Developing quantitative physiological phenotypes of sleep apnea for epidemiological studies

Existing physiological databases have not been sufficiently detailed to provide relevant and important information for characterizing the pathophysiology of obstructive sleep apnea. Critical collapsing pressure (P
_CRIT
) is a standard method for determining upper airway patency during sleep, however is labor intensive and prohibits large-scale studies. Based on previously published data indicating R
_US
does not significantly vary between groups, our aim was to develop an approach to estimate the P
_CRIT
from airflow at atmospheric pressure (V
_atm
). In a dataset of 126 subjects, where P
_CRIT
and R
_US
were measured using standard techniques. We then determined the minimum sample size required to estimate the R
_US
mean and variance by utilizing a bootstrap procedure (30 times for n=3 to 126). We first estimated the minimum number of subjects needed for obtaining a group for a two-tailed (z=1.96) standard error for R
_US
in the population. Then in 75 individuals, quantitative estimates of airflow were obtained at atmospheric pressure. Using the estimated R
_US
and atmospheric, we determined an estimated P
_CRIT
(€P
_CRIT
). Bland-Altman plots were generated to determine the agreement between the measured P
_CRIT
and €P
_CRIT
. For the entire population the mean±SEM R
_US
was 23±1cmH
₂
O/L/s (±95% CI: 21, 25). ~40 subjects represent the minimum sample required to estimate the population variance within ±2 SEM. In the subsample with atmospheric flow measurements, a linear regression model (€P
_CRIT
[cmH
₂
O]=V
_@PN
[L/s]x-23[cmH
₂
O/L/s]), €P
_CRIT
ranged from 0 to -9.6cmH
₂
O. In the Bland-Altman analysis there was no mean difference between the measured P
_CRIT
and €P
_CRIT
(-0.01cmH
₂
O; p=0.8) with upper and lower limits of agreement at ±2.3cmH
₂
O. The variance of upstream resistance approaches a constant value in groups with approximately 40 subjects. Utilizing a fixed up-stream resistance to estimate €P
_CRIT
from the airflow at atmospheric pressure agrees with the measured values. These data suggest that measurements of quantitative airflow during standard polysomnography can be used to determine upper airway properties in large cohorts.