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Objective: During the early follicular phase, sleep-related luteinizing hormone (LH) pulse initiation is positively associated with brief awakenings but negatively associated with rapid eye movement (REM) sleep. The relationship between sleep architecture and LH pulse initiation has not been assessed in other cycle stages or in women with polycystic ovary syndrome (PCOS). Design and Methods: We performed concomitant frequent blood sampling (LH pulse analysis) and polysomnography on 8 normal women (cycle day 7–11) and 7 women with PCOS (at least cycle day 7). Results: In the normal women, the 5 min preceding LH pulses contained more wake epochs and fewer REM epochs than the 5 min preceding randomly determined time points (wake: 22.3 vs. 9.1%, p = 0.0111; REM: 4.4 vs. 18.8%, p = 0.0162). However, LH pulse initiation was not related to wake or REM epochs in PCOS; instead, the 5 min preceding LH pulses contained more slow-wave sleep (SWS) than the 5 min before random time points (20.9 vs. 6.7%, p = 0.0089). Compared to the normal subjects, the women with PCOS exhibited a higher REM-associated LH pulse frequency (p = 0.0443) and a lower proportion of wake epochs 0–5 min before LH pulses (p = 0.0205). Conclusions: Sleep-related inhibition of LH pulse generation during the later follicular phase is normally weakened by brief awakenings and strengthened by REM sleep. In women with PCOS, LH pulse initiation is not appropriately discouraged by REM sleep and may be encouraged by SWS; these abnormalities may contribute to a high sleep-related LH pulse frequency in PCOS.

Key points Adults and children with obstructive sleep disordered breathing make loud high frequency inspiratory sounds (HFIS, defined as inspiratory sounds >2 kHz) while sleeping. In an in vitro model, the intensity of high frequency sounds was found to be an estimate of airflow turbulence as reflected by the Reynold's number (Re). Hydraulic diameter (D) of the in vitro model could be calculated using Re determined by sound intensity, the pressure gradient, the Swamee–Jain formula and the Darcy formula. In four adult humans, D was calculated from measured HFIS intensity and the pressure gradient across the upper airway (estimated with oesophageal pressure, Pes). At apnoea termination when the airway opens, we observed (1) an increase in HFIS intensity suggesting an increase in turbulence (higher Re), and (2) a larger calculated D. This method allows dynamic estimation of changes in relative upper airway D in sleeping humans with narrowed upper airways. Abstract Obstructive sleep disordered breathing can cause death and significant morbidity in adults and children. We previously found that children with smaller upper airways (measured by magnetic resonance imaging while awake) generated loud high frequency inspiratory sounds (HFIS, defined as inspiratory sounds > 2 kHz) while they slept. The purpose of this study was (1) to determine what characteristics of airflow predicted HFIS intensity, and (b) to determine if we could calculate changes in hydraulic diameter (D) in both an in vitro model and in the upper airways of sleeping humans. In an in vitro model, high frequency sound intensity was an estimate of airflow turbulence as reflected by the Reynold's number (Re). D of the in vitro model was calculated using Re, the pressure gradient, Swamee–Jain formula and Darcy formula. D was proportional to but smaller than the actual diameters (r2 = 0.94). In humans, we measured HFIS intensity and the pressure gradient across the upper airway (estimated with oesophageal pressure, Pes) during polysomnography in four adult volunteers and applied the same formulae to calculate D. At apnoea termination when the airway opens, we observed (1) an increase in HFIS intensity suggesting an increase in turbulence (higher Re), and (2) a larger calculated D. This method allows dynamic estimation of changes in relative upper airway hydraulic diameter (D) in sleeping humans with narrowed upper airways.

Background Children with obstructive sleep disordered breathing (OSDB) have both impaired cognitive performance and frequent movements during sleep. It is not known whether movements during sleep are related to cognitive function. Methods We studied 56 children with adenotonsillar hypertrophy suspected of having OSDB with actigraphy for six consecutive days and nights, followed by cognitive and performance tests. Attended polysomnography was performed on the seventh night. Results Slower reaction time correlated with both higher sum of all movements during Time in Bed ( r 2 =0.19, p =0.001) and higher number of minutes with >5 movements/night ( r 2 =0.23, p =0.0003). Low Vocabulary, Similarities and General Memory Index scores correlated with more consolidation of movements (consecutive minutes with >5 movements) ( r 2 =0.16, p =0.002, r 2 =0.16, p =0.0026, respectively). Correlation with Vocabulary and Similarities scores improved when Time in Bed was added as an independently significant covariate ( r 2 =0.25, p =0.0006, r 2 =0.27, p =0.00028, respectively). Actigraphy correlated with Vocabulary and Similarities scores as well as polysomnography. Other cognitive or behavioral scores were not correlated with actigraphy or polysomnography. Children with more consolidation of movements had higher values for log10(OAHI+1) ( r 2 =0.38, p =0.000001). Conclusions (1) Frequency of movement during sleep correlated with impaired vigilance while consolidation of movements correlated with impaired verbal and memory skills. (2) OAHI was associated with more consolidation of movements.

OBJECTIVE. The purpose of this study was to determine if reduced time in bed as well as the degree of obstructive sleep-disordered breathing predicted the risk of impaired cognitive function in children with adenotonsillar hypertrophy suspected of having obstructive sleep-disordered breathing. DESIGN. We studied 56 children, aged 6 to 12 years, with adenotonsillar hypertrophy referred for suspected obstructive sleep-disordered breathing. Children were given a sleep diary and underwent wrist actigraphy for 6 consecutive days and nights. On day 7, the children were given general cognitive tests, memory tests, and continuous performance tests followed by attended polysomnography that night. Parents completed snoring and behavior questionnaires. RESULTS. Shorter mean time in bed for 6 nights and a history of nightly snoring were highly predictive of lower scores for the vocabulary and similarities cognitive function tests. Children who had a mean time in bed of 557 minutes and did not snore nightly were predicted to have vocabulary and similarities scores more than 1 standard deviation higher than children who had a mean time in bed of 521 minutes and snored nightly. Shorter mean time in bed and the log of the apnea hypopnea index also predicted lower vocabulary and similarities scores. Greater night to night variability in time in bed was significantly predictive of lower vocabulary and similarities scores, but variability was not as predictive as mean time in bed. Neither mean time in bed nor the coefficient of variation of time in bed predicted other cognitive or behavioral scores. CONCLUSIONS. Short or variable time in bed and nightly snoring or higher apnea hypopnea index predicted impaired vocabulary and similarities scores in children with adenotonsillar hypertrophy suspected of having obstructive sleep-disordered breathing. The degree of cognitive impairment attributable to short time in bed and obstructive sleep-disordered breathing is clinically very significant.

OBJECTIVE. The purpose of this study was to determine whether risks of impaired cognitive function could be predicted for children or groups of children with adenotonsillar hypertrophy who were suspected of having obstructive sleep-disordered breathing, from historical and polysomnographic variables used separately or in combination.METHODS. We studied 114 consecutive 6- to 12-year-old children with adenotonsillar hypertrophy, who were referred because of suspected obstructive sleep-disordered breathing, with questionnaires, assessment of tonsil size, general and memory cognitive tests, and attended polysomnography with the use of nasal pressure recording to detect flow.RESULTS. There were important significant relationships between snore group (snored every night versus less often), sleep efficiency, and race and 2 of 3 general cognitive tests (vocabulary and similarities). Significant but weaker relationships were observed between sleep latency and 2 memory indices (verbal memory and general memory) and between sleep efficiency and 2 behavior indices (attention-deficit/hyperactivity disorder summary and hyperactive-impulsive summary). The number of episodes of apnea and hypopnea per 1 hour of sleep predicted the vocabulary score as well as did the snore group, but it did not predict other tests as well as other variables. Tonsil size did not predict any cognitive or behavior score. Confidence intervals for group means were small, whereas prediction intervals for individual children were large.CONCLUSIONS. Risk of impaired cognitive function and behavior can be predicted from snoring history, sleep efficiency, sleep latency, and race but not tonsil size. The combination of snoring history and polysomnographic variables predicted impaired cognitive scores better than did either alone. The snoring history predicted more test scores than the number of episodes of apnea and hypopnea per 1 hour of sleep.

Obstructive sleep disordered breathing can cause death and significant morbidity in adults and children. We previously found that children with smaller upper airways (measured by magnetic resonance imaging while awake) generated loud high frequency inspiratory sounds (HFIS, defined as inspiratory sounds > 2 kHz) while they slept. The purpose of this study was (1) to determine what characteristics of airflow predicted HFIS intensity, and (b) to determine if we could calculate changes in hydraulic diameter (D) in both an in vitro model and in the upper airways of sleeping humans. In an in vitro model, high frequency sound intensity was an estimate of airflow turbulence as reflected by the Reynold's number (Re). D of the in vitro model was calculated using Re, the pressure gradient, Swamee–Jain formula and Darcy formula. D was proportional to but smaller than the actual diameters (r2 = 0.94). In humans, we measured HFIS intensity and the pressure gradient across the upper airway (estimated with oesophageal pressure, Pes) during polysomnography in four adult volunteers and applied the same formulae to calculate D. At apnoea termination when the airway opens, we observed (1) an increase in HFIS intensity suggesting an increase in turbulence (higher Re), and (2) a larger calculated D. This method allows dynamic estimation of changes in relative upper airway hydraulic diameter (D) in sleeping humans with narrowed upper airways.

Lonergan, Robert P., III, J. Catsby Ware, Richard L. Atkinson, W. Christopher Winter, and Paul M. Suratt. Sleep apnea in obese miniature pigs. J. Appl. Physiol. 84(2): 531–536, 1998.—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. 0 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.

Winter, W. Christopher, Tom Gampper, Spencer B. Gay, and Paul M. Suratt. Lateral pharyngeal fat pad pressure during breathing in anesthetized pigs. J. Appl. Physiol. 83(3): 688–694, 1997.—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.

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

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.

Quantitative sleep analysis through the use of polysomnography is a well established standard. Finding new ways to approach this, especially over multiple nights, is becoming more important due to a growing recognition of adverse effects from poor sleep and sleep disorders. The Non-Invasive Analysis of Physiological Signals (NAPSTM) system is a ballistocardiography-based monitoring system developed to measure heart rate, breathing rate and musculoskeletal movement that shows promise as a general sleep analysis tool. Overnight sleep studies were conducted on 20 healthy subjects during a validation clinical trial which compared the NAPS system to actigraphy, using polysomnography as the gold standard. The NAPS system [κ = 3D 0.478; 95% CI (0.463, 0.494); p-value < 0.001] outperformed actigraphy [κ = 3D 0.344; 95% CI (0.324, 0.358); p-value < 0.001], largely due to better performance in distinguishing sleep onset times as determined by polysomnography [NAPS mean bias estimate: -2.5 epochs; 95% CI (-16.8, 11.9); p = 3D 0.725 | Actigraphy mean bias estimate: -33.6 epochs; 95% CI (-57.4, -9.7); p = 3D 0.016)].

Snoring used to be a laughing matter. We now know that it can be a sign of obstructive sleep apnea, a serious condition characterized by repeated collapse of the pharynx during sleep, leading to pe...

The National Institutes of Health (NIH) Sleep Disorders Research Plan expresses a need for methods that can non-invasively monitor sleep characteristics. Forty subjects were tested using a novel, passive ballistocardiography-based system during an overnight study. We examined our system's ability to measure heart rate as compared to EKG while we also investigated our system's apnea and arousal detection capabilities as compared to conventional polysomnography. We found a strong correlation (r=0.972, p

The goal of this study was to determine how high-frequency inspiratory sounds (HFIS) are generated by sleeping children with obstructive sleep-disordered breathing (OSDB). We hypothesized that HFIS are generated when a high-velocity jet of air, generated by a narrowed upper airway, induces the upper airway to act as a resonating chamber. We tested two predictions of this hypothesis: 1) the upper airway is narrowed in children who make HFIS and 2) the length of the upper airway, calculated from HFIS harmonic intervals, is similar to that calculated from magnetic resonance imaging (MRI) scans. The study was conducted in the setting of a sleep laboratory. Participants included 29 children between 6 and 12 yr of age with adenotonsillar hypertrophy suspected of having OSDB. Minimum cross-sectional airway area and airway long dimensions (lips to larynx or soft palate) were measured in awake children with MRIs. Later that night, sound was recorded with a microphone suspended above their bed while the children underwent polysomnography. Sounds were later analyzed with fast Fourier transforms. We found that sleeping children who generated HFIS had significantly narrower upper airways compared with children who did not make HFIS [minimum airway area 20.5 ± 4.4 vs. 70.9 ± 22.5 mm2(mean ± SE), respectively; P = 0.02]. There was a significant inverse correlation between the log10of the narrowest airway area and the number of HFIS recorded per hour ( r2= 0.55, P < 0.00001). The harmonics characteristics of HFIS predicted that they were generated by sound resonating in chamber whose length was 12.0 ± 0.9 cm, which is similar to the MRI measured distance from the lips to the larynx of 12.8 ± 0.4 cm. In conclusion, these data suggest that children generate HFIS when 1) they have a narrowed upper airway and 2) their upper airway acts as a resonating chamber.

Study Objectives: We observed that some children with adenotonsillar hypertrophy and obstructive sleep-disordered breathing (SDB) make high-frequency inspiratory sounds (HFIS) during sleep. Our objective was to determine whether HFIS occur in most children with obstructive SDB and adenotonsillar hypertrophy and whether adenotonsillectomy reduces HFIS. Design: Prospective consecutive-entry trial. Setting: Sleep laboratory. Participants: Twenty-six children between 6 and 12 years of age with adenotonsillar hypertrophy suspected of having obstructive SDB. Measurements and Results: We performed polysomnography and measured sounds during sleep with a microphone suspended above the bed. Sounds were recorded on a computer at 44 kHz, analyzed with fast Fourier transformation for frequency content. HFIS were sounds occurring during an inspiration with frequencies greater than 2 kHz. HFIS were different from the low-frequency (< 2 kHz) sounds described in snoring adults. HFIS usually occurred in consecutive breaths, occasionally exceeding 100. We counted the number of HFIS that occurred per hour of sleep. Children who made more HFIS had more obstructive SDB than did those who did not make the HFIS, and there was a significant positive correlation between the number of HFIS and the obstructive apnea-hypopnea index. Children with more than 3 apneas and hypopneas per hour of sleep all made at least 10 HFIS per hour, and all children who had more than 10 HFIS per hour had obstructive apnea-hypopnea index values greater than 1. Children with adenotonsillar hypertrophy made more HFIS than did those children whose tonsils and adenoids had been removed. Conclusions: HFIS may be a marker of disturbed breathing during sleep in children with adenotonsillar hypertrophy.

Publisher Summary This chapter focuses on wavelet modeling and processing of nasal airflow traces. The study involved a careful review of the tracings extracted from sleep studies conducted on a group of 20 patients who were referred to the Sleep Disorders Laboratory of the University of Virginia Medical Center for evaluation of possible sleep apnea. The fundamental observation that nasal airflow varies continuously was made, so that the usual classification of breathing abnormalities into a finite number of categories is unnecessarily restrictive. Aspects of the signal that can be measured on a continuous scale were determined. The algorithm based on wavelet shrinkage estimation that was developed allowed obtaining precise measurements of the duration of the I/E/NF periods. On the basis of these durations derived measures of breathing that vary on a continuous scale and appear to be related to the characteristics and degree of severity of sleep-disordered breathing among subjects can be constructed. The results were obtained with simulation studies to assess how sensitive the performance of the algorithm is to varying input conditions and to the values of several tuning parameters.

Publisher Summary This chapter describes a simple computer algorithm of quantifying inductance plethysmography thoracic and abdominal signals and integrating it with sleep stages, disordered breathing events, and body position that can be used in clinical and research polysomnographic studies. The method of quantifying asynchrony is a modification of the linear transfer function method, a method that has been shown to be extremely accurate. This algorithm can be performed rapidly with a laptop computer and can be easily integrated into results from polysomography. The studies indicate that this algorithm may be useful for the diagnosis of obstructive sleep-disordered breathing. They also indicate that it may also be of use to speed technician scoring polysomnography studies by indicating regions of the study that contain events of interest such as arousals and awake periods. This algorithm is particularly useful because the measurements of chest and abdomen movements are nonintrusive. Thus, it can potentially be used in an outpatient environment and with children.

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.

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, p0.02). 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, p0.03). 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.

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.

Patients with obstructive sleep apnea or narcolepsy report difficulty remaining alert and attentive. To detect impaired vigilance, we designed Steer Clear, a computer program simulating a long and monotonous highway drive that presents 780 obstacles in 30 min. Sixty-two patients with sleep apnea hit a higher percentage of obstacles (4.3 +/- 0.6% [SEM]) than 12 age- and sex-matched subjects without sleep apnea (1.4 +/- 0.3%; p0.05) and 10 age- and sex-matched volunteers (1.2 +/- 0.3%; p0.05). Ten patients with untreated narcolepsy hit a higher percentage of obstacles while performing on Steer Clear (7.7 +/- 3.2%) than 10 age- and sex-matched subjects without narcolepsy (1.2 +/- 0.3%; p0.05). Poor performance on Steer Clear was associated with a higher auto accident rate in the patients with sleep apnea or narcolepsy (p0.01). Twenty-one patients who performed normally on Steer Clear had 1 accident in 5 years (0.05 accident/driver/5 yr), and in none of these accidents were they at fault as drivers. Twenty-five patients who performed poorly on Steer Clear had 5 auto accidents in 5 years (0.20 accident/driver/5 yr), and in 20% of these accidents they were at fault as drivers. Twenty-one patients who performed very poorly on Steer Clear had 8 auto accidents in 5 years (0.38 accident/driver/5 yr), and in 38% of these accidents they were at fault as drivers. These 21 patients who performed very poorly on Steer Clear (hitting4.5% of obstacles) had a significantly higher auto accident rate than the patients who performed normally (hitting1.8%). We conclude: (1) Patients with sleep apnea or narcolepsy performed more poorly on a test of vigilance, Steer Clear, than did control subjects; (2) Impaired vigilance as measured by Steer Clear is associated with a high automobile accident rate in patients with either sleep apnea or narcolepsy.

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.

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.

A 60-year-old man developed urinary stress incontinence and enuresis after a prostatectomy. The patient leaked urine with straining and complained of urine loss during sleep. Naps were associated with immediate enuresis requiring five protective undergarments daily. Incontinent episodes averaged three times a day and nocturia twice per night. His wife reported that he fell asleep quickly with snoring, gasping, and irregular respiration. The patient denied any nasal obstruction, sleep paralysis, or cataplexy. Over 5 years his weight had increased 4·5 kg. His history included hyperthyroidism, diverticulosis, slipped lumbar disc, and dietcontrolled diabetes mellitus. He was on no medication, denied smoking, but consumed alcohol as he had done before surgery. Examination revealed a healthy white man weighing 130·6 kg with a height of 1·88 m. His blood pressure was 146/80 mm Hg with a heart rate of 80 per min. Nose and throat examinations were clear and neurological examination was normal. Extremities revealed no clubbing, oedema, or cyanosis. Urinalysis was normal. Videourodynamics demonstrated stress incontinence with a low abdominal leak point pressure of 97 cm water indicating sphincter deficiency. An involuntary bladder contraction occurred at 322 mL, without evidence of residual urine, outlet obstruction, or sensory loss. Three transurethral collagen injections corrected the stress incontinence. However, enuresis persisted despite imipramine 50 mg three times a day or intanasal desmopressin 20 mg in the evening. Prompted voiding or reduced fluid consumption did not influence incontinence. Because of a history suspicious of sleep apnoea, sleep polysomnography was performed with conventional methods. His sleep study documented 4·8 apnoeas and 42·7 hypopnoeas which correlated with 32 episodes of desaturation per hour of sleep, and upper-airway obstruction. The average lowest saturation was 87·5% and the mean saturation 90·9%. Nasal continuous positive airway pressure (CPAP) at 11 cm water eliminated apnoeas and hypopnoeas and increased mean oxyhaemoglobin saturation to 95·8%. Following institution of home nasal CPAP, enuresis was abolished and undergarments were no longer required. This report represents another case of incontinence temporally linked to sleep apnoea. In both cases correction of sleep apnoea abolished enuresis. Although incontinence following radical prostatectomy can occur, urinary loss with sleep is rare. Sphincter deficiency is the usual cause of postprostatectomy incontinence and in our case, was corrected by the collagen injections. Yet the enuresis persisted indicating an additional cause for incontinence. Enuresis occurs in 0·6 to 1% of adults. Enuresis in childhood has been identified as a risk factor for incontinence. Enuresis has been attributed to a developmental delay in central autonomics or a decrease in nocturnal vasopressin release. During rapid-eye movement sleep serotonin-containing raphe neurons in the brainstem, which inhibit bladder activity, decrease firing. Patients with disorders affecting central autonomics can exhibit apnoea and incontinence. Low oxyhaemoglobin saturation could also have activated autonomic neurons, thereby triggering an involuntary detrusor contraction and enuresis. Indeed, enuresis has been reported in a high percentage of sickle-cell patients with hypoxia. The correction of apnoea and desaturation episodes in this patient suggests that the enuresis is directly triggered by sleep apnoea. Apnoea can evoke release of atrial natriuretic factor as a consequence of hypoxia or low intrapleural pressure. Increased atrial natriuretic factor may explain nocturia as a symptom of sleep apnoea. However, incontinence and enuresis occurring within moments of the patient falling asleep during the daytime is inconsistent with a volume-induced aetiology. Moreover, desmopressin failed to correct enuresis. The appearance of enuresis following surgery is curious. Possibly, subsequent weight gain worsened unsuspected apnoea. Alternatively, surgery could trigger detrusor instability. The onset of enuresis or nocturia in an adult with a history suspicious for apnoea should prompt sleep evaluation. Nasal CPAP may correct both incontinence and apnoea. A decrease in central inhibition during sleep may promote an opportunity for nocturia or enuresis.

(1982). Health Effects of Acute Carbon Disulfide Exposure. Journal of Toxicology: Clinical Toxicology: Vol. 19, No. 1, pp. 87-93.

We describe a pulse-flow method of measuring static lung compliance (CL) that is sensitive to rapid transients in CL. CL is measured by blowing air at a constant flow into the mouth and lungs for 2 s and calculated by dividing airflow in 1/s by the change in transpulmonary pressure in CMH2O/s. Pulse and static inspiratory CL was measured in five normals, four obstructives, five obese, and two patients with pulmonary fibrosis, Pulse CL after tidal breathing was correlated with static CL measured after deep breaths (r = 0.96). Pulse CL after deep breaths was higher than pulse CL after tidal breathing (p less than 0.01) and then static CL after deep breaths (p less than 0.05). In all subjects the lower the forced expiratory volume in 1 s, expressed as a percentage of vital capacity (FEV1/FVC), the greater the increase in pulse CL after a deep breath will be (r = 0.93). After deep breaths pulse CL fell from maximum CL to base-line CL at a rate related to 1/t2 where t equals the time in seconds from the last deep breath. We conclude that the increase in CL after a deep breath is related to the degree of airway obstruction and that the subsequent fall in CL is related to 1/t2.

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.

The constant-flow properties of time-cycled ventilators can be used to measure infant respiratory mechanics. We used a pulse method that does not interrupt inflationary flow to measure lung compliance (Cl) and respiratory system compliance (Crs) of 16 infants who required assisted ventilation. When the infants were relaxed, constant-flow inflation produced transrespiratory pressure tracings with constant slope segments. We calculated pulse Crs from inflationary flow divided by the slope of the pressure tracing, and compared the results to static and dynamic Crs values determined by standard methods. The pulse method accurately measured static Crs (r = .93) with a low intrasubject coefficient of variation (3.4%). Pulse and static Crs values consistently exceeded dynamic Crs (p less than .005). Cl measured with each method exceeded Crs (p less than .05), but the magnitude was clinically unimportant. Pulse Crs is a noninvasive measurement of static respiratory system recoil which proved to be sensitive to changes in respiratory muscle tone.

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.

The radiological features of 4 cases of acute silicosis in sandblasters are described and correlated with the pathological findings. Alveolar involvement was more extensive than in chronic silicosis; in 2 cases an alveolar exudate similar to that found in alveolar proteinosis was present. The radiological changes in acute silicosis differ substantially from those in classical silicosis, mainly on the basis of the differing alveolar response.

Data from flow volume curves suggest that flow measured at the mouth may be lower with maximal effort than with submaximal effort. We consequently studied the effect of maximal vs. submaximal expiratory effort on spirometric values. Significant increases in FVC, FEV1 or FEF25-75% with submaximal effort occurred in 12 of 38 subjects. All subjects who improved spirometric values had peak flows with submaximal efforts that varied from 91 to 65% of peak flow with maximal efforts. We conclude that spirometric values in some subjects are larger with submaximal rather than maximal effort.

We describe a method of measuring total static respiratory system compliance (Crs) in ventilated patients during inflation, which appears to detect relaxation of respiratory muscles and does not require an end-inspiratory pause or disconnection of a constant-flow intermittent mandatory ventilation (IMV) circuit. Flow is measured with a pneumotachometer attached to the endotracheal tube. Transthoracic pressure is taken as the difference between mouth pressure measured at the proximal pneumotachometer port and body surface (atmospheric) pressure. Flow and transthoracic pressure are displayed on separate channels of a strip chart recorder. The ventilator is adjusted to deliver a constant rule of air flow. When inflation begins, the pressure tracing shows an initial step rise related to the flow resistance of the subject followed by a section with a slower rise and a constant slope. Respiratory system compliance is calculated by dividing the flow rate in L/sec by the slope of the pressure tracing in cm H2O/sec. Pulse Crs was compared with static Crs measured with an end-inspiratory pause in nine subjects receiving mechanical ventilation. Correlation between pulse Crs and static Crs in nine ventilated patients was highly significant (4 = .997, pulse Crs = 1.00 static Crs + 0.001). We conclude that with the pulse method, one can measure static Crs during inflation without an inspiratory pause and without disconnecting an IMV circuit.

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.

Two quadriplegic patients suddenly lost consciousness and were found to have an elevated alveolar-arteriolar oxygen gradient. Their chest x-ray films were normal. Perfusion scintiscans of their lungs showed large areas with markedly reduced or absent perfusion. Ventilation scintiscans demonstrated absent or decreased ventilation to the hypoperfused areas, suggesting mucous plugging. In quadriplegic subjects who have an ineffective cough, acute mucous plugging can produce the sudden onset of hypoxia with essentially normal chest x-ray films, thus mimicking acute pulmonary embolism.

A computerized data acquisition and analysis routine was developed to quantitate respiratory disturbances [1,2] in sleeping patients. Polysomnographic recordings of patients consisted of electroencephalograms, electro-occulograms, submental electromyograms, air flow at the nose and mouth, esophogeal pressure, and oxyhemoglobin' saturation (SaO2). SaO2, a physiological effect of ventilatory airflow, was sampled every two seconds and stored on disk' during the night's study for subsequent analysis. Wild points in the data file can be marked so that they will be skipped during analysis. Patient polysomnographs were scored manually for sleep stage by a sleep technician. A file was then created containing the scored sleep information with time marks corresponding to each change in sleep stage during the study. An analysis routine used this file to develop indices of sleep apnea, severity for combinations or specific stages of sleep. These indices were: 1. (A) number of oxyhemoglobin desaturation episodes per hour; 2. (B) average maximum desaturation per episode; and 3. (C) desaturation index, the product of (A) and (B). A graph was plotted showing cumulative sleep time at given SaO2 values [4]. The degree of sleep apnea can be determined using these indices.

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.

We compared the effects of inhaled glycopyrrolate (G), 1.3 mg, and atropine (A), 2.6 mg, and placebo on FEV 1 and specific conductance (sGaw) before and after exercise in six men with exercise-induced asthma. Subjects exercised with cold air (–2°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 FEV 1 and sGaw resulting from exercise were not significantly different among the three treatment groups at either exercise session. Postexercise FEV 1 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.

This study examined the feasibility and yield of spirometric screening in a general medicine clinic. Each of 354 randomly selected patients answered a questionnaire on respiratory symptoms and performed pulmonary function tests. Pulmonary testing required approximately two minutes and cost 95 cents per patient. Former smokers who stopped smoking because of symptoms displayed a higher prevalence of abnormalities than expected, and life-long smokers a lower prevalence (P less than 0.001). Fifty-three percent of current smokers had an abnormal pulmonary function test, and forty-two percent of these had no severe pulmonary symptoms. Pulmonary function tests performed in an outpatient clinic are rapid and expensive. Such tests demonstrate a large number of abnormalities which can be used to encourage smoking cessation.

Although patients with obstructive sleep apnea often report falling asleep while driving, the frequency of auto accidents involving these patients has not been rigorously studied. Therefore, we compared the driving records of 29 patients with obstructive sleep apnea with those of 35 subjects without sleep apnea. The patients with sleep apnea had a sevenfold greater rate of automobile accidents than did the subjects without apnea (p less than 0.01). The percentage of persons with one or more accidents was also greater in the patients with apnea than in the control subjects without apnea (31% versus 6%, p less than 0.01). The percentage of persons having one or more accidents in which they were at fault was also greater in the patients with apnea than in the control subjects (24% versus 3%, p less than 0.02). The automobile accident rate of the patients with sleep apnea was 2.6 times the accident rate of all licensed drivers in the state of Virginia (p less than 0.02). In addition, 24% of patients with sleep apnea reported falling asleep at least once per week while driving. We conclude that patients with obstructive sleep apnea have a significantly higher frequency of auto accidents than do subjects without apnea. Impaired drivers with sleep apnea may cause many preventable auto accidents.

Acute pulmonary silicoproteinosis, massive proteinuria and fatal renal failure developed in a 23 year old male sandblaster. Examination of the kidney by immunofluorescence revealed granular deposits of immunoglobulin M (IgM) and the third component of complement (C3) along the glomerular basement membrane. Light microscopy disclosed mild proliferative glomerulonephritis with loss of colloidal iron staining for sialoprotein, and electron microscopy disclosed an increased density of epithelial cytoplasm, altered lysosomes and endothelial cell microtubular structures. The silicon content of the kidney was 264 parts per million (ppm), but particles of silicon were not demonstrated by electron microscopy. No primary or systemic causes of renal diseases were elucidated. The renal dysfunction apparently resulted from acute renal silicon toxicity, a new complication of acute pulmonary silicoproteinosis.

A respiratory sleep study should be performed in subjects suspected of having sleep apnea or in subjects suspected of hypoventilating during sleep who have unexplained hypersomnolence, erythrocytosis, pulmonary hypertension, or cor pulmonale. Sleep studies should include sleep staging, measurement of airflow, respiratory effort, oxyhemoglobin saturation, and electrocardiogram. Screening and at-home studies may be valuable, but further studies are necessary before they can be generally recommended. Analysis should include the number of apneas and hypopneas and an index of respiratory effort to determine whether the subject has obstructive, central, or mixed apnea. Oxyhemoglobin saturation should be analyzed quantitatively to note the degree of hypoxemia during sleep and to determine whether the subject could benefit from treatment to correct the hypoxia.

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.

Although nasal continuous positive airway pressure (CPAP) is effective therapy for obstructive sleep apnea (OSA), it requires a customfitted nasal appliance and large cumbersome tubing. We therefore designed and tested a new device (NFLOW) to deliver airflow to the nose of patients with OSA. We studied 13 patients the first night without treatment and the following night with NFLOW. The degree of sleep apnea was assessed by the number of desaturations per hour of sleep and the average maximum desaturation per episode. Treatment with NFLOW significantly decreased all parameters (P

Mononuclear cells from patients with sarcoidosis respond to Kveim tissue suspensions in vivo and from granulomas. We attempted to develop an in vitro Kveim test by adding Kveim material to monocytes and lymphocytes from patients with sarcoidosis and observing the cells in tissue culture. Sarcoid leukocytes were grown in culture with either Kveim suspensions (100 microgram/ml), control human spleen extract (100 microgram/ml) or no foreign antigen. After 7 to 9 days, we counted the number of cells adherent to glass, the number of cells with nucleoli, and the number of giant cells. Despite equal monocyte inocula, cultures of sarcoid leukocytes consistently had more cells adherent to glass than did cultures from normal donors regardless of whether Kveim, spleen, or no antigen was added to the cultures. There were no significant differences in giant cell formation or in the number of cells with nucleoli in the sarcoid compared with the control cultures.

Bronchodilation was produced in normal subjects by inhalation of high doses of a quaternary parasympatholytic agent (glycopyrrolate), and responses were compared with those of atropine and a placebo. Both drugs induced significant increases in specific airway conductance (SGaw) and forced expiratory flows, but the effects of glycopyrrolate were sustained significantly longer (> 6 h). Whereas atropine produced an increased heart rate (26%) and severe dry mouth in all subjects, these symptoms were absent with glycopyrrolate and placebo. Therefore, glycopyrrolate produces significant bronchodilation of long duration but free of the side effects of muscarinic blockade that characterize atropine inhalation.