Treatment with nasal CPAP decreases automobile accidents in patients with sleep apnea.

We studied 50 consecutive patients to test the hypothesis that successful treatment of obstructive sleep apnea with nasal continuous positive airway pressure (nasal CPAP) will decrease automobile accidents in patients with sleep apnea. Thirty-six (72%) of the patients reported using nasal CPAP regularly during 2 yr. Fourteen patients reported they had not used CPAP during 2 yr. The patients with sleep apnea in this study had a higher automobile crash rate than all drivers in the state of Colorado (0.07 versus 0. 01 crash per driver per year, p < 0.02). Patients who were treated with nasal CPAP had a lower crash rate while being treated than before treatment (0.07 versus 0 crash per driver per year, p < 0.03). Untreated patients with sleep apnea continued to have a high crash rate (0.07 crash per driver before and after diagnosis). Drivers with sleep apnea were reluctant to report their automobile crashes, for the drivers in this study reported only one-third of the crashes in which they were involved. This is the first study to confirm with traffic records that patients with sleep apnea have fewer automobile crashes while being treated with nasal CPAP.

Time-on-task decrements in "steer clear" performance of patients with sleep apnea and narcolepsy.

Loss of attention with time-on-task reflects the increasing instability of the waking state during performance in experimentally induced sleepiness. To determine whether patients with disorders of excessive sleepiness also displayed time-on-task decrements indicative of wake state instability, visual sustained attention performance on "Steer Clear," a computerized simple RT driving simulation task, was compared among 31 patients with untreated sleep apnea, 16 patients with narcolepsy, and 14 healthy control subjects. Vigilance decrement functions were generated by analyzing the number of collisions in each of six four-minute periods of Steer Clear task performance in a mixed-model analysis of variance and linear regression equations. As expected, patients had more Steer Clear collisions than control subjects (p=0.006). However, the inter-subject variability in errors among the narcoleptic patients was four-fold that of the apnea patients, and 100-fold that of the controls volunteers; the variance in errors among untreated apnea patients was 27-times that of controls. The results of transformed collision data revealed main effects for group (p=0.006), time-on-task (p=0.001), and a significant interaction (p=0.022). Control subjects showed no clear evidence of increasing collision errors with time-on-task (adjusted R2=0.22), while apnea patients showed a trend toward vigilance decrement (adjusted R2=0.42, p=0.097), and narcolepsy patients evidenced a robust linear vigilance decrement (adjusted R2=0.87, p=0.004). The association of disorders of excessive somnolence with escalating time-on-task decrements makes it imperative that when assessment of neurobehavioral performance is conducted in patients, it involves task durations and analyses that will evaluate the underlying vulnerability of potentially sleepy patients to decrements over time in tasks that require sustained attention and timely responses, both of which are key components in safe driving performance.

Colonic motor activity in women during sleep.

The relationship between colonic motility, sleep, and arousals from sleep has never been studied in women and only once in men. The purpose of this study was to determine how sleep and arousals from sleep affected colonic motility in women during the follicular phase of their menstrual cycle. We monitored sleep and segmental colonic motility in six healthy women during the follicular phase of the menstrual cycle. We observed no colonic motility during sleep; during awake periods or during arousals, we observed isolated low-amplitude bursts of colonic motility. This colonic motility occurred during 25% of the arousal and awakening time. In contrast, morning awakening was associated with high-amplitude independent and related colonic motility in all colonic segments. We conclude that in women in the follicular phase of their menstrual cycle, colonic motility is inhibited during sleep; colonic motility at night only occurs during arousals or awakenings from sleep.

Sleep apnea in obese miniature pigs.

We postulated that three extremely obese Yucatan miniature pigs would have more sleep apnea than three nonobese Yucatan miniature pigs. Pigs were studied with the use of electroencephalograms, inductance plethysmography, oximetry, expired nasal CO2, or thermistors. All of the obese pigs, but none of the nonobese pigs, had both sleep apnea (8.5, 10.3, and 97.0 in obese pigs vs. O apnea + hypopnea/h in all nonobese pigs; P < 0.05) and oxyhemoglobin desaturation episodes during sleep [9.4 +/- 3.0 vs. 0 + 0.53 (SD) mean desaturation episodes/h in obese pigs vs. nonobese pigs, respectively; P < 0.05]. Two of the extremely obese pigs had obstructive sleep apnea, whereas the third obese pig had central sleep apnea. We conclude that sleep apnea occurs in extremely obese Yucatan minipigs and suggest that this animal can be used as a model for sleep apnea in obesity.

Lateral pharyngeal fat pad pressure during breathing in anesthetized pigs.

It has been hypothesized that the pressure in tissues surrounding the upper airway is one of the determinants of the size and shape of the upper airway. To our knowledge, this pressure has not been measured. The purpose of this study was to test whether the pressure in a tissue lateral to the upper airway, the lateral pharyngeal fat pad pressure (Pfp), differs from atmospheric and pharyngeal pressures and whether it changes with breathing. We studied six male lightly sedated pigs by inserting a transducer tipped catheter into their fat pad space by using computerized tomographic scan guidance. We measured airflow with a pneumotachograph attached to a face mask and pharyngeal pressure with a balloon catheter. Pfp differed from atmospheric pressure, generally exceeding it, and from pharyngeal pressure. Pfp correlated positively with airflow and with pharyngeal pressure, decreasing during inspiration and increasing during expiration. Changes in Pfp with ventilation were eliminated by oropharyngeal intubation. We conclude that Pfp differs from atmospheric and pharyngeal pressures and that it changes with breathing.

Lateral pharyngeal fat pad pressure during breathing.

The purpose of this study was to test whether pressure in tissue lateral to the upper airway, the lateral pharyngeal fat pad, differs from atmospheric and pharyngeal pressure and whether it changes with breathing. We studied five male pigs by inserting a transducer-tipped catheter into their fat pad space using computed tomography (CT) scan guidance. We measured airflow with a pneumotachograph attached to a face mask and pharyngeal pressure with a balloon catheter. Fat pad pressure correlated positively with airflow and with pharyngeal pressure, decreasing during inspiration and increasing during expiration. Pressure in the fat pad differed from atmospheric pressure, generally exceeding it, and from pharyngeal pressure. We conclude that lateral pharyngeal fat pad pressure differs from atmospheric and pharyngeal pressure and that it changes with breathing.

Pulsatile growth hormone secretion in older persons is enhanced by fasting without relationship to sleep stages.

Spontaneous secretion of GH decreases with aging. To investigate whether fasting increases pulsatile GH secretion in older as it does in younger subjects, we studied six subjects (four postmenopausal women and two men, aged 55-81 yr; body mass indexes, 22-24 kg/ m2). Blood was obtained every 5 min for 24 h on a control (fed) day and on the second day of a fast. Serum GH concentrations, measured by an immunoradiometric assay, were analyzed with a multiple parameter deconvolution method to stimultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 4-fold increase in the 24-h GH production rate (38 +/- 25 vs. 166 +/- 42 micrograms/L distribution volume; P = 0.003) and a 2-fold increase in the amount of GH secreted per pulse (2.4 +/- 1.4 vs. 5.5 +/- 1.2 micrograms/L distribution volume; P = 0.02). The latter was a result of increased secretory burst amplitudes with unchanged secretory burst durations. The number of detectable GH secretory bursts per 24 h was also increased by fasting (13 +/- 1.4 vs. 30 +/- 1.1; P = 0.0004); the GH pulse frequency may have been underestimated in the fed state, as 33 +/- 4.9% of the samples had undetectable ( < 0.2 microgram/L) serum GH concentrations compared to 5.2 +/- 2.6% of the samples on the fasting day (P = 0.004). The t1/2 of endogenous GH was not significantly altered by fasting. The fold increase in GH secretion with fasting was similar to that previously observed in young men, although absolute levels of GH secretion were approximately 50% lower in both fed and fasted conditions. Fasting decreased the proportion of sleep time spent in rapid eye movement sleep (4.7 +/- 1.3 vs. 15 +/- 2.1%; P = 0.005), but did not significantly increase slow wave (stages 3 and 4) sleep. In both fed and fasted conditions, mean GH secretion rates were similar during daytime wakefulness, nocturnal wakefulness, rapid eye movement sleep, and stages 1, 2, and 3 of sleep. We conclude that hyposomatotropism associated with aging is partially reversed by fasting, and the enhancement of GH secretion by fasting is not related to changes in slow wave sleep. These data indicate that GH secretion in older persons can be enhanced by physiological interventions.

Enlargement of the lateral pharyngeal fat pad space in pigs increases upper airway resistance.

Because the upper airway is partially enclosed in a rigid boundary, enlargement of soft tissue structures within this boundary could narrow the airway. The purpose of this study was to determine whether enlargement of the soft tissue space in the region of the lateral pharyngeal fat pad would increase pharyngeal resistance and narrow the retropalateal upper airway. In five young male anesthetized pigs, we inserted balloon occlusion catheters in the lateral pharyngeal fat pad under computerized tomographic scan guidance. We measured pharyngeal resistance with a pharyngeal catheter and a tightly fitting face mask before and after inflation of the balloons. We also measured pharyngeal airway cross-sectional area before and after inflation of the balloons. In all pigs, balloon inflation significantly increased pharyngeal resistance and significantly decreased the area of the retropalateal airway. We conclude that enlargement of the soft tissue space in the region of the lateral pharyngeal fat pad increases pharyngeal resistance and narrows the retropalateal airway in anesthetized pigs.

Breath-holding capability of adults. Implications for spiral computed tomography, fast-acquisition magnetic resonance imaging, and angiography.

PURPOSE: The breath-holding capabilities of various groups of individuals were evaluated to develop protocols so that patients undergoing spiral computed tomography (CT), digital angiography, and breath-hold magnetic resonance imaging (MRI) can be studied successfully. METHODS: Twenty-five outpatients and 25 inpatients (all adults) were studied before undergoing body CT. Each subject was asked to hold his or her breath for as long as possible. Then each patient was asked to perform as many repetitive 12-second breath holds as possible. These data were correlated with demographic and historical information. RESULTS: The maximum breath-hold time for inpatients and those outpatients who were heavy smokers or had chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) was 18 to 32 seconds (95% confidence interval) with a mean of 25 seconds. For all other outpatients, breath-hold time was 38 to 56 seconds (mean = 45 seconds). The 95% confidence interval for the number of 12-second breath holds for these two groups was 4 to 6 breath holds (mean = 4.9) and 6 to 7 breath holds (mean = 6.6), respectively. One inpatient could not hold his breath at all and three others were only able to hold their breath once for short periods. The sex and age of the patient had no significant effect on breath-holding performance. CONCLUSIONS: Breath-holding protocols must account for the diminished capabilities of most inpatients, and outpatients who are heavy smokers or have COPD or CHF. Most outpatients who are not heavy smokers or without COPD or CHF can achieve a single breath hold of 38 seconds, or up to six 12-second breath holds.

Adipose tissue deposition in sleep apnea.

To determine whether adipose tissue is deposited in the neck adjacent to the upper airway in patients with obstructive sleep apnea (OSA), we studied 21 subjects with OSA and nine without OSA using magnetic resonance imaging with a T-1 weighted spin echo sequence and polysomnography. We observed that patients with OSA had a larger volume of adipose tissue adjacent to their upper airway than did subjects without OSA.

Pharyngeal fat in obstructive sleep apnea.

Although most patients with obstructive sleep apnea (OSA) are obese, it is not known how obesity contributes to airway collapse during sleep. The purpose of this study was to determine whether the volume of adipose tissue adjacent to the pharyngeal airway in humans is related to the degree of OSA. We studied 30 subjects, nine without OSA and 21 with OSA; two subjects were studied before and after weight loss. Adipose tissue was detected with magnetic resonance imaging using T1-weighted spin echo sequences. The volume of adipose tissue adjacent to the upper airway was determined by measuring the volume of all pixels in the intensity range of adipose tissue within the region bounded by the ramus of the mandible, the spine, the anterior border of the soft palate, and the hard palate. Polysomnography was performed with conventional techniques. All subjects had a collection of adipose tissue adjacent to the upper airway; the volume of this adipose tissue correlated with the number of apneas plus hypopneas per hour of sleep (r = 0.59, p < 0.001). Both patients who lost weight and had fewer apneas and hypopneas had a marked decrease in the pharyngeal adipose tissue volume. We conclude that adipose tissue is deposited adjacent to the pharyngeal airway in patients with OSA and that the volume of this tissue is related to the presence and degree of OSA.

Mandible enclosure of upper airway and weight in obstructive sleep apnea.

Although anatomic lesions and obesity can produce obstructive sleep apnea (OSA), most subjects with OSA have no recognizable anatomic lesion. We hypothesized that the occurrence of OSA is related to the size of the region enclosed by the mandible and the degree of obesity. We studied 30 subjects with a range of OSA and obesity with magnetic resonance imaging (MRI). MRI was performed with T-1 weighted sequences. Nocturnal polysomnography was performed in all subjects. Univariate regression analysis indicated there was a significant correlation between the number of apneas and hypopneas per hour of sleep (AH/h) and (1) the area enclosed by the mandible ramus (AMR1) (r = 0.48, p < 0.01) and (2) the distance from the teeth to the posterior mandible ramus (r = 0.39, p < 0.05). Stepwise multiple regression analysis indicated that weight, AMR1, and height explained 69% of the variance of AH/h (r2 = 0.69). We conclude that the occurrence of OSA in these subjects is related to the size of the region enclosed by the mandible as well as to their weight.

Effect of very-low-calorie diets with weight loss on obstructive sleep apnea.

To determine the effect of very-low-calorie diets (VLCDs) with weight loss on obstructive sleep apnea (OSA), we studied eight obese subjects with OSA, five males and three females. Subjects consumed a VLCD of 1760 kJ (420 kcal) (67% protein, 4% fat, 29% carbohydrate) or 3350 kJ (800 cal) (20% protein, 30% fat, 50% carbohydrate) with 100% of the recommended daily allowance of vitamins and minerals. Mean (+/- SD) values of weight and respiration before and after weight loss were, for weight, 153 +/- 37 and 132 +/- 29 kg (P less than 0.05); for BMI (kg/m2), 54 +/- 13 and 46 +/- 10 (P less than 0.05); for desaturations/h sleep, 106 +/- 50 and 52 +/- 45 (P less than 0.05); for apneas + hypopneas/h sleep, 90 +/- 32 and 62 +/- 49; for Pco2, 48 +/- 10 and 42 +/- 4 torr (P less than 0.05). Desaturation episodes/h and apnea + hypopneas/h improved in six patients. The most obese subject (female, BMI 81) who lost the most weight (47 kg) did not improve, nor did the subject who lost the least weight, 7 kg. The number of movements + arousals from sleep decreased in all patients (P less than 0.05). We conclude that VLCD with weight loss can produce improvement in OSA; subjects who lose a small amount of weight or subjects who are extraordinarily obese before and after weight loss may not improve.

Mandible position and activation of submental and masseter muscles during sleep.

Movement of the mandible could influence pharyngeal airway caliber because the mandible is attached to the tongue and to muscles that insert on the hyoid bone. In normal subjects and patients with obstructive sleep apnea (OSA) we measured jaw position during sleep with strain gauges, as well as masseter and submental electromyograms, airflow, esophageal pressure, oximetry, electroencephalograms, and electrooculograms. Jaws of patients with OSA were open more than those of normal subjects at end expiration and opened further at end inspiration, particularly at the termination of apneas when the masseter and submental muscles contracted. Masseter activation occurred only in patients with OSA and in a pattern similar to that of submental muscles. Jaw opening at end expiration could narrow the upper airway, whereas opening at end inspiration could reflect efforts to expand the airway with tracheal tug and with submental muscle activation and efforts to open the mouth to allow mouth breathing. Masseter contraction does not close the jaw but may serve to stabilize it.

Evaluation of the upper airway in patients with obstructive sleep apnea.

Multiple methods have been used to study the structure and physiological behavior of the upper airway (UA) in patients with obstructive sleep apnea (OSA). Valuable information may be obtained from the physiologic measurement of pressure and resistance along the UA, as well as from imaging techniques that include: direct or fiberoptic visualization, cephalometric roentgenograms, fluoroscopy, acoustic reflection, computerized tomography, and magnetic resonance imaging. This review summarizes the information that each of these methods has contributed to our understanding of the UA. The results obtained with these different methodologies have generally been complementary with structural narrowing being identified in the majority of patients with OSA. This narrowing is usually focal and located in the velopharyngeal or retropalatal segment of the UA. This is also the predominant site of initial UA collapse. Although obesity with enlargement of soft tissue structures is considered the predominant mechanism leading to UA narrowing, abnormal craniofacial development on a genetic or developmental basis plays an important contributory role.