Faculty Bibliography

Rationale: Twenty-eight percent of people with mild to moderate obstructive sleep apnea experience daytime sleepiness, which interferes with daily functioning. It remains unclear whether treatment with continuous positive airway pressure improves daytime function in these patients. Objectives: To evaluate the efficacy of continuous positive airway pressure treatment to improve functional status in sleepy patients with mild and moderate obstructive sleep apnea. Methods: Patients with self-reported daytime sleepiness (Epworth Sleepiness Scale score >10) and an apnea-hypopnea index with 3% desaturation and from 5 to 30 events per hour were randomized to 8 weeks of active or sham continuous positive airway pressure treatment. After the 8-week intervention, participants in the sham arm received 8 weeks of active continuous positive airway pressure treatment. Measurements and Main Results: The Total score on the Functional Outcomes of Sleep Questionnaire was the primary outcome measure. The adjusted mean change in the Total score after the first 8-week intervention was 0.89 for the active group (n = 113) and -0.06 for the placebo group (n = 110) (P = 0.006). The group difference in mean change corresponded to an effect size of 0.41 (95% confidence interval, 0.14-0.67). The mean (SD) improvement in Functional Outcomes of Sleep Questionnaire Total score from the beginning to the end of the crossover phase (n = 91) was 1.73 +/- 2.50 (t[90] = 6.59; P < 0.00001) with an effect size of 0.69. Conclusions: Continuous positive airway pressure treatment improves the functional outcome of sleepy patients with mild and moderate obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT 00127348).

BACKGROUND: The aim of this study was to evaluate nocturia severity and nocturia-related differences in sleep, daytime symptoms and functional performance among patients with stable heart failure (HF). METHODS AND RESULTS: In this cross-sectional observational study, we recruited 173 patients [mean age 60.3 +/- 16.8 years; female n = 60 (35%); mean left ventricular ejection fraction 32 +/- 14.6%] with stable chronic HF from HF disease management programs in the northeastern United States. Participants reported nocturia and completed a 6-minute walk test (6MWT), 1 night of ambulatory polysomnography, and the SF-36 Medical Outcomes Study, Epworth Sleepiness, Pittsburgh Sleep Quality Index, Multidimensional Assessment of Fatigue, and Centers for the Epidemiological Studies of Depression scales. Participants reported 0 (n = 30; 17.3%), 1-2 (n = 87; 50.2%), and >/=3 (n = 56; 32.4%) nightly episodes of nocturia. There were decreases in sleep duration and efficiency, REM and stage 3-4 sleep, physical function, and 6MWT distance and increases in the percentage of wake time after sleep onset, insomnia symptoms, fatigue, and sleepiness across levels of nocturia severity. CONCLUSIONS: Nocturia is common, severe, and closely associated with decrements in sleep and functional performance and increases in fatigue and sleepiness in patients with stable HF.

STUDY OBJECTIVES: Sleep disordered breathing events conceptually separate into "obstructive" and "central" events. Esophageal manometry is the definitive but invasive means of classifying hypopneas. The purpose of this project was to identify noninvasive markers for discriminating high vs. low resistance hypopneas. METHODS: Forty subjects with obstructive or central sleep apnea underwent diagnostic polysomnography with nasal cannula airflow and esophageal manometry; 200% resistance relative to reference breaths was used to define "high" resistance. Noninvasive parameters from 292 randomly selected hypopneas in 20 subjects were analyzed and correlated to resistance. The best parameter and cutoff for predicting high relative resistance was determined and tested prospectively in 2 test sets in the 20 remaining subjects. Test Set A: 15 randomly selected hypopneas in each subject; Test Set B: all hypopneas in 7 subjects. RESULTS: In the development set, prolongation of inspiratory time during the 2 smallest breaths of a hypopnea (T(i)) relative to baseline had the best correlation to high relative resistance. In the Test Set A, relative T(i) > 110% classified obstructive events with sensitivity = 72%, specificity = 77%, PPV = 64%, NPV = 83%. Similar numbers were obtained for classification of hypopneas based on presence of flow limitation (FL) alone. When either relative T(i) or presence of FL were used to define high resistance, sensitivity = 84%, specificity = 74%, PPV = 65%, NPV = 89%. Similar results were obtained for Test Set B. CONCLUSIONS: Relative prolongation of T(i) is a good noninvasive predictor of high/low resistance in a dataset with both FL and NFL hypopneas. Combination of FL and relative T(i) improves this classification. The use of T(i) to separate obstructive and central hypopneas needs to be further tested for clinical utility (outcomes and treatment effects). CITATION: Mooney AM; Abounasr KK; Rapoport DM; Ayappa I. Relative prolongation of inspiratory time predicts high versus low resistance categorization of hypopneas. J Clin Sleep Med 2012;8(2):177-185.

STUDY OBJECTIVES: Patients with obstructive sleep apnea may have difficulty exhaling against positive pressure, hence limiting their acceptance of continuous positive airway pressure (CPAP). C-Flex is designed to improve comfort by reducing pressure in the mask during expiration proportionally to expiratory airflow (3 settings correspond to increasing pressure changes). When patients use CPAP, nasal resistance determines how much higher supraglottic pressure is than mask pressure. We hypothesized that increased nasal resistance results in increased expiratory supraglottic pressure swings that could be mitigated by the effects of C-Flex on mask pressure. DESIGN: Cohort study. SETTING: Sleep center. PARTICIPANTS: Seventeen patients with obstructive sleep apnea/hypopnea syndrome and a mechanical model of the upper airway. INTERVENTIONS: In patients on fixed CPAP, CPAP with different C-Flex levels was applied multiple times during the night. In the model, 2 different respiratory patterns and resistances were tested. MEASUREMENTS AND RESULTS: Airflow, expiratory mask, and supraglottic pressures were measured on CPAP and on C-Flex. Swings in pressure during expiration were determined. On CPAP, higher nasal resistance produced greater expiratory pressure swings in the supraglottis in the patients and in the model, as expected. C-Flex 3 produced expiratory drops in mask pressure (range -0.03 to -2.49 cm H(2)O) but mitigated the expira-tory pressure rise in the supraglottis only during a sinusoidal respiratory pattern in the model. CONCLUSIONS: Expiratory changes in mask pressure induced by C-Flex did not uniformly transmit to the supraglottis in either patients with obstructive sleep apnea on CPAP or in a mechanical model of the upper airway with fixed resistance. Data suggest that the observed lack of expiratory drop in supraglottic pressure swings is related to dynamics of the C-Flex algorithm. CITATION: Masdeu MJ; Patel AV; Seelall V; Rapoport DM; Ayappa I. The supraglottic effect of a reduction in expiratory mask pressure during continuous positive airway pressure. SLEEP 2012;35(2):263-272.

RATIONALE: Sub-therapeutic pressure has long been used as a sham-control for CPAP studies. We have previously suggested creating an experimental human model of obstructive sleep apnea (Am J Respir Crit Care Med 183;2011:A6073) using suboptimal pressure to induce a controlled amount of S

STUDY OBJECTIVES: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that often have overlapping symptoms, including sleep-related complaints. However, differences between the 2 conditions have been reported, and we hypothesized that dynamic aspects of sleep would be different in the 2 groups of patients. PARTICIPANTS: Subjects were 26 healthy control subjects, 14 patients with CFS but without FM (CFS alone), and 12 patients with CFS and FM (CFS+FM)-all women. MEASUREMENTS AND RESULTS: We studied transition probabilities and rates between sleep stages (waking, rapid eye movement [REM] sleep, stage 1 [S1], stage 2 [S2], and slow-wave sleep [SWS]) and duration distributions of each sleep stage. We found that the probability of transition from REM sleep to waking was significantly greater in subjects with CFS alone than in control subjects, which may be the specific sleep problem for people with CFS alone. Probabilities of (a) transitions from waking, REM sleep, and S1 to S2 and (b) those from SWS to waking and S1 were significantly greater in subjects with CFS+FM than in control subjects; in addition, rates of these transitions were also significantly increased in subjects with CFS+FM. Result (a) might indicate increased sleep pressure in subjects with CFS+FM whereas result (b) may be the specific sleep problem of subjects with CFS+FM. We also found that shorter durations of S2 sleep are specific to patients with CFS+FM, not to CFS alone. CONCLUSIONS: These results suggest that CFS and FM may be different illnesses associated with different problems of sleep regulation.