Combined effects of smoking and HIV infection on the occurrence of aging-related manifestations.

Both HIV-1 infection and smoking may contribute to the development of ageing-related manifestations affecting the prognosis of people living with HIV, but it is unclear whether HIV and smoking exert their effects independently or interact by potentiating each other. We conducted a cross-sectional study in 192 people living with HIV aged- and gender-matched with 192 HIV-uninfected controls, assessing the relative effect of HIV-1/smoking status on lung function (FEV1), bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), aortic pulse-wave velocity (PWV), insulin resistance (HOMA-IR) and renal function. In both unadjusted and adjusted analyses, FEV1, BMD and ASMI significantly differed according to smoking/HIV status, with the worst parameters found in HIV-1 infected patients currently smoking, and BMD and ASMI decreased to a lesser extent in HIV-1 infected patients formerly smoking (> 10 pack-years). Values in people living with HIV with < 10 pack-years exposure were of similar magnitude to those from controls. Regarding PWV, HOMA-R and eGFR, no significant differences were found, with the exception of eGFR values which were globally lower in HIV-1 infected patients. In conclusion HIV infection and smoking acted synergistically and were associated with a wasting phenotype combining muscle mass and bone mineral reduction.Clinical Trial Registration (registrar, website, and registration number), where applicable: CPP 10-023, 09-027, 10-034.

A randomized controlled trial to validate the Alice PDX ambulatory device.

BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent condition; however, the majority of patients remain undiagnosed. There is a potential to expand the diagnostic capacity of sleep laboratories. The study objective was to validate a portable respiratory monitoring device (Alice PDX) against polysomnography (PSG) in the laboratory and to assess its reliability at home. METHODS: A total of 85 patients with suspected OSA (80% male, mean age 49.1±13.5 years, body mass index 29.7±6.9 kg/m2, Epworth Sleepiness Scale 10.0±5.1) were randomized to 3 diagnostic nights: 1 night simultaneous in-laboratory PSG and PDX recording; 1 night self-applied PDX at home, and 1 night in-laboratory PSG. Study data were manually scored according to American Academy of Sleep Medicine criteria. RESULTS: The Alice PDX was in diagnostic agreement with simultaneously recorded reference PSG in 96.4% of studies. In 2.4% of studies the in-laboratory PDX underestimated and in 1.2% of studies it overestimated the apnea hypopnea index (AHI). The difference between the AHI from the reference PSG and the home study was similar to the difference between the PSGs (2.79 vs 0.79, p=0.08). CONCLUSION: In a population with a high suspicion of OSA, the Alice PDX showed a high level of diagnostic agreement with a simultaneous PSG and performed valid home diagnostic studies for OSA. If manually scored, the portable device can be used by sleep specialists for diagnosing moderate-to-severe obstructive sleep apnea in cases with a high pretest probability for the disease over a wide range of disease severity. The technology can be deployed reliably outside of the sleep laboratory setting.

Telomere Shortening in Middle-Aged Men with Sleep-disordered Breathing.

RATIONALE: Sleep disorders may lead to stress-induced premature aging and telomere shortening. OBJECTIVES: To determine whether obstructive sleep apnea syndrome causing intermittent hypoxemic episodes was associated with telomere shortening independently from the comorbidities associated with this syndrome. METHODS: We conducted a cross-sectional study in 161prospectivelly enrolled, untreated, middle-aged men free of known comorbidities related or unrelated to sleep apnea. Each participant underwent full standard overnight polysomnography. Patients with apnea sleep syndrome were naive to treatment. MEASUREMENTS AND MAIN RESULTS: In univariate analysis, we found that telomere shortening was associated with older age, apnea-hypopnea index, oxygen desaturation index, waist circumference, and fat mass. After adjustment for age, only apnea-hypopnea index and oxygen desaturation index were significantly related to telomere shortening. The mean telomere length ratio was 0.70 ± 0.37 in the participants without sleep apnea, compared with 0.61 ± 0.22 and 0.53 ± 0.16 in those with mild to moderate and severe sleep apnea, respectively (P = 0.01). In multivariate analysis, we found that oxygen desaturation index was the only factor independently associated with telomere length. Arterial stiffness assessed by carotid-femoral pulse wave velocity correlated negatively with telomere length. CONCLUSIONS: Intermittent hypoxemia due to obstructive sleep apnea syndrome is a major contributor to telomere shortening in middle-aged men. Oxidative stress may explain this finding.

Aging-related systemic manifestations in COPD patients and cigarette smokers.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear. OBJECTIVES: To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO). METHODS: Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD). MEASUREMENTS AND MAIN RESULTS: Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO. CONCLUSIONS: Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.

Ventricular orexin-A (hypocretin-1) levels correlate with rapid-eye-movement sleep without atonia in Parkinson's disease.

OBJECTIVE: Patients with Parkinson's disease frequently complain of sleep disturbances and loss of muscle atonia during rapid-eye-movement (REM) sleep is not rare. The orexin-A (hypocretin-1) hypothalamic system plays a central role in controlling REM sleep. Loss of orexin neurons results in narcolepsy-cataplexy, a condition characterized by diurnal sleepiness and REM sleep without atonia. Alterations in the orexin-A system have been also documented in Parkinson's disease, but whether these alterations have clinical consequences remains unknown. METHODS: Here, we measured orexin-A levels in ventricular cerebrospinal fluid from eight patients with Parkinson's disease (four males and four females) who underwent ventriculography during deep brain-stimulation surgery and performed full-night polysomnography before surgery. RESULTS: Our results showed a positive correlation between orexin-A levels and REM sleep without muscle atonia. CONCLUSION: Our results suggest that high levels of orexin-A in Parkinson's disease may be associated with loss of REM muscle atonia.

Comparison of sleep quality with mechanical versus spontaneous ventilation during weaning of critically III tracheostomized patients.

BACKGROUND: In mechanically ventilated patients under mechanical ventilation in the ICU, ventilatory mode or settings may influence sleep quality. The aim of this study was to evaluate the direct impact of mechanical ventilation per se on sleep quantity and quality in patients who were able to tolerate separation from mechanical ventilation over prolonged periods. DESIGN AND SETTING: Randomized crossover clinical trial in a medical ICU. PATIENTS: Sixteen conscious patients, free of sedation and tracheostomized because of prolonged weaning from mechanical ventilation, were included in the study when able to tolerate at least 5 hours of spontaneous ventilation. INTERVENTIONS: Patients were randomized to receive either spontaneous ventilation or mechanical ventilation at low levels of pressure support for two crossover periods of 5-hour duration each, from 22:00 to 08:00. Polysomnography was performed throughout the study. MEASUREMENTS AND RESULTS: Total sleep time was higher during mechanical ventilation than during spontaneous ventilation (183 min vs 132 min, p = 0.04). No significant differences between mechanical ventilation and spontaneous ventilation were observed in slow wave sleep time (45 min vs 28 min), rapid eye movement sleep time (11 min vs 3 min), or the fragmentation index (25 vs 23 arousals and awakenings per hr). In four patients, however, our analysis of patient-ventilator interaction suggested that the ventilatory settings were suboptimal and could have been improved to potentially improve sleep. CONCLUSIONS: In difficult-to-wean tracheostomized patients, sleep quality was similar with or without the ventilator. Sleep quantity was higher during mechanical ventilation. Reconnection to the ventilator during the night period may favor sleep efficiency in tracheostomized patients in prolonged weaning.

Prognostic impact of sleep-disordered breathing and its treatment with nocturnal ventilation for chronic heart failure.

AIMS: To determine whether severity patterns or nocturnal ventilation to treat sleep-disordered breathing (SDB) during chronic heart failure (CHF) is associated with adverse outcomes. Although SDB is frequent during CHF, the relationships between SDB and CHF outcomes are unknown. METHODS AND RESULTS: A total of 384 CHF patients (82% men, mean age 59 ± 13 years) with a left ventricular ejection fraction (LVEF) of ≤45% (mean LVEF 29 ± 9%) were assessed by polygraphy in our clinic between 2001 and 2009. Nocturnal ventilation was started according to the severity of SDB. Combined endpoints were death, heart transplant, and implant of a ventricular assist device. The prevalence of obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and Cheyne-Stokes respiration (CSR) was 62, 26, and 29%, respectively. A primary endpoint occurred in 31%. Mean follow-up for survivors was 47 ± 25 months. Those with moderate [apnoea-hypopnoea index (AHI) ≤5-20/h] and severe SDB (AHI ≥20/h), and OSA and CSA, had poor prognoses compared with patients without SDB (P = 0.036, P = 0.003, respectively). A total of 31% of SDB patients were treated with nocturnal ventilation. Treated SDB had a better outcome than untreated severe SDB after adjustment for confounding factors [P = 0.031; hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.33-0.95]. Subgroup analysis that included only OSA showed a similar result after adjustment (P = 0.017; HR 0.40; 95% CI 0.19-0.95). CONCLUSIONS: In CHF, SDB is associated with a poor prognosis whatever the SDB pattern, and nocturnal ventilation is associated with a better outcome.

A new classification for sleep analysis in critically ill patients.

BACKGROUND: Patients in intensive care units (ICUs) experience severe sleep alterations and conventional sleep scoring rules are difficult to use in these patients. In a previous study, we showed that abnormal sleep EEG and wake EEG patterns could predict the outcome of noninvasive ventilation in a group of patients treated for acute respiratory failure. Our aims were to assess the prevalence of these abnormal sleep/wake EEG patterns in a larger group and search for objective parameters to help their identification. METHODS: We reviewed sleep studies previously performed with full polysomnography during 17-h in conscious nonsedated ICU patients receiving invasive ventilation during weaning or noninvasive ventilation for acute respiratory failure. RESULTS: We included 57 patients. Sleep scoring using conventional rules was not feasible in 16 (28%) patients due to the absence of stage-2 markers. Wake EEG in these 16 patients, although recognizable, showed abnormal features, including decreased reactivity to eye opening and slower peak EEG frequency compared to patients with normal sleep-wake EEGs. CONCLUSION: In almost one third of awake mechanically ventilated ICU patients, sleep cannot be classified with standard criteria. Two new states, atypical sleep and pathologic wakefulness, need to be added. We suggest rules for scoring these states. The origin and links with outcomes of these abnormal EEG patterns deserve investigation.

Left ventricle remodelling is associated with sleep-disordered breathing in non-ischaemic cardiopathy with systolic dysfunction.

Sleep-disordered breathing (SDB) is associated with left ventricle (LV) remodelling in patients with normal LV function. Sleep-disordered breathing is common in chronic heart failure (CHF) with systolic LV dysfunction, and may contribute to LV remodelling and CHF progression. Our aim was to determine the consequence of SDB on LV geometry in patients with CHF. We hypothesised that SDB severity was correlated with the degree of LV hypertrophy (LVH). One-hundred and sixty patients with CHF with a non-ischaemic systolic LV dysfunction were assessed by overnight polygraphy and echocardiography. Patients were classified in four groups according to their apnoea-hypopnoea index (AHI): <5 (no-SDB); 5-14 (mild); 15-29 (moderate); ≥30 (severe). Left ventricular mass index (LVM Ind) was calculated using the usual echocardiographic M-Mode parameters. Their mean age, New York Heart Association and left ventricular ejection fraction were, respectively: 56 ± 13 years, 2.4 ± 0.8 and 30 ± 10%, and 77% were men. Body mass index, interventricular septal and posterior LV wall thicknesses, and LVM Ind were significantly increased in severe SDB versus no-SDB. LVM Ind was correlated to the AHI (R = 0.27, P = 0.0006) and, using logistic regression, AHI was the unique independent factor of LVH in this population. In non-ischaemic CHF, SDB severity is associated with LV remodelling.

Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure.

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 +/- 12.3 years; LVEF, 33.5 +/- 9.8%). SDB defined as AHI > or =15 h(-1) was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI (r = 0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5-30 h(-1)) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.

Resolution of sleep-disordered breathing with a biventricular assist device and recurrence after heart transplantation.

Sleep-disordered breathing (SDB) is common in chronic heart failure. Both obstructive sleep apnea syndrome (OSAS) and central sleep apnea with periodic Cheyne-Stokes respiration (CSA-CSR) can occur. CSA-CSR is believed to correlate with heart function. Little information exists about the impact of mechanical assist devices and heart transplantation on SDB in patients with end-stage heart failure. Here, we describe, for the first time, the effects on SDB of a biventricular external assist device and of heart transplantation used successively in the same patient.

Prevalence of sleep-disordered breathing in a 316-patient French cohort of stable congestive heart failure.

BACKGROUND: Heart failure with systolic dysfunction occurs frequently. Studies in North America and Germany have shown a high prevalence of sleep-disordered breathing in patients with heart failure. AIMS: To assess the prevalence of sleep-disordered breathing and its associated risk factors in French patients with heart failure. METHODS: A total of 316patients with stable heart failure and a left ventricular ejection fraction less or equal to 45% underwent polygraphy prospectively to diagnose sleep apnoea syndrome, defined as an apnoea-hypopnoea index greater or equal to 10events/h. RESULTS: Mean age, left ventricular ejection fraction, and body mass index were 59+/-13years, 30+/-11% and 28+/-6kg/m(2), respectively. The prevalence of sleep breathing disorder was 81% (n=256); 30% of syndromes were classified as central and 70% as obstructive. The mean apnoea-hypopnoea index was high (30+/-3events/h) and a large proportion (41%) of syndromes had an apnoea-hypopnoea index greater or equal to 30events/h. A central sleep apnoea syndrome pattern was associated with more severe heart failure and a more elevated apnoea-hypopnoea index than an obstructive pattern. The prevalence of sleep-disordered breathing was lower in women than in men (64% versus 85%; chi(2)=0.0003) as was its severity (mean apnoea-hypopnoea index 15+/-13events/h versus 27+/-19events/h, p=0.0001). CONCLUSION: The prevalence of sleep-disordered breathing was high in a French heart failure population, with most syndromes having an obstructive pattern. Prevalence and severity were higher in men than in women.