Blunted respiratory-related evoked potential in awake obstructive sleep apnoea subjects: A NEP technique study
Highlights
► A deficit in afferent activity is supposed to be present in obstructive sleep apnoea subjects, affecting the reflex mechanisms necessary to promote airway patency and stabilize the upper airway. ► Awake obstructive sleep apnoea subjects had a raised threshold to pressure stimuli and blunted respiratory-related evoked potentials. ► The negative expiratory pressure technique is a reliable neurophysiological method with which to detect reduced afferent traffic from the upper airway.
Introduction
In the human upper airway (UA) dilator muscles develop force against the negative suction within the pharynx due to inspiratory effort (Remmers et al., 1978). This mechanism preserves the pharyngeal patency during wakefulness (Sanna et al., 1993) and sleep (Remmers et al., 1978). Respiratory mechanoreceptors play an important role in maintaining pharyngeal patency during sleep, mediating reflex activation of the UA muscles in response to changes in UA pressure (Horner et al., 1991, Tantucci et al., 1998). Obstructive sleep apnoea (OSA) is characterized by recurrent UA obstruction with a progressive increase in inspiratory efforts, a decrease in arterial oxygen saturation and transient arousals (Remmers et al., 1978). Previous studies suggested that arousal is closely linked to the level of inspiratory effort (Kimoff et al., 1994). Several pieces of evidence therefore point to a prominent role for effort-related mechanoreceptor stimuli generated during obstructed inspiratory efforts in mediating end-apnoeic arousal and termination of apnoea (Kimoff et al., 1994, Cala et al., 1996). Indeed, when activated the UA mechanoreceptors generate afferent stimulations contributing to arousal after airway obstruction (Berry et al., 1995, Berthon-Jones and Sullivan, 1984). Conversely, it has been shown that topical anesthesia-induced UA mechanoreceptor blockade at the beginning of the night lengthens apnoea (Cala et al., 1996). The recurrent high-pressure swings and intensive muscle contractions observed in OSA induce structural changes in UA muscle fibers (Friberg et al., 1998), inflammation within the pharyngeal tissues (Boyd et al., 2004) and sensory nerve damage (Boyd et al., 2004, Friberg et al., 1997). All these data suggest that there may be a deficit in afferent activity in OSA subjects, affecting the reflex mechanisms that promote airway patency and stabilize the UA.
Respiratory-related evoked potentials (RREPs) have been used to study the activation of cortical neurons induced by different stimuli applied to the UA such as inspiratory occlusions (Revelette and Davenport, 1990), positive pressure generated by an expiratory occlusion (Hammond et al., 1999) and resistive loads at the mouth (Knafelc and Davenport, 1999), and also stimuli applied without occlusion by applying a negative pressure to the mouth in early inspiration (Strobel and Daubenspeck, 1993) or during expiration (Grippo et al., 2003). Few studies have investigated RREPs in OSA subjects. Significant dampening of cortical respiratory perceptions was found during NREM sleep (Afifi et al., 2003, Gora et al., 2002). Conversely, studies in awake OSA subjects showed contradictory results, probably due to relevant differences in the experimental settings, such as features of pressure stimuli and/or the timing of stimuli application (Harver et al., 1991, Afifi et al., 2003, Akay et al., 2003, Donzel-Raynaud et al., 2009).
The negative expiratory pressure (NEP) technique (Koulouris et al., 1995), previously used to study RREP in healthy subjects (Grippo et al., 2003), acts without added resistive load or the occlusion maneuver and delivers mechanical stimuli that are highly reproducible in terms of rise time and pressure values. These experimental features allow the methodological confounding factors to be minimized when evaluating the respiratory-related potentials elicited by transmural pressure changes.
If the above mentioned structural changes to the UA tissue in OSA subjects really affect the afferent information in the UA, we would expect abnormal RREP components in OSA subjects during wakefulness. This would lead to the following results: (1) an increased threshold of cortical response to pressure stimuli, and (2) a reduction in RREP component amplitudes for the stimuli applied to the UA. We thus studied RREPs elicited by a negative pressure on the UA delivered by means of the NEP technique in awake OSA subjects. The results were compared to those from a control group of non-snorer, non-apnoeic subjects.
Section snippets
Subjects
We studied 10 subjects with OSA, who had never been treated with continuous positive airway pressure (CPAP), and a control group of 12 healthy volunteers. All were male, had no history of endocrine, neuromuscular or pulmonary disease, head injury, cerebral ischemia, encephalitis, alcohol or drug abuse. After a description of the protocol, informed consent was obtained before testing.
Pulmonary function test and sleep study
On the first day, according to the guidelines of the European Respiratory Society (Miller et al., 2005), subjects
Results
OSA subjects were older than controls (47.2 ± 7.4 vs. 36.4 ± 3.6, p < 0.05). The BMI was similar in OSA subjects (31.9 ± 4.3) and the controls (28.3 ± 3.8). Table 1 summarizes spirometric and polysomnographic data. Lung function and gas exchange were within normal limit in both groups. There were no differences in total sleep time or sleep efficiency. In OSA subjects the percentage of sleep stages was higher for stage 1 and 2 NREM sleep and lower for stage 3 plus 4 NREM and for REM. OSA subjects had a
Discussion
We found that OSA subjects have a raised response threshold to the NEP stimulus and a reduction in RREP amplitude compared to control subjects. According to our research hypothesis these results indicate a deficit in afferent activity from the UA that is consistent with impaired neuromechanical control of the UA.
Six out of 10 OSA subjects showed no response to lower stimuli (−1 cmH2O) and the mean amplitude of RREP evoked by the −5 and −10 cmH2O stimuli was significantly reduced compared to
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2018, American Journal of Otolaryngology - Head and Neck Medicine and SurgeryCitation Excerpt :There have been studies that assessed differences in respiratory related evoked potentials (RREP) as a test for afferent function of oropharynx. The data is mixed with a few favoring afferent neuropathy [41,42] and some finding no evidence to support it [43–47]. Since RREP is not a reliable method for oropharyngeal afferent testing, we decided to not include the RREP studies in this review [48].