Background: Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ...ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA. Methods: Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2–10 cm H2O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred. Results: During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation. Conclusions: Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers.
Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway ...pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep.
Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at "CPAP lung volume", with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2).
The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001).
An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.
Ventilatory instability may play an important role in the pathogenesis of obstructive sleep apnea. We hypothesized that the influence of ventilatory instability in this disorder would vary depending ...on the underlying collapsibility of the upper airway. To test this hypothesis, we correlated loop gain with apnea-hypopnea index during supine, nonrapid eye movement sleep in three groups of patients with obstructive sleep apnea based on pharyngeal closing pressure: negative pressure group (pharyngeal closing pressure less than -1 cm H(2)O), atmospheric pressure group (between -1 and +1 cm H(2)O), and positive pressure group (greater than +1 cm H(2)O). Loop gain was measured by sequentially increasing proportional assist ventilation until periodic breathing developed, which occurred in 24 of 25 subjects. Mean loop gain for all three groups was 0.37 +/- 0.11. A significant correlation was found between loop gain and apnea-hypopnea index in the atmospheric group only (r = 0.88, p = 0.0016). We conclude that loop gain has a substantial impact on apnea severity in certain patients with sleep apnea, particularly those with a pharyngeal closing pressure near atmospheric.
Previous studies have demonstrated that lung volume during wakefulness influences upper airway size and resistance, particularly in patients with sleep apnea. We sought to determine the influence of ...lung volume on the level of continuous positive airway pressure (CPAP) required to prevent flow limitation during non-REM sleep in subjects with sleep apnea. Seventeen subjects (apnea-hypopnea index, 42.6 +/- 6.2 SEM) were studied during stable non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. An epiglottic pressure catheter plus a mask/pneumotachometer were used to assess flow limitation. When lung volume was increased by 1,035 +/- 22 ml, the CPAP level could be decreased from 11.9 +/- 0.7 to 4.8 +/- 0.7 cm H(2)O (p < 0.001) without flow limitation. The decreased CPAP at the same negative extrathoracic pressure yielded a final lung volume increase of 421 +/- 36 ml above the initial value. Conversely, when lung volume was reduced by 732 +/- 74 ml (n = 8), the CPAP level had to be increased from 11.9 +/- 0.7 to 17.1 +/- 1.0 cm H(2)O (p < 0.001) to prevent flow limitation, with a final lung volume decrease of 567 +/- 78 ml. These results demonstrate that relatively small changes in lung volume have an important effect on the upper airway in subjects with sleep apnea during non-REM sleep.
Pharyngeal dilator muscles are important in the pathophysiology of obstructive sleep apnoea syndrome (OSA). We have previously
shown that during wakefulness, the activity of both the genioglossus ...(GGEMG) and tensor palatini (TPEMG) is greater in patients
with OSA compared with controls. Further, EMG activity decreases at sleep onset, and the decrement is greater in apnoea patients
than in healthy controls. In addition, it is known that the prevalence of OSA is greater in middle-aged compared with younger
men. Thus, we had two goals in this study. First we compared upper airway muscle activity between young and middle-aged healthy
men compared with men with OSA. We also explored the mechanisms responsible for the decrement in muscle activity at sleep
onset in these groups. We investigated muscle activity, ventilation , and upper airway resistance (UAR) during wakefulness and sleep onset (transition from α to θ EEG activity) in all three
groups. Measurements were obtained during basal breathing (BB) and nasal continuous positive airway pressure (CPAP) was applied
to reduce negative pressure-mediated muscle activation). We found that during wakefulness there was a gradation of GGEMG and
UAR (younger < older < OSA) and that muscle activity was reduced by the application of nasal CPAP (to a greater degree in
the OSA patients). Although CPAP eliminated differences in UAR during wakefulness and sleep, GGEMG remained greater in the
OSA patients. During sleep onset, a greater initial fall in GGEMG was seen in the OSA patients followed by subsequent muscle
recruitment in the third to fifth breaths following the α to θ transition. On the CPAP night, and GGEMG still fell further in the OSA patients compared with control subjects. CPAP prevented the rise in UAR at sleep
onset along with the associated recruitment in GGEMG. Differences in TPEMG among the groups were not significant. These data
suggest that the middle-aged men had upper airway function midway between that of young normal men and the abnormal airway
of those with OSA. Furthermore it suggests that the initial sleep onset reduction in upper airway muscle activity is due to
loss of a âwakefulnessâ stimulus, rather than to loss of responsiveness to negative pressure, and that this wakefulness stimulus
may be greater in the OSA patient than in healthy controls.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Previous studies in both awake and sleeping humans have demonstrated that lung-volume changes substantially affect upper-airway size and pharyngeal resistance and, thus, may influence pharyngeal ...patency. We sought to systematically investigate the isolated effects of lung-volume changes on pharyngeal collapsibility and mechanics and genioglossus muscle activation during stable non-rapid eye movement sleep. We hypothesized that lower lung volumes would lead to increased pharyngeal collapsibility, airflow resistance, and, in compensation, augmented genioglossus muscle activation.
Nineteen normal individuals (age, 30.4 +/- 0.5 years; body mass index: 24.5 +/- 0.4 kg/m2) were studied during stable non-rapid eye movement sleep in a rigid head-out shell equipped with a variable positive/negative pressure attachment for manipulations of extrathoracic pressure and, thus, lung volume.
Sleep physiology laboratory.
Normal healthy volunteers.
N/A.
We measured change in end-expiratory lung volume (EELV) (magnetometers), genioglossus electromyogram (GGEMG) (intramuscular electrodes), pharyngeal pressure, and collapsibility of the pharynx in response to a brief pulse of negative pressure (-8 to -15 cm H2O) under the following conditions: (1) baseline, (2) increased EELV (+1 liter), and (3) decreased EELV (-0.6 liter). Reduced lung volumes led to increased inspiratory airflow resistance (7.54 +/- 2.80 cm H2O x L(-1) x s(-1) vs 4.53 +/- 1.05 cm H2O x L(-1) x s(-1), mean +/- SEM, P = 0.02) and increased genioglossus muscle activation (GGEMG peak 14.6% +/- 1.5% of maximum vs 8.6% +/- 1.5% of maximum, maximum P = 0.001) compared to baseline. The pharynx was also more collapsible at low lung volumes (4.3 +/- 0.5 cm H2O vs 5.4 +/- 0.6 cm H2O, P = 0.04).
We conclude that upper-airway muscles respond to changes in lung volumes but not adequately to prevent increased collapsibility. These results suggest that lung volume has an important influence on pharyngeal patency during non-rapid eye movement sleep in normal individuals.
Harvard Medical School and Division of Sleep Medicine, Brigham and Women's Hospital, Boston, Massachusetts
Submitted 15 April 2004
; accepted in final form 27 June 2005
Obstructive sleep apnea (OSA) ...is two to three times more common in men as in women. The mechanisms leading to this difference are currently unclear but could include gender differences in respiratory stability loop gain (LG) or upper airway collapsibility pharyngeal critical closing pressure (Pcrit). The aim of this study was to compare LG and Pcrit between men and women with OSA to determine whether the factors contributing to apnea are similar between genders. The first group of 11 men and 11 women were matched for OSA severity (mean ± SE apnea-hypopnea index = 43.8 ± 6.1 and 44.1 ± 6.6 events/h). The second group of 12 men and 12 women were matched for body mass index (BMI; 31.6 ± 1.9 and 31.3 ± 1.8 kg/m 2 , respectively). All measurements were made during stable supine non-rapid eye movement sleep. LG was determined using a proportional assist ventilator. Pcrit was measured by progressively dropping the continuous positive airway pressure level for three to five breaths until airway collapse. Apnea-hypopnea index-matched women had a higher BMI than men (38.0 ± 2.4 vs. 30.0 ± 1.9 kg/m 2 ; P = 0.03), but LG and Pcrit were similar between men and women (LG: 0.37 ± 0.02 and 0.37 ± 0.02, respectively, P = 0.92; Pcrit: 0.35 ± 0.62 and 0.18 ± 0.87, respectively, P = 0.63). In the BMI-matched subgroup, women had less severe OSA during non-rapid eye movement sleep (30.9 ± 7.4 vs. 52.5 ± 8.1 events/h; P = 0.04) and lower Pcrit (2.01 ± 0.62 vs. 1.16 ± 0.83 cmH 2 O; P = 0.005). However, LG was not significantly different between genders (0.38 ± 0.02 vs. 0.33 ± 0.03; P = 0.14). These results suggest that women may be protected from developing OSA by having a less collapsible upper airway for any given degree of obesity.
pharyngeal critical closing pressure; loop gain; gender
Address for reprint requests and other correspondence: A. S. Jordan, Brigham and Women's Hospital, Sleep Disorders Research Program @ BIDMC, 75 Francis St., Boston, MA 02115 (e-mail: ajordan{at}rics.bwh.harvard.edu )
Background: Whether loss of wakefulness itself can influence pharyngeal dilator muscle activity and responsiveness is currently unknown. A study was therefore undertaken to assess the isolated impact ...of sleep on upper airway muscle activity after minimising respiratory/mechanical inputs. Methods: Ten healthy subjects were studied. Genioglossus (GG), tensor palatini (TP) and diaphragm (DIA) electromyography (EMG), ventilation and sleep-wake status were recorded. Non-invasive positive pressure ventilation was applied. Expiratory pressure was adjusted to yield the lowest GGEMG, thereby minimising airway negative pressure (mechanoreceptor) effects. Inspiratory pressure, respiratory rate and inspiratory time were adjusted until the subjects ceased spontaneous ventilation, thereby minimising central respiratory input. Muscle activity during wakefulness, wake-sleep transitions, stable non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep were evaluated in the supine position. Results: In transitions from wakefulness to sleep, significant decrements were observed in both mean GGEMG and TPEMG (1.6 (0.5)% to 1.3 (0.4)% of maximal GGEMG; 4.3 (2.3)% to 3.7 (2.1)% of maximal TPEMG). Compared with sleep onset, the activity of TP during stable NREM sleep and REM sleep was further decreased (3.7 (2.1)% vs 3.0 (2.0)% vs 3.0 (2.0)% of maximal EMG). However, GGEMG was only further reduced during REM sleep (1.3 (0.4)% vs 1.0 (0.3)% vs 1.1 (0.4)% of maximal EMG). Conclusion: This study suggests that wakefulness per se, independent of respiratory/mechanical stimuli, can influence pharyngeal dilator muscle activity.
Pharyngeal muscle dilators are important in obstructive sleep apnea pathogenesis because the failure of protective reflexes involving these muscles yields pharyngeal collapse. Conflicting results ...exist in the literature regarding the responsiveness of these muscles during stable non-rapid eye movement sleep. However, variations in posture in previous studies may have influenced these findings. We hypothesized that tongue protruder muscles are maximally responsive to negative pressure pulses during supine sleep, when posterior tongue displacement yields pharyngeal occlusion.
We studied all subjects in the supine and lateral postures during wakefulness and stable non-rapid eye movement sleep by measuring genioglossus and tensor palatini electromyograms during basal breathing and following negative pressure pulses.
Upper-airway physiology laboratory of Sleep Medicine Division, Brigham and Women's Hospital.
17 normal subjects.
We observed an increase in genioglossal responsiveness to negative pressure pulses in sleep as compared to wakefulness in supine subjects (3.9 percentage of maximum %max +/- 1.1 vs 4.4 %max +/- 1.0) but a decrease in the lateral decubitus position (4.1 %max +/- 1.0 vs 1.5 %max +/- 0.4), the interaction effect being significant. Despite this augmented reflex, collapsibility, as measured during negative pressure pulses, increased more while subjects were in the supine position as compared with the lateral decubitus position. While the interaction between wake-sleep state and position was also significant for the tensor palatini, the effect was weaker than for genioglossus, although, for tensor palatini, baseline activity was markedly reduced during non-rapid eye movement sleep as compared with wakefulness.
We conclude that body posture does have an important impact on genioglossal responsiveness to negative pressure pulses during non-rapid eye movement sleep. We speculate that this mechanism works to prevent pharyngeal occlusion when the upper airway is most vulnerable to collapse eg, during supine sleep.
The objective was to evaluate the responsiveness of upper airway muscles to hypercapnia with and without intrapharyngeal negative pressure during non-rapid eye movement (NREM) sleep and wakefulness.
...We assessed the genioglossal muscle response to CO2 off and on continuous positive airway pressure (CPAP) (to attenuate negative pressure) during stable NREM sleep and wakefulness in the supine position.
Laboratory of the Sleep Medicine Division, Brigham and Women's Hospital.
Eleven normal healthy subjects.
During wakefulness and NREM sleep, we measured genioglossal electromyography (EMG) on and off CPAP at the normal eupneic level and at levels 5 and 10 mm Hg above the awake eupneic level.
We observed that CO2 could increase upper-airway muscle activity during NREM sleep and wakefulness in the supine position with and without intrapharyngeal negative pressure. The application of nasal CPAP significantly decreased genioglossal EMG at all 3 levels of PETCO2 during NREM sleep (13.0 +/- 4.9% vs. 4.6 +/- 1.6% of maximal EMG, 14.6 +/- 5.6% vs. 7.1 +/- 2.3% of maximal EMG, and 17.3 +/- 6.3% vs. 10.2 +/- 3.1% of maximal EMG, respectively). However, the absence of negative pressure in the upper airway did not significantly affect the slope of the pharyngeal airway dilator muscle response to hypercapnia during NREM sleep (0.72 +/- 0.30% vs. 0.79 +/- 0.27% of maximal EMG per mm Hg PCO2, respectively, off and on CPAP).
We conclude that both chemoreceptive and negative pressure reflex inputs to this upper airway dilator muscle are still active during stable NREM sleep.
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