Association between ventilatory response to hypercapnia and obstructive sleep apnea–hypopnea index in asymptomatic subjects

Abstract

The majority of awake ventilatory control studies have shown normal or decreased ventilatory response to hypercapnia (HCVR) in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. These findings are contrary to experimental studies suggesting increased loop gain and greater breathing instability in OSAHS patients. We have investigated the relationship between central chemoreflex sensitivity tested by HCVR and obstructive sleep apnea/hypopnea index (OSAHI) in asymptomatic subjects. Twenty normal volunteers (10 men and 10 women) from the general population without physical complaints including sleep-related symptoms were included. The subjects were studied for awake ventilatory responses to hypoxia (HVR) and hypercapnia. Overnight polysomnography (PSG) was performed in two consecutive nights with the first night used as acclimatization. The subjects have an average body mass index (BMI) of 27 +/- 5 SD kg/m(2), ages of 35 +/- 9 SD years and Epworth sleepiness scale of 2.1 +/- 1.8 SD. A positive linear relationship was found between HCVR and logarithmically transformed OSAHI (r = 0.67, p = 0.001). BMI and age were not significantly correlated to HCVR or Log OSAHI. No relationship was found between HVR and Log OSAHI (r = 0.25, p = 0.29). Percentage oxygen saturation nadir during sleep was found to significantly correlate to both daytime HCVR (r = -0.60, p = 0.005) and Log OSAHI (r = -0.65, p = 0.002) and tended to correlate to HVR (r = -0.41, p = 0.07). Arousal index during sleep was not associated with either HCVR (p = 0.93) or HVR (p = 0.26). In conclusion, heightened central chemosensitivity was positively related to OSAHI in asymptomatic volunteers. We believe these findings are in keeping with the evolving theory of loop gain being a significant factor for respiratory control instability and obstructive apnea genesis. The mechanism can be applied to asymptomatic subjects with even minimal sleep-disordered breathing.

Impaired Vascular Regulation in Patients with Obstructive Sleep Apnea

“…There is considerable disagreement among previous reports of the effects of OSA on hypoxic and hypercapnic ventilatory responses. Some investigators report augmented hypoxic ventilatory responses in patients with OSA versus CON subjects (30,31), whereas others report similar responses in the two groups (32). Hypercapnic ventilatory responses are reported to be increased (32) or the same (15,30) in patients with OSA versus CON subjects.…”

“…Some investigators report augmented hypoxic ventilatory responses in patients with OSA versus CON subjects (30,31), whereas others report similar responses in the two groups (32). Hypercapnic ventilatory responses are reported to be increased (32) or the same (15,30) in patients with OSA versus CON subjects. We speculate that much of the variability in the present and previous findings is attributable to performance of these studies during wakefulness, when nonchemoreceptor, behavioral inputs have a substantial influence on respiratory output.…”

Phenotyping interindividual variability in obstructive sleep apnoea response to temazepam using ventilatory chemoreflexes during wakefulness

“…In turn, this can create ventilation ‘overshoot’/instability and predispose to a cyclical pattern of breathing (Hudgel et al. , 1998; Khoo, 2000; Wang et al. , 2007; White, 2005; Younes et al.…”

“…Recent discussion of the Ôloop gainÕ theory of OSA pathogenesis suggests that an obstructed airway can stimulate an increased loop gain ⁄ controller gain ⁄ chemical drive. In turn, this can create ventilation ÔovershootÕ ⁄ instability and predispose to a cyclical pattern of breathing (Hudgel et al, 1998;Khoo, 2000;Wang et al, 2007;White, 2005;Younes et al, 2001). Conversely, the increased chemical drive may be protective and serve as a compensatory mechanism for the obstructed airway (Younes, 2008).…”

The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats

“…The implications of this chemosensitive braking pathway are significant to studies on human pathology. In cases of obstructive sleep apnea (OSA), multiple clinical studies have documented an association between OSA and an increase in the loop gain, or the ratio of ventilatory increase to a disturbance that initiates ventilation (Verbraecken et al, 1995;Younes et al, 2001;Wang et al, 2007). In other words, an increase in respiratory gain was associated with the onset of irregular breathing, and medications designed to decrease loop gain were demonstrated to be effective treatments (Kiwull-Scho¨ne et al, 2008).…”