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.

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.

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.

[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.

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. (AU)

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.

Noninvasive ventilation in New Zealand: a national prevalence survey.

BACKGROUND: Home-based noninvasive ventilation (NIV) is an effective treatment for a range of conditions that cause respiratory failure which reduces hospitalisation and mortality and improves quality of life. AIMS: To collect NIV prevalence, disease burden and equity data needed for effective national NIV health service planning. METHODS: The authors collected demographics and the primary diagnosis of patients receiving publicly funded NIV in New Zealand in 2018 by surveying all providers. National and regional prevalence rates were calculated using adult population data (aged ≥20 years) for each District Health Board region compared with a 2011 study. A subanalysis of individual-level data was used to calculate age-standardised rates by diagnostic category. RESULTS: A total of 1197 adults were receiving NIV giving a national rate of 32.9 per 100 000; almost twice the 2011 rate (16.7 per 100 000). Significant regional variations in NIV provision (4.5-84.2 per 100 000) were observed. The most frequent indications were obesity hypoventilation syndrome (OHS) (562, 47%), obstructive pathologies (335, 28%) and neuromuscular disorders (175, 15%); all have significantly increased in prevalence since 2011. Maori and Pacific peoples were significantly overrepresented among NIV users (2.24 [95% confidence interval (CI), 1.72-2.93] and 7.03 [95% CI, 5.52-8.94], respectively). The prevalence of NIV-dependent use (>15 h/day) was 4%. CONCLUSIONS: Home-based NIV provision has doubled since the previous survey, reflecting increased burden from OHS and obstructive pathologies and a disproportionate disease burden among Maori and Pacific populations. The large regional variations are concerning and highlight the urgent requirement for national service specifications, education and equipment provision. Further research is needed to address access equity.

Cost-effectiveness of outpatient versus inpatient non-invasive ventilation setup in obesity hypoventilation syndrome: the OPIP trial.

BACKGROUND: Current guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective. METHODS: Patients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO2) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP). RESULTS: Between May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m2 and PaCO2 6.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO2 (difference -0.27 kPa, 95% CI -0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI -£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference -0.006, 95% CI -0.05 to 0.04). There were no differences in secondary outcomes. DISCUSSION: There was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference. TRIAL REGISTRATION NUMBERS: NCT02342899 and ISRCTN51420481.

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.

Use of Positive Airway Pressure in the Treatment of Hypoventilation.

The treatment of chronic hypoventilation usually requires noninvasive ventilation. However, upper airway obstruction can lead to hypoventilation in conditions such as obesity-hypoventilation syndrome, or chronic obstructive lung diseases (overlap syndrome). In these situations, continuous positive airway pressure can be an effective therapeutic option. This article reviews the pathophysiology of sleep-related hypoventilation, discusses situations where treatment with continuous positive airway pressure is feasible and briefly outlines noninvasive ventilation modes and settings for the treatment of common sleep-related hypoventilation disorders.

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.

The Overlap of Obesity-Hypoventilation Syndrome and Obstructive Sleep Apnea: How to Treat?

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A novel case of central hypoventilation syndrome or just heavy breathing?

With the growing prevalence of obesity in the pediatric population, reports of its severe complications are increasing. Obesity hypoventilation syndrome is an uncommon disorder in children with altered respiratory mechanics, sleep-disordered breathing, and impaired ventilatory responses leading to persistent hypercapnia. Presentation is varied, and children may remain relatively asymptomatic until challenged with a respiratory infection, when they may present with acute respiratory failure. With increasing use of genetic testing in pediatric patients, our knowledge of potential contributors to hypoventilation syndromes is growing. Although mutations in the paired-like homeobox 2B gene are known to be causative of congenital central hypoventilation syndrome, other genes may also contribute to hypoventilation phenotypes. We report one of the youngest reported patients with obesity hypoventilation syndrome in pediatrics, with a proposed congenital predisposition for central hypoventilation derived from a deletion in the brain-derived neurotrophic factor gene. CITATION: McCoy J, Karp N, Brar J, Amin R, St-Laurent A. A novel case of central hypoventilation syndrome or just heavy breathing? J Clin Sleep Med. 2022;18(9):2321-2325.

The prevalence of non-invasive ventilation and long-term oxygen treatment in Helsinki University Hospital area, Finland.

BACKGROUND: Chronic respiratory failure (CRF) can be treated at home with non-invasive ventilation (NIV) and/or long-term oxygen (LTOT). The prevalence of these treatments is largely unknown. We aimed to clarify the prevalence and indications of the treatments, and the three-year mortality of the treated patients in the Helsinki University Hospital (HUH) area in Finland. METHODS: In this retrospective study we analyzed the prevalence of adult CRF patients treated with NIV and/or LTOT on 1.1.2018 and followed these patients until 1.1.2021. Data collected included the underlying diagnosis, patient characteristics, information on treatment initiation and from the last follow-up visit, and mortality during the three-year follow-up. Patients with home invasive mechanical ventilation or sleep apnea were excluded. RESULTS: On 1.1.2018, we had a total of 815 patients treated with NIV and/or LTOT in the Helsinki University Hospital (HUH) area, with a population of 1.4 million. The prevalence of NIV was 35.4 per 100,000, of LTOT 24.6 per 100,000 and of the treatments combined 60.0 per 100,000. Almost half, 44.5%, were treated with NIV, 41.0% with LTOT, and 14.4% underwent both. The most common diagnostic groups were chronic obstructive pulmonary disease (COPD) (33.3%) and obesity-hypoventilation syndrome (OHS) (26.6%). The three-year mortality in all patients was 45.2%. In the COPD and OHS groups the mortality was 61.3% and 21.2%. In NIV treated patients, the treatment durations varied from COPD patients 5.3 years to restrictive chest wall disease patients 11.4 years. The age-adjusted Charlson co-morbidity index (ACCI) median for all patients was 3.0. CONCLUSIONS: NIV and LTOT are common treatments in CRF. The prevalence in HUH area was comparable to other western countries. As the ACCI index shows, the treated patients were fragile, with multiple co-morbidities, and their mortality was high. Treatment duration and survival vary greatly depending on the underlying diagnosis.

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.