Breath‐holding as a means to estimate the loop gain contribution to obstructive sleep apnoea

Abstract

Increased "loop gain" of the ventilatory control system promotes obstructive sleep apnoea (OSA) in some patients and offers an avenue for more personalized treatment, yet diagnostic tools for directly measuring loop gain in the clinical setting are lacking. Here we test the hypothesis that elevated loop gain during sleep can be recognized using voluntary breath-hold manoeuvres during wakefulness. Twenty individuals (10 OSA, 10 controls) participated in a single overnight study with voluntary breath-holding manoeuvres performed during wakefulness. We assessed (1) maximal breath-hold duration, and (2) the ventilatory response to 20 s breath-holds. For comparison, gold standard loop gain values were obtained during non-rapid eye movement (non-REM) sleep using the ventilatory response to 20 s pulses of hypoxic-hypercapnic gas (6% CO -14% O , mimicking apnoea). Continuous positive airway pressure (CPAP) was used to maintain airway patency during sleep. Additional measurements included gold standard loop gain measurement during wakefulness and steady-state loop gain measurement during sleep using CPAP dial-ups. Higher loop gain during sleep was associated with (1) a shorter maximal breath-hold duration (r = 0.49, P < 0.001), and (2) a larger ventilatory response to 20 s breath-holds during wakefulness (second breath; r = 0.50, P < 0.001); together these factors combine to predict high loop gain (receiver operating characteristic area-under-curve: 92%). Gold standard loop gain values were remarkably similar during wake and non-REM sleep. The results show that elevated loop gain during sleep can be identified using simple breath-holding manoeuvres performed during wakefulness. This may have implications for personalizing OSA treatment.

Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity

“…Participants were instructed to sleep on their back and given an 8-h sleep opportunity. Prior to sleep, on either one of the study nights, baseline loop gain via breath-holding technique (Messineo et al 2018) and the upper airway collapsibility index via negative pressure pulse administration (Osman et al 2019) were quantified. Participants completed the Insomnia severity index (ISI) and Epworth sleepiness scale (ESS) questionnaires on their first night ß30 min after arrival.…”

Angiotensin II-Type I Receptor Antagonism Does Not Influence the Chemoreceptor Reflex or Hypoxia-Induced Central Sleep Apnea in Men

“…Gain and the Severity of Hypoxia Induced CSA Elevated loop gain contributes to OSA severity and a high controller gain (mostly measured during wakefulness) is associated with CSA in healthy humans at high altitude, in idiopathic CSA (Ainslie et al, 2013;Terrill et al, 2015), and in patients with heart failure (Solin et al, 2000;Javaheri, 2006). Notably, loop gain during sleep, measured using dynamic application of hypoxic-hypercapnia is remarkably similar to values during wakefulness (Messineo et al, 2018). Thus, individuals with high chemoreflex sensitivity likely suffer from worse CSA severity (Messineo et al, 2018).…”

Update on Chemoreception

“…Combination therapies of supplemental O 2 plus hypnotics used to reduce the arousal threshold have also shown promise -again in selected OSA patients 55 . Phenotyping the patient for high loop gain is important in determining the feasibility of these approaches and this might be accomplished by examining patterns of ventilatory overshoot or a high prevalence of "mixed" apneas in the routine polysomnogram or even by simple breath hold or CO 2 chemosensitivity tests in wakefulness 56 . Some claims that continuous positive airway pressure (CPAP) effects on selected cardiovascular outcomes in OSA patients exceeded those of supplemental O 2 , were based on studies which applied these treatments for < 5 hours per night and in OSA patients with very minimal sleep time spent below 90% HbO2 saturation 57 .…”