Faculty Bibliography

STUDY OBJECTIVE/OBJECTIVE:To compare polysomnographic recordings obtained in the home and laboratory setting. DESIGN AND SETTING/METHODS:Multicenter study comparing unsupervised polysomnography performed in the participant's home with polysomnography supervised at an academic sleep disorders center, using a randomized sequence of study setting. Sleep Heart Health Study (SHHS) standardized polysomnographic recording and scoring techniques were used for both settings. PARTICIPANTS/METHODS:64 of 76 non-SHHS participants recruited from 7 SHHS field sites who had both a laboratory and home polysomnogram meeting acceptable quality criteria. MEASUREMENTS AND RESULTS/RESULTS:Median sleep duration was greater in the home than in the laboratory (375 vs 318 minutes, respectively, P < .0001) as was sleep efficiency (86% vs 82%, respectively, P < .0024). Very small, but significant increases in percentage of rapid eye movement sleep and decreases in stage 1 sleep were noted in the laboratory. Employing multiple definitions of respiratory disturbance index (RDI), median RDI was similar in both settings (for example, RDI with 3% desaturation: home 12.4, range 0.6-67; laboratory 9.5, range 0.1-93.4, P = .41). Quartile analysis of laboratory RDI showed moderate agreement with home RDI measurements. Based on the mean of laboratory and home RDI and using a cutpoint of 20, there was a biphasic distribution, with the RDI 3% above 20 being more common in the recordings performed in the laboratory than in the home and below 20 being more common in the recordings performed in the home than in the laboratory. These differences could not be attributed to quality of recording, age, sex, or body mass index. CONCLUSIONS:Using SHHS methodology, median RDI was similar in the unattended home and attended laboratory setting with differences of small magnitude in some sleep parameters. Differences in RDI between settings resulted in a rate of disease misclassification that is similar to repeated studies in the same setting.

OBJECTIVE: To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I). STUDY DESIGN: This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity (FVC) and in 6-minute walk test (6MWT) distance through the use of the Wilcoxon rank sum test. RESULTS: The laronidase (n=22) and placebo (n=23) groups had similar baseline characteristics. After 26 weeks, patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC (median, 3.0; P=.009) and 38.1 meters in 6MWT distance (median, 38.5; P=.066; P=.039, analysis of covariance). Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans, and, in more severely affected patients, improved sleep apnea/hypopnea and shoulder flexion. Laronidase was well-tolerated. Nearly all patients receiving enzyme had development of IgG antibodies, without apparent clinical effects. CONCLUSIONS: In patients with MPS I, laronidase significantly improves respiratory function and physical capacity, reduces glycosaminoglycan storage, and has a favorable safety profile

STUDY OBJECTIVES: To examine the hypothesis that respiratory events in obstructive sleep apnea syndrome (OSAS) end in arousal not detected by conventional electroencephalographic (EEG) leads. DESIGN: Observational. SETTING: The study was conducted at a major metropolitan sleep disorders center. SUBJECTS: 10 patients with untreated OSAS and 5 patients undergoing continuous positive airway pressure (CPAP) titration for OSAS. MEASUREMENTS AND RESULTS: Standard clinical nocturnal polysomnography recordings were supplemented to include frontal EEG leads and airflow measured by nasal cannula pressure. In 10 untreated subjects, 1465 obstructive events (apneas, hypopneas, and flow limitation events), and in 5 subtherapeutic CPAP-titrated subjects, 459 total events were identified during non-rapid eye movement (REM) sleep only. American Academy of Sleep Medicine arousal criteria applied to central leads and to frontal leads allowed detection of an additional 24% respiratory event-related arousals by frontal leads than by conventional leads. Frontal arousal detection differed by event type: 16% of apneas, 21% of hypopneas, and 35% of flow limitation events. Autonomic correlate (increased heart rate) of both conventional and frontal arousals was similar (in a subgroup of 8 untreated patients, analyzing only flow limitation events). Tabulating frontal arousals separately for each frontal lead indicated that Fz as the sole frontal lead (added to conventional leads) increased detection of arousals by 19% over using only conventional leads (total of 92% of all obstructive respiratory events). CONCLUSIONS: The addition of a single frontal lead (Fz) yields additional respiratory-related arousal information that appears physiologically relevant. Future studies are needed to assess clinical relevance to the evaluation and treatment of sleep-disordered breathing.

Disordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index) was determined by unattended, single-night polysomnography at the participant's home. The prevalence of sleep-disordered breathing (apnea-hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing

The upper airway is the primary conduit for passage of air into the lungs. Its physiology has been the subject of intensive study: both passive mechanical and active neural influences contribute to its patency and collapsibility. Different models can be used to explain behavior of the upper airway, including the 'balance of forces' (airway suction pressure during inspiration versus upper airway dilator tone) and the Starling resistor mechanical model.As sleep is the primary state change responsible for sleep disordered breathing (SDB) and the obstructive apnea/hypopnea syndrome (OSAHS), understanding its effects on the upper airway is critical. These include changes in upper airway muscle dilator activity and associated changes in mechanics and reflex activity of the muscles. Currently SDB is thought to result from a combination of anatomical upper airway predisposition and changes in neural activation mechanisms intrinsic to sleep.Detection of SDB is based on identifying abnormal (high resistance) breaths and events, but the clinical tools used to detect these events and an understanding of their impact on symptoms is still evolving. Outcomes research to define which events are most important, and a better understanding of how events lead to physiologic consequences of the syndrome, including excessive daytime somnolence (EDS), will allow physiologic testing to objectively differentiate between 'normal' subjects and those with disease

STUDY OBJECTIVES: To determine the short-term variability of indices of disturbed respiration and sleep during 2 nights of unattended nonlaboratory polysomnography conducted several months apart. DESIGN: Participants were randomly selected using a block design with stratification on preliminary estimates of 2 criteria: respiratory disturbance index [RDI3% (apnea or hypopnea events associated with > or = 3% O2 desaturation): < 15/hour total sleep time, > or = 15/hour total sleep time] and sleep efficiency (SEff: < 85% and > or = 85%). The RDI and sleep data from initial and repeated polysomnography were compared. SETTING: NA. PARTICIPANTS: A subset of 99 participants in the Sleep Heart Health Study who agreed to have a repeat polysomnogram within 4 months of their original study. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Acceptable repeat polysomnograms were obtained in 91 subjects (mean study interval: 77 +/- 18 [sd] days; range: 31-112 days). There was no significant bias in RDI between study nights using several different RDI definitions including RDI3% and RDI4% (apnea or hypopnea events associated with > or = 4% O2 desaturation). Variability between studies estimated using intraclass correlations (ICC) ranged from 0.77 to 0.81. For subjects with a RDI3% < 15, variability increased as a function of increasing RDI, but for those with a RDI3% > or = 15, variability was constant. Body mass index, SEff, gender, or age did not directly predict RDI variability. Using RDI4% cutpoints of < or = 5, < or = 10 and < or = 15 events per hour of sleep demonstrated that 79.1%, 85.7%, and 87.9% of subjects, respectively, had the same classification of SDB status on both nights of study. There also was no significant bias in sleep staging, sleep efficiency, or arousal index between studies. However, variability was greater with ICC values ranging from 0.37 (% time in REM) to 0.76 (arousal index). CONCLUSION: In the Sleep Heart Health Study, accurate estimates of the severity of sleep-disordered breathing and the quality of sleep were obtained from a single night of unattended nonlaboratory polysomnography. These findings may be applicable to other large epidemiologic studies provided that similar recording techniques and quality-assurance procedures are followed

Prevention of acute hypercapnia during obstructive events in obstructive sleep apnea requires a balance between carbon dioxide (CO(2)) loading during the event and CO(2) unloading in the interevent period. Earlier studies have demonstrated that acute CO(2) retention may occur despite high interevent ventilation when the interevent duration is short relative to the duration of the preceding event. The present study examines the relationship between apnea and interapnea durations and relates this assessment of ventilatory periodicity to the degree of chronic hypercapnia in subjects with severe sleep apnea. A total of 18 subjects with sleep apnea (> 40 apnea/hour; chronic awake Pa(CO2) 36-62 mm Hg) and without underlying lung disease underwent polysomnography. For each event, apnea duration, interapnea duration, and apnea/interapnea duration ratio were determined. No relationship was observed between chronic Pa(CO2) and mean apnea or interapnea duration (p > 0.1). However, Pa(CO2) was directly related to apnea/interapnea duration ratio (r = 0.48; p < 0.05) such that with increasing chronic hypercapnia the interapnea duration shortens relative to the apnea duration. The present study suggests that control of the interapnea ventilatory duration relative to the duration of the preceding apnea, is an important component of the integrated ventilatory response to CO(2) loading during apnea and may contribute toward the development and/or maintenance of chronic hypercapnia in obstructive sleep apnea/hypopnea syndrome.