EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke.

BACKGROUND: Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality. AIM: Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology to critically evaluate the evidence regarding potential links and the impact of therapy. MATERIALS AND METHODS: Thirteen research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 were included. Statements were generated regarding current evidence and clinical practice. RESULTS: Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, whilst CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, whilst the pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, whilst treatment data are scarce. DISCUSSION/CONCLUSION: Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.

Hyperlipidaemia prevalence and cholesterol control in obstructive sleep apnoea: Data from the European sleep apnea database (ESADA).

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort. METHODS: The cross-sectional analysis included 11 892 patients (age 51.9 ± 12.5 years, 70% male, body mass index (BMI) 31.3 ± 6.6 kg/m2 , mean oxygen desaturation index (ODI) 23.7 ± 25.5 events/h) investigated for OSA. The independent odds ratio (OR) for hyperlipidaemia in relation to measures of OSA (ODI, apnoea-hypopnoea index, mean and lowest oxygen saturation) was determined by means of general linear model analysis with adjustment for important confounders such as age, BMI, comorbidities and study site. RESULTS: Hyperlipidaemia prevalence increased from 15.1% in subjects without OSA to 26.1% in those with severe OSA, P < 0.001. Corresponding numbers in patients with diabetes were 8.5% and 41.5%, P < 0.001. Compared with ODI quartile I, patients in ODI quartiles II-IV had an adjusted OR (95% CI) of 1.33 (1.15-1.55), 1.37 (1.17-1.61) and 1.33 (1.12-1.58) (P < 0.001), respectively, for hyperlipidaemia. Obesity was defined as a significant risk factor for hyperlipidaemia. Subgroups of OSA patients with cardio-metabolic comorbidities demonstrated higher prevalence of HL. In addition, differences in hyperlipidaemia prevalence were reported in European geographical regions with the highest prevalence in Central Europe. CONCLUSION: Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.

Adipose tissue in obesity and obstructive sleep apnoea.

A European Respiratory Society research seminar on "Metabolic alterations in obstructive sleep apnoea (OSA)" was jointly organised in October 2009 together with two EU COST actions (Cardiovascular risk in the obstructive sleep apnoea syndrome, action B26, and Adipose tissue and the metabolic syndrome, action BM0602) in order to discuss the interactions between obesity and OSA. Such interactions can be particularly significant in the pathogenesis of metabolic abnormalities and in increased cardiovascular risk in OSA patients. However, studying the respective role of OSA and obesity is difficult in patients, making it necessary to refer to animal models or in vitro systems. Since most OSA patients are obese, their management requires a multidisciplinary approach. This review summarises some aspects of the pathophysiology and treatment of obesity, and the possible effects of sleep loss on metabolism. OSA-associated metabolic dysfunction (insulin resistance, liver dysfunction and atherogenic dyslipidaemia) is discussed from the perspective of both obesity and OSA in adults and children. Finally, the effects of treatment for obesity or OSA, or both, on cardio-metabolic variables are summarised. Further interdisciplinary research is needed in order to develop new comprehensive treatment approaches aimed at reducing sleep disordered breathing, obesity and cardiovascular risk.

Obstructive sleep apnoea and metabolic impairment in severe obesity.

Obstructive sleep apnoea (OSA) seems to worsen metabolism. This effect has not been evaluated in morbid obesity (MO). We hypothesised that the metabolic profile is more impaired in MO patients with OSA than in those without, and investigated whether any specific metabolic dysfunction is related to OSA in MO. A prospective multicentre cross-sectional study was conducted in consecutive subjects before bariatric surgery. OSA was defined as apnoea/hypopnoea index (AHI) ≥15 by overnight polysomnography. Anthropometrical, blood pressure (BP) and fasting blood measurements were obtained the morning after. Metabolic syndrome (MetS) was defined according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. 159 patients were studied: 72% were female and 72% had OSA. MetS prevalence was 70% in OSA versus 36% in non-OSA (p<0.001). As AHI severity increased, metabolic parameters progressively worsened, even in those without type 2 diabetes (DM2). AHI was independently associated with systolic and diastolic BP, triglycerides and the percentage of glycosylated haemoglobin (HbA1c) in the total sample, and with systolic BP, high-density lipoprotein cholesterol and HbA1c in those samples without DM2. OSA increased the adjusted odds ratio of having MetS by 2.8 (95% CI 1.3-6.2; p=0.009). In MO, OSA is associated with major metabolic impairment caused by higher BP and poorer lipid and glucose control, independent of central obesity or DM2.

Sleep, sleep-disordered breathing and metabolic consequences.

Sleep profoundly affects metabolic pathways. In healthy subjects, experimental sleep restriction caused insulin resistance (IR) and increased evening cortisol and sympathetic activation. Increased obesity in subjects reporting short sleep duration leads to speculation that, during recent decades, decreased sleeping time in the general population may have contributed to the increasing prevalence of obesity. Causal inference is difficult due to lack of control for confounders and inconsistent evidence of temporal sequence. In the general population, obstructive sleep apnoea (OSA) is associated with glucose intolerance. OSA severity is also associated with the degree of IR. However, OSA at baseline does not seem to significantly predict the development of diabetes. Prevalence of the metabolic syndrome is higher in patients with OSA than in obese subjects without OSA. Treatment with continuous positive airway pressure seems to improve glucose metabolism both in diabetic and nondiabetic OSA but mainly in nonobese subjects. The relative role of obesity and OSA in the pathogenesis of metabolic alterations is still unclear and is intensively studied in clinical and experimental models. In the intermittent hypoxia model in rodents, strong interactions are likely to occur between haemodynamic alterations, systemic inflammation and metabolic changes, modulated by genetic background. Molecular and cellular mechanisms are currently being investigated.

Reticulocytes in untreated obstructive sleep apnoea.

BACKGROUND AND AIM: The short, repetitive hypoxaemic episodes observed in obstructive sleep apnoea (OSA) may determine small augmentations in mature red blood cells. It is unknown whether they affect reticulocyte release. This study explored whether the number and degree of maturation of circulating reticulocytes may be altered in OSA, possibly through the effect of erythropoietin. METHODS: Fifty male adult patients with suspected OSA, normoxic during wakefulness, were studied. After nocturnal polysomnography, a blood sample was withdrawn for blood cells count, erythropoietin, iron and transferrin determination. Reticulocyte concentration and degree of immaturity [high (H), medium (M), or low (L)] were also determined. Immature reticulocyte fraction (IRF) was calculated as (M+H) percentage of reticulocytes. RESULTS: A wide range of OSA severity was found [apnoea/hypopnoea index (AHI): 44.3 +/- 30.4, range 0.3-105; sleep time spent at oxyhaemoglobin saturation <90%: 18.1 +/- 22.2%, range 0-81%]. Both reticulocyte count and IRF slightly exceeded the normal range. Patients with a reticulocyte concentration > 2% had higher EPO levels (p < 0.05), but not worse nocturnal desaturations, than those with values < 2%. By contrast, subjects with IRF < 15% showed worse desaturations (p < 0.05), but similar EPO concentrations, when compared to subjects whose IRF was < 10%. At univariate analysis, reticulocyte count correlated to erythropoietin, while IRF to transferrin saturation, BMI and OSA severity. At multiple regression, only lowest nocturnal oxygen saturation remained a significant contributor to IRF (r2 0.223, p < 0.05). CONCLUSIONS: This data suggests that hypoxaemia due to OSA could influence the release of immature reticulocytes, but this effect is not mediated by erythropoietin.

Carbocysteine counteracts the effects of cigarette smoke on cell growth and on the SIRT1/FoxO3 axis in bronchial epithelial cells.

BACKGROUND: Cigarette smoke may accelerate cellular senescence by increasing oxidative stress. Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence. The effects of carbocysteine on the SIRT1/FoxO3 axis and on downstream molecular mechanisms in human bronchial epithelial cells exposed to cigarette smoke are largely unknown. AIMS: Aim of this study was to explore whether carbocysteine modulated SIRT1/FoxO3 axis, and downstream molecular mechanisms associated to cellular senescence, in a bronchial epithelial cell line (16-HBE) exposed to cigarette smoke. METHODS: 16HBE cells were stimulated with/without cigarette smoke extracts (CSE) and carbocysteine. Flow cytometry and clonogenic assay were used to assess cell proliferation; western blot analysis was used for assessing nuclear expression of SIRT1 and FoxO3. The nuclear co-localization of SIRT1 and FoxO3 was assessed by fluorescence microscopy. Beta galactosidase (a senescence marker) and SIRT1 activity were assessed by specific staining and colorimetric assays, respectively. ChiP Assay and flow cytometry were used for assessing survivin gene regulation and protein expression, respectively. RESULTS: CSE decreased cell proliferation, the nuclear expression of SIRT1 and FoxO3 and increased beta galactosidase staining. CSE, reduced SIRT1 activity and FoxO3 localization on survivin promoter thus increasing survivin expression. In CSE stimulated bronchial epithelial cells carbocysteine reverted these phenomena by increasing cell proliferation, and SIRT1 and FoxO3 nuclear expression, and by reducing beta galactosidase staining and survivin expression. CONCLUSIONS: The study shows for the first time that carbocysteine may revert some senescence processes induced by oxidative stress due to cigarette smoke exposure.

Autonomic cardiac regulation in obstructive sleep apnea syndrome: evidence from spontaneous baroreflex analysis during sleep.

OBJECTIVE: To assess spontaneous baroreceptor-heart rate reflex sensitivity during sleep in patients with obstructive sleep apnea syndrome, a condition associated with increased cardiovascular morbidity and mortality and characterized by marked sympathetic activation, which is believed to originate from hypoxic chemoreceptor stimulation, although little is known of other possible mechanisms such as baroreflex impairment. DESIGN AND METHODS: In 11 patients with severe obstructive sleep apnea syndrome (mean+/-SD age 46.8+/-8.1 years, apnea/hypopnea index 67.9+/-19.1 h), who were normotensive or borderline hypertensive during wakefulness by clinic blood pressure measurements, finger blood pressure was monitored beat-by-beat non-invasively (Finapres) at night during polysomnography. Periods of wakefulness and sleep were identified based on electroencephalographic recordings. Baroreflex sensitivity was assessed by the sequence technique, as the slope of the regression line between spontaneous increases or reductions in systolic blood pressure (SBP) and the related lengthening or shortening in the RR interval, occurring over spontaneous sequences of four or more consecutive beats. The number of these sequences was also computed, as an additional index of baroreflex engagement by the spontaneous blood pressure fluctuations. The controls were age-related normotensive or borderline hypertensive subjects without sleep apnea who had been investigated in previous studies; in these subjects blood pressure was recorded intra-arterially over 24 h in ambulatory conditions and spontaneous baroreflex sensitivity was assessed by the sequence technique. RESULTS: In our patients the lowest nocturnal arterial oxygen saturation was 78.6+/-12.1% (mean+/-SD). During sleep, the number of pooled +RR/+SBP and -RR/-SBP sequences per hour was 20.3+/-2.7 per h in patients with sleep apnea and 27.1+/-2.1 /h in controls (means+/-SEM). The average baroreflex sensitivity during sleep periods was 7.04+/-0.8 ms/mmHg in sleep apnea patients and 10.05+/-2.1 ms/mmHg in controls. Both the pooled number of sequences and baroreflex sensitivity values of the sleep apnea patients were significantly (P < 0.01) less than the corresponding night values of control subjects. In the sleep apnea patients, at variance from controls, baroreflex sensitivity did not show any increase during sleep compared with its values during wakefulness (6.9+/-1.0 ms/mmHg). CONCLUSIONS: Our data provide evidence that spontaneous baroceptor reflex sensitivity is depressed in severe obstructive sleep apnea syndrome. This suggests that in such patients baroreflex dysfunction and not only chemoreceptor stimulation by hypoxia may be involved in the sympathetic activation which occurs during sleep. Such dysfunction may contribute to the higher rate of cardiovascular morbidity and mortality reported in these patients.

Different heart rate patterns in obstructive apneas during NREM sleep.

Both bradycardia and a trend to tachycardia have been reported in obstructive sleep apneas (OSA). Because heart rate (HR) behavior may yield information on parasympathetic activity during OSA, we analyzed HR in samples of consecutive apneic cycles in non-rapid eye movement (NREM) sleep, recorded in normotensive patients breathing room air (n = 7) and supplemental O2 (n = 4). In air, the patients showed different HR trends during apnea, as HR decreased (HR decreased), remained constant (HR=), or increased (HR increased). By multiple regression analysis, development of HR trends correlated with the HR fall in the late interapneic period, HR at first effort, the decrease in esophageal pressure, and the lengthening of inspiration during apnea (R2 = 0.42). O2 abolished HR decreased-OSA, whereas HR= and HR increased-OSA still occurred but at higher HR than in air. In both the air and O2 series, the HR fall preceding apnea correlated significantly with the degree of hypoxia reached in the previous apneic cycle. These data indicate a complex modulation of HR during OSA, with the HR fall in the late interapneic period possibly reflecting the effectiveness of parasympathetic cardiac control in OSA patients during sleep.

Myocardial ischemia during sleep.

The role of sleep in the pathogenesis of coronary ischaemic events such as myocardial infarction, transient myocardial ischaemia, or cardiac sudden death, is unclear. This review will analyse the available data on the subject according to: (i) the autonomic and cardiovascular changes during sleep that may potentially favour myocardial ischaemia; (ii) the evidence of a circadian distribution of coronary events; and (iii) the factors possibly involved in the pathogenesis of nocturnal angina. Available data suggest that myocardial ischaemia may occur by different mechanisms in non-rapid eye movement (NREM) (decreased coronary perfusion pressure) and rapid eye movement (REM) sleep (increased myocardial oxygen demand). Coronary events show a major peak of occurrence between 6.00 a.m. and noon; however, the myocardial ischaemic threshold, defined as the heart rate value at which myocardial ischaemia develops, may be lower at night than during the daytime, suggesting an unexpectedly higher susceptibility to myocardial ischaemia during sleep than during wakefulness. These data warrant further study on the pathophysiology of coronary circulation during sleep. Finally, some evidence is available that sleep disordered breathing may precipitate nocturnal angina especially in REM sleep, through decreased arterial oxygen content secondary to hypoventilation or true apnoeas. More data are needed to better understand the effects of sleep on the coronary circulation, and to improve the therapeutic approach of nocturnal angina.

Airway remodelling in the pathogenesis of asthma.

The inflammatory and remodelling processes that underlie asthma result from a highly complex interaction between various cell types. Apart from inflammatory cells, such as eosinophils, activated T cells, mast cells and macrophages, structural tissue cells such as epithelial cells, fibroblasts and smooth muscle cells can also play an important effector role through the release of a variety of mediators, cytokines and chemokines. This results in an acute inflammatory response that is characterized by vascular leakage, mucus hypersecretion, epithelial shedding and widespread airway narrowing. At the same time, through the release of mediators, cytokines, chemokines and growth factors, epithelial and mesenchymal cells cause persistence of the inflammatory infiltrate and induce structural changes in the airway wall, such as increased thickness of the basement membrane, increased collagen deposition, changes in bronchial microcirculation, and smooth muscle hypertrophy and hyperplasia. The end result of airway inflammation and remodelling is an increased thickness of the airway wall, leading to a reduced baseline airway calibre and exaggerated airway narrowing.

Catecholamines and blood pressure in obstructive sleep apnea syndrome.

To evaluate the release of catecholamines and their relationship with systemic blood pressure (BP) in normotensive patients with obstructive sleep apnea syndrome (OSAS), diurnal and nocturnal urinary norepinephrine (NE) and epinephrine (E) excretion in 12 normal subjects and in 10 OSAS patients were compared; in addition, nocturnal NE and E excretion were measured in the patients while receiving short-term CPAP. Blood pressure was continuously monitored in the patients during both nights of urine collection. In normal subjects, both NE and E excretion decreased from day to night. In the patients without CPAP, only NE excretion decreased at night, and BP increased from wakefulness to sleep; both NE and E excretion were higher in patients than in normal subjects. With CPAP, which prevented apneas, only E excretion decreased with respect to the previous night, while BP no longer increased during sleep. The extent of nocturnal E decrease with CPAP was not correlated to BP variations. These results suggest that in normotensive OSAS subjects, sympathetic nervous system activity, based on NE excretion, is continuously increased and is not affected by short-term CPAP treatment. Conversely, adrenal activity, based on E excretion, is also increased, but it tends to be normalized by short-term CPAP. No clear relationship could be found between sympatho-adrenal behavior and BP during sleep.

Tumor necrosis factor-alpha does not cause lung edema in rabbits.

Although tumor necrosis factor-alpha (TNF) is a key mediator in the pathophysiology of sepsis and septic shock, its role in lung microvascular injury is controversial. In isolated blood-perfused rabbit lungs, we studied the microvascular effects of human recombinant TNF by measuring the capillary filtration coefficient (Kf,c) as an index of microvascular leakiness and the arterial and venous resistances and occlusion pressures to define the microvascular pressure profile. At the end of the experiments, the lung wet-to-dry weight ratio (W/D) was determined as an index of edema. TNF increased the pulmonary venous resistance slightly but did not affect Kf,c or W/D. Furthermore, TNF at different doses failed to increase W/D less than or equal to 8 h after in vivo administration. Our data suggest that 1) the pulmonary microvascular response to TNF differs from the systemic response, which is characterized by arteriolar vasodilation, and 2) TNF is insufficient to cause lung edema, both in vivo and in vitro. Thus the development of lung microvascular injury may require the combined action of TNF and other mediators.

Alpha-adrenergic agents have little effect during air embolism lung injury in awake sheep.

Since it is not clear whether alpha-adrenergic receptors can modulate lung microvascular liquid and protein leakiness, we studied the effects of alpha-adrenergic receptor stimulation or blockade on lung filtration under base-line conditions and during the acute lung injury caused by a 4-h infusion of venous air emboli in six unanesthetized, chronically instrumented sheep with lung lymph fistulas. During the experiments we continuously infused the alpha-adrenergic receptor agonist phenylephrine hydrochloride (1.0 microgram X kg-1 X min-1 iv) or the alpha-adrenergic receptor antagonist phentolamine mesylate (1.0 mg X kg-1 X min-1 iv), and we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and the lymph-to-plasma protein concentration ratio. During air embolism, alpha-receptor stimulation increased pulmonary vascular resistance and decreased lung lymph flow by 25%; alpha-receptor blockade had the opposite effects. During recovery, neither agent significantly affected pulmonary hemodynamics or lymph flow. Our results indicate that alpha-adrenergic receptors are active during air embolism and modulate pulmonary filtration by causing arteriolar constriction, which reduces the surface area or the perfusion pressure in the pulmonary microvascular bed. They may also affect venous smooth muscle tone. We found no evidence that alpha-adrenergic receptors modulate lung microvascular liquid or protein leakiness directly.

Effects of beta-adrenergic agents in lungs of normal and air-embolized awake sheep.

It is unclear whether beta-adrenergic agonists or antagonists affect lung liquid and protein exchange by changing pulmonary hemodynamics or microvascular leakiness. In 23 unanesthetized, instrumented sheep with long-term lung lymph fistulas, we assessed the effect of the beta-agonist terbutaline or the beta-antagonists propranolol, nadolol, and atenolol, all infused intravenously, on lung lymph flow under base-line conditions and during the acute lung injury caused by 4 h of venous air embolism. Under base-line conditions, neither beta-stimulation nor blockade had any effect. During air embolism, terbutaline decreased pulmonary vascular resistance and lymph flow by 25%. Propranolol and nadolol (non-selective beta 1,beta 2-antagonists) but not atenolol (selective beta 1-antagonist) also decreased lymph flow by 22% on average. We favor the more conservative (hemodynamic) over the more liberal (altered permeability) explanation for our results. First, beta-stimulation clearly caused vasodilation, which lowered the pulmonary microvascular pressure at the site of injury. beta-blockade caused changes similar to alpha-stimulation (J. Appl. Physiol. 62: 2147-2153, 1987). We therefore interpret the beta-blockade as unmasking pulmonary arterial alpha-receptors stimulated by the air-embolism injury, thus allowing vasoconstriction upstream to the site of injury. We do not believe the explanation of the beta-agent effects requires any modulation of lung microvascular leakiness by beta-adrenergic agents.

Blood pressure and heart rate during periodic breathing while asleep at high altitude.

The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia during wakefulness progressively increased in normal subjects staying 4 wk at 5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724-1730, 1996). In the same subjects (n = 5, age 28-34 yr) and expedition, nocturnal polysomnography with ABP and heart rate (HR) recordings were obtained during the 1st and 4th week to study the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs. tonic (i. e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR fluctuated during non-rapid eye movement sleep periodic breathing. None of the subjects exhibited an ABP increase during the ventilatory phases that correlated with the lowest arterial oxygen saturation of the preceding pauses. Despite attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were similar to those in the 1st wk. Because ABP during periodic breathing in the ventilatory phase increased similarly to the ABP response to progressive hypoxia during wakefulness, ABP variations during ventilatory phases may reflect ABP responsiveness to peripheral chemoreflex sensitivity rather than the absolute value of hypoxemia, suggesting a major tonic effect of hypoxia on cardiorespiratory control at high altitude.

Airway inflammation in patients affected by obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper airway inflammation. The object of the present study was to establish the presence of bronchial inflammation in OSAS subjects. In 16 subjects affected by OSAS, and in 14 healthy volunteers, airway inflammation was detected by the cellular analysis of the induced sputum. OSAS patients, as compared to control subjects, showed a higher percentage of neutrophils (66.7+/-18.9 vs. 25.8+/-15.6) (P<0.001) and a lower percentage of macrophages (29.4+/-18.4 vs. 70.8+/-15.3) (P<0.001). The percentage of eosinophils and lymphocytes were not significantly different in the two groups. OSAS subjects show bronchial inflammation characterized by a significant increase in neutrophils.

Ventilation and entrainment of breathing during cycling and running in triathletes.

PURPOSE: To assess whether entrainment of breathing (E) during exercise: 1) differed according to the test protocol in well-trained triathletes, and 2) improved ventilatory efficiency during exercise. METHODS: Eight triathletes performed three incremental tests until exhaustion: while cycling (CE), while running at increasing grade and constant speed (increasing GRADE) and while running at increasing speed and constant grade (increasing SPEED), respectively. E was evaluated as the percentage of breaths occurring at respiratory rates (F) corresponding to integer ratios of the exercise cycle rate. To assess whether E improved ventilatory efficiency, deltaVE/VO2 between nonentrained and entrained breaths was measured at each load. RESULTS: Mean E was higher in CE (57.2+/-21.9%) than in increasing GRADE (46.9+/-18.7%) and increasing SPEED (41.4+/-17.2%). E decreased at high loads in CE and increasing SPEED but not in increasing GRADE. In the group of subjects, E correlated with the degree of fitness (evaluated as VO2Tvent/VO2peak%) only during increasing GRADE. By multiple regression analysis on all data, minute ventilation correlated with CO2 production but not with the exercise cycle rate; however, either F or tidal volume correlated significantly with both these variables. VE/VO2 was lower in entrained than nonentrained breaths at each load in CE and increasing GRADE experiments, but the difference was small. CONCLUSIONS: In spite of some differences among protocols, triathletes showed significant E during incremental exercise tests. Spontaneous E appeared to slightly improve ventilatory efficiency during CE and increasing GRADE protocols.

Acute and chronic influences of obstructive sleep apnoea on the pulmonary circulation.

Obstructive sleep apnoea (OSA) produces immediate effects on pulmonary haemodynamics during sleep in all subjects. In addition, in some subjects, OSA is accompanied by chronic abnormalities of the pulmonary circulation. During sleep, pressure in the main pulmonary artery oscillates within each apnoea, in synchrony with intrathoracic pressure changes; in addition, it may increase progressively as a consequence of prolonged severe hypoxaemia. Pulmonary capillary wedge pressure may increase during inspiratory efforts, possibly reflecting a mechanical limitation of left ventricular function. Cardiac output decreases at apnoea resolution as an effect of a decreased right ventricular stroke volume, despite increased cardiac frequency. During wakefulness, postcapillary pulmonary hypertension occurs on exercise in many OSA patients, whilst pulmonary hypertension at rest is precapillary and occurs in patients with an altered daytime respiratory function. Development of right ventricular hypertrophy and a decrease in right ventricular ejection fraction appear to be related to the severity of respiratory alterations during sleep, whilst an overt right heart failure requires an altered daytime respiratory function. Long-term treatment of the obstructive sleep apnoea syndrome is more effective in increasing right ventricular ejection fraction than in decreasing pulmonary artery pressure during wakefulness.