Faculty Bibliography

STUDY OBJECTIVES: Evaluate the utility of overnight monitoring limited to nasal cannula airflow and oximetry in the diagnosis of obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: Prospective randomized study, blinded analysis. SETTING: Sleep disorder center, academic institution. PARTICIPANTS: 56 patients with suspected OSAHS, 10 normal volunteers. MEASUREMENTS AND RESULTS: In-laboratory full nocturnal polysomnography (NPSG) and unattended ambulatory study with monitoring of only airflow and oximetry performed in randomized order. Obstructive respiratory events were scored on the full NPSG while visualizing all signals and then rescored on the full NPSG and on the ambulatory study while visualizing only airflow and oximetry signals. Respiratory disturbance indexes (RDI) for the limited studies (RDIFlowNPSG and RDIFlowAmbulatory) were calculated as the sum of the apneas and hypopneas (defined using airflow amplitude and O2 desaturation) divided by the valid flow-signal time. The reference RDIFullNPSG was calculated from the sum of the apneas and hypopneas (defined using flow amplitude, O2 desaturation and electroencephalographic arousal) identified on the full NPSG divided by the total sleep time. RDIFullNPSG was greater than RDIFlowNPSG (bias = 5.6 events per hour) and RDIFlowAmbulatory (bias = 10.9 events per hour), but the differences were mainly in subjects with an RDI > 40 events per hour. The diagnostic sensitivity and specificity for the diagnosis of OSAHS using a cutoff of 18 events per hour were 96% and 93% using the flow signal from the NPSG and 88% and 92% using the flow signal from the ambulatory study performed on a separate night. CONCLUSIONS: In subjects with OSAHS, analysis of the flow signal from a nasal cannula can provide an RDI similar to that obtained in a full NPSG.

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