Sleep Disordered Breathing in Children with Neuromuscular Disease.

Sleep disordered breathing (SDB) in children with neuromuscular disease (NMD) is more prevalent compared to the general population, and often manifests as sleep-related hypoventilation, sleep-related hypoxemia, obstructive sleep apnea, central sleep apnea, and/or disordered control of breathing. Other sleep problems include, sleep fragmentation, abnormal sleep architecture, and nocturnal seizures in certain neuromuscular diseases. The manifestation of sleep disordered breathing in children depends on the extent, type, and progression of neuromuscular weakness, and in some instances, may be the first sign of a neuromuscular weakness leading to diagnosis of an NMD. In-lab diagnostic polysomnography (PSG) remains the gold standard for the diagnosis of sleep disordered breathing in children, but poses several challenges, including access to many children with neuromuscular disease who are non-ambulatory. If SDB is untreated, it can result in significant morbidity and mortality. Hence, we aimed to perform a comprehensive review of the literature of SDB in children with NMD. This review includes pathophysiological changes during sleep, clinical evaluation, diagnosis, challenges in interpreting PSG data using American Academy of Sleep (AASM) diagnostic criteria, management of SDB, and suggests areas for future research.

Utility of Mid-Upper Arm Circumference in Diagnosing Malnutrition in Children With Cystic Fibrosis.

BACKGROUND: Standardized diagnostic indicators for malnutrition using growth percentile z-scores (weight for length or body mass index [BMI]) and mid-upper arm circumference (MUAC) z-scores are being used in clinical practice; however, their application to the pediatric cystic fibrosis (CF) population is not well described. In this study, we aim to compare growth percentile z-scores and MUAC z-scores in diagnosing and classifying malnutrition in children with CF and assess the relationship between their degree of malnourishment and corresponding pulmonary function tests (PFTs). METHODS: In this retrospective observational outpatient study of 49 pediatric CF patients, data were collected on baseline characteristics, anthropometrics, and PFTs over 12 months. Agreement in malnutrition diagnoses was quantified by Cohen κ statistics. Pearson test assessed the correlation between MUAC and BMI z-scores as well as PFTs and anthropometrics. Serial anthropometrics and PFTs were obtained and compared for a subset of patients (n = 28). RESULTS: Growth percentile and MUAC z-scores were positively correlated in diagnosing malnutrition (Pearson correlation r = 0.87), but MUAC z-scores identified more patients as malnourished compared with growth percentile z-scores (49% vs 12%, Cohen κ of 0.22 [95% CI, 0.04-0.40]). There was no significant relationship between anthropometrics and PFTs. MUAC z-scores increased significantly over time, but BMI z-scores did not show this trend. CONCLUSIONS: Our small-scale data suggest a promising role for MUAC z-scores in classifying malnutrition and in measuring changes in nutrition status over time in pediatric CF.

Vaping in today's pandemic: E-cigarette, or vaping, product use-associated lung injury mimicking COVID-19 in teenagers presenting with respiratory distress.

The clinical presentation of children and adolescents infected with severe acute respiratory syndrome coronavirus 2 can range from asymptomatic to mild or moderate manifestations. We present a case series of three adolescents who presented during the coronavirus disease 2019 (COVID-19) pandemic with symptoms concerning for COVID-19, including fever, abdominal symptoms, cough, respiratory distress, and hypoxemia. Their laboratory results showed elevated inflammatory markers that are also commonly seen in COVID-19. The chest imaging studies mimicked COVID-19 with non-specific ground glass opacities and interstitial prominence patterns. However, severe acute respiratory syndrome coronavirus 2 testing was negative and further questioning of these adolescents and their parents revealed a history of vaping marijuana-related products leading to the eventual diagnosis of e-cigarette, or vaping, product use-associated lung injury. Our patients were successfully treated with corticosteroids. The providers caring for pediatric patients, especially adolescents, should continue to have a high index of suspicion for e-cigarette, or vaping, product use-associated lung injury in patients presenting with unexplained respiratory failure, while ruling out COVID-19.

Five-fold increase in pediatric parapneumonic empyema since introduction of pneumococcal conjugate vaccine.

A retrospective review of medical records for all pediatric parapneumonic empyema (PPE) patients admitted to our hospital from 1996 to 2006 revealed that PPE increased 5-fold in the post-heptavalent pneumococcal conjugate vaccine (PCV7) period (2001-2005) relative to the pre-PCV7 period (1996-2000), from 13 cases to 65. Most of this increase was associated with culture-negative empyema, which accounted for 61% of all post-2000 cases; 19% was culture-positive pneumococcal empyema. Our analysis indicates that non-PCV7 serotypes became more prevalent at our institution after introduction of the vaccine.

Longitudinal pulmonary function testing outcome measures in Duchenne muscular dystrophy: Long-term natural history with and without glucocorticoids.

We describe changes in pulmonary function measures across time in Duchenne muscular dystrophy patients treated with glucocorticoids (GCs) > 1 year compared to GC naïve patients in the Cooperative International Research Group Duchenne Natural History Study, a multicenter prospective cohort study. 397 participants underwent 2799 pulmonary function assessments over a period up to 10 years. Fifty-three GC naïve participants (< 1 month exposure) were compared to 322 subjects with > 1 year cumulative GC treatment. Forced vital capacity (FVC), peak expiratory flow rate (PEFr), maximal inspiratory and expiratory pressures were performed and calculated as a percent predicted (%p). GC treatment slowed the rate of pulmonary decline as measured by FVC%p, in patients aged 7-9.9 years. GC treatment slowed 12 and 24-month progression of percent predicted spirometry to a greater degree in those with baseline FVC%p from < 80-34%. GC treatment resulted in higher peak absolute FVC and PEFr values with later onset of decline. Progression to an absolute FVC < 1 liter was delayed by GC treatment. Patients who reached a FVC below 1 L were 4.1 times more likely to die (p = 0.017). Long-term glucocorticoid treatment slows pulmonary disease progression in Duchenne dystrophy throughout the lifespan.

The role of high-resolution chest CT in the diagnosis of neuroendocrine cell hyperplasia of infancy - A rare form of pediatric interstitial lung disease.

Interstitial lung disease (ILD) is rare in infancy or early childhood. Differentiating between the different types of ILD is important for reasons of treatment, monitoring of clinical course and prognosis. We present a case of a 5-month old female with tachypnea and hypoxemia. The clinical suspicion of neuroendocrine cell hyperplasia of infancy (NEHI) was confirmed by high-resolution chest CT and subsequent lung biopsy. We conclude that high-resolution chest CT has characteristics findings that can be used as a non-invasive test to support the clinical diagnosis of neuroendocrine cell hyperplasia of infancy.

Severe bronchiolitis in children.

Bronchiolitis is a common, acute, contagious lower respiratory tract illness of infants and young children. The majority of cases are secondary to respiratory syncytial virus. There are a number of risk factors for severe disease, including children less than six weeks of age and patients with atopy and/or asthma. The management requires vigilant monitoring and high-quality supportive care, including impressive use of fluids and nutritional support. Further research on anti-virals is essential to prevent respiratory syncytial virus induced bronchiolitis. Fortunately, the prognosis for the majority of normal infants who develop bronchiolitis is good.

Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California.

California uses a unique method to screen newborns for cystic fibrosis (CF) that includes gene scanning and DNA sequencing after only one California-40 cystic fibrosis transmembrane conductance regulator (CFTR) panel mutation has been identified in hypertrypsinogenemic specimens. Newborns found by sequencing to have one or more additional mutations or variants (including novel variants) in the CFTR gene are systematically followed, allowing for prospective assessment of the pathogenic potential of these variants. During the first 3 years of screening, 55 novel variants were identified. Six of these novel variants were discovered in five screen-negative participants and three were identified in multiple unrelated participants. Ten novel variants (c.2554_2555insT, p.F1107L, c.-152G>C, p.L323P, p.L32M, c.2883_2886dupGTCA, c.2349_2350insT, p.K114del, c.-602A>T, and c.2822delT) were associated with a CF phenotype (42% of participants were diagnosed at 4 to 25 months of age), whereas 26 were associated with CFTR-related metabolic syndrome to date. Associations with the remaining novel variants were confounded by the presence of other diseases or other mutations in cis or by inadequate follow-up. These findings have implications for how CF newborn screening and follow-up is conducted and will help guide which genotypes should, and which should not, be considered screen positive for CF in California and elsewhere.

Effect of secondhand cigarette smoke, RSV bronchiolitis and parental asthma on urinary cysteinyl LTE4.

Cysteinyl leukotrienes promote airway inflammation, bronchoconstriction and mucus hypersecretion. Cigarette smoking and respiratory syncytial virus (RSV) bronchiolitis are known to increase urinary cysteinyl leukotriene E4 (uLTE4), the end product of the cysteinyl leukotriene biosynthetic pathway. We tested the following hypotheses: (1) Secondhand smoke (SHS) exposure increases uLTE4 in well infants and in those hospitalized for RSV bronchiolitis; (2) Length of hospital stay for those with RSV bronchiolitis correlates with uLTE4; and (3) Infants with parent(s) with asthma will have higher uLTE4. Parental asthma for infants hospitalized with RSV bronchiolitis (n = 79) and Well babies (n = 31) was determined by questionnaire. Urine was analyzed for LTE4, cotinine, and creatinine. SHS exposure was determined by cotinine to creatinine ratio. Chi square, or t-tests were used to determine significant differences between two groups. A three-way analysis of variance compared the effects of SHS exposure and parental asthma on uLTE4 in Well versus RSV babies. Independent variables predicting length of hospital stay were determined by stepwise multiple regression. High SHS exposure and RSV significantly increased uLTE4. The SHS induced increase in uLTE4 was seen in infants with no parental asthma but not in those with parental asthma. Length of hospital stay positively correlated with uLTE4. We concluded that SHS exposure may increase the severity of bronchiolitis in RSV-infected infants by enhancing production of cysLTs in infants with no parental asthma.