Gabriel Roisman

Diabetes Mellitus Prevalence and Control in Sleep-Disordered Breathing: The European Sleep Apnea Cohort (ESADA) Study

BACKGROUND OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OSA and glycemic control among patients with diabetes. We assessed the relationship between OSA severity and T2DM prevalence and control in a large multinational population. METHODS We performed a cross-sectional analysis of 6,616 participants in the European Sleep Apnea Cohort (ESADA) study, using multivariate regression analysis to assess T2DM prevalence according to OSA severity, as measured by the oxyhemoglobin desaturation index. Patients with diabetes were identified by previous history and medication prescription, and by screening for undiagnosed diabetes with glycosylated hemoglobin (HbA1c) measurement. The relationship of OSA severity with glycemic control was assessed in diabetic subjects. RESULTS T2DM prevalence increased with OSA severity, from 6.6% in subjects without OSA to 28.9% in those with severe OSA. Despite adjustment for obesity and other confounding factors, in comparison with subjects free of OSA, patients with mild, moderate, or severe disease had an OR (95% CI) of 1.33 (1.04-1.72), 1.73 (1.33-2.25), and 1.87 (1.45-2.42) (P < .001), respectively, for prevalent T2DM. Diabetic subjects with more severe OSA had worse glycemic control, with adjusted mean HbA1c levels 0.72% higher in patients with severe OSA than in those without sleep-disordered breathing (analysis of covariance, P < .001). CONCLUSIONS Increasing OSA severity is associated with increased likelihood of concomitant T2DM and worse diabetic control in patients with T2DM.

High occurrence of hypoxemic sleep respiratory disorders in precapillary pulmonary hypertension and mechanisms.

BACKGROUND The occurrence and mechanisms of nocturnal hypoxemia in precapillary pulmonary hypertension (PH) are not clearly defined. METHODS In an observational, prospective, and transversal design, we studied 46 clinically stable patients with PH and a BMI < 35 kg/m(2), an FEV(1) > 60% predicted, and idiopathic pulmonary arterial hypertension (n = 29) or chronic thromboembolic pulmonary hypertension (n = 17). They underwent nocturnal polysomnography with transcutaneous capnography. RESULTS Most patients (69.6%) had New York Heart Association functional class II disease. Mean pulmonary artery pressure was 44 ± 13 mm Hg, and the cardiac index was 3.2 ± 0.6 L/min/m(2). Duration of sleep time spent with oxygen saturation as measured by pulse oximetry <90% was 48.9% ± 35.9%, and 38 of 46 patients (82.6%) had nocturnal hypoxemia. Mean apnea-hypopnea index was 24.9 ± 22.1/h, and 41 patients (89%) had sleep apnea. The major mechanism of nocturnal hypoxemia was a ventilation/perfusion mismatch alone or associated with obstructive apneic events. Multivariate logistic regression identified both FEV(25%-75%) (OR, 0.9519; 95% CI, 0.9089-0.9968; P = .036) and mean pulmonary artery pressure (OR, 1.1068; 95% CI, 1.0062-1.2175; P = .037) as significant predictors of nocturnal hypoxemia. Clinical symptoms were not predictive of nocturnal hypoxemia. CONCLUSIONS The occurrence of nocturnal hypoxemia is high in PH and should be screened for systematically. Further studies are needed to determine the impact of nocturnal hypoxemia on the outcome of patients with PH. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01371669; URL: www.clinicaltrials.gov

Overnight heart rate variability in patients with obstructive sleep apnoea: A time and frequency domain study

Heightened sympathetic activity plays a role in the cardiovascular sequelae of obstructive sleep apnoea (OSA). Cardiac autonomic function may be assessed non‐invasively by studying heart rate variability (HRV). The aim of the present study was to compare overnight HRV between a control group and a group of subjects with severe OSA. The potential confounding effects of age, sex, baseline autonomic status and sleep stage distribution were taken into account. Our prospective Holter study compared overnight (0030–0530 hours) HRV in 23 controls (apnoea hypopnoea index (AHI) = 5 ± 3 /h) and 23 subjects with severe OSA (AHI = 65 ± 23 /h), matched for age and sex and with a similar percentage of rapid eye movement sleep. The mean normal‐to‐normal RR interval (NN) was shorter in the OSA compared with control group (903 vs 1039 ms, respectively), whereas the other time‐domain indices of HRV, as well as the classic frequency‐domain indices, were similar. Essentially similar results were obtained hourly and when only subjects with high mean values of the standard deviation of all NN (≥ 90 ms) were evaluated. In the 0.01–0.06 Hz range corresponding to the typical OSA pattern of bradycardia–tachycardia termed cyclic variation of heart rate (CVHR), higher power was documented hourly in OSA, with a significant correlation between overnight power and both AHI and mean oxyhaemoglobin saturation. The percentage of NN > x ms different from the previous one (pNNx family) had no diagnostic value. The results of the present study suggest that NN may be the best index to quantify the overnight sympathovagal balance in OSA and that a spectral band overlapping the apnoea‐related pattern of CVHR slightly improved the characterization of the apnoea‐related HRV patterns.

All APAPs Are Not Equivalent for the Treatment of Sleep Disordered Breathing: A Bench Evaluation of Eleven Commercially Available Devices.

STUDY OBJECTIVES This study challenged on a bench-test the efficacy of auto-titrating positive airway pressure (APAP) devices for obstructive sleep disordered breathing treatment and evaluated the accuracy of the device reports. METHODS Our bench consisted of an active lung simulator and a Starling resistor. Eleven commercially available APAP devices were evaluated on their reactions to single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and snoring), and to a long general breathing scenario (5.75 h) simulating various SDB during four sleep cycles and to a short scenario (95 min) simulating one sleep cycle. RESULTS In the single-type sequence of 30-minute repetitive obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline breathing amplitude). Similarly, normalized breathing was recorded with 8 devices only for a 20-min obstructive hypopnea sequence. Five devices increased the pressure in response to snoring. Only 4 devices maintained a constant minimum pressure when subjected to repeated central apneas with an open upper airway. In the long general breathing scenario, the pressure responses and the treatment efficacy differed among devices: only 5 devices obtained a residual obstructive AHI < 5/h. During the short general breathing scenario, only 2 devices reached the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by > 10% (p < 0.001). The long scenario led to more consistent device reports. CONCLUSION Large differences between APAP devices in the treatment efficacy and the accuracy of report were evidenced in the current study.

A mandibular advancement device for the treatment of obstructive sleep apnea: Long-term use and tolerance

Long-term efficacy and compliance with mandibular advancement devices (MAD) in the treatment of obstructive sleep apnea syndrome (OSAS) are under-studied. Our objective was to conduct a long-term assessment of the OPM4J device, measuring symptoms, compliance rate, and adverse effects in a cohort of consecutive patients treated with OPM4J for an average period of nearly three years. Out of 140 patients aged 62 ± 10 years with body mass index (BMI) 27 ± 4 kg/m(2) and initial apnea-hypopnea index (AHI) 27 ± 16, complete reversal of OSAS was achieved in 65%. A total of 76% reported regular MAD use, with 24% stopping treatment and half of those 24% falling back on continuous positive airway pressure (CPAP). Patients with lower residual AHI or residual Epworth scores at month 3 were more likely to continue treatment (P < 0.007 and P < 0.02). Reasons for discontinuing treatment included tooth pain, persistent snoring or fatigue, loss or breakage of the device, and the cost of replacing it. OPM4J reduced OSAS symptoms in the long-term. Regular use was reported in 76% of patients. Adverse effects were common but minor. Half of non-users were lost to follow-up and probably remain without treatment.

Pressure-Relief Features of Fixed and Autotitrating Continuous Positive Airway Pressure May Impair Their Efficacy: Evaluation with a Respiratory Bench Model.

STUDY OBJECTIVES Pressure-relief features are aimed at improving the patients comfort during continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea. The objective of this study was to determine the effect of these therapy features on fixed CPAP and autotitrating CPAP (APAP) treatment efficacy. METHODS Seven pressure-relief features applied by three CPAP devices were included in our study (Remstar Auto: C-Flex 3, C-Flex+ 3, A-Flex 3, P-Flex; AirSense 10: EPR 3; Prisma 20A: SoftPAP 2 and 3). In fixed CPAP, the devices were subjected to a 10-min bench-simulated obstructive apnea sequence (initial apnea-hypopnea index, AHI = 60/h) with and without pressure-relief features. In APAP, the sequence was lengthened to 4.2 h (initial AHI = 58.6/h). The residual AHI and mean/median pressure were compared with and without pressure-relief features. RESULTS Compared to conventional CPAP, where pressure was adjusted to be just sufficient to control the simulated obstructive events, C-Flex+ 3, P-Flex, and EPR 3 failed to normalize the breathing flow and did not reduce the AHI. The mean pressures with the three features, respectively, were 1.8, 2.6, and 2.6 cmH2O lower than the conventional CPAP. Compared to conventional APAP, similar levels of control were observed with pressure-relief features, apart from P-Flex where the delivered mean pressure was lower and residual AHI greater. The device-reported mean/median pressures in APAP with A-Flex 3, P-Flex, EPR 3, and SoftPAP 3 were higher than that measured on the bench. CONCLUSIONS Pressure-relief features may attenuate CPAP efficacy if not adjusted for at the time of their introduction. In clinical practice, efficacy can be ensured by increasing the therapeutic pressure delivered by fixed CPAP or by enabling the pressure-relief features prior to initial pressure titration. Device-reported pressures in APAP devices with pressure relief activated may overstate delivered pressures.

Fixed But Not Autoadjusting Positive Airway Pressure Attenuates the Time-dependent Decline in Glomerular Filtration Rate in Patients With OSA

Background The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. Methods In patients of the European Sleep Apnea Database, eGFR prior to and after follow‐up was calculated by using the Chronic Kidney Disease‐Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n = 144), patients receiving fixed CPAP (fCPAP) (n = 1,178), and patients on autoadjusting CPAP (APAP) (n = 485). Results In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42 mL/min/1.73 m2) at baseline (P < .0001 for effect of baseline eGFR). This decline was attenuated or absent (P < .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow‐up duration exceeding the median (541 days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P < .0001 by two‐way ANOVA for interaction between treatment and follow‐up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow‐up duration, whereas there was a protective effect of fCPAP. Conclusions fCPAP but not APAP may prevent eGFR decline in OSA.