Faculty Bibliography

STUDY OBJECTIVES: Inspiratory flow limitation (IFL) during sleep occurs when airflow remains constant despite an increase in respiratory effort. This respiratory event has been recognized as an important parameter for identifying sleep breathing disorders. The purpose of this study was to investigate how much IFL normal individuals can present during sleep. DESIGN: Cross-sectional study derived from a general population sample. SETTING: A "normal" asymptomatic sample derived from the epidemiological cohort of Sao Paulo. PATIENTS AND PARTICIPANTS: This study was derived from a general population study involving questionnaires and nocturnal polysomnography of 1,042 individuals. A subgroup defined as a nonsymptomatic healthy group was used as the normal group. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All participants answered several questionnaires and underwent full nocturnal polysomnography. IFL was manually scored, and the percentage of IFL of total sleep time was considered for final analysis. The distribution of the percentage of IFL was analyzed, and associated factors (age, sex, and body mass index) were calculated. There were 95% of normal individuals who exhibited IFL during less than 30% of the total sleep time. Body mass index was positively associated with IFL. CONCLUSIONS: Inspiratory flow limitation can be observed in the polysomnography of normal individuals, with an influence of body weight on percentage of inspiratory flow limitation. However, only 5% of asymptomatic individuals will have more than 30% of total sleep time with inspiratory flow limitation. This suggests that only levels of inspiratory flow limitation > 30% be considered in the process of diagnosing obstructive sleep apnea in the absence of an apnea-hypopnea index > 5 and that < 30% of inspiratory flow limitation may be a normal finding in many patients. CITATION: Palombini LO; Tufik S; Rapoport DM; Ayappa IA; Guilleminault C; de Godoy LBM; Castro LS; Bittencourt L. Inspiratory flow limitation in a normal population of adults in Sao Paulo, Brazil. SLEEP 2013;36(11):1663-1668.

OBJECTIVES: Electroencephalography (EEG) assessment in research and clinical studies is limited by the patient burden of multiple electrodes and the time needed to manually score records. The objective of our study was to investigate the accuracy of an automated sleep-staging algorithm which is based on a single bipolar EEG signal. METHODS: Three raters each manually scored the polysomnographic (PSG) records from 44 patients referred for sleep evaluation. Twenty-one PSG records were scored by Rechtschaffen and Kales (R&K) criteria (group 1) and 23 PSGs were scored by American Academy of Sleep Medicine (AASM) 2007 criteria (group 2). Majority agreement was present in 98.4% of epochs and was used for comparison to automated scoring from a single EEG lead derived from the left and right electrooculogram. RESULTS: The kappa coefficients for interrater manual scoring ranged from 0.46 to 0.89. The kappa coefficient for the auto algorithm vs manual scoring by rater ranged from 0.42 to 0.63 and was 0.61 (group 1, kappa=0.61 and group 2, kappa=0.62) for majority agreement for all studies. The mean positive percent agreement across subjects and stages was 72.6%, approximately 80% for stages wake (78.3%), stage 2 sleep (N2) (80.9%), and stage 3 sleep (N3) (78.1%); the percentage slightly decreased to 73.2% for rapid eye movement (REM) sleep and dropped to 31.9% for stage 1 sleep (N1). Differences in agreement were observed based on raters, obstructive sleep apnea (OSA) severity, medications, and signal quality. CONCLUSIONS: Our study demonstrated that automated scoring of sleep obtained from a single-channel of forehead EEG results in agreement to majority manual scoring are similar to results obtained from studies of manual interrater agreement. The benefit in assessing auto-staging accuracy with consensus agreement across multiple raters is most apparent in patients with OSA; additionally, assessing auto-staging accuracy limited disagreements in patients on medications and in those with compromised signal quality.

A major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS. We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced worsening of CFS.

Effects of exercise on dynamic aspects of sleep have not been studied. We hypothesized exercise altered dynamic sleep morphology differently for healthy controls relative to chronic fatigue syndrome (CFS) patients. Sixteen controls (38 +/- 9 years) and 17 CFS patients (41 +/- 8 years) underwent polysomnography on baseline nights and nights after maximal exercise testing. We calculated transition probabilities and rates (as a measure of relative and temporal transition frequency, respectively) between sleep stages and cumulative duration distributions (as a measure of continuity) of each sleep stage and sleep as a whole. After exercise, controls showed a significantly greater probability of transition from N1 to N2 and a lower rate of transition from N1 to wake than at baseline; CFS showed a significantly greater probability of transition from N2 to N3 and a lower rate of transition from N2 to N1. These findings suggest improved quality of sleep after exercise. After exercise, controls had improved sleep continuity, whereas CFS had less continuous N1 and more continuous rapid eye movement (REM) sleep. However, CFS had a significantly greater probability and rate of transition from REM to wake than controls. Probability of transition from REM to wake correlated significantly with increases in subjective fatigue, pain, and sleepiness overnight in C

Background: Glucose hypometabolism measured with FDG-PET in the medial temporal lobe (MTL) has been associated with longitudinal cognitive decline in normal elderly. Other studies find the temporal lobe may be relevant in the regulation of normal breathing, such that apneas and dyspnea are elicited with lesions and electrical stimulation in this region. Our recent work has shown that sleep-disordered breathing (S

OBJECTIVES: The authors examined magnitude/variability of residual sleep disordered breathing (SDB) at pressures around the therapeutic continuous positive airway pressure (CPAP), and described a multinight approach to CPAP titration/retitration consisting of recording airflow and summarizing SDB over multiple nights at multiple pressures and choosing an optimal pressure from these summarized data. DESIGN: Prospective, single-center nonblinded study. PATIENTS: Ten female/18 male patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) (respiratory disturbance index [RDI] 67/h), 17 newly-initiated, 11 chronic CPAP users. INTERVENTIONS: A custom CPAP device (Fisher & Paykel Healthcare) recording airflow and pre-programmed to vary CPAP between 2-3 cm H2O below and 1-2 cm H2O above prescription pressure as determined by a full laboratory titration. RESULTS: Airflow and pressure continuously recorded for multiple nights (15.9 +/- 5.1 nights) at four to seven different pressures in each patient. SDB events manually scored from the airflow as apnea (airflow reduction > 90%), hypopnea (airflow reduction > 30% lasting 10 to 120 sec with inspira-tory flow limitation [IFL]) and runs of sustained IFL > 2 min identified. RDI = (apnea + hypopnea)/total sleep time calculated for each night and an obstruction index, including sustained IFL, also was calculated. PressureMultinight was obtained for each patient from multiple nights of data using two mathematical techniques. Night-to-night variability of SDB indices was low in some patients and significant in others. PressureMultinight could be determined in 17 of 28 patients and was similar to the in-laboratory pressure. CONCLUSIONS: This study showed that recording multiple nights of CPAP airflow in the home and analyzing these data for residual SDB provided useful information, including the possibility of determining a therapeutic prescription for fixed CPAP in most patients and identification of others with significant physiologic variability of SDB. CITATION: Callahan CY; Norman RG; Taxin Z; Mooney AM; Rapoport DM; Ayappa I. Multinight recording and analysis of continuous positive airway pressure airflow in the home for titration and management of sleep disordered breathing. SLEEP 2013;36(4):535-545.

BACKGROUND: Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. STUDY OBJECTIVE: Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. PATIENTS AND INTERVENTIONS: Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 +/- 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% < 30/h, n = 22) and severe (AHI4% > 30/h, n = 20) SDB. RESULTS: Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. CONCLUSIONS: Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. CITATION: Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. 2013;36(3):405-412.

MPS encompasses a group of rare lysosomal storage disorders that are associated with the accumulation of glycosaminoglycans (GAG) in organs and tissues. This accumulation can lead to the progressive development of a variety of clinical manifestations. Ear, nose, throat (ENT) and respiratory problems are very common in patients with MPS and are often among the first symptoms to appear. Typical features of MPS include upper and lower airway obstruction and restrictive pulmonary disease, which can lead to chronic rhinosinusitis or chronic ear infections, recurrent upper and lower respiratory tract infections, obstructive sleep apnoea, impaired exercise tolerance, and respiratory failure. This review provides a detailed overview of the ENT and respiratory manifestations that can occur in patients with MPS and discusses the issues related to their evaluation and management.