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.

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.

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.

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.

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.

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.

Obesity-associated sleep hypoventilation and increased adverse postoperative bariatric surgery outcomes in a large clinical retrospective cohort.

STUDY OBJECTIVES: Although obesity hypoventilation syndrome (OHS) is associated with increased morbidity and mortality, post-bariatric surgery OHS risk remains unclear due to often nonsystematic OHS assessments. METHODS: We leverage a clinical cohort with nocturnal CO2 monitoring during polysomnography to address the hypothesis that patients with obesity-associated sleep hypoventilation (OaSH; ie, stage II OHS) have increased adverse postoperative bariatric surgery outcomes. We retrospectively analyzed data from patients undergoing pre-bariatric surgery polysomnography at the Cleveland Clinic from 2011-2018. OaSH was defined by body mass index ≥ 30 kg/m2 and either polysomnography-based end-tidal CO2 ≥ 45 mmHg or serum bicarbonate ≥ 27 mEq/L. Outcomes considered were as follows: intensive care unit stay, intubation, tracheostomy, discharge disposition other than home or 30-day readmission individually and as a composite, and all-cause mortality. Two-sample t test or Wilcoxon rank-sum test for continuous variables and chi-square or Fisher's exact test for categorical variables were used for OaSH vs non-OaSH comparisons. All-cause mortality was compared using Kaplan-Meier estimation and Cox proportional hazards models. RESULTS: The analytic sample (n = 1,665) was aged 45.2 ± 12 years, 20.4% were male, had a body mass index of 48.7 ± 9 kg/m2, and 63.6% were White. OaSH prevalence was 68.5%. OaSH patients were older and more likely to be male with a higher BMI, apnea-hypopnea index, and glycated hemoglobin. The composite outcome was higher in OaSH vs non-OaSH patients (18.9% vs 14.3%, P = .021). Although some individual outcomes were respectively higher in OaSH vs non-OaSH patients, differences were not statistically significant: intubation (1.5% vs 1.3%, P = .81) and 30-day readmission (13.8% vs 11.3%, P = .16). Long-term mortality (median follow-up: 22.9 months) was not significantly different between groups, likely due to overall low event rate (hazard ratio = 1.39, 95% confidence interval: 0.56, 3.42). CONCLUSIONS: In this largest sample to date of systematically phenotyped OaSH in a bariatric surgery cohort, we identify increased postoperative morbidity in those with sleep-related hypoventilation in stage II OHS when a composite outcome was considered, but individual contributors of intubation, intensive care unit admission, and hospital length of stay were not increased. Further study is needed to identify whether perioperative treatment of OaSH improves post-bariatric surgery outcomes. CITATION: Chindamporn P, Wang L, Bena J, et al. Obesity-associated sleep hypoventilation and increased adverse postoperative bariatric surgery outcomes in a large clinical retrospective cohort. J Clin Sleep Med. 2022;18(12):2793-2801.

Leptin-mediated neural targets in obesity hypoventilation syndrome.

Obesity hypoventilation syndrome (OHS) is defined as daytime hypercapnia in obese individuals in the absence of other underlying causes. In the United States, OHS is present in 10%-20% of obese patients with obstructive sleep apnea and is linked to hypoventilation during sleep. OHS leads to high cardiorespiratory morbidity and mortality, and there is no effective pharmacotherapy. The depressed hypercapnic ventilatory response plays a key role in OHS. The pathogenesis of OHS has been linked to resistance to an adipocyte-produced hormone, leptin, a major regulator of metabolism and control of breathing. Mechanisms by which leptin modulates the control of breathing are potential targets for novel therapeutic strategies in OHS. Recent advances shed light on the molecular pathways related to the central chemoreceptor function in health and disease. Leptin signaling in the nucleus of the solitary tract, retrotrapezoid nucleus, hypoglossal nucleus, and dorsomedial hypothalamus, and anatomical projections from these nuclei to the respiratory control centers, may contribute to OHS. In this review, we describe current views on leptin-mediated mechanisms that regulate breathing and CO2 homeostasis with a focus on potential therapeutics for the treatment of OHS.

Obesity hypoventilation syndrome in bariatric surgery patients: an underestimated disease.

BACKGROUND: Obesity is a known risk factor for obesity hypoventilation syndrome (OHS). However, study on the prevalence and clinical characteristics of OHS among bariatric surgery patients is scarce. OBJECTIVES: To investigate the prevalence of OHS in bariatric surgery patients and to identify its related predictors. SETTING: The study was conducted at a bariatric surgery center in a tertiary university hospital. METHODS: A cross sectional analysis was performed in the patients undergoing bariatric surgery between March 2017 and January 2020. Anthropometric, laboratory, pulmonary function, blood gas analysis, and polysomnographic data was collected and analyzed. RESULTS: Of 522 patients, the overall prevalence of OHS was 15.1%, with men (22.8 %) having a greater frequency than women (9.4%) (P < .001). The prevalence increases with obesity severity, from 4.1% in those with body mass index (BMI) <35 kg/m2 to 39.1% in those with BMI ≥50 kg/m2. Of 404 patients with obstructive sleep apnea (OSA), OHS was present in 17.3%, with 9.8% in mild OSA, 10.0% in moderate OSA, and 27.3%in severe OSA. Only 11.4% of patients diagnosed with OHS had no OSA. On logistic regression, BMI (odds ratio [OR]: 1.10; 95% confidence interval [CI], 1.01-1.21; P = .033), neck circumference (OR: 1.15; 95% CI, 1.03-1.28; P = .014), serum bicarbonate (OR: 1.39; 95% CI, 1.20-1.61; P = .000), C-reactive protein (CRP) (OR: 1.04; 95% CI, 1.00-1.07; P = .034) were independently associated with OHS. CONCLUSION: In bariatric surgery patients, OHS presented a high prevalence, especially in men. Higher levels of BMI, neck circumference, serum bicarbonate, and CRP indicated higher risk of OHS.

Obesity Hypoventilation Syndrome and Postsurgical Outcomes in a Bariatric Surgery Cohort.

PURPOSE: Patients with obesity and elevated serum bicarbonate suggesting obesity hypoventilation syndrome (OHS) undergoing bariatric surgery may represent a unique subgroup. Information regarding surgical outcomes in this population remains limited. We sought to test the hypothesis that an elevated bicarbonate would be an important predictor of perioperative complications (i.e., length of hospital stay) and postsurgical outcomes (i.e., weight loss at 1 year). MATERIALS AND METHODS: Consecutive patients undergoing bariatric surgery between January 2015 and December 2018 were included. Patients with a preoperative serum bicarbonate ≥ 27 mEq/L were classified as suspected OHS. RESULTS: Of 297 patients, the prevalence of suspected OHS based on an elevated bicarbonate was 19.5% (95% CI: 15.3 to 24.6%). Length of hospital stay was similar in the suspected OHS and non-OHS control group (1.50 vs 1.49 days, P = 0.98). The achieved weight loss from peak preoperative weight to 1 year post-surgery was less in the suspected OHS vs the control group (4.2% [95% CI 1.6 to 6.8]; P = 0.002). CONCLUSION: Patients with serum bicarbonate ≥ 27 mEq/L as a surrogate marker for OHS experienced weight loss that was significantly less than their normal serum bicarbonate counterparts, but still achieved weight loss deemed clinically important by current guidelines. We observed no significant difference in length of hospital stay at time of surgery.

Veno-venous extracorporeal membrane oxygenation rescue for pulmonary hypertension and hypoxemic respiratory failure to obesity hypoventilation syndrome: a case report.

BACKGROUND: Effective pharmacological options for acute hypoxemic or hypercapnic respiratory failure, associated with obesity hypoventilation syndrome (OHS), have not been fully elucidated. Although weight reduction, non-invasive ventilation (NIV), and continuous positive airway pressure (CPAP) lead to improvements in long-term clinical outcomes and cardiac function, there is no rapid reversal method in serious situations requiring mechanical ventilation. Veno-venous extracorporeal life support by extracorporeal membrane oxygenation is a widely used modality that can support patients with refractory hypoxemia or hypercapnia as a bridging therapy for recovery. CASE DESCRIPTION: We present the case of a morbidly obese [body mass index (BMI) of 42 kg/m2] 58-year-old man with refractory hypoxemic respiratory failure, resulting from severe right ventricular failure and pulmonary hypertension (PH), who underwent emergency support with extracorporeal membrane oxygenation. During extracorporeal life support and mechanical ventilation, careful diuresis and nutritional control were provided for body weight loss, and body weight was significantly reduced by approximately 30 kg. Nocturnal NIV was initiated immediately after cessation of positive pressure ventilation and endotracheal intubation. After 5 weeks of hospitalization, transthoracic echocardiography (TTE) showed robust improvements in right ventricular cardiac function and PH. CONCLUSIONS: Here, we describe that veno-venous extracorporeal life support may sufficiently support patients with obesity and sleep hypoventilation who have suffered a pulmonary hypertensive crisis.

Severity stages of obesity-related breathing disorders - a cross-sectional cohort study.

INTRODUCTION: There is a general underappreciation of the spectrum of obesity-related breathing disorders and their consequences. We therefore compared characteristics of obese patients with eucapnic obstructive sleep apnea (OSA), OSA with obesity-related sleep hypoventilation (ORSH) or obesity hypoventilation syndrome (OHS) to identify the major determinants of hypoventilation. PATIENTS AND METHODS: In this prospective, diagnostic study (NCT04570540), obese patients with OSA, ORSH or OHS were characterized applying polysomnography with transcutaneous capnometry, blood gas analyses, bodyplethysmography and measurement of hypercapnic ventilatory response (HCVR). Pathophysiological variables known to contribute to hypoventilation and differing significantly between the groups were specified as potential independent variables in a multivariable logistic regression to identify major determinants of hypoventilation. RESULTS: Twenty, 43 and 19 patients were in the OSA, ORSH and OHS group, respectively. BMI was significantly lower in OSA as compared to OHS. The extent of SRBD was significantly higher in OHS as compared to OSA or ORSH. Patients with ORSH or OHS showed a significantly decreased forced expiratory volume in 1 s and forced vital capacity compared to OSA. HCVR was significantly lower in OHS and identified as the major determinant of hypoventilation in a multivariable logistic regression (Nagelkerke R2 = 0.346, p = 0.050, odds ratio (95%-confidence interval) 0.129 (0.017-1.004)). CONCLUSION: Although there were differences in BMI, respiratory mechanics and severity of upper airway obstruction between groups, our data support HCVR as the major determinant of obesity-associated hypoventilation.

A pilot randomized trial comparing CPAP vs bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease.

STUDY OBJECTIVES: Both obesity and airways disease can lead to chronic hypercapnic respiratory failure, which can be managed with positive airway pressure (PAP) therapy. The efficacy of PAP has been studied in obesity hypoventilation syndrome as well as in chronic hypercapnic chronic obstructive pulmonary disease patients, but not in patients where both obesity and airway obstruction coexist. This pilot study aims to compare the efficacy of continuous positive airway pressure vs bilevel positive airway pressure spontaneous mode in the treatment of hypoventilation disorder with obesity and obstructive airways disease. METHODS: We sequentially screened PAP-naïve patients with stable chronic hypercapnic respiratory failure (PaCO2 > 45 mm Hg), obesity (body mass index > 30 kg/m2), and obstructive airways disease. Participants were randomized to continuous positive airway pressure or bilevel positive airway pressure spontaneous mode treatment for 3 months. Participants were blinded to their PAP allocation. Change in awake PaCO2 was the primary endpoint. Secondary endpoints included change in lung function, daytime sleepiness, sleep quality, quality of life, PAP adherence, and neurocognitive function. RESULTS: A total of 32 individuals were randomized (mean ± SD: age 61 ± 11 years, body mass index 43 ± 7 kg/m2, PaCO2 54 ± 7 mm Hg, forced expiratory volume in 1 second 1.4 ± 0.6L, apnea-hypopnea index 59 ± 35 events/h). Sixteen participants in each PAP group were analyzed. Bilevel positive airway pressure yielded a greater improvement in PaCO2 compared to continuous positive airway pressure (9.4 mm Hg, 95% confidence interval, 4.3-15 mm Hg). There were no significant differences in PAP adherence, sleepiness, sleep quality, or neurocognitive function between the two therapies. CONCLUSIONS: Although both PAP modalities improved hypercapnic respiratory failure in this group of individuals, bilevel positive airway pressure spontaneous mode showed greater efficacy in reducing PaCO2. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Nocturnal ventilatory support in obesity hypoventilation syndrome; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12605000096651; Identifier: ACTRN12605000096651. CITATION: Zheng Y, Yee BJ, Wong K, Grunstein R, Piper A. A pilot randomized trial comparing CPAP vs bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease. J Clin Sleep Med. 2022;18(1):99-107.

Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity.

STUDY OBJECTIVES: The main cause of death in patients with obesity hypoventilation syndrome (OHS) is cardiac rather than respiratory failure. Here, we investigated autonomic-respiratory coupling and serum cardiac biomarkers in patients with OHS and obstructive sleep apnea (OSA) with comparable body mass index and apnea-hypopnea index. METHODS: Cardiopulmonary coupling (CPC) and cyclic variation of heart rate analysis was performed on the electrocardiogram signal from the overnight polysomnogram. Cardiac serum biomarkers were obtained in patients with OHS and OSA with a body mass index > 40 kg/m2. Samples were obtained at baseline and after 3 months of positive airway pressure (PAP) therapy in both groups. RESULTS: Patients with OHS (n = 15) and OSA (n = 36) were recruited. No group differences in CPC, cyclic variation of heart rate, and serum biomarkers were observed at baseline and after 3 months of PAP therapy. An improvement in several CPC metrics, including the sleep apnea index, unstable sleep (low-frequency coupling and elevated low-frequency coupling narrow band), and cyclic variation of heart rate were observed in both groups with PAP use. However, distinct differences in response characteristics were noted. Elevated low-frequency coupling narrow band coupling correlated with highly sensitive troponin-T (P < .05) in the combined cohort. Baseline highly sensitive troponin-T inversely correlated with awake oxygen saturation in the OHS group (P < .05). CONCLUSIONS: PAP therapy can significantly improve CPC stability in patients with obesity with OSA or OHS, with key differences. Elevated low-frequency coupling narrow band may function as a surrogate biomarker for early subclinical cardiac disease. Low awake oxygen saturation could also increase this biomarker in OHS. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Obesity Hypoventilation Syndrome and Neurocognitive Dysfunction; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367492; Identifier: ACTRN12615000122550. CITATION: Sivam S, Wang D, Wong KKH, et al. Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity. J Clin Sleep Med. 2022;18(4):1063-1071.

Obstructive sleep apnoea/hypopnoea syndrome and obesity hypoventilation syndrome in over 16s

This guideline covers the diagnosis and management of obstructive sleep apnoea/hypopnoea syndrome (OSAHS), obesity hypoventilation syndrome (OHS) and chronic obstructive pulmonary disease with OSAHS (COPD­OSAHS overlap syndrome) in people over 16. It aims to improve recognition, investigation and treatment of these related conditions.

Diagnostic approach to sleep disordered-breathing among patients with grade III obesity.

Sleep apnea test (SAT) is a cost-effective approach to evaluate subjects without associated comorbidities suspected for obstructive sleep apnea (OSA), a disorder particularly common in obese subjects. The association of obesity with awake hypercapnia (carbon dioxide arterial pressure, PaCO2 ≥45 mmHg) defines the obesity-hypoventilation syndrome (OHS), which in turn results in increased morbidity and mortality compared to simple OSA. Isolated hypoventilation during sleep in obese patients (obesity-related sleep hypoventilation, ORSH) is now considered as an early stage of OHS. The aim of this study was to assess the performance of SAT in diagnosing OSA and predicting the presence of ORHS among patients with grade III obesity without awake hypercapnia. METHODS: Over a 14-months period, patients with grade III obesity (body mass index≥40 kg/m2) presenting moderate-to-severe OSA (apnea-hypopnea index [AHI]≥15) upon SAT and normal awake PaCO2 at arterial blood gas analysis, systematically underwent in-lab nocturnal polysomnography combined with transcutaneous carbon dioxide pressure (PtcCO2) monitoring. RESULTS: Among 48 patients included in the study, 16 (33%) presented an AHI<15 upon polysomnography and 14 (29%) had ORSH. The test revealed no difference in ORSH prevalence between patients with AHI <15 or ≥15 (31% vs. 25%). No SAT variables were independently associated with increased PtCO2. CONCLUSIONS: This study shows that SAT overestimates OSA severity and ORSH affects one third of patients with grade III obesity without awake hypercapnia and with moderate-to-severe OSA at SAT, suggesting how polysomnography combined with PtCO2 monitoring is the most appropriate diagnostic approach for OSA and ORSH in this population.

Heart rate variability changes by non-invasive ventilation in obesity hypoventilation syndrome.

BACKGROUND: Non-invasive positive pressure ventilation (NIPPV) is known to enhance hypoventilation and is particularly adopted as a treatment for patients diagnosed with obesity hypoventilation syndrome (OHS). The augmented risk of cardiovascular morbidity is known as a side effect of OHS. AIMS: In this paper, this inference is examined that hypoventilation and the increased risk of morbidity can be diagnosed via the assessment of changes in heart rate variability (HRV). More specifically, the study investigates the effect of NIPPV on both HRV and hypoventilation among OHS patients. The linear relationship between different HRV measures and ventilation parameters is also examined. MATERIALS & METHODS: The reported results are attained via an interventional clinical trial study. HRV measures are evaluated before and after treatment, in a group of patients which are newly diagnosed with OHS and receive bi-level positive airway pressure (BiPAP) treatment for three months. RESULTS: The results are compared and interpreted via statistical analysis. DISCUSSION: Throughout the study, the relationship between hypoventilation and HRV is confirmed, as well as the effect of BiPAP on some HRV measures in both time and frequency domains. Particularly significant connections are observed between hypoventilation and low-frequency components of HRV. CONCLUSION: The enhanced respiration due to the application of BiPAP can improve the performance of autonomous nervous and cardiovascular systems, in terms of HRV. Moreover, it is suggested to consider some HRV parameters to control the cardiovascular side-effects of OHS and confine the resulting mortality rate in long term.

Trastorno de hipoventilación central del sueño en pediatría: causas poco frecuentes / Central hypoventilation disorders sleep-related in pediatrics: unusual causes

Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity syndrome with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare causes of hypoventilation during sleep in the pediatric population. This group of disorders are characterized by the absence or decrease in the automatic control of ventilation, decreased sensitivity of chemoreceptors to CO2, causing hypoventilation during sleep and even in wakefulness, in the most severe cases. For these reasons it is important to diagnose and treat them promptly. The objective of this review is to provide current and complete literature, to be able to identify, treat and refer this group of children early, and thus reduce the complications and/or associated comorbidities in the short and long term, improving their quality of life.

El síndrome de hipoventilación central congénita (CCHS) y síndrome de obesidad de inicio rápido con disfunción hipotalámica, hipoventilación y desregulación autonómica (ROHHAD), son causas poco comunes de hipoventilación durante el sueño en la población pediátrica. Este grupo de trastornos se caracterizan por ausencia o disminución en el control automático de la ventilación, sensibilidad disminuida de los quimioreceptores al CO2, provocando hipoventilación durante el sueño e incluso en vigilia, en los casos más severos. Por estas razones es importante diagnosticarlos y tratarlos oportunamente. El objetivo de esta revisión es proporcionar literatura actual y completa, para poder identificar, tratar y referir a éste grupo de niños tempranamente, y así disminuir las complicaciones y/o comorbilidades asociadas a corto y largo plazo, mejorando su calidad de vida.

ROHHAD syndrome - A still unrecognized cause of childhood obesity: report of three cases.

Objectives Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare, potentially fatal, pediatric syndrome. Case presentations We describe three cases of ROHHAD-syndrome in Greece. The main and earliest symptom was the excessive and rapid weight gain at 5, 2, and 3 years of age. Years after the onset of obesity, the patients developed hypothalamic dysfunction with various endocrinological abnormalities (at 9, 8, and 6.8 years, respectively), autonomic dysregulation and finally, alveolar hypoventilation (at 14.6, 8, and 7.8 years, respectively), leading to the diagnosis of ROHHAD-syndrome. Conclusions The rarity of the syndrome, the variable symptoms' presentation, and the lack of specific diagnostic tests could explain why no previous cases have been reported from our country. The rapid onset of obesity was underestimated, and the patients were misdiagnosed with other more common obesity syndromes. Therefore, we propose a questionnaire to help physicians identify patients with ROHHAD-syndrome.

Ventilatory response to exercise is preserved in patients with obesity hypoventilation syndrome.

STUDY OBJECTIVES: Blunted ventilatory responses to hypoxia and hypercapnia during resting conditions are common findings in patients with obesity hypoventilation syndrome (OHS). Exercise increases the work and oxygen cost of breathing and produces excessive carbon dioxide (CO2). The aim of this investigation was to study ventilatory responses to incremental exercise in patients with OHS. METHODS: Sixty-eight obese adults with OHS (n = 15), eucapnic obstructive sleep apnea (n = 26), or simple obesity (n = 27) participated in an incremental exercise test on a cycle ergometer and an in-laboratory sleep study. RESULTS: The peak oxygen uptake (peak VO2) and peak pulse oxygen was decreased in patients with OHS compared with patients with either obstructive sleep apnea or simple obesity. The ventilatory response to exertional metabolic demand (nadir VE/VCO2, ∆VE/∆VCO2 slope, and VE/VCO2 at peak exercise) did not significantly differ among the 3 groups. Minute ventilation, tidal volume, respiratory frequency, tidal volume/respiratory frequency, and inspiratory time/total time ratio at a given work rate were comparable among the 3 groups. Among the whole cohort, apnea-hypopnea index was not independently associated with peak VO2, and no association was found between the ∆VE/∆VCO2 slope and resting arterial partial pressure of CO2. CONCLUSIONS: The ventilatory response to incremental exercise is preserved in patients with OHS compared with patients with obstructive sleep apnea and simple obesity who were matched for age and body mass index. This result highlights the complexity of the respiratory control system during exercise for patients with OHS, which may be uncoupled with the ventilatory response during sleep and resting conditions.