A case of recurrent pneumothoraces in a newborn.

Pneumothoraces are not an uncommon finding in the newborn period. Recurrent pneumothoraces can be associated with complications of prematurity or use of ventilators but can be seen in rapidly progressive cystic lung disease. We report a case of recurrent pneumothoraces in an infant with the rapidly progressive cystic disease in the setting of an absent right pulmonary artery. The patient ultimately underwent pneumonectomy for definitive management of the recurrent unilateral pneumothoraces.

Utility of polysomnography and video swallow studies in the management of pediatric patients with congenital idiopathic bilateral vocal fold dysfunction.

OBJECTIVES: Congenital idiopathic bilateral vocal fold dysfunction (BVFD) is an uncommon cause of neonatal stridor and respiratory distress postnatally. Approximately 50% of affected neonates or infants will historically require tracheostomy for this condition. Timing and candidacy for tracheostomy in BVFD patients is often subjective and poorly understood. Polysomnography (PSG) and video swallow studies (VSS) may be helpful in the management of patients with BVFD prior to tracheostomy by quantifying their degree of upper airway obstruction during sleep and feeding dysfunction while awake. METHODS: We performed a single-institution retrospective case series of BVFD patients from 2000 to 2018 who had postnatal PSGs performed prior to tracheostomy. Demographics, gestational age, and VSS results prior to PSG were recorded for all patients. Findings from PSGs included non-REM AHI, REM AHI, oxygen nadir, % total sleep time (TST) O2<90%, peak end-tidal (ET) CO2, % TST ETCO2 >52 torr. Rates of post-PSG tracheostomy, gastrostomy tube (G-tube) placement, and home O2 supplementation were noted for all patients. RESULTS: From 2000 to 2018, 12/46 (26%) BVFD patients had postnatal PSGs performed prior to tracheostomy. Median patient age at BVFD diagnosis, VSS, and PSG was 5.5 days, 12.5 days, and 17.5 days, respectively. Mild, moderate, and severe obstructive sleep apnea (OSA) was found in 7/12, 3/12, and 4/12 patients, respectively. Hypercapnia (ETCO2 >52 torr) was found in 5/12 patients on PSG while hypoxemia (SpO2 <90% for >4% TST) was not found in any patient. VSS results demonstrated normal swallowing, inconsistent laryngeal penetration, and silent aspiration in 7/12, 2/12, and 3/12 patients, respectively. Tracheostomy and G-tube placement was performed in 3/12 and 2/12 patients, respectively. There was no association between the severity of OSA or any PSG abnormality, VSS findings, and the performance of tracheostomy in any BVFD patient. CONCLUSIONS: OSA was found in all BVFD patients undergoing postnatal PSG at our institution while feeding dysfunction was found in approximately 50% of patients. The presence of feeding dysfunction, severe OSA, or any PSG abnormality was not individually associated with the subsequent performance of a tracheostomy in our patients. PSG is likely useful in supporting but not supplanting one's clinical decision-making in the management of patients with congenital idiopathic BVFD.

Author Correction: Baseline and Disease-Induced Transcriptional Profiles in Children with Sickle Cell Disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Baseline and Disease-Induced Transcriptional Profiles in Children with Sickle Cell Disease.

Acute chest syndrome (ACS) is a significant cause of morbidity and mortality in sickle cell disease (SCD), but preventive, diagnostic, and therapeutic options are limited. Further, ACS and acute vasoccclusive pain crises (VOC) have overlapping features, which causes diagnostic dilemmas. We explored changes in gene expression profiles among patients with SCD hospitalized for VOC and ACS episodes to better understand ACS disease pathogenesis. Whole blood RNA-Seq was performed for 20 samples from children with SCD at baseline and during a hospitalization for either an ACS (n = 10) or a VOC episode (n = 10). Respiratory viruses were identified from nasopharyngeal swabs. Functional gene analyses were performed using modular repertoires, IPA, Gene Ontology, and NetworkAnalyst 3.0. The VOC group had a numerically higher percentage of female, older, and hemoglobin SS participants compared to the ACS group. Viruses were detected in 50% of ACS cases and 20% of VOC cases. We identified 3004 transcripts that were differentially expressed during ACS episodes, and 1802 transcripts during VOC episodes. Top canonical pathways during ACS episodes were related to interferon signaling, neuro-inflammation, pattern recognition receptors, and macrophages. Top canonical pathways in patients with VOC included IL-10 signaling, iNOS signaling, IL-6 signaling, and B cell signaling. Several genes related to antimicrobial function were down-regulated during ACS compared to VOC. Gene enrichment nodal interactions demonstrated significantly altered pathways during ACS and VOC. A complex network of changes in innate and adaptive immune gene expression were identified during both ACS and VOC episodes. These results provide unique insights into changes during acute events in children with SCD.

The MSLT is Repeatable in Narcolepsy Type 1 But Not Narcolepsy Type 2: A Retrospective Patient Study.

STUDY OBJECTIVES: To examine repeatability of Multiple Sleep Latency Test (MSLT) results in narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) according to the criteria of the International Classification of Sleep Disorders, Third Edition (ICSD-3). METHODS: Repeatability of the MSLT was retrospectively evaluated in NT1 (n = 60) and NT2 (n = 54) cases, and controls (n = 15). All subjects had documented HLA-DQB1*06:02 status and/or hypocretin-1 levels from cerebrospinal fluid. All subjects had undergone 2 MSLTs (≥ 1 meeting ICSD-3 criteria for narcolepsy). Repeatability was explored in children versus adults and in those on versus not on medication(s). Subsample and multivariate analysis were performed. RESULTS: Both MSLTs in unmedicated patients were positive for narcolepsy in 78%, 18%, and 7% of NT1, NT2, and controls, respectively. NT2 cases changed to idiopathic hypersomnia or to a negative MSLT 26% and 57% of the time, respectively. Although NT1 cases were 10 to 14 times more likely to demonstrate a second positive MSLT compared to NT2 cases (P < 10-5) and controls (P < 10-4), respectively, NT2 cases were not significantly different from controls (P = .64). Medication use (P = .009) but not adult versus children status (P = .85) significantly decreased the likelihood of a repeat positive MSLT. CONCLUSIONS: In a clinical setting, a positive MSLT for narcolepsy is a more reproducible and stable feature in NT1 than NT2. The retrospective design of this study hinders interpretation of these data, as there are many different, and possibly opposing, reasons to repeat a MSLT in NT1 versus NT2 (ie, ascertainment bias). Additional systematic MSLT repeatability studies independent of confounds are ideally needed to confirm these findings.

Sleep and the Cardiovascular System in Children.

Subspecialty pediatric practice provides comprehensive medical care for a range of ages, from premature infants to children, and often includes adults with complex medical and surgical issues that warrant multidisciplinary care. Normal physiologic variations involving different body systems occur during sleep and these vary with age, stage of sleep, and underlying health conditions. This article is a concise review of the cardiovascular (CV) physiology and pathophysiology in children, sleep-disordered breathing (SDB) contributing to CV morbidity, congenital and acquired CV pathology resulting in SDB, and the relationship between SDB and CV morbidity in different clinical syndromes and systemic diseases in the expanded pediatric population.

The obstructive sleep apnoea syndrome in adolescents.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO2 during sleep would be major predictors of OSAS risk. METHODS: 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO2 during wakefulness and sleep. RESULTS: ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO2 during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. CONCLUSIONS: OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents.

Dexmedetomidine for infant pulmonary function testing.

For the last thirty years, oral chloral hydrate has been used for sedation of infants for lung function testing. Recently, however, availability of chloral hydrate became severely limited in the United States after two manufacturers discontinued manufacturing in 2012. Due to these limitations and the recent and ongoing shortage of chloral hydrate, other medications have been proposed for lung function testing, including midazolam and propofol. Herein, we describe our limited experience using intravenous dexmedetomedine (DMED), a medication thus far described as having minimal effect on pulmonary function or respiratory drive.

Upper airway collapsibility and genioglossus activity in adolescents during sleep.

STUDY OBJECTIVES: Obese patients develop obstructive sleep apnea syndrome (OSAS), at least in part because of a narrowed upper airway. However, many obese adolescents do not develop OSAS, despite having a presumably narrower airway. The reasons for this phenomenon are unclear. The authors hypothesized that obese controls have a compensatory neuromuscular response to subatmospheric pressure loads during sleep, making them less likely to develop upper airway collapse. DESIGN: Patients underwent pressure-flow measurements during sleep while wearing intraoral electrodes to measure genioglossal electromyography (EMGgg). Two techniques were applied to decrease nasal pressure (P(N)) to subatmospheric levels, resulting in an activated and relatively hypotonic upper airway. SETTING: Sleep laboratory. PARTICIPANTS: There were 35 obese patients with OSAS, 28 obese controls, and 43 lean controls. RESULTS: In the activated state, the two control groups had a flatter slope of the pressure-flow relationship and a more negative critical closing pressure (less collapsible) than the OSAS group. In the hypotonic state, the lean controls had a flatter slope of the pressure-flow relationship than the OSAS and obese control groups. In the activated state, the slope of EMGgg versus P(N) was greater in the obese control group than in the OSAS or lean control groups (P = 0.002 and P = 0.028, respectively); there were no differences in the hypotonic state. CONCLUSIONS: Obese controls have vigorous upper airway neuromuscular responses during sleep. Upper airway reflexes normally decline during adolescent development. It is speculated that obese adolescents without OSAS maintain protective upper airway reflexes during adolescent development, whereas those who go on to develop OSAS do not.

Ventilatory responses to hypercapnia during wakefulness and sleep in obese adolescents with and without obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Abnormal ventilatory drive may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). Concomitant with the obesity epidemic, more adolescents are developing OSAS. However, few studies have specifically evaluated the obese adolescent group. The authors hypothesized that obese adolescents with OSAS would have a blunted hypercapnic ventilatory response (HCVR) while awake and blunted ventilatory responses to carbon dioxide (CO(2)) during sleep compared with obese and lean adolescents without OSAS. DESIGN: CVR was measured during wakefulness. During nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, respiratory parameters and genioglossal electromyogram were measured during CO(2) administration in comparison with room air in obese adolescents with OSAS, obese control study participants, and lean control study participants. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-eight obese patients with OSAS, 21 obese control study participants, and 37 lean control study participants. RESULTS: The obese OSAS and obese control groups had a higher HCVR compared with the lean control group during wakefulness. During both sleep states, all 3 groups had a response to CO(2); however, the obese OSAS group had lower percentage changes in minute ventilation, inspiratory flow, inspiratory time, and tidal volume compared with the 2 control groups. There were no significance differences in genioglossal activity between groups. CONCLUSIONS: HCVR during wakefulness is increased in obese adolescents. Obese adolescents with OSAS have blunted ventilatory responses to CO(2) during sleep and do not have a compensatory prolongation of inspiratory time, despite having normal CO(2) responsivity during wakefulness. Central drive may play a greater role than upper airway neuromotor tone in adapting to hypercapnia.

Upper airway collapsibility during wakefulness in children with sleep disordered breathing, as determined by the negative expiratory pressure technique.

STUDY OBJECTIVES: Upper airway (UA) collapsibility is a major factor in the pathophysiology of sleep disordered breathing (SDB). We hypothesized that the negative expiratory pressure (NEP) technique could distinguish between normal children and children with SDB even during wakefulness. DESIGN: During wakefulness, NEP of -5 and -10 cm H(2)O was applied during expiration in seated and supine positions. UA muscle activity (EMG) was measured using intra-oral electrodes. SETTING: Sleep laboratory. PARTICIPANTS: Twenty children with snoring, 20 with obstructive sleep apnea syndrome (OSAS), and 20 controls. MEASUREMENTS AND RESULTS: The ratio of the area under the expiratory flow-volume curve during NEP compared to tidal breathing (RatioNEP) was calculated. Similarly, EMG area under the curve during NEP as a ratio of baseline was measured (RatioEMG). There were significant differences in RatioNEP between controls and snorers and controls and OSAS, at both pressures, in both the seated and supine positions; P < 0.0001 for all (e.g., RatioNEP at -5 cm H(2)O, seated: 1.8 ± 0.5, 2.1 ± 0.4, and 3.0 ± 0.6 for OSAS, snorers, and controls, respectively). However, no significant differences were found between snorers and OSAS. For RatioEMG, no significant differences were found between groups. CONCLUSIONS: RatioNEP distinguishes between normal children and children with SDB, be it snoring or OSAS, indicating that these children have a more collapsible UA even during wakefulness. However, it does not differentiate between snorers and OSAS, highlighting the important role of UA muscle activity during sleep. NEP technique does not elicit a different UA muscle activity response between controls and children with SDB.

Upper airway genioglossal activity in children with sickle cell disease.

STUDY OBJECTIVES: The prevalence of obstructive sleep apnea syndrome (OSAS) in sickle cell disease (SCD) has been reported to be higher than that in the general pediatric population. However, not all subjects with SCD develop OSAS. We hypothesized that SCD patients with OSAS have a blunted neuromuscular response to subatmospheric pressure loads during sleep, making them more likely to develop upper airway collapse. DESIGN: Subjects with SCD with and without OSAS underwent pressure-flow measurements during sleep using intraoral surface electrodes to measure genioglossal EMG (EMGgg). Two techniques were applied to decrease the nasal pressure (P(N)) to subatmospheric levels, resulting in an activated and relatively hypotonic upper airway. The area under the curve of the inspiratory EMGgg moving time average was analyzed. EMGgg activity was expressed as a percentage of baseline. Changes in EMGgg in response to decrements in nasal pressure were expressed as the slope of the EMGgg vs. nasal pressure (slope of EMGgg-P(N)). SETTING: Sleep laboratory. PARTICIPANTS: 4 children with SCD and OSAS and 18 children with SCD but without OSAS. RESULTS: THE MAJOR FINDINGS OF THIS STUDY WERE: (1) using the activated but not the hypotonic technique, the slope of EMGgg-P(N) was more negative in SCD controls than SCD OSAS; (2) the slope of EMGgg-P(N) was significantly lower using the activated technique compared to the hypotonic technique in SCD controls only; (3) similarly, the critical closing pressure, Pcrit, was more negative using the activated technique than the hypotonic technique in SCD controls but not in SCD OSAS. CONCLUSION: This preliminary study has shown that children with SCD but without OSAS have more prominent upper airway reflexes than children with SCD and OSAS.

Effects of race on upper airway dynamic function during sleep in children.

STUDY OBJECTIVE: Studies in adults and children have shown that African American race is a risk factor for the obstructive sleep apnea syndrome (OSAS). Therefore, we hypothesized that non-obese, non-snoring African American children would have a more collapsible upper airway during sleep than age-, gender-, and size-matched Caucasians. DESIGN: Upper airway dynamic function was measured during sleep in normal African American and Caucasian children. SETTING: Sleep laboratory. PATIENTS OR PARTICIPANTS: 56 normal children between the ages of 8-18 years. INTERVENTIONS: Pressure-flow relationships were measured during NREM sleep. Nasal pressure was decreased to subatmospheric levels, using previously described techniques that resulted in an activated and relatively hypotonic upper airway. MEASUREMENTS AND RESULTS: The activated and hypotonic critical pressures (Pcrit) were -25 (-25, -3) (median, range) and -19 (-25, -3) for African Americans, and -25 (-25, -4) and -25 (-25.0, -4) cm H(2)O, respectively, for Caucasians. The slopes of the pressure-flow response (SPF) under activated and hypotonic conditions for African Americans were 10 (-9, 46) and 13 (-20, 46), and for Caucasians 9 (-9, 64) and 8 (-5, 54) mL/s/cm H(2)O, respectively. There were no significant differences between groups for Pcrit or SPF under either activated or hypotonic conditions. CONCLUSION: Upper airway collapsibility was similar in asymptomatic, non-obese African American and Caucasian children. Differences in upper airway characteristics and neuromotor function cannot explain the increased prevalence of OSAS in African American children.