Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep-related breathing disorders (SRBDs) represent a spectrum of abnormalities that range from simple snoring to upper airway resistance syndrome to sleep apnea. The clinical presentation may include obesity, snoring, neuropsychological dysfunction, and daytime hypersomnolence and tiredness. The acute hemodynamic alterations of obstructive sleep apnea include systemic and pulmonary hypertension, increased right and left ventricular afterload, and increased cardiac output. Earlier reports attributed the coexistence of SRBDs with cardiovascular diseases to the shared risk factors such as age, sex, and obesity. However, recent epidemiologic data confirm an independent association between SRBDs and the different manifestations of cardiovascular diseases. Possible mechanisms may include a combination of intermittent hypoxia and hypercapnia, repeated arousals, sustained increase in sympathetic tone, reduced baroreflex sensitivity, increased platelet aggregation, and elevated plasma fibrinogen and homocysteine levels. The strength of the association, its pathogenesis, and the impact of treatment of SRBDs on the health outcome of patients with cardiovascular diseases are issues to be addressed in future studies.
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PMID:Cardiovascular consequences of sleep-related breathing disorders. 1235 Feb 42

Hyperventilation is the key factor contributing to the development of idiopathic nonhypercapnic central sleep apnoea (ICSA), where left ventricular systolic function is normal. ICSA is reported to occur in 20% of patients with left ventricular diastolic dysfunction, in whom elevated pulmonary vascular pressures and resultant increased pulmonary vagal afferent traffic may contribute to hyperventilation. The contribution of the two potential mechanisms responsible for the hyperventilation seen in the following ICSA was measured: 1) left ventricular diastolic dysfunction-induced pulmonary hypertension; and 2) increased peripheral and central hypercapnic ventilatory responses (HCVR). The pulmonary artery pressure, left ventricular diastolic function and chemosensitivity to hypercapnia were measured during wakefulness in 16 subjects with ICSA. All subjects had systolic pulmonary artery pressures <3.99 kPa (<30 mmHg) and only four had diastolic dysfunction. All subjects had elevated peripheral and central HCVR compared with historical normal control subjects. Diastolic dysfunction correlated with increasing age but not with HCVR or markers of central sleep apnoea severity. Idiopathic nonhypercapnic central sleep apnoea is likely to be dependent upon raised hypercapnic ventilatory responses, and not pulmonary hypertension due to left ventricular diastolic dysfunction.
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PMID:Cardiac diastolic function and hypercapnic ventilatory responses in central sleep apnoea. 1235 52

The role of patent foramen ovale (PFO) in cryptogenic stroke is still debated, but from recent follow-up studies it seems that the amount of right-to-left shunt (RLS) and the association with atrial septal aneurysm (ASA) are major determinants of stroke recurrence. PFO and RLS through the atrial chambers have been recently studied in a number of conditions not or marginally related to cerebrovascular disease. Historically the first studies addressed the presence of RLS in scuba divers as a possible abnormality related to decompression sickness (DS) of unknown aetiology. Despite initial debate there is now robust evidence to claim that patency of foramen ovale increases the risk of developing DS by two and half to four times. Patients with PFO-related DS tend to have early occurrence of symptoms after surfacing and a clinical presentation that indicates brain or upper cervical spinal cord involvement. Recent reports suggest that divers with hemodynamically significant RLS may have an increased risk of developing clinically asymptomatic multiple brain lesions. PFO has been found in patients suffering from migraine with aura with approximately the same frequency as that encountered in cryptogenic stroke patients. This finding has prompted speculations on the possible role of RLS in increasing the stroke risk in migraineurs and in the pathophysiology of the aura. Recent reports showing that migraine with aura is dramatically improved after transcatheter closure of PFO suggest that migraine with aura may indeed be triggered by humoral factors that reach the brain by escaping the pulmonary filter. A RLS is involved in a rare condition known as platypnea-orthodeoxia and perhaps underlies an increased risk of cerebral complications after major orthopedic surgery. Valsalva-like activities often precede the occurrence of attacks of transient global amnesia (TGA) and abnormalities consistent with hypoperfusion of deep limbic structures have been reported during a typical TGA episode. This had raised the hypothesis that TGA may be triggered by paradoxical embolism of platelets aggregates in the posterior circulation, but the search for an increased frequency of PFO in TGA patients has yielded conflicting results. Conditions that determine an increase in pulmonary pressure may facilitate the opening of the virtual interatrial valve and thus promoting shunting of blood to the left heart chambers which in turn might contribute to further desaturation of arterial blood. It is therefore not surprising that RLS has been found in 70% of patients with chronic obstructive pulmonary disease and increased pulmonary pressure and in the same proportion of patients with obstructive sleep apnoea, a condition that ultimately may result in pulmonary hypertension. In conclusion, from the evidence gathered so far the picture is emerging of an important role of PFO in a number of non-stroke conditions, either as causative factor or as associated condition predisposing to complications. The availability of simple diagnostic techniques such as transcranial Doppler (TCD) to assess RLS will undoubtedly contribute a great deal of knowledge on the relevance in medicine of this hitherto neglected condition.
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PMID:Clinical impact of patent foramen ovale diagnosis with transcranial Doppler. 1247 Aug 46

In patients with obstructive sleep apnoea syndrome (OSAS), pulmonary haemodynamics can show both transient perturbations during sleep and permanent alterations. During sleep, repeated fluctuations in pulmonary artery pressure and pulmonary wedge pressure, coincident with apnoeas, can be observed. Calculation of transmural pressure values is preferable to intravascular pressures in OSAS, due to the marked swings in intrathoracic pressure associated with obstructive apnoeas. Pulmonary artery pressure may progressively increase during sleep, particularly in close sequences of highly desaturating apnoeas. Apnoea-induced hypoxia appears as the most important determinant of this pulmonary artery pressure behaviour. Stroke volume and cardiac output during obstructive apnoeas show changes mainly related to intrathoracic pressure variations. Permanent precapillary pulmonary hypertension at rest is observed in <50% OSAS patients, and is poorly reversible after OSAS treatment. It correlates best with diurnal respiratory function parameters. However, the finding of pulmonary hypertension in some patients with near normal diurnal lung function led to suggest that sleep respiratory disorders may contribute to permanent pulmonary haemodynamic impairment in predisposed subjects. Knowledge on right ventricle hypertrophy in OSAS is inconsistent. As to right ventricle failure, it is clinically evident in subjects with associated lung disease or morbid obesity, while it may be detected instrumentally in subjects without such alterations, presumably as effect of apnoeas themselves. Besides, it appears more fully reversible after long-term OSAS treatment than pulmonary hypertension.
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PMID:Pulmonary haemodynamics in obstructive sleep apnoea. 1253 Nov 20

A 6-year-old boy with Hurler's syndrome presented with right heart failure and pulmonary hypertension secondary to severe obstructive sleep apnoea. Both his sleep apnoea and cor pulmonale were effectively controlled with continuous positive airway pressure therapy.
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PMID:Hurler's syndrome with cor pulmonale secondary to obstructive sleep apnoea treated by continuous positive airway pressure. 1296 15

Obstructive sleep apnea is an increasingly well-recognized disease characterized by periodic collapse of the upper airway during sleep. This leads to either complete or partial obstruction of the airway, resulting in apneas, hypopneas, or both. This disorder causes daytime somnolence, neurocognitive defects, and depression. It affects almost every system in the body, resulting in an increased incidence of hypertension, cardiovascular disease, stroke, pulmonary hypertension, cardiac arrhythmias, and altered immune function. It also increases the risk of having an accident, presumably as a result of associated somnolence. The gold standard for the diagnosis of sleep apnea is an overnight polysomnogram. Split-night studies are becoming increasingly common and allow for quicker implementation of therapy at a reduced cost. Treatment options for sleep apnea include weight loss, positional therapy, oral devices, continuous positive airway pressure (CPAP), and upper airway surgery. CPAP is the most efficacious and widely used therapy. Its complications include nasal congestion or dryness, mask discomfort, and claustrophobia. Heated humidifiers, newer types of masks, and nasal steroids have improved tolerance of this therapy. Bilevel positive-pressure therapy can be considered for patients who find it difficult to exhale against the consistently increased pressure of CPAP. The disease requires aggressive treatment to improve quality of life and prevent its complications.
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PMID:Obstructive sleep apnea. 1456 40

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a prevalent disorder associated with substantial cardiovascular and neurobehavioral morbidity. Yet this is a disorder for which there are no widely effective pharmacotherapies. The pathophysiology of obstructive sleep apnea namely, normal respiration in waking with disordered breathing only in sleep, suggests that this disorder should be readily amenable to drug therapy. Over the past 10 years, we have gained tremendous insight into the neurochemical mechanisms involved in state-dependent control of respiration. It is apparent from this work that there are many potential avenues for pharmacotherapies, including several seemingly conflicting directions for serotonergic therapies. Serotonin delivery is reduced to upper airway dilator motor neurons in sleep, and this contributes, at least in part, to sleep-related reductions in dilator muscle activity and upper airway obstruction. The dilator motor neuron post-synaptic serotonin receptors are 5-HT(2A) and 5-HT(2C) subtypes, and in adults the presynaptic 5-HT receptor in motor nuclei is 5-HT(1B), an inhibitory receptor. Serotonin receptors are also found within central respiratory neuronal groups, and these receptor subtypes include 5-HT(1A) (inhibitory) and 5-HT(2) receptors. Peripherally, stimulation of 5-HT(2A), 5-HT(2C) and 5-HT(3) receptor subtypes have an inhibitory effect on respiration via action at the nodose ganglion. Many of these receptor subtypes and their signal transduction pathways may be affected by oxidative stress in obstructive sleep apnea. These alterations will make finding drug therapies for sleep apnea more challenging, but not insurmountable. Future directions are suggested for elucidating safe, well-tolerated serotonergic drugs for this disorder. Tryptophan was one of the first serotonergic drugs tested for OSAHS. This drug was withdrawn from the market as a result of reports linking tryptophan use with eosinophilic myalgia syndrome and life-threatening pulmonary hypertension. Newer drugs with serotonergic activity tested in persons with sleep-disordered breathing include buspirone, fluoxetine and paroxetine. Trials are presently being conducted to evaluate the effects of 5-HT(2A) and 5-HT(3) antagonists on OSAHS. Many of the drugs tested have not shown significant improvement in sleep apnea. However, with continued effort to elucidate the pharmacology of neurochemical control of state-dependent changes in respiratory control, the availability of pharmacological therapy for this disorder is not too far away.
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PMID:Serotonin agonists and antagonists in obstructive sleep apnea: therapeutic potential. 1472 19

Frequent and loud snoring is a very frequent condition in prepubertal children affecting approximately 10% of all 2-8 year old children. If polysomnographical evaluations are performed in these snoring children, approximately 10% will be diagnosed with obstructive sleep apnoea (OSA). The pathophysiology of OSA in children is still poorly understood. Indeed, while adenotonsillar hypertrophy is certainly a major contributor to OSA, other factors need to be implicated for OSA to develop. In recent years, it has become apparent that OSA and snoring are not as innocuous as previously thought. Indeed, epidemiological and pre-post treatment analyses have identified substantial morbidities that primarily affect cardiovascular and neurobehavioural systems, namely pulmonary hypertension, systemic elevation of arterial blood pressure, nocturnal enuresis, reduced somatic growth, behavioural problems that resemble attention deficit-hyperactivity disorder, as well as learning and cognitive deficits. These problems are associated with marked increases in healthcare-related costs. More importantly, if timely diagnosis and intervention are not implemented, some of these morbid complications may not be completely reversible, leading to long-lasting residual consequences.
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PMID:Snoring and obstructive sleep apnoea in children: why should we treat? 1498 Feb 99

Sleep-disordered breathing in humans is a common condition associated with serious cardiovascular and other abnormalities. The prevalence and pathogenesis of increased haematocrit and pulmonary hypertension is controversial and it has been suggested that these changes only occur in patients who also have daytime continuous hypoxaemia. The hypothesis tested here is that the chronic intermittent hypoxia and asphyxia associated with sleep-disordered breathing causes erythropoiesis and pulmonary hypertension and that this occurs in the absence of periods of continuous hypoxia. In humans and animals with obstructive sleep apnoea, there are abnormalities of upper airway muscle structure that have been ascribed to increased load placed on these muscles. An alternative hypothesis is that chronic intermittent hypoxia and asphyxia cause changes in upper airway muscle structure and function. To test these hypotheses, rats were exposed to intermittent hypoxia and asphyxia for 8 h per day for 5 weeks. This caused an increase in haematocrit, right ventricular weight and pulmonary arterial pressure. There were only slight changes in diaphragm, upper airway and limb muscle structure and force production but in general, muscle fatigability was increased. In conclusion chronic intermittent hypoxia and asphyxia cause an increase in haematocrit and pulmonary arterial pressure in the absence of periods of continuous hypoxia. Chronic intermittent hypoxia and asphyxia have little effect on skeletal muscle structure and force production but increase muscle fatigue. Increased upper airway muscle fatigue could lead to a vicious cycle of further compromise in upper airway patency and further hypoxia and asphyxia.
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PMID:Effects of chronic intermittent asphyxia on haematocrit, pulmonary arterial pressure and skeletal muscle structure in rats. 1510 8

Patients with COPD who are hypoxaemic during wakefulness become more hypoxaemic during sleep. The most severe episodes of nocturnal desaturation generally occur during REM sleep. There is a strong relationship between nocturnal O2 saturation and the level of daytime PaO2: the more pronounced daytime hypoxaemia, the more severe nocturnal hypoxaemia. The worsening of hypoxaemia is due to a variable combination of alveolar hypoventilation and ventilation-perfusion mismatching, alveolar hypoventilation being the predominant mechanism, at least during REM sleep. The consequences of sleep-related hypoxaemia include peaks of pulmonary hypertension due to hypoxic pulmonary vasoconstriction, generally observed in patients with marked daytime hypoxaemia. Cardiac arrhythmias have been described but their clinical relevance has not been established. The prevalence of obstructive sleep apnoea syndrome (OSAS) is not greater in chronic obstructive pulmonary disease (COPD) patients than in the general population, but this association (Overlap Syndrome) is not rare since COPD and OSAS are both frequent diseases. Overlap patients are at a higher risk of developing respiratory insufficiency than are pure OSAS patients. Polysomnography is only indicated in COPD patients who are suspected of having OSAS. The treatment of nocturnal hypoxaemia is conventional O2 therapy (> or = 16/24 h) in COPD patients with marked daytime hypoxaemia (PaO2 < 55-60 mmHg) and conventional O2 therapy plus nocturnal non-invasive ventilation in some patients with marked hypercapnia. At present data are not sufficient for justifying the use of isolated nocturnal oxygen therapy in COPD patients with nocturnal desaturation but with mild daytime hypoxaemia (PaO2 > 60 mmHg).
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PMID:Sleep and chronic obstructive pulmonary disease. 1523 53


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