Nocturnal Bilevel Positive Airway Pressure Research Articles

0994 Neuroblastoma as the Initial Manifestation of Familial PHOX2B NPARM Positive Congenital Central Hypoventilation Syndrome

Abstract Introduction Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disorder of the autonomic nervous system caused by mutations in the PHOX2B gene. Children with CCHS often present as neonates in hypoxemic, hypercarbic respiratory failure. Most causative mutations are de novo Polyalanine Repeat Mutations (PARMs). Non-Polyalanine Repeat Mutations (NPARMs) have been associated with more severe disease, specifically the need for 24-hour ventilatory support, Hirschsprung disease, and neural crest tumors; however, NPARMs may have variable expressivity and incomplete penetrance, resulting in delayed or atypical presentations. We report a toddler with maxillary sinus neuroblastoma, which led to the diagnosis of familial PHOX2B NPARM positive CCHS. Report of case(s) A two-year-old boy presented with right-sided facial swelling. A facial CT uncovered a right maxillary sinus lytic lesion, and biopsy confirmed neuroblastoma. After full recovery from the procedure, he had persistent nocturnal hypoxemia and hypercapnia requiring bilevel positive airway pressure (PAP) during sleep, raising concern for CCHS. Genetic testing revealed a novel PHOX2B NPARM, c.428dup, which likely causes a frameshift and premature protein termination (p.Val144Glyfs*34). His maternal grandfather, mother and brothers tested positive for the same mutation. Family history revealed that his maternal grandfather and maternal great-uncles had frequent childhood apneic spells associated with syncope, his maternal grandfather is currently on nocturnal bilevel PAP, and his mother almost drowned as a younger child while having a breath-holding contest under water. His six-year-old brother underwent polysomnography which showed hypoventilation, now managed with bilevel PAP. His five-year-old brother also underwent polysomnography and does not require nocturnal ventilatory support at this time. Conclusion We report a rare case of familial PHOX2B NPARM positive CCHS which initially presented as maxillary sinus neuroblastoma. Additionally, the child and his family display varying disease severity despite having the same NPARM, highlighting the variable expressivity in this novel NPARM. Support (if any) None

Pulmonary Hypertension and Diastolic Heart Failure in an Adolescent African-American Cantú Syndrome Patient

<h3>Introduction</h3> Cantú syndrome is a rare congenital condition characterized by hypertrichosis, coarse facial features, cardiomegaly, skeletal abnormalities, and tortuous vasculature. While progress has been made in the understanding of the molecular basis of this disease, there is still much to be uncovered regarding its natural history. Here, we present the clinical course of an African-American male with Cantú syndrome. <h3>Case Report</h3> A 4-month-old African-American male presented to the hospital with respiratory distress. A large pericardial effusion was identified, which required a pericardial window. Cardiac catheterization revealed pulmonary hypertension. At age 4, a diagnosis of Cantú syndrome was made on the basis of developmental delay, cardiomegaly, history of pericardial effusion, pulmonary hypertension, coarse facial features, hypertrichosis, wide/thickened ribs, and osteopenia. He developed chronic diastolic heart failure secondary to cardiomegaly and chronic hypercarbic respiratory failure requiring home oxygen and nocturnal bi-level positive airway pressure (BiPAP) therapy. Pulmonary hypertension treatment was initiated with sildenafil at age 13, resulting in significant improvement in exercise tolerance. Cardiac catheterization at 17 years of age demonstrated worsening pulmonary hypertension with baseline RV pressures of 85/18 mmHg and pulmonary artery (PA) pressures of 85/40 mmHg. Baseline pulmonary vascular resistance (PVR) was 15.7 Woods Units/m2. Vasoreactivity to O2 and inhaled nitric oxide was demonstrated with PVR decreasing to 6.6 and 5.5 Woods Units/m2 respectively. Carvedilol and cardiac rehabilitation therapy were initiated at age 19. On a recent admission, he required milrinone support due to worsening right ventricular (RV) dysfunction which was weaned prior to discharge. <h3>Summary</h3> Cantú syndrome is a rare genetic condition and its prevalence and prognosis are still unknown. Interestingly, nearly all patients in the International Cantú Syndrome Registry are Caucasian while our patient is African-American. Additionally, with no family history of the disease, it is possible that his case represents a sporadic mutation. Unfortunately, our patient exhibited progressive heart failure, pulmonary hypertension, and hypercarbic respiratory failure during his adolescent years.

Macroglossia: A potentially severe complication of late-onset Pompe disease.

Pompe disease is a rare neuromuscular disorder caused by a deficiency of a lysosomal enzyme, acid α-glucosidase. Macroglossia is a classic clinical sign of several inherited myopathies and has also been reported to occur progressively in late-onset Pompe disease (LOPD). We describe patients with LOPD and macroglossia included in the French national Pompe disease registry. Clinical, functional, and radiological data were collected during periodic follow-up and analyzed retrospectively. These cases were compared with 15 previously reported cases. Five patients, three females and twomales, aged 71-88years, were included in this study. All but one of the patients suffered from symptoms related to macroglossia before the diagnosis of Pompe disease. Three had localized tongue atrophy and one had significant localized tongue hypertrophy which led to glossectomy 10years before diagnosis. Two patients had severe dysphagia, one of whom underwent gastrostomy for enteral nutritional support. One patient experienced the persistence of numerous sleep apneas despite nocturnal bilevel positive airway pressure (BiPAP) ventilation. All our patients had dysarthria, and two required speech therapy. Four patients had a tongue hypersignal on magnetic resonance imaging (MRI) T1sequences. Detection of macroglossia should be part of the clinical diagnosis and follow-up of patients with LOPD, with a careful evaluation of its main consequences. Macroglossia can have severe functional impacts on speech, swallowing, and sleep. Whole-body MRI with facial sections may facilitate the early diagnosis of Pompe disease with the "bright tongue sign".

Is bilevel PAP more effective than CPAP in treating hypercapnic obese patients with COPD and severe OSA?

Commentary on Zheng Y, Yee BJ, Wong K, Grunstein R, Piper A. A pilot randomized trial comparing CPAP versus bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease. J Clin Sleep Med. 20XX;XX(XX):XXX-XXX. doi:10.5664/jcsm.9506.

Central Sleep Apnea Syndrome Can Complicate Neuromyelitis Optica Spectrum Disorder: A Case Report

Neuromyelitis optica spectrum disorder is a rare, relapsing autoimmune disease of the central nervous system. Various initial presentations can delay diagnosis and treatment. A 14-year-old girl was admitted to the emergency department owing to respiratory insufficiency. Repeated history-taking and neuroimaging revealed an area postrema syndrome. A diagnosis of neuromyelitis optica spectrum disorder with positive aquaporin-4 antibodies has finally been established. The patient improved significantly with immunosuppressive therapy. However, her 3-year follow-up still showed sleep-disordered breathing requiring nocturnal bilevel positive airway pressure therapy. We report an original case of NMOSD leading to persistent central sleep apnea syndrome.

Nocturnal bilevel positive airway pressure for the treatment of asthma

Nocturnal worsening of asthma may be due to reduced lung volumes and fewer sigh breaths, which have been shown to increase airway resistance and bronchoreactivity. We hypothesized that mimicking deep inspiration using nocturnal mechanical support would improve symptoms in patients with asthma.Subjects with asthma underwent usual care and bilevel positive airway pressure (PAP) therapy for 4 weeks, separated by 4 weeks, and methacholine challenge (PC20) and subjective assessments.13 patients with asthma alone and 8 with asthma + OSA completed the protocol. Change in bronchoreactivity (ratio of Post/Pre PC20) was not significantly different during usual care and bilevel PAP [0.86 (IQR 0.19, 1.82) vs 0.94 (IQR 0.56, 2.5), p = 0.88], nor was the change in Asthma Control Test different: 0.1 ± 2.2 vs. –0.2 ± 2.9, p = 0.79, respectively.Bilevel PAP therapy for four weeks did not improve subjective or objective measures of asthma severity in patients with asthma or those with asthma and OSA, although there was heterogeneity in response.

Study of the value of percutaneous nocturnal oximetry in the monitoring of obese hypoventilation syndrome patients under non invasive home ventilation

BackgroundNocturnal noninvasive ventilation (NIV) is often a treatment option for obesity hypoventilation syndrome (OHS). Monitoring this treatment is important to verify its efficacy.AimThe aim of the present study was to assess the role of overnight pulse oximetry in the monitoring of OHS patients under NIV.Patients and methodsTwenty patients with OHS using nocturnal bilevel positive airway pressure therapy without supplemental oxygen were included in the present study. Overnight pulse oximetry study was performed, and according to the results, the patients were divided into two groups: group I (normal study) and group II [abnormal study showing nocturnal percutaneous oxygen saturation (SpO2) <90% in ≥10% of the total recorded time]. Group II patients were subjected to respiratory polygraphy for more detailed assessment, and then, appropriate therapeutic modifications were done, after which a second overnight pulse oximetry study was performed to verify the efficacy of ventilation after these modifications.ResultsTwenty OHS patients using nocturnal NIV were included in the present study. There were eight (40%) male patients and 12 (60%) female patients, with a mean age of 58.7±7.39 years. The mean BMI was 45.86±3.71 kg/m2. Group I consisted of 11 (55%) patients and group II had nine (45%) patients. Respiratory polygraphy performed to group II detected airway obstruction in two patients, insufficient ventilation in five patients and significant nonintentional leaks in two patients. Therapeutic modifications were done, and then a second overnight pulse oximetry performed showing normal results in seven patients, whereas two patients showed lesser desaturations but results were still abnormal.ConclusionOvernight pulse oximetry is a very useful tool in assessment of NIV efficacy in OHS patients, it is portable, simple, and it can detect oxygen desaturations that direct to perform further tests to apply appropriate therapeutic modifications to optimize NIV.

Prevalence and phenotypes of congenital myopathy due to α-actin 1 gene mutations.

Congenital myopathy due to mutations in the α-actin 1 gene (ACTA1) was identified in 1999, but knowledge of prevalence and phenotype in patients who survive 5 years is lacking. A national cohort of 91 patients aged ≥5 years and diagnosed with congenital myopathy was assessed for ACTA1 mutations and investigated clinically. Four patients with ACTA1 mutations were identified, yielding a prevalence of 4.4%. Patients were 10-23 years of age, and all but 1 were ambulatory. Vital capacity ranged from 47% to 70% predicted, and 1 patient needed nocturnal bi-level positive airway pressure. Limb flexor/extensor muscles and upper and lower extremities were affected equally. Pronounced neck flexor weakness was noted. Congenital myopathy caused by ACTA1 mutations is fatal in infancy in most cases. This study shows that the prevalence of α-actin myopathy in older patients with congenital myopathy is not negligible and that phenotypes can be quite mild.

Upper Airway Obstruction during Noninvasive Ventilation Induced by the Use of an Oronasal Mask

In patients with neuromuscular disorders, no randomized studies have been performed whether nasal or oronasal masks should be preferred. Oronasal masks are often used in acute respiratory failure, while nasal masks are preferred in patients with chronic respiratory failure. However, the use of nasal masks can result in mouth leaks with implications on sleep quality. To reduce these leaks, oronasal masks have been applied during home noninvasive ventilation (NIV). Until now, upper airway obstruction during NIV has been thought to be induced by nasal obstruction, pharyngeal collapse, and/or glottis closure. We report a case indicating another cause of upper airway obstruction: use of an oronasal mask can induce obstructive events in the upper airways, possibly resulting in sleep fragmentation and decreased efficiency of NIV.

Radiofrequency Ablation in the Lung Complicated by Positive Airway Pressure Ventilation

A patient receiving bilevel positive airway pressure therapy underwent radiofrequency ablation of a pulmonary metastasis from a primary malignant fibrous histiocytoma of the scapula. The patient's postablation course was complicated by a bronchopleural fistula, which was exacerbated by the detrimental effects of positive airway pressure on necrotic lung tissue after the ablation. The use of positive airway pressure devices, including bilevel positive airway pressure and continuous positive airway pressure, in patients undergoing radiofrequency ablation of the lung should be considered as an added risk for developing bronchopleural fistula.

Use of bilevel positive airway pressure (BIPAP) in end-stage patients with cystic fibrosis awaiting lung transplantation.

Nine consecutive end-stage patients with cystic fibrosis (CF) awaiting lung transplantation were admitted to the pediatric intensive care unit (PICU) in respiratory decompensation. They all received noninvasive bilevel positive airway pressure (BIPAP) support and were evaluated to determine whether or not it improved their oxygenation and provided them with long-term respiratory stability. BIPAP was applied to all patients after a brief period of assessment of their respiratory status. Inspiratory and expiratory positive airway pressures (IPAP, EPAP) were initially set at 8 and 4 cm H2O respectively. IPAP was increased by increments of 2 cm H2O and EPAP was increased by 1 cm H2O increments until respiratory comfort was achieved and substantiated by noninvasive monitoring. Patients were observed in the PICU for 48 to 72 hours and then discharged to home with instructions to apply BIPAP during night sleep and whenever subjectively required. Regular follow-up visits were scheduled through the hospital-based CF clinic. The patients' final IPAP and EPAP settings ranged from 14 to 18 cm H2O and 4 to 8 cm H2O, respectively. All nine patients showed a marked improvement in their respiratory status with nocturnal use of BIPAP at the time of discharge from the PICU. Their oxygen requirement dropped from a mean of 4.6 +/- 1.1 L/min to 2.3 +/- 1.5 L/min (P < 0.05). Their mean respiratory rate decreased from 34 +/- 4 to 28 +/- 5 breaths per minute (P < 0.05). The oxygen saturation of hemoglobin measured by pulse oximetry, significantly increased from a mean of 80% +/- 15% to 91% +/- 5% (P < 0.05). The patients have been followed up for a period of 2 to 43 months and have all tolerated the use of home nocturnal BIPAP without any reported discomfort. Six patients underwent successful lung transplantation after having utilized nocturnal BIPAP for 2, 6, 14, 15, 26, and 43 months, respectively. Three patients have utilized home BIPAP support for 2, 3, and 19 months, respectively, and continue to await lung transplantation. An acute development of refractory respiratory failure resulted in the demise of the remaining three patients after having utilized BIPAP for 3, 6, and 10 months, respectively. The authors conclude that BIPAP therapy improves the respiratory status of decompensating end-stage CF patients. It is well tolerated for long-term home use and provides an extended period of respiratory comfort and stability for CF patients awaiting lung transplantation.

Bi-level positive airway pressure (BiPAP) ventilation in an infant with central hypoventilation syndrome

A 4-month-old baby girl, after a period of apparent good health, began to have aphonia, dyspnea, difficulties with swallowing, cyanosis, apnea, and hypopnea during sleep that resulted in admission to an intensive care unit for intubation and mechanical ventilation. At the age of 9 months she was admitted to our hospital with a possible diagnosis of central hypoventilation syndrome. A polysomnographic study showed apnea and hypopnea (apnea + hypopnea index = 47.1), hypercapnia (mean end-tidal PCO2 89 +/- 15.0 mmHg), and arterial desaturation (mean SaO2 91 +/- 1.7%; lowest SaO2 < 50%; 68% of total sleep time at SaO2 below 93%); the study also showed an absent ventilatory response to CO2, absent cardiac responses to apnea during sleep, and right ventricular hypertrophy. Nocturnal nasal bi-level positive airway pressure (BIPAP), applied initially at 6 cmH2O and gradually increased to 16 cmH2O, caused the sleep-related abnormal respiratory events to disappear. End-tidal PCO2 decreased to 39 mmHg, and SaO2 increased to 94%. After 6 months of nocturnal BiPAP ventricular right hypertrophy reversed and arrested growth and hypotonia normalized. The child has tolerated and has remained on BiPAP support up to her current age of 3 years and continues to use this form of ventilatory assistance without difficulties.

Bi‐level positive airway pressure (BiPAP) ventilation in an infant with central hypoventilation syndrome

A 4-month-old baby girl, after a period of apparent good health, began to have aphonia, dyspnea, difficulties with swallowing, cyanosis, apnea, and hypopnea during sleep that resulted in admission to an intensive care unit for intubation and mechanical ventilation. At the age of 9 months she was admitted to our hospital with a possible diagnosis of central hypoventilation syndrome. A polysomnographic study showed apnea and hypopnea (apnea + hypopnea index = 47.1), hypercapnia (mean end-tidal P 89 ± 15.0 mmHg), and arterial desaturation (mean Sa 91 ± 1.7%; lowest Sa < 50%; 68% of total sleep time at Sa below 93%); the study also showed an absent ventilatory response to CO2, absent cardiac responses to apnea during sleep, and right ventricular hypertrophy. Nocturnal nasal bi-level positive airway pressure (BiPAP), applied initially at 6 cmH2O and gradually increased to 16 cmH2O, caused the sleep-related abnormal respiratory events to disappear. End-tidal Pco2 decreased to 39 mmHg, and Sao2 increased to 94%. After 6 months of nocturnal BiPAP ventricular right hypertrophy reversed and arrested growth and hypotonia normalized. The child has tolerated and has remained on BiPAP support up to her current age of 3 years and continues to use this form of ventilatory assistance without difficulties. Pediatr. Pulmonol. 1997;24:66–69. © 1997 Wiley-Liss, Inc.

Nocturnal ventilatory assistance with bi-level positive airway pressure

Administration of bi-level positive airway pressure (BIPAP) via nasal mask can provide substantial benefit to patients with obstructive sleep apnea (OSA) and nocturnal alveolar hypoventilation. This modality maintains upper airway patency as well as assists patients in maintaining adequate ventilation during sleep without mandating oral/nasal tracheal intubation or tracheostomy. In OSA patients, BIPAP allows greater flexibility than conventional nasal continuous positive airway pressure (CPAP) by permitting independent adjustment of inspiratory and expiratory positive airway pressure (IPAP and EPAP, respectively). Therapy may therefore be achieved with lower expiratory pressure, improved patient comfort, and reduced mechanical impedance to ventilation with less potential for hypoventilation. Additionally, BIPAP allows patients to determine their own tidal volume, respiratory rate, and inspiratory flow. A back-up mode is also available in which the IPAP is delivered if the patient does not spontaneously initiate a breath within a prescribed interval. In this article we describe two representative OSA patients who underwent therapeutic trials of both nasal CPAP and BIPAP. In both patients, effective treatment was achieved at lower expiratory pressure and with greater comfort using BIPAP compared with CPAP. We also describe the effect of nocturnal BIPAP on a representative patient with ventilatory muscle weakness and chronic ventilatory failure. During sleep on BIPAP, there was improved alveolar ventilation and ventilatory muscle rest. On long-term home therapy with nocturnal BIPAP, there was a significant improvement in daytime alertness and performance of daily activities. We conclude that bi-level positive airway pressure therapy is a useful addition to the therapeutic armamentarium for patients with OSA as well as patients with compromised ventilatory muscle function and hypercapnia.