Joaquín Durán

Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment

The episodes of hypoxia/re-oxygenation associated with the respiratory disturbances observed in patients with obstructive sleep apnoea syndrome (OSAS) may induce the generation of oxygen free radicals. Indeed, several studies suggest that OSAS is associated with oxidative stress. The present study tested the hypothesis that patients with OSAS have an alteration in antioxidant defences. The plasma levels of total antioxidant status (TAS), glutathione peroxidase (GPX), γ-glutamyltransferase (GGT), vitamins A, E, B12 and folate, and homocysteine were determined in 47 patients with OSAS and 37 healthy subjects. Of these, 27 patients who used continuous positive airway pressure (CPAP) for >4 h·night−1 were re-examined 12 months later. Patients with OSAS had lower TAS (1.4±0.16 versus 1.50±0.10 mmol·L−1), vitamin A (64±19 versus 74±17 μg·dL−1) and vitamin E levels (1,525±499 versus 1,774±503 μg·dL−1), and increased values of GGT (42±22 versus 32±16 U·L−1) than controls. There was no difference between groups in GPX, homocysteine, vitamin B12 and folate plasma levels. CPAP treatment normalised the levels of TAS (1.50±0.13 mmol·L−1) and the activity of GGT (30±14 U·L−1) without any influence on vitamins levels. In conclusion, the results indicate that patients with obstructive sleep apnoea syndrome have a decreased antioxidant capacity that is partially reversed by continuous positive airway pressure treatment.

Daytime sleepiness and polysomnography in obstructive sleep apnea patients

BACKGROUND Excessive daytime sleepiness (EDS) is the major complaint in subjects with obstructive sleep apnea syndrome (OSAS). However, EDS is not universally present in all patients with OSAS. The mechanisms explaining why some patients with OSAS complain of EDS whereas others do not are unknown. OBJECTIVE To investigate polysomnographic determinants of excessive daytime sleepiness (EDS) in a large multicenter cohort of patients with obstructive sleep apnea (OSAS). METHODS All consecutive patients with an apnea-hypopnea index greater than 5h(-1) who were evaluated between 2003 and 2005. EDS was assessed using the Epworth Sleepiness Scale (ESS), and patients were considered to have EDS if the ESS was >10. RESULTS A total of 1649 patients with EDS ((mean [+/-SD] Epworth 15+/-3) and 1233 without EDS (Epworth 7+/-3) were studied. Patients with EDS were slightly younger than patients without EDS (51+/-12 vs 54+/-13 years, p<0.0001), had longer total sleep time (p<0.007), shorter sleep latency (p<0001), greater sleep efficiency (p<0.0001) and less NREM sleep in stages 1 and 2 (p<0.007) than those without EDS. Furthermore, patients with EDS had slightly higher AHI (p<0.005) and arousal index (p<0.001) and lower nadir oxygen saturation (p<0.01). CONCLUSIONS Patients with OSAS and EDS are characterized by longer sleep duration and increased slow wave sleep compared to those without EDS. Although patients with EDS showed a mild worsening of respiratory disturbance and sleep fragmentation, these results suggest that sleep apnea and sleep disruption are not the primary determinants of EDS in all of these patients.

Diagnostic accuracy of a portable recording device (MESAM IV) in suspected obstructive sleep apnoea

This study evaluated the accuracy of a portable recording device (MESAM IV) in identifying obstructive sleep apnoea (OSA). The MESAM IV system measures arterial oxygen saturation (Sa,O2), heart rate, snoring sounds and body position, and allows both automatic and manual scoring of the recordings. Nocturnal polysomnography and MESAM IV recordings were performed simultaneously in 150 patients with suspected OSA, and were analysed blindly by a different observer. Patients with an apnoea-hypopnoea index (AHI) greater than or equal to 10 were diagnosed as having OSA. In the evaluation of the discriminatory ability of MESAM IV scores, the cut-off point was set to minimize first the exclusion of truly diseased patients (i.e. false-negative interpretations), and then confirmation of nondiseased subjects (i.e. false-positives). When used as an exclusion test, the portable device reached a sensitivity of 0.98 and a specificity of 0.78; as a confirmation test, these values were 0.69 and 0.97, respectively. These results were achieved with manual scoring, which was superior to automatic scoring. Manual scoring was also better than automatic scoring when OSA was defined according to other threshold values (> or = 5, 15 and 20) for the AHI. The combination of MESAM IV manual scores could reduce the need for diagnostic polysomnography in three quarters of the patients clinically suspected of having obstructive sleep apnoea, substantially reducing costs associated with diagnostic procedures.

Comparison of a cardiorespiratory device versus polysomnography for diagnosis of sleep apnoea

This study assessed the accuracy of a cardiorespiratory monitoring device versus polysomnography for the diagnosis of suspected sleep apnoea/hypoponea syndrome (SAS). A total of 86 patients (89% male, mean age 52 yrs) that had been referred to a sleep laboratory with a clinical diagnosis of SAS underwent cardiorespiratory polygraphy in an unattended mode using an ambulatory device (MERLIN). Analysis was carried out both automatically and manually. Conventional overnight full-channel polysomnography was performed simultaneously. Valid polygraphical recordings were obtained from 79 patients. The mean±sd apnoea/hypopnoea index (AHI) was 34.4±29.2. The results obtained with manual scoring were superior to automatic scoring for all AHI thresholds. For an AHI of ≥5, which is diagnostic SAS, the optimum cut-off value for the manual respiratory event index was 6.7 and the cardiorespiratory monitoring device had 97.1% sensitivity and 90.9% specificity. Correct classification according to the different cut-off points obtained via polysomnography and the corresponding cut-off points in the MERLIN manual index were confirmed in 90–96% of patients. The MERLIN device is a useful diagnostic approach for the initial assessment of adult patients with clinical suspicion of sleep apnoea/hypopnoea syndrome. Manual scoring is clearly better than automatic scoring in terms of agreement with the apnoea/hypopnoea index and to discern patients with sleep apnoea/hypopnoea syndrome.

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial

Background Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. Aim To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. Methods A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. Results We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. Conclusions A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). Trial register number NCT01716676.

Vitamin D status and parathyroid hormone levels in patients with obstructive sleep apnea.

Background: Vitamin D insufficiency and high levels of parathyroid hormone (PTH) appear to be emerging risk factors for metabolic syndrome (MS), diabetes and cardiovascular disease, conditions that occur frequently in patients with obstructive sleep apnea syndrome (OSAS). Objectives: This study examined whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated with the presence of MS, diabetes and hypertension among an OSAS population. Methods: A total of 826 patients (635 men and 191 women) with newly diagnosed OSAS were studied. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III clinical criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL cholesterol, creatinine and uric acid were determined. Results: In 55.3% of the men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml (insufficient status). After adjusting for age, sex and seasonality, there was a significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.33-0.94, ptrend = 0.038] and MS (OR 0.34, 95% CI 0.21-0.56, ptrend < 0.001) with increasing vitamin D levels. Higher PTH levels were associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, ptrend < 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, ptrend = 0.049). Conclusions: These data suggest an inverse association of 25(OH)D with diabetes and MS and a positive association of PTH with obesity and hypertension among patients with OSAS. Based on our observational study, the causative nature of the associations cannot be established. These findings require further examination in prospective studies including clinical trials.

Automatic CPAP Performance in Patients with Sleep Apnea Plus COPD

Abstract Background: Automatic CPAP devices have demonstrated good results in obtaining optimal fixed CPAP pressure to eliminate respiratory events in patients with sleep apnea-hypopnea syndrome (SAHS). However, automatic CPAP has not been fully studied in patients with COPD plus SAHS. Objectives: To analyse the performance of an automatic CPAP in severe COPD patients compared with SAHS patients with no associated co-morbidity. Methods: We compared 10 consecutive patients with SAHS and no associated co-morbidity and 10 patients with SAHS plus severe COPD who required CPAP titration. Automatic CPAP performance was studied during full-night PSG. Inadequate pressure increase periods, absence of pressure increases in reaction to respiratory events, air leak periods, and pressure behaviour in the face of erratic breathing periods were analysed. Results: The SAHS patients without co-morbidities vs. SAHS plus COPD patients presented: mean sleep efficiency, 80.2 (11.5)% vs. 76.5 (12.1)%; residual AHI, 6.3 (5.2) vs. 5.1 (7.7); residual CT90, 1 (3)% vs. 14 (1)%. The device´s performance demonstrates a mean of 1.2 (1.5) vs. 1.3 (1.2) periods of inadequate pressure increases; absence of pressure increases in reaction to respiratory events, 4.1 (5.4) vs. 0.6 (0.7) times; periods of air leaks, 1.3 (3.8) vs. 13.9 (11.7); mean optimal pressure, 9.1 (1.4) vs. 9.0 (1.9) cm H2O. Conclusion: Titration with automatic CPAP could be as effective in patients with SAHS plus severe COPD as in patients with SAHS without COPD. However, the presence of more leakages must be taken into account.

Sleep Breathing Flow Characteristics as a Sign for the Detection of Wakefulness in Patients with Sleep Apnea

Background: To improve the performance of simplified sleep studies, it is essential to properly estimate the sleep time. Objectives: Our aim is to estimate sleep efficiency on the basis of flow breathing signal characteristics. Methods: Twenty subjects with sleep apnea-hypopnea syndrome diagnosed by polysomnography were studied. A characteristic pattern of flow signal defined our criteria for wakefulness and sleep. Sleep was analyzed in 2 different runs: (1) in the usual manner (neurological and respiratory variables), and (2) only the nasal cannula flow signal was displayed on the computer screen and the sleep and wakefulness periods were scored according to our criteria. At the end of the scoring process, all the signals were displayed on the screen to analyze the concordance. Results: Three thousand and sixty-nine screens were analyzed. The polysomnography sleep efficiency measured was 80.8%. The estimated sleep efficiency measured by nasal prongs was 78.9%. The detection and concordance of wakefulness had a sensitivity of 58.7%, a specificity of 96.4%, a positive predictive value of 81.3% and a negative predictive value of 89.6%. Conclusions: Our criteria for sleep and wakefulness based on airflow waveform morphology are a helpful parameter for estimating sleep efficiency in a simplified sleep study.

Cardiac Troponin Values in Patients With Acute Coronary Syndrome and Sleep Apnea: A Pilot Study

Background An analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS. Methods Blood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size. Results We included 89 patients with OSA and 38 patients without OSA with an apnea‐hypopnea index of a median of 32 (interquartile range [IQR], 20.8‐46.6/h and 4.8 [IQR, 1.6‐9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78‐40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37‐24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA. Conclusions The results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies.

Non-synonymous polymorphism in the neuropeptide S precursor gene and sleep apnea

BackgroundObstructive sleep apnea syndrome (OSAS) is a complex disease with a strong genetic basis. One of the primary molecular domains affected by OSAS is sympathetic activity. Neuropeptide S (NPS) plays an important role in the regulation of the sleep–wakefulness cycle, anxiety states, and daytime sleepiness. It is important to study neuropeptides related to sympathetic activity regulation and how their function could be modified by genetic variants affecting the expression of these molecules.ObjectivesWe investigated the association of the non-synonymous polymorphism rs4751440 in the NPS precursor gene with OSAS and certain variables related to OSAS (daytime sleepiness, body mass index (BMI), insulin resistance, and blood pressure). This polymorphism causes an amino acid substitution in exon 3 of the human NPS precursor gene.Patients and methodsWe included 253 OSAS patients and 70 healthy subjects. Genotyping was done by polymerase chain reaction using specific flanking primers and agarose gel electrophoresis. Daytime sleepiness, BMI, plasma levels of high-density lipoprotein, glucose, total cholesterol, insulin, triglycerides, and the homeostasis model assessment index were also determined.ResultsA similar genotypic and allelic distribution was found in OSAS patients and controls. The risk of OSAS was not associated with the rs4751440 polymorphism. There was no significant interaction between daytime sleepiness or metabolic variables and the rs4751440 polymorphism.ConclusionGenotypic and allelic frequency distribution of the rs4751440 polymorphism was similar in OSAS patients and controls. In this population-based study, we could not show a significant association between rs4751440 polymorphism and susceptibility to OSAS or certain phenotypes related to OSAS (daytime sleepiness, BMI, systolic blood pressure, and insulin resistance) with the exception of diastolic blood pressure.