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The Effect of Supplemental Oxygen in Obesity Hypoventilation Syndrome.

ABSTRACT: Low flow supplemental oxygen is commonly prescribed to patients with obesity hypoventilation syndrome (OHS). However, there is a paucity of data regarding its efficacy and safety. The objective of this study was to assess the medium-term treatment efficacy of adding supplemental oxygen therapy to commonly prescribed treatment modalities in OHS.In this post hoc analysis of a previous randomized controlled trial, we studied 302 sequentially screened OHS patients who were randomly assigned to noninvasive ventilation, continuous positive airway pressure, or lifestyle modification. Outcomes at 2 mo included arterial blood gases, symptoms, quality of life, blood pressure, polysomnography, spirometry, 6-min walk distance, and hospital resource utilization. Statistical analysis comparing patients with and without oxygen therapy in the three treatment groups was performed using an intention-to-treat analysis.In the noninvasive ventilation group, supplemental oxygen reduced systolic blood pressure although this could be also explained by a reduction in body weight experienced in this group. In the continuous positive airway pressure group, supplemental oxygen increased the frequency of morning confusion. In the lifestyle modification group, supplemental oxygen increased compensatory metabolic alkalosis and decreased the apnea-hypopnea index during sleep. Oxygen therapy was not associated with an increase in hospital resource utilization in any of the groups.After 2 mo of follow-up, chronic oxygen therapy produced marginal changes that were insufficient to consider it, globally, as beneficial or deleterious. Because supplemental oxygen therapy did not increase hospital resource utilization, we recommend prescribing oxygen therapy to patients with OHS who meet criteria with close monitoring. Long-term studies examining outcomes such as incident cardiovascular morbidity and mortality are necessary.Clinicaltrial.gov, ID: NCT01405976.

SUBMITTER: Masa JF

PROVIDER: S-EPMC5033740 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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The Effect of Supplemental Oxygen in Obesity Hypoventilation Syndrome.

Masa Juan F JF Corral Jaime J Romero Auxiliadora A Caballero Candela C Terán-Santos Joaquin J Alonso-Álvarez Maria L ML Gomez-Garcia Teresa T González Mónica M López-Martínez Soledad S De Lucas Pilar P Marin José M JM Marti Sergi S Díaz-Cambriles Trinidad T Chiner Eusebi E Merchan Miguel M Egea Carlos C Obeso Ana A Mokhlesi Babak B

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 20161015 10

<h4>Study objectives</h4>Low flow supplemental oxygen is commonly prescribed to patients with obesity hypoventilation syndrome (OHS). However, there is a paucity of data regarding its efficacy and safety. The objective of this study was to assess the medium-term treatment efficacy of adding supplemental oxygen therapy to commonly prescribed treatment modalities in OHS.<h4>Methods</h4>In this <i>post hoc</i> analysis of a previous randomized controlled trial, we studied 302 sequentially screened ...[more]

PMID: 27568890

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Project description:OSA is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first-line treatment for OSA, as well as for obesity hypoventilation syndrome (OHS), its most severe phenotype. However, the molecular and cellular mechanisms underlying OHS-induced morbidities and their response to PAP treatment remain unclear, and could be mediated, in part, by OSA-induced epigenetic changes.Blood was collected before starting PAP treatment (PRE group), as well as 6 weeks after PAP treatment (POST group) in 15 adult patients with OHS. DNA methylation profiles were studied by methylated DNA immunoprecipitation coupled to microarrays (MeDIP-chip) in six representative patients and further verified in a cohort of 15 patients by MeDIP-quantitative PCR.We identified 1,847 regions showing significant differential DNA methylation (P < .001; model-based analysis of tiling arrays score, > 4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPARs). Single-locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR-responsive elements (PPAREs) of eight genes in the post-treatment samples (PRE/POST fold changes: ABCA1, 3.11; ABCG1, 1.72; CD36, 5.04; FABP4, 2.49; HMOX, 2.74; NOS2, 7.78; PEPCK, 9.27; and ADIPOQ, 1.73), suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPAR-? complex and downstream gene expression.Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in patients with OHS who are responsive to PAP treatment.

Project description:STUDY OBJECTIVES:Longitudinal studies support the usage of positive airway pressure (PAP) therapy in treating obstructive sleep apnea (OSA) to improve cardiovascular disease. However, the anticipated benefit is not ubiquitous. In this study, we elucidate whether PAP therapy leads to immediate improvements on endothelial function, a subclinical marker of cardiovascular status, by examining the effect of circulating exosomes, isolated from patients before and after PAP therapy, on naive endothelial cells. METHODS:We isolated plasma-derived circulating exosomes from 12 patients with severe OSA and obesity hypoventilation syndrome (OHS) before and after 6 weeks of PAP therapy, and examined their effect on cultured endothelial cells using several in vitro reporter assays. RESULTS:We found that circulating exosomes contributed to the induction and propagation of OSA/OHS-related endothelial dysfunction (ie, increased permeability and disruption of tight junctions along with increased adhesion molecule expression, and reduced endothelial nitric oxide synthase expression), and promoted increased monocyte adherence. Further, when comparing exosomes isolated before and after PAP therapy, the disturbances in endothelial cell function were attenuated with treatment, including an overall cumulative decrease in endothelial permeability in all 12 subjects by 10.8% (P = .035), as well as detection of a subset of 4 differentially expressed exosomal miRNAs, even in the absence of parallel changes in systemic blood pressure or metabolic function. CONCLUSIONS:Circulating exosomes facilitate important intercellular signals that modify endothelial phenotype, and thus emerge as potential fundamental contributors in the context of OSA/OHS-related endothelial dysfunction. Exosomes may not only provide candidate biomarkers, but are also a likely and plausible mechanism toward OSA/OHS-induced cardiovascular disease. CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov, Title: AVAPS-AE Efficacy Study, URL: https://clinicaltrials.gov/ct2/show/NCT01368614, Identifier: NCT01368614.

Dataset Information

The Effect of Supplemental Oxygen in Obesity Hypoventilation Syndrome.

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The Effect of Supplemental Oxygen in Obesity Hypoventilation Syndrome.

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