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.

Prolonged relaxation rate of inspiratory muscles in patients with sleep apnea.

To evaluate whether inspiratory muscle function is impaired in patients with sleep apnea, we measured inspiratory muscle strength and relaxation rate before and after sleep in 13 patients. The sleep apnea group was composed of eight patients with severe obstructive sleep apnea, and the non-apnea group was composed of five patients without significant sleep apnea. We chose the time constant of relaxation (TauR) as an index of impaired inspiratory muscle contractility, and in subsets of each group, we measured the inspiratory pressure-time index as an indicator of a fatiguing breathing pattern. In patients with sleep apnea, presleep TauR was 79 +/- 22 ms (SD), longer than that of normal subjects (normal, 59 +/- 7 ms) (p less than 0.05). TauR increased by 21 +/- 16 ms during sleep (p less than 0.01). In patients without apnea, presleep TauR was 67 +/- 7 ms and it did not change after sleep. Maximal inspiratory and expiratory pressures were unchanged after sleep. We conclude that patients with sleep apnea do not develop overt inspiratory muscle failure but do have impaired contractility. We speculate that hypoxemia as well as increased work load was responsible.

Upper airway muscle activation is augmented in patients with obstructive sleep apnea compared with that in normal subjects.

Although phasic electromyographic (EMG) activity of upper airway muscles in patients with obstructive sleep apnea (OSA) decreases at apnea onset, the presence of phasic activity in normal subjects has not been studied and compared with that in patients. We consequently compared the percentage of total sleep time in which phasic activity of the genioglossal EMG activity was present in 8 adult patients with OSA and 3 control groups without OSA, one consisting of 6 young, normal subjects, one matched for age, and one matched for age and obesity. From wakefulness to sleep, genioglossal EMG phasic activity time increased in patients but not in control subjects. Patients with OSA had more phasic genioglossal group EMG activity during non-REM sleep than did control subjects. At apnea onset, phasic EMG activity decreased in patients but remained greater than zero. In many control subjects, phasic activity was not detected, yet their pharyngeal airway remained patent. We conclude that phasic genioglossal group EMG activity occurs more frequently during sleep in patients with OSA than in control subjects, suggesting that it is a compensatory mechanism that occurs when patency of the pharyngeal airway is precarious.

Effect of nasal obstruction on upper airway muscle activation in normal subjects.

It is not known whether nasal occlusion produces obstructive sleep apnea (OSA) by decreasing upper airway muscle activation via nasal reflexes or by increasing upper airway resistance and hence lowering the pressure in the pharnyx. The purpose of this study was to determine the effect of nasal occlusion on upper airway muscle activation. We studied seven men and measured alae nasi (AN) and genioglossal (GG) electromyograms (EMGs) during two nights of sleep, one with their nose open and the other with their nose occluded. Nasal occlusion produced OSA in all subjects and also increased the percentage of time during sleep in which phasic AN and GG EMG activity was present. Apneas tended to occur at the nadirs of EMG activity. This suggests that nasal occlusion generally increases respiratory drive to upper airway muscles during sleep and that it does not cause OSA by merely decreasing respiratory drive to these muscles.

Changes in breathing and the pharynx after weight loss in obstructive sleep apnea.

The effect of weight loss following dietary restriction on disordered breathing on the pharyngeal airway is controversial in patients with obstructive sleep apnea (OSA). We therefore prospectively studied eight patients before and after dietary-induced weight loss. Mean weight loss was 20.6 kg +/- 12.8 SD. After weight loss there were significant improvements in PO2 and PCO2 measured during wakefulness, and in the number of desaturation episodes per hour of sleep, average desaturation per episode, and number of movement arousals. The number of apneas and hypopneas significantly decreased in six of eight patients. There was a significant correlation between body mass index and number of disordered breathing events. Nasopharyngeal collapsibility and pulse flow resistance decreased in awake patients after weight loss. We conclude that moderate weight loss in obese patients with OSA improves oxygenation during both sleep and wakefulness, decreases the number of disordered breathing events in many patients, decreases the collapsibility of the nasopharyngeal airway.

Obstructive sleep apnea in premenopausal women. A comparison with men and with postmenopausal women.

Because obstructive sleep apnea (OSA) is unusual in premenopausal women, we describe ten women with this syndrome and compare them to 13 postmenopausal women and with 32 men with OSA. Two premenopausal women had structural abnormalities of their pharynx, and the remaining eight were significantly more obese than men with OSA. In these eight patients, there was no relationship between pulse flow resistance and the degree of OSA in contrast to significant relationships in postmenopausal women, and men. Hypercapnia occurred in three premenopausal women, no postmenopausal women and in two men. We conclude that premenopausal women with OSA are more likely than men and postmenopausal women to have structural abnormalities of their upper airway, to be extremely obese, and to be hypercapneic, and that OSA occurs in them independent of their upper airway dimensions.

Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia.

Twenty-six patients with sleep apnea had neuropsychologic testing prior to nocturnal sleep study in a sleep disorders clinic. The cognitive functioning of patients who had sleep apnea with associated hypoxemia was compared to nonhypoxemic patients with sleep apnea. The patients who had sleep apnea with hypoxemia had more severe cognitive impairment than those with sleep apnea without hypoxemia. The hypoxemic patients with sleep apnea had significantly poorer cognitive functioning on four of eight tests (p less than 0.05). In addition, the patients who had sleep apnea with hypoxemia had mean performance scores in the impaired range on measures of attention, concentration, complex problem-solving, and short-term recall of verbal and spatial information. In contrast, the patients who had sleep apnea without hypoxemia had no mean performance score in the impaired range. The degree of hypoxemia during sleep and wakefulness significantly correlated with the degree of overall cognitive impairment as rated by a neuropsychologist; however, measures of sleep fragmentation did not significantly correlate with overall cognitive impairment in patients with sleep apnea. We conclude that patients who have sleep apnea with associated hypoxemia have cognitive impairment which is more severe than those with sleep apnea without hypoxemia.

Effect of intranasal obstruction on breathing during sleep.

While nasal mucosal stimulation in animals has been reported to produce central apneas and while nasal packing in humans is known to produce sleep-disordered breathing, it is controversial whether intranasal obstruction in humans produces predominantly central or obstructive apnea. To answer this question, we studied eight normal men by having them sleep in random order with their nose open or occluded with petrolatum gauze. Esophageal pressure was measured to detect respiratory effort, and standard techniques were used to monitor and score the stages of sleep. Intranasal occlusion increased both the number of apneas plus hypopneas per hour of sleep and the minutes of obstructive events per hour of sleep (p less than 0.05). The minutes of central events per hour of sleep also increased significantly but not to the degree that occurred with obstructive events. Nasal obstruction produced no immediate changes in pulmonary function. The subject with the highest resistance measured through the mouth with the pulse flow method had the most apneas following nasal occlusion. We conclude that intranasal obstruction produces predominantly obstructive apneas and hypopneas during sleep.

Effect of doxapram on obstructive sleep apnea.

To determine whether treatment with a respiratory stimulant, doxapram hydrochloride, would improve obstructive sleep apnea, we administered the drug to four patients with this disease. Subjects were given a bolus of doxapram, 0.5 mg X kg-1 lean body mass, followed by a 1 mg X min-1 infusion throughout the night on one night and placebo another night. Doxapram produced improvement in the average oxyhemoglobin desaturation during apneic and hypopneic episodes and decreased average apnea length, but did not change the average number of oxyhemoglobin desaturations per hour of sleep or sleep efficiency. We conclude that doxapram, when administered at levels known to increase ventilatory drive, does not decrease the number of disordered breathing events during sleep but does cause termination of these events at higher levels of oxyhemoglobin saturation.

Collapsibility of the nasopharyngeal airway in obstructive sleep apnea.

To determine whether there is a relationship between pharyngeal airway collapsibility in awake subjects with obstructive sleep apnea (OSA) and the degree of disordered breathing during sleep, we studied 11 men with OSA and 10 normal men. Collapsibility of the nasopharyngeal airway was assessed by measuring nasopharyngeal resistance during the application of subatmospheric pressure. The pressure in a tightly fitting face mask was lowered at the end of expiration, drawing air out of the respiratory system and through the mask and a pneumotachygraph. Nasopharyngeal resistance was measured as the difference between mask and pharyngeal pressure divided by the flow rate. There was a highly significant correlation between nasopharyngeal resistance and both the number of apneas and hypopneas per hour of sleep (r = 0.71, p less than 0.001) and the number of oxyhemoglobin desaturation episodes (greater than 4%) per hour of sleep (r = 0.80, p less than 0.001). We conclude that the pharyngeal airway of awake patients with sleep apnea is more collapsible and has a higher resistance than normal when subatmospheric pressure is applied, and that the level of resistance correlates with the degree of sleep-disordered breathing.

Oxyhemoglobin saturation during sleep in subjects with and without the obesity-hypoventilation syndrome.

The etiology of the obesity-hypoventilation syndrome (OHS) is unknown. Recent reports that treatment of obstructive sleep apnea with nasal continuous positive-airway pressure eliminates the manifestations of OHS suggests that obstructive sleep apnea may contribute to OHS. The purpose of this study was to determine whether hypoxemia during sleep was more severe in patients with OHS than in those without OHS. In our sleep laboratory, we studied 32 subjects with a ratio of the forced expiratory volume in one second over the forced vital capacity (FEV1/FVC) greater than 0.73 and no neuromuscular disease. Seven subjects had OHS characterized by obesity and daytime hypercapnia, and 25 subjects did not. The seven patients with OHS all had sleep apnea. Of the 25 without OHS, 23 had sleep apnea. Subjects with OHS had significantly greater oxyhemoglobin desaturation during sleep than subjects without OHS, even when subjects with and without OHS were matched for sex and weight. These findings are consistent with the hypothesis that severe sleep apnea is a contributing cause of OHS.

Alae nasi electromyographic activity and timing in obstructive sleep apnea.

The alae nasi is an accessible dilator muscle of the upper airway located in the nose. We measured electromyograms (EMG) of the alae nasi to determine the relationship between their activity and timing to contraction of the rib cage muscles and diaphragm during obstructive apnea in nine patients. Alae nasi EMG were measured with surface electrodes and processed to obtain a moving time average. Contraction of the rib cage and diaphragm during apneas was detected with esophageal pressure. During non-rapid-eye-movement (NREM) sleep, there was a significant correlation in each patient between alae nasi EMG activity and the change in esophageal pressure. During rapid-eye-movement (REM) sleep, correlations were significantly lower than during NREM sleep. As the duration of each apnea increased, the activation of alae nasi EMG occurred progressively earlier than the change in esophageal pressure. We conclude that during obstructive apneas in NREM sleep, activity of the alae nasi increases when diaphragm and rib cage muscle force increases and the activation occurs earlier as each apneic episode progresses.

Apnea duration and hypoxemia during REM sleep in patients with obstructive sleep apnea.

Nocturnal sleep studies of 12 patients with obstructive sleep apnea and a matched control group of 12 subjects without the sleep apnea syndrome were analyzed to compare arterial oxyhemoglobin saturation (SaO2) during REM and non-REM sleep. Mean percentage of total sleep time spent in REM sleep was not significantly different in patients with obstructive sleep apnea and in subjects without significant apnea (14.2 +/- SEM 2.2 percent in patients vs 12.0 +/- 2.2 percent in nonapnea subjects). Apneas were longer during REM than non-REM sleep in all 12 patients (p less than 0.01). Oxyhemoglobin desaturations were more frequent during REM than non-REM sleep in both apnea patients and the control subjects. In addition, there was a greater mean fall in SaO2 per desaturation episode in both the apnea patients and non-apnea subjects. We conclude: 1) sleep apneas are longer during REM sleep than non-REM sleep in patients with obstructive sleep apnea; 2) hypoxemia is greater during REM sleep than non-REM sleep in subjects with and without the sleep apnea syndrome.

Naloxone improves sleep apnea in obese humans.

To test the hypothesis that endogenous opiates play a role in the etiology of the sleep apnea syndrome, we administered naloxone, an opiate antagonist, to ten obese humans with sleep apnea. On two separate nights we measured the frequency and severity of sleep apnea during naloxone infusion vs saline control infusion. The number of oxyhemoglobin desaturation episodes was not significantly lowered but the average maximal oxyhemoglobin desaturation fell significantly (P less than 0.01) with naloxone. The desaturation index (average maximal oxyhemoglobin desaturation times desaturations per hour) fell by 21 percent (P less than 0.05) on the night of naloxone infusion. Nine of the ten patients had a lower desaturation index with naloxone. REM sleep decreased by 80 percent (P less than 0.05) in the subjects in whom it was measured. We conclude that opiate antagonists hold promise in the treatment of sleep apnea and that the endogenous opiate system may be involved in the production of sleep apnea.

Comparison of indices used to detect hypoventilation during sleep.

Because there is no uniform method of measuring the severity of sleep apnea, we compared respiratory indices calculated from airflow and oxyhemoglobin saturation (SaO2) signals in 16 subjects during a night's sleep. Airflow was measured with a loosely fitting pneumotachograph or thermister and the following indices calculated manually: total apneas (A) and hypopneas (H); A and H per hour of sleep; total A H time; average duration of A H episodes, and A H index (the product of 2 and 4). SaO2 was measured with a Hewlett-Packard ear oximeter and the following indices calculated with a microcomputer; total number of desaturation (D) episodes; D episodes per hour of sleep; average maximum D; D index (the product of 7 and 8); SaO2 50 (1), and SaO2 10(1). There was a significant correlation among all indices; the highest correlation was between total A and H and total D (r = 0.97). We conclude that SaO2 indices calculated with a microcomputer correlate well with flow indices.

Compliance of chest wall in obese subjects.

Whereas studies in awake subjects have demonstrated that chest wall compliance (Ccw) is low in obese subjects, the one study performed on paralyzed obese subject found Ccw to be normal. The purpose of this study was to measure Ccw in awake obese subjects with the pulse-flow technique, a method which appears to detect respiratory muscle relaxation. Seven normal males, 14 obese males, and 8 obese females [body mass index (BMI) varied from 20 to 83 kg/m2] were studied in the seated position. Ccw was measured by blowing air at a constant flow into the mouth and lungs for approximately 2 s and calculated by dividing airflow in liters per second by the change in esophageal minus body surface pressure in centimeters of water per second. In normal and obese subjects we found no correlation between BMI and Ccw. We conclude that obesity does not decrease Ccw.

Induction of airway collapse with subatmospheric pressure in awake patients with sleep apnea.

To determine whether the pharyngeal airway is abnormal in awake patients with obstructive sleep apnea (OSA), we measured the ability of the pharyngeal airway to resist collapse from subatmospheric pressure applied to the nose in awake subjects, 12 with OSA and 12 controls. Subatmospheric pressure was applied to subjects placed in the supine position through a tightly fitting face mask. We measured airflow at the mask as well as mask, pharyngeal, and esophageal pressures. Ten patients developed airway obstruction when subatmospheric pressures between 17 and 40 cmH2O were applied. Obstruction did not occur in two patients with the least OSA. Obstruction did not occur in 10 controls; one obese control subject developed partial airway obstruction when -52 cmH2O was applied as did another with -41 cmH2O. We conclude that patients with significant OSA have an abnormal airway while they are awake and that application of subatmospheric pressure may be a useful screening test to detect OSA.

Effect of inhaled glycopyrrolate and atropine in asthma. Precipitated by exercise and cold air inhalation.

We compared the effects of inhaled glycopyrrolate (G), 1.3 mg, and atropine (A), 2.6 mg, and placebo on FEV1 and specific conductance (sGaw) before and after exercise in six men with exercise-induced asthma. Subjects exercised with cold air (-2 degrees C) 30 and 120 minutes after each aerosol treatment. Spirometry was performed and sGaw determined before aerosol treatment (baseline) and before and after exercise. Decreased airway tone was noted before exercising with A and G but not with placebo. The decreases in FEV1 and sGaw resulting from exercise were not significantly different among the three treatment groups at either exercise session. Postexercise FEV1 and sGaw were significantly higher after A and G compared to P. Dry mouth, flushing, and resting tachycardia were prominent with group A. Symptoms in G did not differ from those in P. This study suggests that A and G do not prevent bronchoconstriction induced by exercise and cold air but improve postexercise pulmonary function by achieving preexercise bronchodilation. Systemic side effects were minimal with G compared to A.

Treatment of obstructive sleep apnea with continuous nasal airflow delivered through nasal prongs.

We describe a new device for treating obstructive sleep apnea (OSA) which is similar to nasal CPAP, but less cumbersome. The device consists of a 7 mm diameter flexible tube terminating at one end in nasal prongs covered with foam cylinders. The foam cylinders are compressed, inserted into the nostrils and released, forming a tight seal. The other end of the catheter is attached to a compressor delivering between 7 and 15 L/min of air. We studied four men and two women with OSA, the first night without treatment and the following night with continuous nasal airflow. A desaturation index was calculated by multiplying the average number of desaturation episodes per hour of sleep times the average maximum desaturation per episode. With continuous nasal airflow there was a significant decrease in all parameters (p less than .025). We conclude that continuous nasal airflow decreased oxyhemoglobin desaturation in patients with OSA and may be useful in patients with mild-to-moderate OSA and in patients who do not tolerate nasal CPAP.