Effect of surfactant on pharyngeal mechanics in sleeping humans: implications for sleep apnoea.

Instillation of surfactant into the pharyngeal lumen reduces the pressure required to reopen an occluded airway, and decreases the apnoea/hypopnoea index (AHI). The authors hypothesised that surfactant also reduces the sleep-related increase in pharyngeal resistance. To test this hypothesis two single blind, crossover, placebo-controlled studies were performed. In protocol A seven male, asymptomatic snoring subjects were studied during sleep. Inspiratory pharyngeal resistance was calculated from plots of airflow versus supraglottic pressure (seven breaths) before and after surfactant or saline instillation. In protocol B, in a different group of seven male subjects with sleep apnoea (AHI 15.2 (12) events x h(-1)) the effect of surfactant or saline on sleep disordered breathing was measured, for 1 h immediately before and after surfactant or saline instillation. Surfactant decreased pharyngeal resistance calculated at peak pressure (group mean (SD): pre versus post 83.7 (76.4) versus 49.4 (71.1) cmH2O x L(-1) x s(-1)) and significantly reduced the respiratory disturbance index (RDI pre versus post 79.7 (58.7) versus 59.6 (56.9) events x h(-1)). Saline did not decrease resistance (pre versus post 58.6 (31.1) versus 72.5 (73.4) cmH2O x L(-1) x s(-1)) or RDI (pre versus post 75.3 (42.4) versus 79.9 (46.1) events x h(-1)). Surfactant reduced the collapsibility of the pharynx and led to a modest reduction in respiratory disturbance index. The authors speculate that surfactant may delay occlusion by reducing the liquid "bridging" within the folded pharyngeal lining.

Effect of REM sleep on retroglossal cross-sectional area and compliance in normal subjects.

It has been proposed that the upper airway compliance should be highest during rapid eye movement (REM) sleep. Evidence suggests that the increased compliance is secondary to an increased retroglossal compliance. To test this hypothesis, we examined the effect of sleep stage on the relationship of retroglossal cross-sectional area (CSA; visualized with a fiber-optic scope) to pharyngeal pressure measured at the level of the oropharynx during eupneic breathing in subjects without significant sleep-disordered breathing. Breaths during REM sleep were divided into phasic (associated with eye movement, PREM) and tonic (not associated with eye movements, TREM). Retroglossal CSA decreased with non-REM (NREM) sleep and decreased further in PREM [wake 156.8 +/- 48.6 mm(2), NREM 104.6 +/- 65.0 mm(2) (P < 0.05 wake vs. NREM), TREM 83.1 +/- 46.4 mm(2) (P = not significant NREM vs. TREM), PREM 73.9 + 39.2 mm(2) (P < 0.05 TREM vs. PREM)]. Retroglossal compliance, defined as the slope of the regression CSA vs. pharyngeal pressure, was the same between all four conditions (wake -0.7 + 2.1 mm(2)/cmH(2)O, NREM 0.6 +/- 3.0 mm(2)/cmH(2)O, TREM -0.2 +/- 3.3 mm(2)/cmH(2)O, PREM -0.6 +/- 5.1 mm(2)/cmH(2)O, P = not significant). We conclude that the intrinsic properties of the airway wall determine retroglossal compliance independent of changes in the neuromuscular activity associated with changes in sleep state.

Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep.

We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25-35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21-43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (VT) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal PCO(2) (PET(CO(2))) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in VT to 155 +/- 29% (mean +/- SD) and a reduction of PET(CO(2)) by -4.72 +/- 0.57 Torr. In men, induction of a central apnea required an increase in VT to 142 +/- 13% and a reduction of PET(CO(2)) by -3.54 +/- 0.31 Torr (P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.

The effect of rapid eye movement (REM) sleep on upper airway mechanics in normal human subjects.

1. It has been proposed that the upper airway is more compliant during rapid eye movement (REM) sleep than during non-rapid eye movement (NREM) sleep. The purpose of this study was to test this hypothesis in a group of subjects without sleep-disordered breathing. 2. On the first night, the effect of sleep stage on the relationship of retropalatal cross-sectional area (CSA; visualized with a fibre-optic scope) to pharyngeal pressure (PPH) measured at the soft palate during eupnoeic breathing was studied. Breaths during REM sleep were divided into phasic (associated with eye movements) and tonic (not associated with eye movements). There was a significant decrease in pharyngeal CSA during NREM sleep compared with wakefulness. There was no further decrease observed during either tonic or phasic REM sleep. Pharyngeal compliance, defined as the slope of the regression CSA versus PPH, was significantly increased during NREM sleep compared with wakefulness and REM sleep, with the compliance during both tonic and phasic REM sleep being similar to that observed in wakefulness. 3. On the second night, the effect of sleep stage on pressure-flow relationships of the upper airway was investigated. There was a trend towards the upper airway resistance being highest in NREM sleep compared with wakefulness and REM sleep. 4. We conclude that the upper airway is stiffer and less compliant during REM sleep than during NREM sleep. We postulate that this difference is secondary to differences in upper airway vascular perfusion between REM and NREM sleep.

Effect of induced hypocapnic hypopnea on upper airway patency in humans during NREM sleep.

We wished to determine the effect of reduced ventilatory drive (hypopnea) on upper airway patency in humans during non-rapid-eye-movement (NREM) sleep. We studied nine subjects (58 trials) spanning the spectrum of susceptibility to upper airway collapse including normals, snorers and patients with mild sleep apnea. Hypocapnic hypopnea was induced by abrupt cessation of brief (1 min) nasal mechanical hyperventilation. Surface inspiratory EMG (EMGinsp) was used as an index of drive. Upper airway resistance and supraglottic pressure-flow plots were used as indexes of upper airway patency. Termination of nasal mechanical ventilation resulted in reduced VE to 4904 of pre-mechanical ventilation eupneic control. Upper airway resistance at a fixed flow did not change significantly in inspiration or expiration. Likewise, pressure-flow plots showed no increase in upper airway resistance except in one subject. However, maximum flow (Vmax) decreased during hypopnea in four subjects who demonstrated inspiratory flow-limitation (IFL) during eupneic control. In contrast, no IFL was noted in subjects who showed no evidence of IFL during eupnea. We concluded: (1) Reduced ventilatory drive does not compromise upper airway patency in normal subjects during NREM sleep; (2) the reduction in Vmax during hypopnea in subjects with IFL during eupneic control, suggests that reduced drive is associated with increased upper airway compliance in these subjects; and (3) upper airway susceptibility to narrowing/closure is an important determinant of the response to induced hypopnea during NREM sleep.