surrogate ventilation data (derived from airflow) during sleep. The best model is one that best matches the elevated ventilatory drive (measured as ventilation in the absence of airflow obstruction) based on the prior apneic/hypopneic fall in ventilation. Loop gain is calculated from this model. We aim to use loop gain measured on and off oxygen to determine whether a strong response (reduction in apnea severity) can be predicted by a higher loop gain (in the sham arm) using our method. We also assessed whether assessing upper airway anatomy/collapsibility, dilator muscle responsiveness, and the arousal threshold helped to predict responses to treatment.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Inspired Oxygen First	Inspired oxygen (40%)	Participants breathe air with additional inspired oxygen (40%) for 1 night during an overnight sleep study (15 L/min via venturi mask). 1 week later participants will crossover to Sham (sham comparator).
Sham First	Inspired oxygen (40%)	Participants breathe air without additional inspired oxygen for 1 night during sleep (15 L/min via Venturi mask). 1 week later participants will crossover to Inspire Oxygen (active intervention).
Inspired Oxygen First	Sham	Participants breathe air with additional inspired oxygen (40%) for 1 night during an overnight sleep study (15 L/min via venturi mask). 1 week later participants will crossover to Sham (sham comparator).
Sham First	Sham	Participants breathe air without additional inspired oxygen for 1 night during sleep (15 L/min via Venturi mask). 1 week later participants will crossover to Inspire Oxygen (active intervention).

Primary Outcome Measures

Name	Time	Method
Apnea-hypopnea Index	1 night	Apnea-hypopnea index (AHI) will be compared between oxygen and sham nights. Hypopneas are based on 30% reduction in airflow (no desaturation or arousal criteria). AHI data are exclusive to non-REM supine sleep. The results presented here are for the AHI at each intervention ("per intervention") regardless of the sequence (preferred clinicaltrials.gov format). Please note, however, that the a priori outcome measure was the reduction in AHI with oxygen as a percent of sham values, i.e. (AHI on sham - AHI on oxygen)/(AHI on sham) % (a comparison with greater statistical power), compared between patient subgroups (see Statistical Analysis section). Subgroups were defined a priori as higher (\>=0.7) versus lower loop gain (\<0.7), but tests were also performed in subgroups defined by "favorable" versus "unfavorable" pathophysiology.

Secondary Outcome Measures

Name	Time	Method
Overnight Change in Diastolic Blood Pressure	1 night	The change in diastolic blood pressure overnight. Two supine oscillometric measurements of blood pressure are made: just prior to lights out (evening), and after lights on (morning).
Overnight Change in Systolic Blood Pressure	1 night	The change in systolic blood pressure overnight. Two supine oscillometric measurements of blood pressure are made: just prior to lights out (evening), and after lights on (morning).
Frequency of EEG Arousals (Events Per Hour)	1 night	Frequency of scored EEG arousals per hour of non-REM sleep. Note: Our objective was to describe changes in secondary outcomes within phenotypic subgroups. Overall effects (unselected patients / ignoring phenotypic subgroups) are first presented below, followed by effects in favorable vs. unfavorable subgroups.
Subjective Sleep Quality (Oxygen vs Sham)	1 night	Better(+1)/Same(0)/Worse(-1) on oxygen vs sham, i.e. "a relative comparison between arms". When subjects had completed the entire study, they were asked to compare subjectively their sleep quality on the first versus second study.
Subjective Sleepiness/Alertness (Stanford Sleepiness Scale)	1 night	Assessed in the morning after the single night of treatment. Minimum score: 1 (alert), maximum score: 7 (not alert).