Background and Objective: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypotonia and failure to thrive in infancy, followed by hyperphagia and obesity later in life. Phenotypic features include obesity, shot stature, small hands and feet, almond-shaped eyes, and narrow bifrontal diameter. There is multisystem involvement with cognitive, behavioral, and endocrine abnormalities including growth hormone deficiency (GHD), hypogonadism, and obesity from hyperphagia, with its attendant complications of type 2 diabetes mellitus and metabolic syndrome. Additionally, PWS is associated with respiratory system abnormalities due to generalized hypotonia, obesity, and scoliosis that affect the mechanics of respiration, as well as impaired ventilatory and arousal responses to hypercapnia and hypoxia. Respiratory failure is the leading cause of mortality in individuals with PWS, making early diagnosis and the treatment of respiratory problems crucial for their survival. This review summarizes and updates the current knowledge about the mechanisms and screening recommendations for respiratory system abnormalities associated with PWS. Methods: The only English-language literature search was conducted via PubMed, MeSH, and Google Scholar with keywords that included “Prader-Willi syndrome” and “respiratory” between 1976 and 2021. Additional papers were found via references from articles related to the original search. Key Content and Findings: A total of 2,111 review articles were identified with keyword “PWS”. When we added keywords “respiratory” or “respiratory failure” to PWS, 171 articles were detected. Of those, 74 articles were selected for inclusion based on their relevance to the objectives of this article. Conclusions: Respiratory system abnormalities in PWS include abnormalities in respiratory control, dysphagia and silent aspiration, abnormal chest wall and pulmonary mechanics, and sleep-disordered breathing. Consideration of the respiratory problems that occur in PWS and the effect of growth hormone treatment (GHT) on these problems contributes significantly to improving prognosis of these individuals. Reports of unexpected mortality with GHT in a subset of PWS patients have raised concerns over safety, though a causal relationship between growth hormone (GH) and sudden death has not been demonstrated. The recommendations are to perform a sleep study, and treat any obstructive sleep apnea (OSA) or respiratory-compromising obesity, prior to initiation of GH.

Prader-Willi syndrome (PWS) is a rare and complex genomic imprinting disorder caused by an absence of expression of paternal genes from chromosome 15q11.2-q13. Clinical manifestations of PWS depends on age. In early infancy, PWS patients is characterized by hypotonia and failure to thrive. Later in life, they can also exhibit hyperphagia, obesity, short stature, hypogonadism, behavioral issues and cognitive disability. Multiple sleep abnormalities including obstructive and/or central sleep apnea, daytime hypersomnolence, and impaired responses to hypercapnia and hypoxia have been described in patients with PWS. Recent studies also demonstrated an increased risk of seizures in PWS patients. Electrical status epilepticus in sleep (ESES) is an age-limited epilepsy with various seizure types, neurophysiological and motor impairment. The classic electroencephalogram (EEG) pattern of ESES involves continuous epileptic activity at 2-3 Hz occupying greater than 85% of non-rapid eye movement (REM) sleep. Treatment of the ESES syndrome consists of anti-epileptic drugs in routine cases, and corticosteroids, gamma globulins, the ketogenic diet, and surgery in refractory cases. In this project, we describe ESES during polysomnography in a 5-year-old female with PWS and no history of seizure disorder. To the best of our knowledge, this is the first case report on ESES in a PWS patient.

Purpose:To describe the socio-demographics and clinical characteristics of children in a pulmonology clinic or admitted to a children's hospital with well-controlled and poorly controlled asthma, and to assess caregiver knowledge of asthma pathogenesis, treatment, and self-management.Patients and Methods:A cohort of 132 children aged 2-18 years and their caregivers seen in a pediatric pulmonology clinic with a diagnosis of asthma (n=112) or admitted to the hospital with a diagnosis of asthma exacerbation (n=20) were invited to participate in a cross-sectional study. Caregivers completed a survey, which healthcare providers then used to tailor asthma education to the patient and caregiver. Two-tail t-tests and Chi-square tests were used to compare demographics and clinical characteristics of children with well-controlled vs poorly controlled asthma.Results:Of 132 children, 111 children in this cohort had poorly controlled asthma (84%). Medicaid insurance was associated with poorly controlled asthma versus well-controlled asthma (63% vs 35% p=0.01). Asthma action plans (AAP) had previously been given to 113 caregivers (86%), but caregivers of children with both well-controlled and poorly controlled asthma still reported misconceptions about asthma pathology and management, such as stopping daily medications when asthma is controlled.Conclusion:This study contributes to the existing evidence that socio-demographics have a significant impact on asthma prevalence and proper management. Our study suggests that caregivers of children with asthma need comprehensive asthma education beyond the AAP focusing on asthma-related misconceptions.

None:Catathrenia, also known as sleep-related groaning, is a relatively rare sleep disorder with characteristics consistent with loud groaning on expiration during sleep. Organic causes of catathrenia are unknown and the decision of whether or not to treat is unclear. Limited research is available concerning appropriate treatment and none of the literature focuses primarily on pediatrics. We report a series of three, male pediatric cases with catathrenia that were treated with continuous positive airway pressure (CPAP) while identifying and comparing clinical symptoms, polysomnogram findings, treatment, and patient response to treatment. Catathrenia may be associated with abnormal nocturnal oxygenation and ventilation and may lead to negative clinical daytime symptoms which may warrant treatment. If catathrenia leads to sleep disruption and negative daytime symptoms, treatment with CPAP should be considered.

Background: Pulmonary exacerbations (PExs) are common in individuals with cystic fibrosis (CF). Data regarding outcomes of outpatient parenteral antimicrobial therapy (OPAT) in children are sparse. Methods: Retrospective data of PEx episodes treated in the hospital versus OPAT collected. Children <= 18 years were included. Outcome measures included FEV1, FVC, FEF25-75%P, time to the next PEx, and weight gain. Results: Eighty-three subjects with 290 PEx events were eligible. The hospital group had 242 and the OPAT group had 48 PEx events. The median age was 13.1 years for the OPAT and 13.4 years for the hospital group. Medicaid coverage was higher in the hospital group (82.2%) versus OPAT group (48.9%, P < 0.0001). The hospital group had lower FEV1%P on admission [72%P (interquartile range [IQR] = 59.7 and 84) versus 80%P (IQR = 70.7 and 89); P = 0.001] and at the end of treatment [86%P (IQR = 72 and 96.7) versus 92%P (IQR = 82 and 101); P = 0.003] in comparison with OPAT group. FEV1%P improved more in the hospital group, [12%P (IQR = 4 and 20)] versus in the OPAT group [8%P (IQR = 2 and 22.5); (P = 0.41)] but did not quite reach a statistically significant level. The hospital intravenous (IV) group gained more weight (P < 0.0001). There was no difference between the 2 groups in time to the first PEx (P = 0.47) and adverse events. Conclusion: OPAT was safe and comparable with hospital therapy in a select group of children with CF. Hospital IV should be considered for sicker children and families with limited resources.

Objective: Obese youth are more likely to report difficulties with sleep, depression, and quality of life (QOL). This study aims to characterize sleep problems, QOL, and symptoms of depression by degree of obesity. Method: The cross-sectional study was conducted in a specialized obesity clinic. Obese youth and their caregivers (N = 150) were evaluated with the Child Sleep Habits Questionnaire and Pediatric Quality of Life. Youth completed the Children's Depression Inventory. Regression models and correlations were calculated. Results: Degree of obesity was predictive of increased sleep difficulties and decreased QOL scores. Children's Depression Inventory scores showed that children with more symptoms of depression had more sleep problems, and these were not associated with the degree of obesity. Adolescents with more difficulties sleeping also reported more symptoms of depression and lower QOL. Conclusions: Degree of obesity negatively affected QOL and sleep variables. Patients with greater sleeping difficulties reported more symptoms of depression.

Introduction In 2015, 11.9% of people with cystic fibrosis (CF) in the United States had osteopenia, 5.1% osteoporosis, and 0.3% experienced a fracture. Screening for CF-related bone disease starts in childhood, and dual energy x-ray absorptiometry (DXA) is the recommended method. It is unknown whether peripheral quantitative computed tomography (pQCT) can detect deficits earlier than DXA. This study compared pQCT and DXA scans in a group of pre-pubertal children with CF and healthy controls. Methods This was a cross-sectional study of children at Tanner stage 1. A pQCT scan of the radius at proximal and distal sites was performed plus a total body DXA scan. Serum C-reactive protein, interleukin-6 and tumor necrosis factor-alpha were also measured. Results A total of 34 subjects completed the study; 14 with CF and 20 controls. At the distal radius, pQCT showed a lower total bone mineral density (BMD) Z-score for the CF group (P = 0.01 and P = 0.03 for 2 different reference databases) compared to controls. At the proximal site, the polar strength-strain index was lower in the CF group (P = 0.017). Finally, the total body BMD Z-score by DXA was lower in the CF group, although it did not meet the definition of reduced bone density (P = 0.004). Biomarkers of inflammation were not different. Conclusions In this group of pre-pubertal children with CF, measures of bone strength and density by both pQCT and DXA were reduced compared to healthy controls.

Cutaneovisceral angiomatosis with thrombocytopenia (CAT), also called multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT), is a rare and newly described vascular malformation. Skin manifestations and thrombocytopenia are the hallmark of CAT/MLT, and visceral lesions are described. We report an infant with pulmonary hemorrhage, thrombocytopenia, and antiplatelet antibodies. There was no cutaneous involvement and the child was initially diagnosed with immune thrombocytopenia. Poor response to immune thrombocytopenia-directed therapy raised suspicion for an alternative diagnosis, and the ultimate diagnosis of CAT/MLT was made by lung tissue sampling. Unexpectedly, 2 years after resolution of pulmonary lesions and thrombocytopenia, the child developed typical cutaneous lesions.

Recent advances in medicine have allowed children with chronic life‐threatening disorders to survive longer than ever before with the use of complex medical device technology (e.g., mechanical ventilation, dialysis, etc.). The care of children with chronic pulmonary disorders and respiratory‐technology dependence is often complex, involving a high level of ongoing interaction between caregivers and the health care team. Unmanaged, non‐standardized transition of respiratory technology dependent (RTD) patients to adult care potentially increases the risk of adverse outcomes. Pediatric Pulmonary programs at US children's hospitals were surveyed to ascertain whether a standardized process is utilized for transitioning RTD patients from pediatric to adult subspecialty pulmonology care.

BACKGROUND:We describe the clinical characteristics and epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in children with cystic fibrosis (CF) from the U.S. CF center with the highest MRSA prevalence.METHODS:Medical records of children with CF were retrospectively reviewed from 1997-2009. MRSA clinical isolates from 2007-2009 were analyzed by polymerase chain reaction and pulsed field gel electrophoresis.RESULTS:The prevalence of MRSA was 1% in 1997 and 49% in 2009. Fifty-five children (26%) had persistent MRSA infection. Sixty-eight percent of MRSA isolates were hospital-associated (HA) MRSA, of which 52% were pulsed-field type USA 100. Ninety-three percent of HA MRSA isolates were clindamycin resistant. Twelve children acquired MRSA before 1 year of age, 83% of whom were hospitalized prior to acquisition of MRSA. Ten of 11 sibling pairs carried indistinguishable MRSA strains. Children with persistent MRSA were hospitalized more often (P = .01), required inhaled medications more frequently (P = .01), and had higher rates of Pseudomonas aeruginosa coinfection (P < .001).CONCLUSION:MRSA prevalence in children with CF is increasing, and most children are infected with HA MRSA. Exposure to health care facilities and gastrointestinal surgeries may facilitate early acquisition of MRSA. Siblings carry indistinguishable MRSA strains, indicating household transmission of MRSA. Children with persistent MRSA had worse pulmonary morbidity. Coinfection with MRSA and P aeruginosa is likely associated with further increased pulmonary morbidity.

STUDY OBJECTIVES:To describe characteristics and surgical and clinical outcomes of obese children with obstructive sleep apnea (OSA). METHODS:At our institution from 2000 to 2010, 143 obese children with an overnight polysomnography (OPSG) diagnosis of OSA, excluding children with comorbidities, were identified. Relationships between demographics, clinical findings, and the severity of OSA were assessed. Presurgery and postsurgery OPSG indices were compared. We defined cure as an apneahypopnea index (AHI) < 1.5/h on the postsurgery OPSG, and we compared the cure rates of different surgeries. RESULTS:A total of 143 children, median age 12.4 y (interquartile range [IQR] 9.6-14.9) and BMI z-scores 2.8 (IQR 2.6-2.9), were included. Seventy-eight (55%) (Median age 12 y [IQR 9-15]) underwent surgery: 1 had tonsillectomy; 1 tonsillectomy + uvulopharyngopalatoplasty (UPPP); 23 adenotonsillectomy (AT); 27 AT + UPPP; 11 adenoidectomy + UPPP; 8 UPPP; and 7 AT + turbinate trim ± tongue base suspension. Overall, surgery cured 19 children (26%), but AHI improved in the majority of children (p = 0.001). Similarly, the arousal index, PETCO2, and SpO2 nadir improved significantly (p < 0.002, p = 0.019, p < 0.001, respectively). AHI improved significantly in children with mild-to-moderate OSA in comparison to severe OSA (p < 0.001). Children with enlarged tonsils and no history of prior surgery benefitted more often from surgery (p < 0.004 and p = 0.002, respectively). AT was the only surgery reducing the AHI significantly (p = 0.008). Children did not lose weight despite intervention. Adherence with PAP was poor. CONCLUSIONS:Surgery improved OPSG indices in the majority of obese children with OSA.

Duke University Gulnur Com, Pediatric Pulmonologist, Department of Pediatrics, Pediatric Pulmonology, University of Arkansas Medical Sciences, Little Rock, AR. Aliye Uc, Pediatric Gastroenterologist, Department of Pediatrics, University of Iowa, Iowa City, IA.

Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic and hypnopompic hallucinations, and abnormal sleep–wake patterns. Cataplexy is described as sudden and transient loss of muscle tone, often triggered by intense emotion or excitement. Hallucinations and sleep paralysis occur during sleep–wakefulness transitions and are associated with rapid eye movement (REM) sleep. Although presence of all characteristics of narcolepsy is common in adult patients, the initial presentation of narcolepsy in children maybe subtle, and concomitant cataplexy, sleep paralysis, and hallucinations may not always present. In addition, symptoms may be difficult to recognize leading to delay in the diagnosis. We present the case history of a child with narcolepsy and cataplexy who was challenging to diagnose in the primary care setting. Our patient’s presentation points out the difficulty in arriving at the diagnosis of narcolepsy with cataplexy due to the clinical picture that can resemble other conditions. In this article, we review the clinical presentation of narcolepsy with or without cataplexy in childhood and discuss the disease pathogenesis, diagnostic tools, and treatment.

Background & aims: Adequate protein intake and digestion are necessary to prevent muscle wasting in cystic fibrosis (CF). Accurate and easy-to-use methodology to quantify protein maldigestion is lacking in CF.Objective: To measure protein digestibility and the response to pancreatic enzyme intake in CF by using a new stable isotope methodology.Design: In 19 CF and 8 healthy subjects, protein digestibility was quantified during continuous (sip) feeding for 6 h by adding N-15-labeled spirulina protein and L-[ring-H-2(5)]phenylalanine (PHE) to the nutrition and measuring plasma ratio [N-15]PHE to [H-2(5)]PHE. Pancreatic enzymes were ingested after 2 h in CF and the response in protein digestibility was assessed. To exclude difference in mucosal function, postabsorptive whole-body citrulline (CIT) production rate was measured by L-[5-C-13-5,5-H-2(2)]-CIT pulse and blood samples were taken to analyze tracer-tracee ratios.Results: Protein digestibility was severely reduced in the CF group (47% of healthy subjects; P < 0.001). Intake of pancreatic enzymes induced a slow increase in protein digestibility in CF until 90% of values obtained by healthy subjects. Maximal digestibility was reached at 100 min and maintained for 80 min. Stratification into CF children (n = 10) and adults showed comparable values for protein digestibility and similar kinetic responses to pancreatic enzyme intake. Whole-body citrulline production was elevated in CF indicating preserved mucosal function.Conclusion: Protein digestibility is severely compromised in patients with CF as measured by this novel and easy-to-use stable isotope approach. Pancreatic enzymes are able to normalize protein digestibility in CF, albeit with a severe delay. (C) 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.