Model-based stability assessment of ventilatory control in overweight adolescents with obstructive sleep apnea during NREM sleep

Abstract

Obstructive sleep apnea (OSA) involves the interplay of several different factors such as an unfavorable upper airway anatomy, deficiencies in pharyngeal muscle responsiveness, a low arousal threshold, and ventilatory control instability. Although the stability of ventilatory control has been extensively studied in adults, little is known about its characteristics in the pediatric population. In this study, we developed a novel experimental setup that allowed us to perturb the respiratory system during natural non-rapid eye movement (NREM) sleep conditions by manipulating the inspiratory pressure, provided by a bilevel pressure ventilator, to induce sighs after upper airway stabilization. Furthermore, we present a modeling framework that utilizes the noninvasively measured ventilatory responses to the induced sighs and spontaneous breathing data to obtain representations of the processes involved in the chemical regulation of respiration and extract their stability characteristics. After validation with simulated data, the modeling technique was applied to data collected experimentally from 11 OSA and 15 non-OSA overweight adolescents. Statistical analysis of the model-derived stability parameters revealed a significantly higher plant gain and lower controller gain in the OSA group (P = 0.046 and P = 0.007, respectively); however, no differences were found in loop gain (LG) and circulatory time delay between the groups. OSA severity and LG, within the 0.03-0.04-Hz frequency band, were significantly negatively associated (r = -0.434, P = 0.026). Contrary to what has been found in adults, our results suggest that in overweight adolescents, OSA is unlikely to be initiated through ventilatory instability resulting from elevated chemical loop gain.

Role of ventilatory control instability in children with sleep‐disordered breathing

“…Similar to our study which showed no difference in LG between controls and those with SDB, previous studies have reported no difference in LG between overweight adolescents with and without OSA (OSA defined as OAHI >5 events/h) 24 or between clusters of term and preterm born children aged 6 months to 7 years at various degrees of risk for OSA (OSA defined as OAHI >2 events/h). 23 In addition, it has also been reported that there was no difference in ventilatory responses to hypoxia and hypercapnia (a component of LG) in children with and without OSA during both wakefulness 34 and sleep.…”

Cardioventilatory Control in Preterm-born Children and the Risk of Obstructive Sleep Apnea

“…Contrary to what has been described in adults with OSA who have an increase in LG, our pediatric population with OSA did not show a significant difference in LG compared with that in healthy control subjects. Similar observations were made in studies of overweight adolescents (24) and obese women (57), where subjects with OSA also had high PG, low CG, and a low LG. These data suggest that different mechanisms of ventilatory control abnormalities may lead to respiratory instability and OSA.…”

“…Estimations of LG, PG, and CG were extracted from the spontaneous sigh recordings by using an adaptation of the technique employed by Nava-Guerra and colleagues (24). A slight modification extending the frequencies for periodic breathing between 0.01 and 0.125 Hz was done to account for breathing frequency being considerably faster in young children than in adolescents.…”

Assessing ventilatory control stability in children with and without an elevated central apnoea index

“…Similar to our study, the authors estimated LG from the ventilatory response that followed spontaneous sighs. Although they utilized a different technique to estimate LG, the mean values in their study (~0.28) were identical to those of our low CAI group. This may suggest that the high LG observed in our high CAI group may be moving into an ‘abnormal’ range for this age group, or at least making them more prone to ventilatory instability in response to a perturbation.…”