Long-term myocardial effects of noninvasive ventilation in patients with obesity hypoventilation syndrome.

INTRODUCTION: Chronic effects of noninvasive ventilation on myocardial function in patients with obesity hypoventilation syndrome (OHS) are scarcely understood. The aim of the present study was to evaluate the long-term effects of volume-targeted bilevel positive airway pressure ventilation (BiPAP) on cardiac parameters and myocardial biomarkers in patients with OHS. METHODS: Clinically stable patients with OHS referred to the tertiary center for the initiation of long-term BiPAP therapy were consecutively enrolled. At baseline, all participants underwent overnight cardiorespiratory polygraphy. BiPAP therapy using volume-targeted spontaneous/timed mode delivered via an oro-nasal mask was initiated. Beat-to-beat noninvasive monitoring by impedance cardiography was used to assess heart function at baseline and after 3 and 12 months of BiPAP use. Serum troponin 1, N-Terminal Pro-B-Type Natriuretic Peptide (NT-ProBNP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were monitored. RESULTS: Thirteen patients (10 men; mean age, 55.8 ± 9.8 years; mean body mass index of 47.8 ± 5.9 kg/m2) were recruited. From baseline to 3, and to 12 months of BiPAP use, left ventricular stroke volume (SV), ejection time (LVET), and ejection time index significantly increased (P = 0.030; P < 0.001; P = 0.003, respectively), while heart rate and systolic time ratio significantly decreased (P = 0.004; P = 0.034, respectively). Reductions in serum NT-proBNP, IL-6 and TNF-α were observed (P = 0.045; P = 0.018; P = 0.003, respectively). No significant changes in serum troponin were detected throughout the study. CONCLUSIONS: The present findings of increased SV, in association with lengthening of LVET, reductions of NT-proBNP and reductions in circulatory inflammatory markers in patients with stable OHS and chronic moderate-to-severe daytime hypercapnia treated with BiPAP over 1 year support the role of this therapeutic mode in such patients.

Sleep Disorders and Traffic Accidents: Unveiling the Hidden Risks.

BACKGROUND Numerous countries, Vietnam included, have persistently high annual rates of traffic accidents. Despite concerted government efforts to reduce the annual traffic accident rate, the toll of fatalities and consequential injuries from these accidents rises each year. Various factors contribute to these incidents, notably including alcohol consumption while driving, inadequate awareness of traffic regulations, and substandard traffic infrastructure. However, an under-recognized risk in developing nations such as Vietnam is the prevalence of sleep disorders. Conditions such as obstructive sleep apnea syndrome and obesity hypoventilation syndrome, while prevalent, remain inadequately assessed and treated. These disorders represent significant yet largely unaddressed contributors to the heightened risk of traffic accidents. CASE REPORT We describe the case of a 55-year-old Vietnamese man hospitalized due to long-standing respiratory complications and profound daytime sleepiness. Over the past 2 years, the patient gained 10 kg. Consequently, he frequently experienced drowsiness, leading to 4 traffic accidents. Despite previous hospitalizations, this sleep disorder had gone undiagnosed and untreated. Diagnostic assessments confirmed concurrent obstructive sleep apnea and obesity hypoventilation syndrome through polysomnography and blood gas analyses. Treatment involving non-invasive positive airway pressure therapy notably alleviated symptoms and substantially improved his quality of life within a concise 3-month period. CONCLUSIONS Obstructive sleep apnea and obesity hypoventilation syndrome are contributory factors to excessive daytime somnolence, significantly increasing vulnerability to traffic accidents. Regrettably, this critical intersection remains inadequately addressed. Addressing these concerns comprehensively through dedicated research initiatives should be imperative before considering the universal issuance of driver's licenses to all road users in Vietnam.

Obstructive Sleep Apnea, Obesity Hypoventilation Syndrome, and Pulmonary Hypertension: A State-of-the-Art Review.

The pathophysiological interplay between sleep-disordered breathing (SDB) and pulmonary hypertension (PH) is complex and can involve a variety of mechanisms by which SDB can worsen PH. These mechanistic pathways include wide swings in intrathoracic pressure while breathing against an occluded upper airway, intermittent and/or sustained hypoxemia, acute and/or chronic hypercapnia, and obesity. In this review, we discuss how the downstream consequences of SDB can adversely impact PH, the challenges in accurately diagnosing and classifying PH in the severely obese, and review the limited literature assessing the effect of treating obesity, obstructive sleep apnea, and obesity hypoventilation syndrome on PH.

Targeting Hypercapnia in Chronic Lung Disease and Obesity Hypoventilation: Benefits and Challenges.

Hypoventilation is a complication that is not uncommon in chronic obstructive pulmonary disease and calls for both medical treatment of the underlying disease and, frequently, noninvasive ventilation either during exacerbations requiring hospitalization or in a chronic state in the patient at home. Obesity hypoventilation syndrome by definition is associated with ventilatory failure and hypercapnia. It may or may not be accompanied by obstructive sleep apnea, which when detected becomes an additional target for positive airway pressure treatment. Intensive research has not completely resolved the best choice of treatment, and the simplest modality, continuous positive airway pressure, may still be entertained.

A case of accidental self-enucleation caused by obstructive sleep apnea.

A novel form of injury associated with obstructive sleep apnea (OSA) that was comorbid with obesity hypoventilation syndrome and severe daytime somnolence is reported in a 55-year-old woman, manifesting as severe ocular and extraocular muscle injuries sustained from suddenly falling asleep and colliding with a sharp object, resulting in surgical enucleation of the right eye and orbital implant. The literature on injuries (falls, motor vehicle accidents) related to OSA and excessive day time sleepiness is reviewed, along with the literature on injuries from OSA-related parasomnias. The diverse health hazards, including physical injury, associated with OSA-excessive daytime sleepiness, are emphasized, further encouraging the need to educate primary care providers on early detection of OSA with prompt treatment intervention. CITATION: Baker N, Schenck CH, Golden E, Varghese R. A case of accidental self-enucleation caused by obstructive sleep apnea. J Clin Sleep Med. 2024;20(8):1395-1397.

Indications and evidence for domiciliary noninvasive ventilation.

INTRODUCTION: Home noninvasive ventilation (HNIV) has expanded globally, with a greater evidence base for its use. HNIV improves multiple patient related outcomes in patients with chronic hypercapnic respiratory failure. Obesity hypoventilation syndrome (OHS) is rapidly taking over as the primary indication for HNIV and COPD patients who overlap with obstructive sleep apnea hypoventilation syndromes (OSAHS) and are increasingly recognized but add to the complexity of HNIV prescribing. Optimal settings vary for differing diseases, with higher inspiratory pressures often required in those with OHS and COPD, yet which settings translate into greatest patient benefit remains unknown. AREAS COVERED: We cover the evidence base underpinning the common indications for HNIV in COPD, OHS, neuromuscular disease (NMD), and chest wall disease (CWD) and highlight common HNIV modes used. EXPERT OPINION: Active screening for nocturnal hypoventilation in OHS and COPD may be important to guide earlier ventilation. Further research on which HNIV modalities best improve patient related outcomes and the right time for initiation in different patient phenotypes is rapidly needed. Worldwide, clinical research trials should aim to bridge the gap by reporting on patient-related outcomes and cost effectiveness in real-world populations to best understand the true benefit of HNIV amongst heterogenous patient populations.

Using intra-breath oscillometry in obesity hypoventilation syndrome to detect tidal expiratory flow limitation: a potential marker to optimize CPAP therapy.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy has profound effects in obesity hypoventilation syndrome (OHS). Current therapy initiation focuses on upper airway patency rather than the assessment of altered respiratory mechanics due to increased extrapulmonary mechanical load. METHODS: We aimed to examine the viability of intra-breath oscillometry in optimizing CPAP therapy for OHS. We performed intra-breath oscillometry at 10 Hz in the sitting and supine positions, followed by measurements at increasing CPAP levels (none-5-10-15-20 cmH2O) in awake OHS patients. We plotted intra-breath resistance and reactance (Xrs) values against flow (V') and volume (V) to identify tidal expiratory flow limitation (tEFL). RESULTS: Thirty-five patients (65.7% male) completed the study. We found a characteristic looping of the Xrs vs V' plot in all patients in the supine position revealing tEFL: Xrs fell with decreasing flow at end-expiration. Intra-breath variables representing expiratory decrease of Xrs became more negative in the supine position [end-expiratory Xrs (mean ± SD): -1.9 ± 1.8 cmH2O·s·L- 1 sitting vs. -4.2 ± 2.2 cmH2O·s·L- 1 supine; difference between end-expiratory and end-inspiratory Xrs: -1.3 ± 1.7 cmH2O·s·L- 1 sitting vs. -3.6 ± 2.0 cmH2O·s·L- 1 supine, p < 0.001]. Increasing CPAP altered expiratory Xrs values and loop areas, suggesting diminished tEFL (p < 0.001). 'Optimal CPAP' value (able to cease tEFL) was 14.8 ± 4.1 cmH2O in our cohort, close to the long-term support average of 13.01(± 2.97) cmH2O but not correlated. We found no correlation between forced spirometry values, patient characteristics, apnea-hypopnea index and intra-breath oscillometry variables. CONCLUSIONS: tEFL, worsened by the supine position, can be diminished by stepwise CPAP application in most patients. Intra-breath oscillometry is a viable method to detect tEFL during CPAP initiation in OHS patients and tEFL is a possible target for optimizing therapy in OHS patients.

Sleep-disordered Breathing and Inpatient Outcomes in Nonsurgical Patients: Analysis of the Nationwide Inpatient Cohort.

Rationale: Sleep-disordered breathing (SDB) is associated with increased complications and length of stay (LOS) after surgery. SDB-related adverse consequences for nonsurgical admissions are not well defined. Objectives: Evaluate associations between SDB and subtypes and LOS, cost, and mortality in nonsurgical patients. Methods: This retrospective cohort analysis used adult nonsurgical admissions from the 2017 National Inpatient Sample of the Healthcare Costs and Utilization Project. SDB associations with LOS (primary outcome), costs, and mortality were evaluated via logistic regression. Covariates included age, sex, Elixhauser Comorbidity Index, socioeconomic status, hospital type, and insurance type. Results: The cohort included 6,046,544 hospitalizations. Compared with those without SDB, patients with SDB were older (63.6 ± 13.5 vs. 57.4 ± 20.7 yr), higher proportion male (55.8% vs. 40.9%), and more likely to be White (75.7% vs. 66.5%). SDB was associated with increased odds of increased LOS and hospitalization costs (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.16-1.17 and OR, 1.67; 95% CI, 1.66-1.67 in adjusted analyses, respectively) but lower mortality (OR, 0.79; 95% CI, 0.77-0.81). The results for obstructive sleep apnea (OSA) echoed those for SDB. Obesity hypoventilation syndrome had substantially increased LOS (OR, 3.05; 95% CI, 2.98-3.13), mortality (1.76; 95% CI, 1.66-1.86), and costs (OR, 2.67; 95% CI, 2.60-2.73) even after adjustment. Conclusions: Obesity hypoventilation syndrome is associated with higher LOS, mortality, and costs during hospitalization, whereas OSA, despite higher LOS and costs, is associated with decreased mortality. Investigation is warranted on whether paradoxically higher costs but lower mortality in OSA may be indicative of less vigilance in hospitalized patients with undiagnosed SDB.

[From morbid obesity to complex obesity: somato-psychic issues]. / De l'obésité morbide à l'obésité complexe : des enjeux somato-psychiques.

Complex obesity is a chronic, multifactorial pathology. These repercussions (respiratory insufficiency, hypoventilation syndrome, cardiac insufficiency, loss of functional autonomy and mobility with a tendency to grabatization, depression, behavioral disorders) directly sustain the disease. Access to care is virtually impossible for them outside specialized obesity centers (CSO) and specialized medical and rehabilitation care (SMR). We need to support healthcare teams by analyzing their practices, including those of expert patients, to ensure that complex obesity is treated with the humanity it requires.

ER stress aggravates diaphragm weakness through activating PERK/JNK signaling in obesity hypoventilation syndrome.

OBJECTIVE: Obesity hypoventilation syndrome is associated with diaphragmatic dysfunction. This study aimed to explore the role of endoplasmic reticulum (ER) stress in mediating obesity-induced diaphragmatic dysfunction. METHODS: A pulmonary function test and ultrasound were applied to evaluate diaphragmatic function and magnetic resonance imaging was applied to measure diaphragmatic lipid deposition in human patients. For the mechanistic study, obese mice were introduced to a high-fat diet for 24 weeks, followed by diaphragmatic ultrasound measurement, transcriptomic sequencing, and respective biochemical analysis. Automatic force mapping was applied to measure the mechanical properties of C2C12 myotubes. RESULTS: People with obesity showed significant diaphragm weakness and lipid accumulation, which was further confirmed in obese mice. Consistently, diaphragms from obese mice showed altered gene expression profile in lipid metabolism and activation of ER stress response, indicated by elevated protein kinase R-like ER kinase (PERK) and c-Jun NH2 -terminal kinase (JNK) activation. In C2C12 myotubes, inhibition of PERK or JNK signaling abrogated lipotoxicity-induced intracellular lipid deposition and insulin resistance. Inhibition of JNK signaling reversed lipotoxicity-induced impairment of elasticity in C2C12 myotubes. CONCLUSIONS: These data suggest that ectopic lipid deposition impairs the diaphragmatic function of people with obesity. Activation of PERK/JNK signaling is involved in the pathogenesis of lipotoxicity-induced diaphragm weakness in obesity hypoventilation syndrome.

Prevalence of suspected obesity hypoventilation syndrome in Hungarian Intensive Care Units during the COVID-19 pandemic.

INTRODUCTION: The symptoms of obesity hypoventilation syndrome (OHS) may be present for years with concomitant progressive comorbidities, and the condition is frequently diagnosed late as a result of acute-on-chronic hypercapnic respiratory failure. Although some data exist on intensive care unit (ICU) prevalence, mortality and morbidity of OHS, little is known about the ICU mortality of these chronic respiratory failure patients during the COVID-19 pandemic. METHODS: We performed a cross-sectional observational study in five Hungarian Intensive Care Units for 4 months during the COVID-19 pandemic. All ICU patients were screened for OHS risk factors by treating physicians. Risk factors were defined as obesity (body mass index [BMI] ≥ 30 kg/m2 ) and at least one of the following: Epworth Sleepiness Score ≥ 6; symptoms of right heart failure; daytime or night-time hypoxemia; presence of loud snoring; witnessed apnoea. We calculated prevalence, mortality and factors associated with unfavourable outcome. RESULTS: A total of 904 ICU patients were screened for OHS risk factors. Overall 79 (8.74 ± 5.53%) patients were reported to have met the criteria for suspected OHS with a mortality rate of 40.5%; 69% (54 patients) of the cohort displayed at least 3 symptoms related to OHS before their acute illness. COVID-19 infection was associated with higher mortality in OHS-suspected patients, independently of actual BMI. CONCLUSION: Despite the increased risk of obese patients, suspected OHS did not show higher prevalence than expected during the COVID-19 pandemic in critically ill patients. COVID-19 infection however was a risk for mortality in these patients, independent of actual BMI.

The assessment and management of obstructive sleep apnoea-hypopnoea syndrome and obesity hypoventilation syndrome in obesity.

Obesity is associated with respiratory dysfunction. It is a key risk and contributory factor in the sleep related breathing disorders, obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and obesity hypoventilation syndrome (OHS). Weight management is an integral part of the management of these disorders, in addition to continuous positive airways pressure (CPAP) and non-invasive ventilation (NIV). Untreated, these conditions are associated with a high disease burden and as treatment is effective, early recognition and referral is critical. Best practice in on-going care is multidisciplinary.

Respiratory Center Function and Its Impact in Obesity Hypoventilation Syndrome Treatment.

INTRODUCTION: Patients with obesity hypoventilation syndrome (OHS) need treatment with positive pressure either with continuous (CPAP) or double pressure (NIV). The apnea-hypopnea index (AHI) is considered a key data for making therapeutic decisions. We hypothesized that HR may be an useful tool to establish different phenotypes and individualize treatment in patients with OHS. Our objective was to analyze the role of the respiratory center response to hypercapnia (HR) in the adequacy of positive airway pressure therapy. METHOD: We included subjects with OHS treated with CPAP or NIV according to AHI and baseline pCO2. We analyzed therapeutic effectiveness and treatment changes prioritizing CPAP if AHI>30/h. Therapy was considered adequate if it was effective after two years. HR was measured with the p0.1/pEtCO2 ratio and its capability to select therapy was analyzed. The statistical study was performed by means comparison (Student's t) and multivariate analysis (logistic regression). RESULTS: 67 subjects were included of 68(11) years old, 37 (55%) males, initially 45 (67%) treated with NIV and 22 (33%) with CPAP, one case was excluded and in 25 (38%) the treatment was changed. Finally, CPAP was adequate for 29 subjects (44%) and NIV for 37 (56%). The CPAP group showed AHI 57/h (24) and p0.1/pEtCO2 0.37cmH2O/mmHg (0.23), NIV group AHI 43/h (35) and p0.1/pEtCO2 0.24 (0.15) with p=0.049 and 0.006. In multivariate analysis, p0.1/pEtCO2 (p=0.033) and AHI>30 (p=0.001) were predictors of adequate therapy. CONCLUSION: Measuring the RH of the respiratory center helps to select the most appropriate treatment for patients with OHS.

Ketogenic diet acutely improves gas exchange and sleep apnoea in obesity hypoventilation syndrome: A non-randomized crossover study.

BACKGROUND AND OBJECTIVE: Obesity hypoventilation syndrome (OHS) causes hypercapnia which is often refractory to current therapies. We examine whether hypercapnia in OHS can be improved by a ketogenic dietary intervention. METHODS: We conducted a single-arm crossover clinical trial to examine the impact of a ketogenic diet on CO2 levels in patients with OHS. Patients were instructed to adhere to 1 week of regular diet, 2 weeks of ketogenic diet, followed by 1 week of regular diet in an ambulatory setting. Adherence was assessed with capillary ketone levels and continuous glucose monitors. At weekly visits, we measured blood gases, calorimetry, body composition, metabolic profiles, and sleep studies. Outcomes were assessed with linear mixed models. RESULTS: A total of 20 subjects completed the study. Blood ketones increased from 0.14 ± 0.08 during regular diet to 1.99 ± 1.11 mmol/L (p < 0.001) after 2 weeks of ketogenic diet. Ketogenic diet decreased venous CO2 by 3.0 mm Hg (p = 0.008), bicarbonate by 1.8 mmol/L (p = 0.001), and weight by 3.4 kg (p < 0.001). Sleep apnoea severity and nocturnal oxygen levels significantly improved. Ketogenic diet lowered respiratory quotient, fat mass, body water, glucose, insulin, triglycerides, leptin, and insulin-like growth factor 1. Rebound hypercapnia was observed after resuming regular diet. CO2 lowering was dependent on baseline hypercapnia, and associated with circulating ketone levels and respiratory quotient. The ketogenic diet was well tolerated. CONCLUSION: This study demonstrates for the first time that a ketogenic diet may be useful for control of hypercapnia and sleep apnoea in patients with obesity hypoventilation syndrome.

Acetazolamide for metabolic alkalosis complicating respiratory failure with chronic obstructive pulmonary disease or obesity hypoventilation syndrome: a systematic review.

BACKGROUND: Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression. METHODS: We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I2 value and χ2 test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology. RESULTS: Four studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference -0.8 days (95% CI -7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty). CONCLUSION: Acetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required. PROSPERO REGISTRATION NUMBER: CRD42021278757.

Designing a program to support weight loss for patients attending the sleep medicine clinic: a qualitative study.

STUDY OBJECTIVES: Excess body weight is the most important risk factor in sleep-disordered breathing. Weight loss is a treatment alternative to positive airway pressure therapy, but there is a knowledge gap of what is feasible, acceptable, and sustainable in this population. We seek to add the voices of sleep medicine patients and providers to the medical literature to understand what makes this population unique when considering weight loss, and what we can do differently to create more sustainable weight loss interventions. METHODS: We conducted one-on-one semistructured interviews with 12 patients with obstructive sleep apnea/obesity hypoventilation syndrome and obesity and with 9 sleep medicine providers regarding previous weight loss efforts, perceptions of barriers to and facilitators of weight loss, and potential components of a program to support those with sleep apnea and excess weight. RESULTS: Patients indicated they appreciated direct conversation with their sleep physician regarding weight loss and providers felt the patient population was generally very receptive to weight loss conversations. Patients emphasized the most important aspects of a future weight loss program would be personalized diet, exercise, accountability, integration of technology, and an individualized approach to addressing the psychological aspects of eating. CONCLUSIONS: This is a unique population of patients who are very receptive to conversations about weight loss. We plan to use this data to inform a future weight loss program based in health coaching to address the specific needs of this population. CITATION: Dupuy-McCauley K, Benzo R, Barwise A. Designing a program to support weight loss for patients attending the sleep medicine clinic: a qualitative study. J Clin Sleep Med. 2023;19(3):459-471.

Comparing the influence of foot reflexology and fasting mimicking diet on quality of life and sleep quality in obesity hypoventilation syndrome.

OBJECTIVES: Obesity hypoventilation syndrome is one of the most serious outcomes of obesity-related respiratory difficulties, resulting in higher healthcare costs as well as increased cardio-respiratory morbidity and mortality. METHODS: Sixty-two males who had a high risk of obstructive sleep apnea according to the STOP-BANG Sleep Apnea Questionnaire were enrolled in the study. Their age is 50-60 years old, and they have a BMI of 35-40 kg/m2, daytime hypercapnia, and sleep breathing problems. The patients were divided into two equal groups at random reflexology fasting-mimicking diet groups. Weight, height, waist, and neck circumference were assessed at the beginning of the study and after two months of the intervention. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), which is used to evaluate sleep quality. The Maugeri Obstructive Sleep Apnea Syndrome (MOSAS) questionnaire was used to assess a patient's quality of life. RESULTS: There was a significant change in the MOSAS and PSQI questionnaires for both groups post-intervention, as the p-value was less than 0.05. The percentage change in the MOSAS questionnaire score and PSQI questionnaire was higher in the mimic diet group than in the reflexology group. Also, the mimic diet group's weight and neck circumference were considerably reduced after the intervention, with no change in the reflexology group. CONCLUSIONS: Reflexology and a fasting-mimicking diet were found to have a substantial impact on enhancing the quality of life and sleep in people with obesity hypoventilation syndrome.