Hypoventilation in patients with Prader-Willi syndrome across the pediatric age.

OBJECTIVES: Few data on alveolar hypoventilation in Prader-Willi syndrome (PWS) are available and the respiratory follow-up of these patients is not standardized. The objectives of this study were to evaluate the prevalence of alveolar hypoventilation in children with PWS and identify potential risk factors. STUDY DESIGN: This retrospective study included children with PWS recorded by polysomnography (PSG) with transcutaneous carbon dioxide pressure (PtcCO2) or end-tidal CO2 (ETCO2) measurements, between 2007 and 2021, in a tertiary hospital center. The primary outcome was the presence of alveolar hypoventilation defined as partial pressure of carbon dioxide (pCO2) ≥ 50 mmHg during ≥2% of total sleep time (TST) or more than five consecutive minutes. RESULTS: Among the 57 included children (38 boys, median age 4.8 years, range 0.1-15.6, 60% treated with growth hormone [GH], 37% obese), 19 (33%) had moderate-to-severe obstructive sleep apnea syndrome (defined as obstructive apnea-hypopnea index ≥5/h) and 20 (35%) had hypoventilation. The median (range) pCO2 max was 49 mmHg (38-69). Among the children with hypoventilation, 25% were asymptomatic. Median age and GH treatment were significantly higher in children with hypoventilation compared to those without. There was no significant difference in terms of sex, BMI, obstructive or central apnea-hypopnea index between both groups. CONCLUSION: The frequency of alveolar hypoventilation in children and adolescents with PWS is of concern and may increase with age and GH treatment. A regular screening by oximetry-capnography appears to be indicated whatever the sex, BMI, and rate of obstructive or central apneas.

Respiratory Insufficiency in Neuromuscular Disease (RIND): A Delphi Study to Establish Consensus Criteria to Define and Diagnose Hypoventilation in Pediatric Neuromuscular Disease.

Chronic respiratory failure is a common endpoint in the loss of respiratory muscle function in patients with progressive neuromuscular disease (NMD). Identifying the onset of hypoventilation is critical to allow for the timely introduction of ventilator support and effectively manage respiratory failure [1-3]. While there are accepted criteria governing the diagnosis of hypoventilation during polysomnography (PSG) [4], there is concern that criteria are insufficient for identifying hypoventilation in the earlier stages of respiratory insufficiency related to NMD. The purpose of this project was to identify more sensitive criteria for identifying hypoventilation. METHODS: Fifteen pediatric pulmonologists with broad experience in managing patients with NMD, 10 of whom were board certified in and practice sleep medicine, were assembled and performed a review of the pertinent literature and a two-round Delphi process with 6 domains (Table 1). RESULTS: Within the 6 domains there were three pertinent items per domain (Table 2). There was clear agreement on findings on history (morning headaches) and pulmonary function testing (FVC < 50% or awake TcCO2 > 45 mmHg) indicating a high concern for nocturnal hypoventilation. There was close agreement on the definitions for nocturnal hypercapnia and hypoxemia. PSG criteria were identified that indicate a patient is likely in the transitional phase from adequate ventilation to hypoventilation. DISCUSSION: We identified a set of clinical criteria that may allow for more sensitive diagnosis of hypoventilation in NMD and earlier initiation of non-invasive ventilation leading to a reduction in the respiratory morbidity in progressive NMD. These criteria need to be further and more broadly validated prospectively to confirm their utility.

Hypercarbia and high-flow nasal oxygen use during anaesthesia - risking a failure to thrive?

Prevention of arterial oxygen desaturation during anaesthesia with high-flow nasal oxygen (HFNO) has gained greater acceptance for a widening range of procedures. However, during HFNO use there remains the potential for development of significant anaesthesia-associated apnoea or hypoventilation and the possibility of hypercarbia, with harmful cardiovascular or neurological sequelae. The aim of this study was to determine whether any HFNO-related hypercarbia adverse incidents had been reported on webAIRS, an online database of adverse anaesthesia-related incidents. Two relevant reports were identified of complications due to marked hypercarbia during HFNO use to maintain oxygenation. In both reports, HFNO and total intravenous anaesthesia were used during endoscopic procedures through the upper airway. In both, the extent of hypoventilation went undetected during HFNO use. An ensuing cardiac arrest was reported in one report, ascribed to acute hypercarbia-induced exacerbation of the patient's pre-existing pulmonary hypertension. In the other report, hypercarbia led to a prolonged duration of decreased level of consciousness post procedure, requiring ventilatory support. During the search, an additional 11 reports of postoperative hypercarbia-associated sedation were identified, unrelated to HFNO. In these additional reports an extended duration of severe acute hypercarbia led to sedation or loss of consciousness, consistent with the known effects of hypercarbia on consciousness. These 13 reports highlight the potential dangers of unrecognised and untreated hypercarbia, even if adequate oxygenation is maintained.

Nocturnal Hypoventilation in the Patients Submitted to Thoracic Surgery.

Introduction: Nocturnal hypoventilation may occur due to obesity, concomitant chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and/or the use of narcotic analgesics. The aim of the study was to evaluate the risk and severity of nocturnal hypoventilation as assessed by transcutaneous continuous capnography in the patients submitted to thoracic surgery. Materials and Methods: The material of the study consisted of 45 obese (BMI 34.8 ± 3.7 kg/m2) and 23 nonobese (25.5 ± 3.6 kg/m2) patients, who underwent thoracic surgery because of malignant (57 patients) and nonmalignant tumors. All the patients received routine analgesic treatment after surgery including intravenous morphine sulfate. Overnight transcutaneous measurements of CO2 partial pressure (tcpCO2) were performed before and after surgery in search of nocturnal hypoventilation, i.e., the periods lasting at least 10 minutes with tcpCO2 above 55 mmHg. Results: Nocturnal hypoventilation during the first night after thoracic surgery was detected in 10 patients (15%), all obese, three of them with COPD, four with high suspicion of moderate-to-severe OSA syndrome, and one with chronic daytime hypercapnia. In the patients with nocturnal hypoventilation, the mean tcpCO2 was 53.4 ± 6.1 mmHg, maximal tcpCO2 was 59.9 ± 8.4 mmHg, and minimal tcpCO2 was 46.4 ± 6.7 mmHg during the first night after surgery. In these patients, there were higher values of minimal, mean, and maximal tcpCO2 in the preoperative period. Nocturnal hypoventilation in the postoperative period did not influence the duration of hospitalization. Among 12 patients with primary lung cancer who died during the first two years of observation, there were 11 patients without nocturnal hypoventilation in the early postoperative period. Conclusion: Nocturnal hypoventilation may occur in the patients after thoracic surgery, especially in obese patients with bronchial obstruction, obstructive sleep apnea, or chronic daytime hypercapnia, and does not influence the duration of hospitalization.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): a collaborative review of the current understanding.

PURPOSE: To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents. METHODS: The literature (1965-2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause. RESULTS: ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions. CONCLUSION: ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype.

Unveiled central hypoventilation after tracheotomy in anti-IgLON5 disease: a case report.

Anti-IgLON5 disease is a recently described entity that has been associated with neurological symptoms and sleep disturbances including sleep breathing disorders. Sleep stridor as well as obstructive and less often central sleep apnea have been reported but rarely needing ventilation on tracheotomy. We report the case of a patient in whom obstructive sleep apnea with secondary development of dysphagia and recurrent aspiration pneumonia led to the diagnosis of anti-IgLON 5 disease. Acute respiratory failure due to laryngospasm required intubation and eventually tracheotomy. Yet hypoventilation persisted, and polysomnography demonstrated central sleep apnea alternating with sleep-related tachypnea. Nocturnal ventilation was thus reintroduced. The association of obstructive sleep apnea with dysphagia is a potential red flag for anti-IgLON5 disease, which remains an overlooked diagnosis. Breathing disorders can be complex in this context, with a mixed obstructive and central pattern whose central component can be unveiled after tracheotomy. This highlights the importance of closely monitoring sleep and respiration even after tracheotomy. CITATION: Tankéré P, Le Cam P, Folliet L, et al. Unveiled central hypoventilation after tracheotomy in anti-IgLON5 disease: a case report. J Clin Sleep Med. 2023;19(9):1701-1704.

Sleep apnoea and hypoventilation in patients with five major types of muscular dystrophy.

BACKGROUND: The characteristics of and relationship between sleep apnoea and hypoventilation in patients with muscular dystrophy (MD) remain to be fully understood. METHODS: We analysed 104 in-laboratory sleep studies of 73 patients with MD with five common types (DMD-Duchenne, Becker MD, CMD-congenital, LGMD-limb-girdle and DM-myotonic dystrophy). We used generalised estimating equations to examine differences among these types for outcomes. RESULTS: Patients in all five types had high risk of sleep apnoea with 53 of the 73 patients (73%) meeting the diagnostic criteria in at least one study. Patients with DM had higher risk of sleep apnoea compared with patients with LGMD (OR=5.15, 95% CI 1.47 to 18.0; p=0.003). Forty-three per cent of patients had hypoventilation with observed prevalence higher in CMD (67%), DMD (48%) and DM (44%). Hypoventilation and sleep apnoea were associated in those patients (unadjusted OR=2.75, 95% CI 1.15 to 6.60; p=0.03), but the association weakened after adjustment (OR=2.32, 95% CI 0.92 to 5.81; p=0.08). In-sleep average heart rate was about 10 beats/min higher in patients with CMD and DMD compared with patients with DM (p=0.0006 and p=0.02, respectively, adjusted for multiple testing). CONCLUSION: Sleep-disordered breathing is common in patients with MD but each type has its unique features. Hypoventilation was only weakly associated with sleep apnoea; thus, high clinical suspicion is needed for diagnosing hypoventilation. Identifying the window when respiratory muscle weakness begins to cause hypoventilation is important for patients with MD; it enables early intervention with non-invasive ventilation-a therapy that should both lengthen the expected life of these patients and improve its quality.Cite Now.

Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome - neuro-endocrine tumours (ROHHAD-NET): case series and learning points.

OBJECTIVES: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) is a rare syndrome associated with high morbidity and mortality. Diagnosis is often challenging. We describe three cases of ROHHAD with heterogeneous presentations but some consistent clinical features, including hyperprolactinaemia at diagnosis. We highlight when the diagnosis of ROHHAD should be considered at an early stage. CASE PRESENTATION: All three patients presented between 4 and 6 years old with rapid-onset obesity. They all have central hypoventilation requiring nocturnal BiPAP, varying degrees of hypothalamic dysfunction with hyperprolactinaemia being a consistent feature, and autonomic dysfunction. One patient has a neuro-endocrine tumour (NET) and two have glucose dysregulation. CONCLUSIONS: High prolactin was a consistent early feature. Central hypoventilation and NET may present later and therefore regular sleep studies and screening for NETs are required. A high suspicion of ROHHAD is warranted in patients with rapid, early-onset obesity and hyperprolactinaemia without structural pituitary abnormality.

Modified hypoxic challenge testing in children needing nocturnal ventilation: An observational study.

BACKGROUND: Guidelines for air passengers with respiratory disease focus on primary lung pathology. Little evidence exists to guide professionals advising children needing ventilatory support because of neuromuscular or central hypoventilation conditions; these children might risk hypoxia and hypercapnia if unable to mount an adequate hyperventilation response. OBJECTIVE: This study assessed the response to low ambient oxygen using a modified hypoxic challenge test. In addition to measuring pulse oximetry and response to supplementary oxygen, we also measured transcutaneous carbon dioxide and response to ventilatory support. METHODS: Twenty children on nocturnal ventilatory support aged 1.6-18 years were recruited in a pragmatic sample from outpatient clinics; 10 with neuromuscular weakness and 10 with central hypoventilation. Participants underwent a two-stage, modified hypoxic challenge test; a conventional stage, where oxygen alone was titrated according to SpO2, and a new stage, where participants used their routine ventilatory support with oxygen titrated if needed. Participants were interviewed to understand their experiences of testing and of air travel. RESULTS: Thirteen participants needed supplemental oxygen during the conventional stage, but only two did when using ventilatory support. Transcutaneous carbon dioxide remained within normal range for all participants, on or off ventilatory support. Whilst some participants found testing challenging, participants generally reported both testing and air travel to be valuable. CONCLUSIONS: Evaluating response to patients' usual ventilation through "fitness-to-fly" assessment aids decision making when considering whether children who receive nocturnal ventilation can travel by air, since for some using a ventilator reduces or avoids the need for supplemental oxygen.

Hypoventilation in the PACU is associated with hypoventilation in the surgical ward: Post-hoc analysis of a randomized clinical trial.

OBJECTIVE: To evaluate the association between early postoperative hypoventilation in the last hour of the post-anesthesia care unit (PACU) stay and hypoventilation during the rest of the first 48 postoperative hours in the surgical ward. DESIGN: Sub-analysis of a clinical trial. SETTING: PACU and surgical wards of a single medical center. PATIENTS: Adults having abdominal surgery under general anesthesia. INTERVENTIONS: Monitoring with a respiratory volume monitor from admission to PACU until the earlier of 48 h after surgery or discharge. MEASUREMENTS: The exposure was having at least one low minute-ventilation (MV) event during the last hour of PACU stay, defined as MV lower than 40% the predicted value lasting at least 1 min. The primary outcome was low MV events lasting at least 2 min during the rest of the first 48 postoperative hours, while in the surgical ward. The secondary outcome was the rate of low MV events per monitored hour. MAIN RESULTS: Data of 292 patients were analyzed, of which 20 (6.8%) patients had a low MV event in PACU. Low MV events in the surgical ward were found in 81 (28%) patients. All patients who had low MV events in PACU had events again in the ward, while 61/272 (22%) had an event in the ward but not in PACU. The incidence rate of low MV events per hour was 24 (95% CI: 13, 46) among patients having an event in the PACU, and 2 (1, 4) among those who did not. CONCLUSIONS: In adults recovering from abdominal surgery, events of hypoventilation during the first postoperative hour are associated with similar events during the rest of the first 48 postoperative hours, with positive predictive value approaching 100%. Sixty-one patients had ward hypoventilation that was not preceded by hypoventilation in PACU.

Central Hypoventilation Following Pontomedullary Tumor Decompression - Is Routine Brainstem Monitoring Adequate?

Neurophysiological monitoring assesses the functional integrity of the brainstem by using monitoring and mapping techniques. We report an operated case of a pontomedullary lesion in a patient who developed central hypoventilation postoperatively. The intraoperative use of neurophysiological and cardiovascular monitoring was unable to predict/prevent this hypoventilation. We describe the inherent limitations of monitoring the respiratory system, including spontaneous respiration. Moreover, we suggest the novel application of diaphragmatic motor evoked potential for real-time monitoring of respiratory pathways during brainstem surgeries.

Successful Total Management of Multi-Causative Sleep-Disordered Breathing Complicated with Patient with Adult Congenital Heart Disease.

Sleep-disordered breathing is one of the complications commonly seen in patients with adult congenital heart disease (ACHD) due to multiple causes including complex underlying cardiac defects, cardiomegaly, previous thoracotomies, obesity, scoliosis, and paralysis of the diaphragm. It is often hard to determine its main cause and predict the efficacy of each treatment in its management. We herein report a 30-year-old woman after biventricular repair of pulmonary atresia with intact ventricular septum diagnosed as sleep-related hypoventilation disorder. Simultaneous treatment targeting obesity, paralysis of the diaphragm, and cardiomegaly followed by respiratory muscle reinforcement through non-invasive ventilation resolved her sleep-related hypoventilation disorder. Such management for each factor responsible for the hypoventilation is expected to provide synergetic therapeutic efficacy and increase daily activity in a patient with ACHD.

Respiratory Function and Sleep Disordered Breathing in Pediatric Duchenne Muscular Dystrophy.

BACKGROUND AND OBJECTIVES: The decline of respiratory function in Duchenne muscular dystrophy (DMD) is associated with sleep disordered breathing (SDB) and alteration of nocturnal gas exchange, first manifesting as nocturnal hypoventilation (NH). However, the correlation between the pulmonary function measured by spirometry (PFT) and the onset of SDB with or without NH is unclear. The aims of this study are to identify the prevalence and features of SDB and to investigate the relationship between lung function determined by forced vital capacity (FVC) and sleep abnormalities in a large pediatric DMD population. METHODS: This was a retrospective, single-center cohort study. FVC% predicted (FVC%) was calculated using predicted equations from the Global Lung Function Initiative. NH was defined by transcutaneous (tc) CO2 >50 mm Hg for >25% of total sleep time (TST), borderline NH by a mean tcCO2 between 45 and 50 mm Hg or tcCO2>50 mm Hg for ≤25% of TST, and clinically meaningful obstructive sleep apnea (OSA) by obstructive apnea-hypopnea index >5. The sensitivity, specificity, and positive and negative predictive values of FVC < 50% to indicate the presence of nocturnal hypoventilation were calculated. RESULTS: One hundred thirty-four patients underwent 284 sleep studies and 1222 PFT. The mean (SD) age at the first and the last sleep study was 12.9 (2.7) and 14.3 (2.6) years, respectively. Borderline NH (n = 31) was detected in both ambulant and early-nonambulant participants, while 100% of NH cases (n = 14) were nonambulant. NH was detected in 4 of the 14 patients despite an FVC >50%. Seventeen of the 26 patients with OSA presented with concomitant NH or borderline NH. FVC <50% was associated with NH indicating a sensitivity and specificity of 73% and 86%, respectively. Positive and negative predictive values were 32% and 97%, respectively. PFT showed a nonlinear, sudden FVC% decline in 18% of cases. DISCUSSION: FVC% <50 was associated with NH in close to a third of patients. CO2 elevation can be associated with obstructive/pseudo-obstructive events and was also observed in early nonambulant cases or in the presence of FVC >50%. These results are relevant for the clinical management of SDB.

Nocturnal Hypoventilation as a Respiratory Complication of Acute Flaccid Myelitis.

Detailed accounts of long-term respiratory complications among children with acute flaccid myelitis have not been reported systematically. We describe respiratory complications and outcomes in a single-center cohort of 19 children with acute flaccid myelitis. Significantly, 3 of the 19 children had a prolonged course of nocturnal hypoventilation that required intervention.

Airway strategy and ventilation rates in the pragmatic airway resuscitation trial.

BACKGROUND: We sought to describe ventilation rates during out-of-hospital cardiac arrest (OHCA) resuscitation and their associations with airway management strategy and outcomes. METHODS: We analyzed continuous end-tidal carbon dioxide capnography data from adult OHCA enrolled in the Pragmatic Airway Resuscitation Trial (PART). Using automated signal processing techniques, we determined continuous ventilation rates for consecutive 10-second epochs after airway insertion. We defined hypoventilation as a ventilation rate < 6 breaths/min. We defined hyperventilation as a ventilation rate > 12 breaths/min. We compared differences in total and percentage post-airway hyper- and hypoventilation between airway interventions (laryngeal tube (LT) vs. endotracheal intubation (ETI)). We also determined associations between hypo-/hyperventilation and OHCA outcomes (ROSC, 72-hour survival, hospital survival, hospital survival with favorable neurologic status). RESULTS: Adequate post-airway capnography were available for 1,010 (LT n = 714, ETI n = 296) of 3,004 patients. Median ventilation rates were: LT 8.0 (IQR 6.5-9.6) breaths/min, ETI 7.9 (6.5-9.7) breaths/min. Total duration and percentage of post-airway time with hypoventilation were similar between LT and ETI: median 1.8 vs. 1.7 minutes, p = 0.94; median 10.5% vs. 11.5%, p = 0.60. Total duration and percentage of post-airway time with hyperventilation were similar between LT and ETI: median 0.4 vs. 0.4 minutes, p = 0.91; median 2.1% vs. 1.9%, p = 0.99. Hypo- and hyperventilation exhibited limited associations with OHCA outcomes. CONCLUSION: In the PART Trial, EMS personnel delivered post-airway ventilations at rates satisfying international guidelines, with only limited hypo- or hyperventilation. Hypo- and hyperventilation durations did not differ between airway management strategy and exhibited uncertain associations with OCHA outcomes.

Daytime predictors of nocturnal hypercapnic hypoventilation in children with neuromuscular disorders.

OBJECTIVES: To examine objective daytime predictors of nocturnal hypercapnic hypoventilation (NHH) and identify a forced vital capacity (FVC) z-score cut off that predicts NHH using the 2012 Global Lung Function Initiative (GLI) reference equations in pediatric neuromuscular patients. DESIGN: Single-centre retrospective medical record review. SETTING: Tertiary pediatric hospital in Australia. PATIENTS: Children (<18 years old) with a neuromuscular disorder (NMD) who had a diagnostic sleep study over a 5-year period. RESULTS: Fifty children were included, median age 11.9 years (interquartile range [IQR]: 4.5-14.3). The majority of children had a diagnosis of Duchenne Muscular Dystrophy (32%). NHH was diagnosed in 18 children (36%). Multivariate logistic regression analysis performed for the entire cohort confirmed a statistically significant association between NHH and scoliosis (odds ratio [OR]: 3.3, p = 0.03), but not age (OR: 1.01, p = 0.26), body mass index z-score (OR: 0.86, p = 0.26) or use of a wheelchair for mobility (OR: 1.25, p = 0.72). For the subset of 29 children who had spirometry testing (median age 12.9 years [IQR: 10.2-14.3]), FVC z-score was the only statistically significant predictor of NHH (OR: 0.45, p = 0.02). NHH was predicted by an FVC z-score <-3.24 (sensitivity 78%, specificity 73%), or FVC <60% predicted (sensitivity 78%, specificity 73%). There was a strong positive correlation between FVC and forced expiratory volume in 1 s z-scores (rp = 0.98, p = 0.00) and FVC and peak expiratory flow  z-scores (rp = 0.72, p = 0.00). CONCLUSION: Children with a NMD and scoliosis or a lower FVC z-score have increased odds of having NHH.

Alkalosis-induced hypoventilation in cystic fibrosis: The importance of efficient renal adaptation.

The lungs and kidneys are pivotal organs in the regulation of body acid-base homeostasis. In cystic fibrosis (CF), the impaired renal ability to excrete an excess amount of HCO3- into the urine leads to metabolic alkalosis [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711-1727 (2020); F. Al-Ghimlas, M. E. Faughnan, E. Tullis, Open Respir. Med. J. 6, 59-62 (2012)]. This is caused by defective HCO3- secretion in the ß-intercalated cells of the collecting duct that requires both the cystic fibrosis transmembrane conductance regulator (CFTR) and pendrin for normal function [P. Berg et al., J. Am. Soc. Nephrol. 31, 1711-1727 (2020)]. We studied the ventilatory consequences of acute oral base loading in normal, pendrin knockout (KO), and CFTR KO mice. In wild-type mice, oral base loading induced a dose-dependent metabolic alkalosis, fast urinary removal of base, and a moderate base load did not perturb ventilation. In contrast, CFTR and pendrin KO mice, which are unable to rapidly excrete excess base into the urine, developed a marked and transient depression of ventilation when subjected to the same base load. Therefore, swift renal base elimination in response to an acute oral base load is a necessary physiological function to avoid ventilatory depression. The transient urinary alkalization in the postprandial state is suggested to have evolved for proactive avoidance of hypoventilation. In CF, metabolic alkalosis may contribute to the commonly reduced lung function via a suppression of ventilatory drive.

Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report.

OBJECTIVES: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural endocrine tumor (ROHHAD-NET) syndrome is a youth-onset constellation of symptoms including rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Despite growing understanding of the clinical classification of this syndrome there is limited investigation into treatment of the rapid-onset obesity which can be progressive and life-limiting. The purpose of this case report is to describe the clinical timeline and treatment of severe obesity in a patient with of ROHHAD-NET and propose recommendations for the treatment of associated obesity. CASE PRESENTATION: We present the case of a 10-year-old female with a clinical presentation consistent with ROHHAD-NET who achieved clinically meaningful weight loss with a combination of lifestyle modification and anti-obesity pharmacotherapies. We report on the use of three separate pharmacological agents and ultimately the referral for bariatric surgery. CONCLUSIONS: Given that early-onset obesity and hypoventilation are life-limiting components of this condition, early recognition and treatment are essential to improve health outcomes.

COPD sleep phenotypes: Genesis of respiratory failure in COPD.

The chronic obstructive pulmonary disease (COPD) patients could have respiratory failure during sleep without daytime overt arterial blood gas (ABG) abnormality. We undertook a study first of its kind to attempt in distinguishing the underlying pathophysiological mechanisms.  It was a prospective observational study in stable COPD patients. The inclusion criterion was presence of day time PaO2>60 mmHg and PaCO2<45 mmHg. Twenty five out of 110 patients were excluded because of the ABG abnormality. The remaining 85 patients were subjected to overnight pulse oximetry and end-tidal (ET)-CO2 monitoring. The nocturnal oxygen desaturation was defined as per Fletcher's criteria. The nocturnal hypoventilation was defined as per American academy of sleep medicine (AASM) guidelines. Patients having saw-tooth pattern on pulse oximetry and/or snoring were subjected to polysomnography. 38/85(44.8%) patients had nocturnal gas exchange abnormality in absence of daytime respiratory failure and were identified into 3 different phenotypes: obstructive sleep apnoea (OSA), nocturnal hypoventilation and nocturnal oxygen desaturation. The isolated abnormality was seen in 24 patients: 10 patients had OSA, 9 had nocturnal hypoventilation and 5 had nocturnal oxygen desaturation. Overlap of two or more phenotypes was seen in 14 patients. As compared to the nocturnal hypoventilation and desaturation phenotypes, the OSA phenotype had a significantly higher BMI & FEV1. The nocturnal hypoventilation and the desaturation phenotypes did not have significant difference in FEV1 and BMI, but the daytime SpO2 and PaO2 differed significantly.  Such parameters could help in identifying the three distinct COPD-sleep phenotypes (OSA, nocturnal hypoventilation and nocturnal oxygen desaturation). A phenotype based nocturnal management may help in delaying the process of overt respiratory failure in COPD.