Sleep-Disordered Breathing and Vascular Function in Patients With Chronic Mountain Sickness and Healthy High-Altitude Dwellers

Rexhaj, Emrush; Rimoldi, Stefano F.; Pratali, Lorenza; Brenner, Roman; Andries, Daniela; Soria, Rodrigo; Salinas, Carlos; Villena, Mercedes; Romero, Catherine; Allemann, Yves; Lovis, Alban; Heinzer, Raphaël; Sartori, Cláudio; Scherrer, Urs

doi:10.1378/chest.15-1450

Cited by 35 publications

(28 citation statements)

References 54 publications

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“…Spicuzza et al ( 36 ) showed no differences in the number and duration of apneas or hypopneas between patients with EE and healthy controls, while Julian et al ( 10 ) have reported that young male residents with EE show a higher frequency of apneas (central and obstructive) and hypopneas during REM sleep and a greater apnea-hypopnea index. Despite controversy on the occurrence of sleep abnormalities, both studies agree on the presence of lower nocturnal pulse O 2 saturation (SpO 2 ) in subjects with EE compared with their healthy counterparts, which is consistent with other studies of nocturnal SpO 2 in HA polycythemic patients ( 8 , 14 , 31 ).…”

Section: New and Noteworthysupporting

confidence: 88%

Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness

et al. 2016

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Andean highlanders suffering from Chronic Mountain Sickness (CMS) show consistently lower levels of plasma soluble erythropoietin (Epo) receptor (sEpoR) and higher Epo-to-EpoR ratios (Epo/sEpoR) during sleep compared with their healthy counterparts. This indicates higher blood Epo availability in CMS patients and continuous nocturnal erythropoietic stimulus. Additionally, morning Epo/sEpoR and mean sleep-time SpO2 are independent main predictors of Hct. These findings support the role of the Epo system in the development of excessive erythrocytosis in CMS.

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Section: New and Noteworthysupporting

confidence: 88%

Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness

et al. 2016

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“…Finally, although our analysis suggests that hypoxemia mediates sleep apnea pathogenesis, causality cannot be determined due to the cross-sectional design of this study, which might also be influenced by residual confounding. Nevertheless, the hypothesis that hypoxemia plays a role in sleep apnea pathogenesis in highlanders is biologically plausible and consistent with results from a recent study that demonstrated an association between hypoxemia and sleep apnea severity (Rexhaj et al, 2015).…”

Section: Figsupporting

confidence: 88%

Cross-Sectional Comparison of Sleep-Disordered Breathing in Native Peruvian Highlanders and Lowlanders

Pham

Meinzen

Arias

et al. 2017

High Altitude Medicine & Biology

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. Cross-sectional comparison of sleep-disordered breathing in native Peruvian highlanders and lowlanders. High Alt Med Biol. 18:11-19, 2017. Background: Altitude can accentuate sleep disordered breathing (SDB), which has been linked to cardiovascular and metabolic diseases. SDB in highlanders has not been characterized in large controlled studies. The purpose of this study was to compare SDB prevalence and severity in highlanders and lowlanders. Methods: 170 age-, body-mass-index-(BMI), and sex-matched pairs (age 58.2 -12.4 years, BMI 27.2 -3.5 kg/m 2 , and 86 men and 84 women) of the CRONICAS Cohort Study were recruited at a sea-level (Lima) and a highaltitude (Puno, 3825 m) setting in Peru. Participants underwent simultaneous nocturnal polygraphy and actigraphy to characterize breathing patterns, movement arousals, and sleep/wake state. We compared SDB prevalence, type, and severity between highlanders and lowlanders as measured by apnea-hypopnea index (AHI) and pulse oximetry (S P O 2 ) during sleep. Results: Sleep apnea prevalence was greater in highlanders than in lowlanders (77% vs. 54%, p < 0.001). Compared with lowlanders, highlanders had twofold elevations in AHI due to increases in central rather than obstructive apneas. In highlanders compared with lowlanders, S P O 2 was lower during wakefulness and decreased further during sleep ( p < 0.001). Hypoxemia during wakefulness predicted sleep apnea in highlanders, and it appears to mediate the effects of altitude on sleep apnea prevalence. Surprisingly, hypoxemia was also quite prevalent in lowlanders, and it was also associated with increased odds of sleep apnea. Conclusions: High altitude and hypoxemia at both high and low altitude were associated with increased SDB prevalence and severity. Our findings suggest that a large proportion of highlanders remain at risk for SDB sequelae.

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“…Adaptive increases in the hypoxic ventilatory response with acclimatization appear to improve symptoms of acute mountain sickness (via raising PO 2 ) but come at the cost of exacerbating CSA . CSA is also linked with hypoxaemia and pulmonary hypertension accompanying chronic mountain sickness, likely acting via hypoxaemic effects on chemosensitivity under these circumstances …”

Section: Pathogenesis In Patient Populationsmentioning

confidence: 99%

“…63 CSA is also linked with hypoxaemia and pulmonary hypertension accompanying chronic mountain sickness, likely acting via hypoxaemic effects on chemosensitivity under these circumstances. 64 Other factors beyond chemosensitivity may play some role in CSA at altitude. Decreases in plant gain due to hyperventilation with resulting hypocapnia, and increases in cardiac output with short circulatory delays would act as compensatory mechanisms to stabilize breathing 61,65 and thus individuals with less strong compensatory mechanisms may have more severe CSA.…”

Section: Periodic Breathing At Altitudementioning

confidence: 99%

Pathogenesis of central and complex sleep apnoea

2016

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Central sleep apnoea (CSA)—the temporary absence or diminution of ventilator effort during sleep—is seen in a variety of forms including periodic breathing in infancy and healthy adults at altitude and Cheyne-Stokes respiration in heart failure. In most circumstances, the cyclic absence of effort is paradoxically a consequence of hypersensitive ventilatory chemoreflex responses to oppose changes in airflow, i.e. elevated loop gain, leading to overshoot/undershoot ventilatory oscillations. Considerable evidence illustrates overlap between CSA and obstructive sleep apnoea (OSA), including elevated loop gain in patients with OSA and the presence of pharyngeal narrowing during central apnoeas. Indeed, treatment of OSA, whether via CPAP, tracheostomy, or oral appliances, can reveal CSA, an occurrence referred to as complex sleep apnoea. Factors influencing loop gain include increased chemosensitivity (increased controller gain), reduced damping of blood gas levels (increased plant gain) and increased lung to chemoreceptor circulatory delay. Sleep-wake transitions and pharyngeal dilator muscle responses effectively raise the controller gain and therefore also contribute to total loop gain and overall instability. In some circumstances, for example apnoea of infancy and central congenital hypoventilation syndrome, central apnoeas are the consequence of ventilatory depression and defective ventilatory responses, i.e. low loop gain. The efficacy of available treatments for CSA can be explained in terms of their effects on loop gain, e.g. CPAP improves lung volume (plant gain), stimulants reduce the alveolar-inspired PCO2 difference, supplemental oxygen lowers chemosensitivity. Understanding the magnitude of loop gain and the mechanisms contributing to instability may facilitate personalised interventions for CSA.

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Sleep-Disordered Breathing and Vascular Function in Patients With Chronic Mountain Sickness and Healthy High-Altitude Dwellers

Cited by 35 publications

References 54 publications

Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness

Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness

Cross-Sectional Comparison of Sleep-Disordered Breathing in Native Peruvian Highlanders and Lowlanders

Pathogenesis of central and complex sleep apnoea

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