Sleep apneic activity in older healthy subjects

The percentage of subjects with sleep apneic activity was significantly greater in a group of 60 healthy subjects who were 50 yr and older compared with a control group of 69 subjects who were younger than 50 yr. Sixteen of the older subjects (26.7%) and six of the younger subjects (8.7%) met the criteria for sleep apneic activity, i.e., 3-29 episodes per night. However, only one of the older subjects (1.7%) had enough sleep apneic activity (30 or more episodes in a night) to meet the definition of the condition of sleep apnea. In both age groups, sleep apneic activity (SAA) was slightly more prevalent in males than females. Older subjects with SAA were not significantly heavier than those without SAA but were so when compared with the younger subjects with SAA. In the 29 older subjects for whom hemoglobin O2 saturation (Sao2) was recorded, those with SAA had a significantly lower mean minimum Sao2 value (87%) than those without (92%).     

Sleep Apnea-Hypopnea Quantification by Cardiovascular Data Analysis

Sleep disorders are a major risk factor for cardiovascular diseases. Sleep apnea is the most common sleep disturbance and its detection relies on a polysomnography, i.e., a combination of several medical examinations performed during a monitored sleep night. In order to detect occurrences of sleep apnea without the need of combined recordings, we focus our efforts on extracting a quantifier related to the events of sleep apnea from a cardiovascular time series, namely systolic blood pressure (SBP). Physiologic time series are generally highly nonstationary and entrap the application of conventional tools that require a stationary condition. In our study, data nonstationarities are uncovered by a segmentation procedure which splits the signal into stationary patches, providing local quantities such as mean and variance of the SBP signal in each stationary patch, as well as its duration . We analysed the data of 26 apneic diagnosed individuals, divided into hypertensive and normotensive groups, and compared the results with those of a control group. From the segmentation procedure, we identified that the average duration , as well as the average variance , are correlated to the apnea-hypoapnea index (AHI), previously obtained by polysomnographic exams. Moreover, our results unveil an oscillatory pattern in apneic subjects, whose amplitude is also correlated with AHI. All these quantities allow to separate apneic individuals, with an accuracy of at least . Therefore, they provide alternative criteria to detect sleep apnea based on a single time series, the systolic blood pressure.     

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.     

Behavioral arousal in newborn infants and its association with termination of apnea

Arousal is an important protective mechanism that aids in the resolution of obstructive sleep apnea in adults and children, but its role in neonatal apnea has not been investigated. The primary aim of the present study was to determine the role of arousal in the termination of apnea in preterm infants. Videorecording was used to identify spontaneous behavioral arousal in a group of healthy full-term (n = 7) and preterm (n = 10) infants before and during polygraphic monitoring of cardiorespiratory variables and in a group of preterm infants with apnea (n = 10) during similar polygraphic monitoring. Spontaneous arousal rates (mean +/- SE) in full-term infants before and during polygraphic monitoring were 0.18 +/- 0.03 and 0.23 +/- 0.07 episodes/min, respectively. Corresponding values in nonapneic preterm infants were 0.24 +/- 0.03 and 0.24 +/- 0.02 episodes/min. In apneic preterm infants, mean spontaneous arousal rate during polygraphic recording was 0.26 +/- 0.02, but it was considerably higher during apneic sleep periods (0.59 +/- 0.17) than during nonapneic sleep periods (0.25 +/- 0.01). The frequency of occurrence of arousal was significantly higher (P less than 0.005) in long vs. short apnea, mixed vs. central apnea, and severe vs. mild apnea. Although a clear association between arousal and apneic resolution was observed in preterm infants, lack of arousal responses in a large number of apneic episodes suggests that behavioral arousal is not essential for the termination of apnea in these infants.     

Obstructive sleep apnea. Trends in therapy.

The National Commission on Sleep Disorders Research, in its report to Congress, concluded that the primary care community generally does not understand sleep disorders. Obstructive sleep apnea carries a risk of substantial morbidity and mortality. Excessive daytime sleepiness results from fragmented sleep and microarousals associated with apneic events. It causes poor work performance and increases the incidence of automobile accidents due to driving while drowsy. The commission estimates that the loss of productivity in the United States from excessive daytime sleepiness is more than $20 billion per year. Obstructive sleep apnea is strongly associated with hypertension, myocardial infarction, and stroke. Risk factors for obstructive sleep apnea include male sex, obesity, older age, craniofacial anomalies, and familial risk. Treatment is based on documenting the disorder by polysomnography. Medical management of the syndrome includes weight loss and nasal continuous positive airway pressure. A network of follow-up and support is necessary to maintain compliance. Surgical treatment is reserved for those for whom nasal airway pressure treatment fails. A surgical protocol is presented that demonstrates efficacy equal to nasal airway pressure treatment. Primary care physicians should assume the responsibility of identifying patients at risk for obstructive sleep apnea and refer them appropriately.     

Compensatory responses to upper airway obstruction in obese apneic men and women

Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age (n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow (P = 0.003) and inspiratory duty cycle (P = 0.017) in response to prolonged periods of UAO and an ～20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) (P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.     

Increased ventricular premature contraction frequency during rem sleep in patients with coronary artery disease and obstructive sleep apnea

Background

Patients with obstructive sleep apnea are reported to have a peak of sudden cardiac death at night, in contrast to patients without apnea whose peak is in the morning. We hypothesized that ventricular premature contraction (VPC) frequency would correlate with measures of apnea and sympathetic activity.

Methods

Electrocardiograms from a sleep study of 125 patients with coronary artery disease were evaluated. Patients were categorized by apnea-hypopnea index (AHI) into Moderate (AHI <15) or Severe (AHI>15) apnea groups. Sleep stages studied were Wake, S1, S2, S34, and rapid eye movement (REM). Parameters of a potent autonomically-based risk predictor for sudden cardiac death called heart rate turbulence were calculated.

Results

There were 74 Moderate and 51 Severe obstructive sleep apnea patients. VPC frequency was affected significantly by sleep stage (Wake, S2 and REM, F=5.8, p<.005) and by AHI (F=8.7, p<.005). In Severe apnea patients, VPC frequency was higher in REM than in Wake (p=.011). In contrast, patients with Moderate apnea had fewer VPCs and exhibited no sleep stage dependence (p=.19). Oxygen desaturation duration per apnea episode correlated positively with AHI (r²=.71, p<.0001), and was longer in REM than in non-REM (p<.0001). The heart rate turbulence parameter TS correlated negatively with oxygen desaturation duration in REM (r²=.06, p=.014).

Conclusions

Higher VPC frequency coupled with higher sympathetic activity caused by longer apnea episodes in REM sleep may be one reason for increased nocturnal death in apneic patients.     

The Severity of Nocturnal Hypoxia but Not Abdominal Adiposity Is Associated with Insulin Resistance in Non-Obese Men with Sleep Apnea

Background

Beyond obesity, sleep apnea syndrome is frequently associated with excess abdominal adiposity that could contribute to the deteriorated cardiometabolic risk profile of apneic patients.

Methods

The present study addressed the respective contribution of the severity of sleep apnea syndrome and excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15 events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic men with high-waist circumference (>94 cm) were compared to 17 apneic men with low-waist circumference.

Results

Apneic men with high-waist circumference had higher AUC glucose and AUC insulin than apneic men with low-waist circumference. Accordingly, apneic men with high-waist circumference had higher hepatic insulin resistance as reflected by higher HOMA-resistance index, and lower global insulin sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived from OGTT). The sleep structure and the apnea-hypopnea index were not different between the two groups. However, apneic men with high-waist circumference presented with lower mean nocturnal oxyhemoglobin (SpO₂). In the 38 men, waist circumference and mean nocturnal SpO₂ were inversely correlated (r = −0.43, p = 0.011) and were both associated with plasma glucose/insulin homeostasis indices: the higher the waist circumference, the lower the mean nocturnal SpO₂, the lower the insulin-sensitivity. Finally, in multivariable regression model, mean nocturnal SpO₂ and not waist circumference was associated with insulin-resistance.

Conclusion

Thus, excess abdominal adiposity in non obese apneic men was associated with a deteriorated insulin-sensitivity that could be driven by a more severe nocturnal hypoxemia.     

Increased propensity for apnea via dopamine-induced carotid body inhibition in sleeping dogs.

We determined the effects of specific carotid body chemoreceptor inhibition on the propensity for apnea during sleep. We reduced the responsiveness of the carotid body chemoreceptors using intravenous dopamine infusions during non-rapid eye movement sleep in six dogs. Then we quantified the difference in end-tidal Pco(2) (Pet(CO(2))) between eupnea and the apneic threshold, the "CO(2) reserve," by gradually reducing Pet(CO(2)) transiently with pressure support ventilation at progressively increased tidal volume until apnea occurred. Dopamine infusions decreased steady-state eupneic ventilation by 15 +/- 6%, causing a mean CO(2) retention of 3.9 +/- 1.9 mmHg and a brief period of ventilatory instability. The apneic threshold Pet(CO(2)) rose 5.1 +/- 1.9 Torr; thus the CO(2) reserve was narrowed from -3.9 +/- 0.62 Torr in control to -2.7 +/- 0.78 Torr with dopamine. This decrease in the CO(2) reserve with dopamine resulted solely from the 20.5 +/- 11.3% increase in plant gain; the slope of the ventilatory response to CO(2) below eupnea was unchanged from normal. We conclude that specific carotid chemoreceptor inhibition with dopamine increases the propensity for apnea during sleep by narrowing the CO(2) reserve below eupnea. This narrowing is due solely to an increase in plant gain as the slope of the ventilatory response to CO(2) below eupnea was unchanged from normal control. These findings have implications for the role of chemoreceptor inhibition/stimulation in the genesis of apnea and breathing periodicity during sleep.     

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.     

Effects of increase in body temperature on the breathing pattern in premature infants

This study was designed to determine the effects of a mild increase in body temperature within the physiological range (0.8 degrees C) in healthy premature infants. Seven unsedated premature infants (38.4 wk +/- 1.5 postconceptional age) were monitored polygraphically during "morning naps" in an incubator under two different environmental temperatures: (1) normothermia with the incubator temperature set at 25 degrees C and the rectal temperature equal to 36.9 degrees C +/- 0.1; (2) hyperthermia with the incubator temperature set at 35 degrees C and the rectal temperature equal to 37.7 degrees C +/- 0.15. Respiratory frequency and heart rate, respiratory events, i.e., central and obstructive apnea, and periodic breathing with and without apneic oscillations were tabulated. Results for respiratory events were expressed as (1) indices of the total number of respiratory events, and of specific respiratory events per hour of total, quiet and active sleep times; (2) duration of total and specific respiratory events expressed as a percentage of total sleep, quiet and active sleep times. Respiratory frequency and heart rate were significantly increased by hyperthermia (P less than 0.05). Hyperthermia did not significantly modify the indices or the duration of central and obstructive apnea. But the indices and the duration of periodic breathing with and without apneic oscillations were significantly increased by hyperthermia during active sleep (P less than 0.05) but not during quiet sleep. The present study shows that a mild increase in body temperature within the physiological range in premature infants enhances the instability of the breathing pattern during active sleep.     

Effects of progesterone on apneic events during behaviorally defined sleep in male rats

Drug therapy with progesterone has been applied to the patients with sleep apnea syndrome, but its clinical efficacy is equivocal. In the present study, we examined the effects of progesterone (1 and 30 mg/kg, i.p.) on the apneic events during behaviorally defined sleep in male rats at 4, 14 and 26 weeks of age by using a whole body plethysmographic measurement. The number of events of spontaneous apnea (SA) and post-sigh apnea (PSA) increased with aging. The duration of SA or PSA was also prolonged in old rats. A low dose (1 mg/kg) of progesterone significantly decreased the number of both SA and PSA, and this effect increased in an age-dependent manner. However, progesterone had no effect on the duration of SA and PSA. Neither the basal respiratory rate nor the total sleep time was changed. On the other hand, a higher dose (30 mg/kg) of progesterone had no effect on the number of SA and PSA, while it prolonged the duration of PSA. It also prolonged the total sleep time without affecting the basal respiratory rate. Pretreatment with mifepristone (5 mg /kg, i.p.), an antagonist of progesterone receptors, inhibited the effects of the low dose of progesterone, but did not show any antagonistic effect on the high dose-induced changes. These results suggest that the progesterone-mediated mechanisms are involved, at least partly, in respiratory function during sleep and the progesterone therapy is possibly effective within an appropriate dose range for the sleep apnea syndrome.     

Automated sleep breath disorders detection utilizing patient sound analysis

Results of clinical studies suggest that there is a relationship between breathing-related sleep disorders and behavioral disorder and health effects. Apnea is considered one of the major sleep disorders with great accession in population and significant impact on patient's health. Symptoms include disruption of oxygenation, snoring, choking sensations, apneic episodes, poor concentration, memory loss, and daytime somnolence. Diagnosis of apnea and breath disorders involves monitoring patient's biosignals and breath during sleep in specialized clinics requiring expensive equipment and technical personnel. This paper discusses the design and technical details of an integrated low-cost system capable for preliminary detection of sleep breath disorders at patient's home utilizing patient sound signals. The paper describes the proposed architecture and the corresponding HW and SW modules, along with a preliminary evaluation.     

Hypercalcemia in infants presenting with apnea.

To our knowledge apnea in infants has not been associated with hypercalcemia. We describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea; six of the seven were otherwise healthy. The apneic attacks were brief, and normal breathing was restored spontaneously or after tactile stimulation. The attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age. The only abnormal finding common to all of the patients was hypercalcemia. Idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one. Our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy.     

Tracheal hysteresis in sleep apnea

The collapsibility of pharyngeal walls, characteristic of patients with obstructive sleep apnea, likely results from reduced tone of the pharyngeal muscles. This reduction in the upper airway muscle tone may not end at the pharynx but may extend further distally, e.g., into the trachea. Because tracheal tone cannot be measured directly in conscious humans, we inferred the tone from the relative hysteresis of the tracheal area compared with the lung. Relative hysteresis was measured by plotting the cross-sectional area of a tracheal segment obtained by the acoustic reflection technique vs. lung volume. All measurements were performed during wakefulness. We found that in 42 patients with obstructive sleep apnea (apnea/hypopnea index greater than 10), relative hysteresis of the proximal trachea was predominantly clockwise, i.e., smaller than that of the lung parenchyma; in the 33 nonapneic patients (apnea/hypopnea index less than or equal to 10), it was predominantly counter-clockwise, i.e., larger than that of the lung parenchyma. For the distal trachea all patients, apneic and nonapneic, had similar, clockwise, relative hysteresis. We conclude that reduction in the upper airway muscle tone in patients with obstructive sleep apnea extends into the trachea.     

Spectral analysis of ventilation in elderly subjects awake and asleep

We studied the periodicities of ventilation in elderly subjects using digital comb filtering. Two groups of subjects were studied, those with and without sleep apnea. Measurements were made in wakefulness, stage 1-2 sleep, and where possible in stage 3-4 sleep. For each of the digital filters we calculated the average power of the oscillatory output. To compare subject groups we first specifically determined the average power in the filter with the maximum output. The mean of this measurement was greater in elderly subjects with apnea compared with those without apnea, both during wakefulness and stage 1-2 sleep. In both groups of subjects the cycle time of the major ventilatory oscillations was on the order of 40-60 s. There was no difference in this cycle time between the two groups of subjects in wakefulness or stage 1-2 sleep. Thus, whereas similar oscillatory processes occur in subjects with and without apnea, it is the magnitude of the oscillation that differs between the two groups. These conclusions are supported by analysis of the output of individual filters of the digital comb filter. In both groups, stage 1-2 sleep produced significantly increased oscillations in ventilation. Both in wakefulness and stage 1-2 sleep, significantly greater periodicities occurred in the apneic compared with the nonapneic group. In the few subjects who had sufficient data in stage 3-4 sleep for spectral analysis, ventilatory oscillations were virtually absent in this state. Our data suggest that subjects who develop apnea during sleep have an increased propensity for periodic breathing even while awake.     

A model of ventilatory instability induced in the unrestrained rat.

A classic conditioning paradigm was used to examine the hypothesis that perturbations during sleep in the neonate rat can have a lasting impact on breathing. During the first 4 wk of life, stimuli were presented to rats during behaviorally defined sleep. In a conditioned hypoxic (CH) group, brief periods of hypoxic gas were used as the unconditioned stimulus. Tactile and auditory stimuli were used as the conditioned stimuli. In a conditioned control (CC) group, air was used as the unconditioned stimulus. A third group of unconditioned control (UC) rats was not exposed to the conditioning paradigm. Animals were provided routine care for 3.5 mo; ventilation was then assessed using plethysmography. Conditioning during neonatal life produced increased ventilatory irregularities and apnea during behaviorally defined sleep in adult rats. Both CH and CC rats showed a significantly greater number of apneic events compared with UC rats. Over a 2-h sleep period, CH rats exhibited a total of 105.1 +/- 9.4 (SE) apneic events, CC rats 69.4 +/- 4.2 events, and UC rats 42.1 +/- 3.1 events [F(2,18) = 25.568; P < 0.0001]. These findings suggest that experiences in the first few weeks of life will alter ventilatory patterning in the adult animal.     

High-frequency ventilation-induced apnea: interaction of frequency, volume, FRC, and CO2

Apnea is often observed during high-frequency oscillatory ventilation (HFOV). This study on anesthetized dogs varied the oscillator frequency (f) and determined the stroke volume (SV) at which apnea occurred. Relaxation functional residual capacity (FRC) and the eupneic breathing end-tidal CO2 level were held constant. Airway pressure and CO2 were measured from a side port of the tracheostomy cannula. An arterial cannula was inserted for blood gas analysis. Diaphragm electromyogram (EMG) was recorded with bipolar electrodes. Apnea was defined as the absence of phasic diaphragm EMG activity for a minimum of 60 s. During HFOV, SV was increased at each f (5-40 Hz) until apnea occurred. The apnea inducing SV decreased as f increased. SV was minimal at 25-30 Hz. Frequencies greater than 30 Hz required increased SV to produce apnea. The f-SV curve was defined as the apneic threshold. Increased FRC resulted in a downward shift (less SV at the same f) in the apneic threshold. Elevated CO2 caused an upward shift (more SV at the same f) in the apneic threshold. These results demonstrate that the apnea elicited by HFOV is dependent on the interaction of oscillator f and SV, the FRC, and CO2.     

Impact of age on breathing and resistive pressure in people with and without sleep apnea.

We investigated the effect of age on breathing and total pulmonary resistance (RL) during sleep by studying elderly (>65 yr) and young (25-38 yr) people without sleep apnea (EN and YN, respectively) matched for body mass index (BMI). To determine the impact of sleep apnea on age-related changes in breathing, we studied elderly and young apneic patients (EA and YA, respectively) matched for apnea and BMI. In all groups (n = 11), breathing during periods of stable sleep was analyzed to evaluate the intrinsic variability of respiratory control mechanisms. In the absence of sleep apnea, the variability of the breathing was similar in the elderly and young [mean (+/- SD) coefficient of variation (CV) of tidal volume (VT); wake: EN 21.0 +/- 14.9%, YN 14.7 +/- 5.5%; sleep: EN 14.0 +/- 6.0%; YN 11.5 +/- 6.4%]. In patients with sleep apnea, breathing during stable sleep was more irregular, but there were no age-related differences (CV of VT; wake: EA 22.0 +/- 11.6%, YA 16.7 +/- 11.3%; sleep: EA 32.8 +/- 24.9%, YA 25.2 +/- 16.3%). In addition, EN tended to have a higher RL (n = 6, RL midinspiration, wake: EN 7.1 +/- 3.0; YN 9.1 +/- 6.4 cmH(2)O. l(-1). s, sleep: EN 17.5 +/- 11.7; YN 9.8 +/- 2.0 cmH(2)O. l(-1). s). We conclude that aging per se does not contribute to the intrinsic variability of respiratory control mechanisms, although there may be a lower probability of finding elderly people without respiratory instability.