Eficacia a medio y largo plazo de la ventilación no invasiva en el síndrome de hipoventilación-obesidad (estudio Pickwick)

López-Jiménez, María José; Masa, Juan F.; Corral, Jaime; Terán, Joaquín; Ordaz, Estrella; Troncoso, María F.; González-Mangado, Nicolás; González, Mónica; López-Martínez, Soledad; Lucas, Pilar de; Marı́n, José Marı́a; Martí, Sergi; Díaz-Cambriles, Trinidad; Díaz-de-Atauri, Josefa; Chiner, Eusebi; Aizpuru, Felipe; Egea, Carlos; Romero, Odile; Benítez, José María; Sánchez-Gómez, Jesús; Golpe, Rafael; Santiago-Recuerda, Ana; Gómez, Sílvia; Barbé, Ferrán; Bengoa, Mónica

doi:10.1016/j.arbres.2015.10.003

Cited by 14 publications

(5 citation statements)

References 16 publications

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“…The human subjects were recruited as part of a larger multicenter, randomized, controlled trial conducted in 14 Spanish teaching hospitals (NCT01405976), and patient characteristics have been described in detail elsewhere 17 . Every patient underwent a diagnostic sleep study.…”

Section: Methodsmentioning

confidence: 99%

“…Although metabolic dysfunction is now clearly associated with OSA, the impact of OHS on insulin resistance and dyslipidemia is still virtually unexplored 15 , 16 . Indeed, there have been few if any longitudinal studies evaluating the metabolic changes resulting from OHS treatment 17 , and the exact molecular mechanisms of OHS-associated insulin resistance are unclear. Identification of biomarkers indicating which OHS patients are at greater metabolic risk would be extremely useful.…”

Section: Introductionmentioning

confidence: 99%

“…Based on aforementioned considerations, we hypothesized that plasma exosomes in OHS contribute to adipose tissue insulin resistance, and that such effects will improve with treatment over time. To examine this issue, we took advantage of the Pickwick’s Spanish Sleep Network Study 17 , and assessed the in vitro effects of plasma exosomes from OHS patients before and following up to 2 years of adherent CPAP treatment on insulin sensitivity and adipocyte biology in naïve human adipocytes. To further understand the potential contributions of chronic intermittent hypoxia (IH) and sleep fragmentation (SF) to circulating exosomes and their putative functional alterations, we conducted parallel and similar studies in mice (please, see Fig.…”

Section: Introductionmentioning

confidence: 99%

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Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes

et al. 2018

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BackgroundSleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, the effects of plasma exosomes on adipocyte metabolism in patients with OHS or in mice subjected to IH or SF mimicking SDB are unclear.MethodsExosomes from fasting morning plasma samples from obese adults with polysomnographically-confirmed OSA before and after 3 months of adherent CPAP therapy were assayed. In addition, C57BL/6 mice were randomly assigned to (1) sleep control (SC), (2) sleep fragmentation (SF), and (3) intermittent hypoxia (HI) for 6 weeks, and plasma exosomes were isolated. Equivalent exosome amounts were added to differentiated adipocytes in culture, after which insulin sensitivity was assessed using 0 nM and 5nM insulin-induced pAKT/AKT expression changes by western blotting.ResultsWhen plasma exosomes were co-cultured and internalized by human naïve adipocytes, significant reductions emerged in Akt phosphorylation responses to insulin when compared to exosomes obtained after 24 months of adherent CPAP treatment (n=24; p<0.001), while no such changes occur in untreated patients (n=8). In addition, OHS exosomes induced significant increases in adipocyte lipolysis that were attenuated after CPAP, but did not alter pre-adipocyte differentiation. Similarly, exosomes from SF- and IH-exposed mice induced attenuated p-AKT/total AKT responses to exogenous insulin and increased glycerol content in naïve murine adipocytes, without altering pre-adipocyte differentiation.ConclusionsUsing in vitro adipocyte-based functional reporter assays, alterations in plasma exosomal cargo occur in SDB, and appear to contribute to adipocyte metabolic dysfunction. Further exploration of exosomal miRNA signatures in either human subjects or animal models and their putative organ and cell targets appears warranted.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes

et al. 2018

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“…The present study is part of the ‘Pickwick’ project. 26 This project has two parallel randomised clinical trials based on the presence or absence of severe OSA (polysomnographic apnoea–hypopnoea index (AHI) ≥30) with identical methodology (see online supplementary data ).…”

Section: Methodsmentioning

confidence: 99%

“…One published on the results of the first phase in OHS patients with severe sleep apnoea 3 and one describing the methodology. 26 Another paper on the baseline cardiovascular risk (without any treatment) according to the sleep apnoea severity in total population (OHS patients with and without severe sleep apnoea) is in press (Epub ahead of print). 30 Finally, a paper on the influence of supplemental oxygen therapy (the effect of supplemental oxygen in obesity hypoventilation syndrome) has been submitted to the Journal of Clinical Sleep Medicine .…”

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confidence: 99%

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Masa

Corral

Caballero

et al. 2016

Thorax

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BackgroundNon-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure.MethodsBetween May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis.ResultsA total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of −6 (95% CI −7.7 to −4.2) mm Hg versus −2.8 (95% CI −4.3 to −1.3) mm Hg, (p<0.001) and serum bicarbonate of −3.4 (95% CI −4.5 to −2.3) versus −1 (95% CI −1.7 to −0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group.ConclusionsNIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality.Trial registration numberNCT01405976; results.

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Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea

Kennedy

Lasserson

Woźniak

et al. 2019

Cochrane Database of Systematic Reviews

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Eficacia a medio y largo plazo de la ventilación no invasiva en el síndrome de hipoventilación-obesidad (estudio Pickwick)

Cited by 14 publications

References 16 publications

Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes

Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Pressure modification or humidification for improving usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea

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