Influence of Sleep Stage on LH Pulse Initiation in the Normal Late Follicular Phase and in Polycystic Ovary Syndrome.

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.

Airway turbulence and changes in upper airway hydraulic diameter can be estimated from the intensity of high frequency inspiratory sounds in sleeping adults.

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 (r(2) = 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.

Movements during sleep correlate with impaired attention and verbal and memory skills in children with adenotonsillar hypertrophy suspected of having obstructive sleep disordered breathing.

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.

Sleep assessment using a passive ballistocardiography-based system: preliminary validation.

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 (NAPS) 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 [kappa=0.478; 95% CI (0.463, 0.494); p-value<0.001] outperformed actigraphy [kappa=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=0.725|Actigraphy mean bias estimate: -33.6 epochs; 95% CI (-57.4, -9.7); p=0.016)].

Development and preliminary validation of heart rate and breathing rate detection using a passive, ballistocardiography-based sleep monitoring system.

Techniques such as ballistocardiography (BCG) that can provide noninvasive long-term physiological monitoring have gained interest due to a growing recognition of adverse effects from poor sleep and sleep disorders. The noninvasive analysis of physiological signals (NAPS) system is a BCG-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 40 healthy subjects during a clinical trial at the University of Virginia. The NAPS system's measures of heart rate and breathing rate were compared to ECG, pulse oximetry, and respiratory inductance plethysmography (RIP). The subjects were split into a training dataset and a validation dataset, maintaining similar demographics in each set. The NAPS system accurately detected heart rate, averaged over the prescribed 30-s epochs, to within less than 2.72 beats per minute of ECG, and accurately detected breathing rate, averaged over the same epochs, to within 2.10 breaths per minute of RIP bands used in polysomnography.

Reduced time in bed and obstructive sleep-disordered breathing in children are associated with cognitive impairment.

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.

Cognitive function and behavior of children with adenotonsillar hypertrophy suspected of having obstructive sleep-disordered breathing.

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.

Increases in overweight after adenotonsillectomy in overweight children with obstructive sleep-disordered breathing are associated with decreases in motor activity and hyperactivity.

OBJECTIVE: To examine the effect of adenotonsillectomy (T&A) in children with obstructive sleep-disordered breathing on growth, hyperactivity, and sleep and waking motor activity. METHODS: We studied 54 children who were aged 6 to 12 years and had adenotonsillar hypertrophy and an obstructive apnea-hypopnea index of > or =1 before and 12 months after they all received adenotonsillectomy (T&A). We measured their height, weight, percentage overweight (patient BMI - BMI at 50th percentile)/BMI at 50th percentile x 100) and obtained a hyperactivity score from parent report on a standardized behavior questionnaire scale. A subset of 21 of these children were also studied for motor activity by wrist actigraphy for 7 consecutive days and nights before and 12 months after T&A. RESULTS: After T&A, mean obstructive apnea-hypopnea index decreased from 7.6 to 0.6. Height percentile did not change, but weight percentile increased; as a consequence, percentage overweight increased from 32.0% to 36.3%. Hyperactivity scores and total daily motor activity were reduced after T&A. From linear regression, the reduction in hyperactivity scores predicted an increase in percentage overweight. Reduced motor activity was correlated with increased percentage overweight. CONCLUSIONS: An increase in percentage overweight after T&A in children with obstructive sleep-disordered breathing is correlated to decreased child hyperactivity scores and to decreased measured motor activity in the subset studied. These associations suggest that the increase in overweight may be attributable to reductions in physical activity and fidgeting energy expenditure.

An upper airway resonator model of high-frequency inspiratory sounds in children with sleep-disordered breathing.

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 mm(2) (mean +/- SE), respectively; P = 0.02]. There was a significant inverse correlation between the log(10) of the narrowest airway area and the number of HFIS recorded per hour (r(2) = 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.

Children with obstructive sleep-disordered breathing generate high-frequency inspiratory sounds during sleep.

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.