Project description:Obesity hypoventilation syndrome (OHS) is defined as the presence of obesity (body mass index ? 30 kg/m²) and daytime arterial hypercapnia (PaCO2 ? 45 mmHg) in the absence of other causes of hypoventilation. OHS is often overlooked and confused with other conditions associated with hypoventilation, particularly COPD. The recognition of OHS is important because of its high prevalence and the fact that, if left untreated, it is associated with high morbidity and mortality. In the present review, we address recent advances in the pathophysiology and management of OHS, the usefulness of determination of venous bicarbonate in screening for OHS, and diagnostic criteria for OHS that eliminate the need for polysomnography. In addition, we review advances in the treatment of OHS, including behavioral measures, and recent studies comparing the efficacy of continuous positive airway pressure with that of noninvasive ventilation.
Project description: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.
Project description:BACKGROUND:Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown. QUESTION:To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients. METHODOLOGY:14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays. PRINCIPAL FINDINGS:OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11). CONCLUSIONS:Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk. TRIAL REGISTRATION:ClinicalTrials.gov NCT00603096.
Project description:The mortality rate for respiratory failure resulting from obesity hypoventilation syndrome is high if it requires ventilator management. We describe a case of severe acute respiratory failure resulting from obesity hypoventilation syndrome (BMI, 60.2?kg/m2) successfully treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). During ECMO management, a mucus plug was removed by bronchoscopy daily and 18?L of water was removed using diuretics, resulting in weight loss of 24?kg. The patient was weaned from ECMO on day 5, extubated on day 16, and discharged on day 21. The fundamental treatment for obesity hypoventilation syndrome in morbidly obese patients is weight loss. VV-ECMO can be used for respiratory support until weight loss has been achieved.
Project description:Purpose:Data on hypothyroidism in patients with obesity hypoventilation syndrome (OHS) are scarce. This study assessed the prevalence of hypothyroidism among a large group of patients with OHS. Patients and Methods:This was a prospective observational study of 308 consecutive patients with OHS seen between January 2002 and December 2018. Serum thyroid-stimulating hormone (TSH) and free-thyroxine (FT4) levels were measured in all patients. The OHS patients were compared with 445 patients with obstructive sleep apnoea (OSA) matched for age, sex, and body mass index (BMI). Results:The OHS patients had a mean age of 55.1 ± 13.8 years and a BMI of 43.9 ± 14.8 kg/m2; apnoea hypopnea index was ?30 events/hr in 222 (72%). Clinical hypothyroidism was diagnosed in 58 (18.8%) of the OHS patients; only two cases (0.6%) were diagnosed in the sleep disorders clinic (newly diagnosed cases). Subclinical hypothyroidism was diagnosed in 19 (6.2%) of the OHS patients based on elevated TSH and normal FT4 levels; all cases were newly diagnosed. A logistic regression model identified female sex as the only predictor of clinical hypothyroidism in OHS patients (odds ratio: 2.801 [1.386-5.662], p = 0.004). There was no significant difference in clinical hypothyroidism prevalence between the OHS and OSA patients; however, subclinical hypothyroidism was more common in OHS than in OSA patients (6.2% vs 2.9%, respectively, p = 0.03). Conclusion:Clinical hypothyroidism was prevalent among patients with OHS; however, newly diagnosed cases of clinical hypothyroidism were relatively low. Female sex was the only predictor of clinical hypothyroidism.
Project description:Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.
Project description:Introduction:The prevalence of obesity is continually increasing worldwide, which increases the incidence of obesity hypoventilation syndrome (OHS) and its consequent mortality. Methods:We reviewed the therapy mode, comorbidity and mortality of all OHS patients treated at our hospital between 2005 and 2016. The control group consisted of randomly selected patients with obstructive sleep apnoea (OSA) treated during the same period. Results:We studied 206 OHS patients and 236 OSA patients. The OHS patients were older (56.3 versus 52.3?years, p<0.001) and heavier (body mass index 46.1 versus 32.2?kg·m-2, p<0.001), and the percentage of women was higher (41.2% versus 24.2%, p<0.001), respectively. The OHS patients had more hypertension (83% versus 61%, p<0.001) and diabetes (62% versus 31%, p<0.001) than the OSA patients, but no higher stroke (4% versus 8%, p=0.058) or ischaemic heart disease (14% versus 15%, p=0.437) incidence. The 5- and 10-year, unadjusted survival rates were lower among the OHS patients than among the OSA patients (83% versus 96% and 74% versus 91%, respectively; p<0.001). Differences in mortality rates were not related to age, sex or body mass index; covariates such as Charlson Comorbidity Index and ventilation therapy predicted survival. The mortality rate decreased significantly (p<0.001) both in OHS and OSA patients even after adjusting for covariates. Conclusions:The mortality rate in OHS was significantly higher than that in OSA patients even after adjusting for covariates. Ventilation therapy by continuous positive airway pressure or noninvasive ventilation have reduced mortality significantly in all patients.
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.
Project description:PURPOSE:Obesity is associated with both obstructive sleep apnea (OSA) and obesity hypoventilation. Differences in adipose tissue distribution are thought to underlie the development of both OSA and hypoventilation. We explored the relationships between the distribution of upper airway, neck, chest, abdominal and muscle fat in very obese individuals. METHODS:We conducted a cross-sectional cohort study of individuals presenting to a tertiary sleep clinic or for assessment for bariatric surgery. Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; respiratory polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to determine carbon dioxide partial pressure and base excess. RESULTS:Fifty-three individuals were included, with mean age of 51.6?±?8.4 years and mean BMI of 44.3?±?7.9 kg/m2; there were 27 males (51%). Soft palate, tongue and lateral wall volumes were significantly associated with the AHI in univariable analyses (p?<?0.001). Gender was a significant confounder in these associations. No significant associations were found between MRI measures of adiposity and hypoventilation. CONCLUSIONS:In very obese individuals, our results indicate that increased volumes of upper airway structures are associated with increased severity of OSA, as previously reported in less obese individuals. Increasingly large upper airway structures that reduce pharyngeal lumen size are likely to lead to OSA by increasing the collapsibility of the upper airway. However, we did not show any significant association between regional fat distribution and propensity for hypoventilation, in this population.
Project description:Background and aimROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes.Materials and methodsWe firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes.ResultsIn total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering.ConclusionsThis study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.