https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71141-7.pdf

Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study

Duchenne muscular dystrophy (DMD) is a severe, progressive disease that aff ects 1 in 3600–6000 live male births. Although guidelines are available for various aspects of DMD, comprehensive clinical care recommendations do not exist. The US Centers for Disease Control and Prevention selected 84 clinicians to develop care recommendations using the RAND Corporation–University of California Los Angeles Appropriateness Method. The DMD Care Considerations Working Group evaluated assessments and interventions used in the management of diagnostics, gastroenterology and nutrition, rehabilitation, and neuromuscular, psychosocial, cardiovascular, respiratory, orthopaedic, and surgical aspects of DMD. These recommendations, presented in two parts, are intended for the wide range of practitioners who care for individuals with DMD. They provide a framework for recognising the multisystem primary manifestations and secondary complications of DMD and for providing coordinated multidisciplinary care. In part 1 of this Review, we describe the methods used to generate the recommendations, and the overall perspective on care, pharmacological treatment, and psychosocial management.

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Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management

BackgroundObstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. MethodsAfter a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. ResultsMost of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1606599

CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea

Background and Methods Drowsiness and lack of concentration may contribute to traffic accidents. We conducted a case–control study of the relation between sleep apnea and the risk of traffic accidents. The case patients were 102 drivers who received emergency treatment at hospitals in Burgos or Santander, Spain, after highway traffic accidents between April and December 1995. The controls were 152 patients randomly selected from primary care centers in the same cities and matched with the case patients for age and sex. Respiratory polygraphy was used to screen the patients for sleep apnea at home, and conventional polysomnography was used to confirm the diagnosis. The apnea–hypopnea index (the total number of episodes of apnea and hypopnea divided by the number of hours of sleep) was calculated for each participant. Results The mean age of the participants was 44 years; 77 percent were men. As compared with those without sleep apnea, patients with an apnea–hypopnea index of 10 or higher had an odds ratio ...

https://www.nejm.org/doi/pdf/10.1056/NEJM199903183401104

The association between sleep apnea and the risk of traffic accidents. Cooperative Group Burgos-Santander.

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making.

/pdf/control-of-sleep-and-wakefulness-51vkuya5ho.pdf

Control of Sleep and Wakefulness

Introduction: Many studies on the impact of type 2 diabetes mellitus (T2DM) on sleep breathing have shown a higher prevalence and severity of sleep apnea-hypopnea syndrome (SAHS) in those with T2DM. Moreover, an increased activity of the sympathetic nervous system has been described in both pathologies. This cross-sectional study aimed to assess sympathetic activity in patients with T2DM, and to investigate the relationship between sympathetic activity and polysomnographic parameters. Materials and Methods: Thirty-six patients with T2DM without known clinical macrovascular nor pulmonary disease and 11 controls underwent respiratory polygraphy, and their cardiac variability and 24-h urine total metanephrines were measured. Results: SAHS was highly prevalent with a mean apnea-hypopnea index (AHI) in the range of moderate SAHS. In patients with T2DM, the nocturnal concentration of total metanephrines in urine were higher than diurnal levels [247.0 (120.0-1375.0) vs. 210.0 (92.0-670.0), p = 0.039]. The nocturnal total metanephrine concentration was positively and significantly associatedwith the percentage of sleeping time spent with oxygen saturation <90%(CT90). In the entire population and in subjects with T2DM, the multivariate regression analysis showed a direct interaction between the nocturnal concentration of urine metanephrines and the CT90. Conclusion: These findings suggest that the increase in sympathetic activity previously described in patients with T2DM could be mediated through nocturnal breathing disturbances. The diagnosis and treatment of SAHS may influence sympathetic activity disorders and may contribute to an improvement in T2DM and cardiovascular risk.

/pdf/sympathetic-hyperactivity-and-sleep-disorders-in-individuals-2mgmxeutx1.pdf

Sympathetic Hyperactivity and Sleep Disorders in Individuals With Type 2 Diabetes

Ventilación mecánica domiciliaria a presión positiva intermitente por vía nasal

El síndrome de apneas obstructivas del sueño (SAOS) se caracteriza por la repetición de episodios de colapso de la vía aérea superior (VAS) durante el sueño, que interrumpen el flujo aéreo parcial (hipopneas) o totalmente (apneas). Las causas de este colapso son desconocidas, probablemente múltiples y podrían no ser las mismas en todos los individuos1. En los sujetos normales, durante la vigilia, la resistencia al flujo aéreo de la VAS es baja. Durante el sueño esta resistencia aumenta fisiológicamente2, pero existe una gran variabilidad interindividual: desde algunos sujetos en los que apenas cambia respecto a la vigilia, hasta otros en los que la resistencia al flujo aéreo se multiplica por cinco3. Parece, por tanto, que existe un segmento de la población cuya VAS está constitucionalmente predispuesta al colapso3,4. Sin embargo, incluso en estos sujetos con mayor predisposición al colapso de la VAS durante el sueño, no se interrumpe el flujo aéreo. Son sujetos sanos, a menudo roncadores, que no presentan SAOS. Sólo cuando algún otro factor o factores (todavía desconocidos) se suman a la predisposición individual aparece el colapso5,6. La identificación de estos “otros” factores potencialmente implicados en el colapso de la VAS, su papel en la fisiopatología del SAOS y su importancia relativa han sido objeto de gran número de estudios en las últimas décadas. A continuación se revisan las principales líneas de investigación seguidas en este campo, la información disponible en estos momentos y las perspectivas que pueden abrirse en el futuro.

Papel de la vía aérea superior en la patogenia del síndrome de apneas obstructivas del sueño

Obstructive 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. We 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. We 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. A 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. Genotypic 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.

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

with immunohistochemical techniques. Lancet 1 985;i: 1302-5. 2 Hainsworth JD, Wright EP, Gray GF, Greco FA. Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based chemotherapy. J Clin Oncol 1987;5: 127580. 3 Collis CH. Chemotherapy-related morbidity to the lungs. In: Plowman PN, McElwain T, Meadows A, eds. Complications of cancer management. Oxford: Butterworth Heinemann, 1991:250-71. 4 Isaacson PG, Androulakis PA, Diss TC, Pan L, Wright DH. Follicular colonization in thyroid lymphoma. Am J Pathol 1991;141:43-52. 5 Tsang RW, Gospodarowicz MK, Sutcliffe SB, Sturgeon JF, Panzarella T, Patterson BJ. Non-Hodgkin's lymphoma of the thyroid gland: prognostic factors and treatment outcome. The Princess Margaret Hospital Lymphoma Group. Int J Radiat Oncol Biol Phys 1993;27:599-604. 6 Chan JK, Ng CS, Lau WH, Lo ST. Most nasal/nasopharyngeal lymphomas are peripheral T-cell neoplasms. Am J Surg Pathol 1987;11:418-29.

https://thorax.bmj.com/content/thoraxjnl/50/10/1123.2.full.pdf

Ferran Barbé

Papers

Sympathetic Hyperactivity and Sleep Disorders in Individuals With Type 2 Diabetes

Ventilación mecánica domiciliaria a presión positiva intermitente por vía nasal

Papel de la vía aérea superior en la patogenia del síndrome de apneas obstructivas del sueño

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

Apnoea in Duchenne muscular dystrophy.