E-cigarette or vaping product use associated lung injury (EVALI) in the time of COVID-19: A clinical dilemma.

AIM: To report on the clinical, laboratory, and radiological findings of adolescents who presented during the SARS-CoV-2 surge with symptoms of Coronavirus disease 2019 (COVID-19), did not test positive for the infection, and were diagnosed with E-cigarette and vaping product use associated lung injury (EVALI). METHODS: A retrospective review of 12 cases of EVALI admitted to the Bristol Meyers Squibb Children's Hospital between February 2020 and June 2020 was conducted. RESULTS: The ages of the patients ranged from 14 to 19 years. There were six males and six females. Three patients had a past history of anxiety, depression, or other psychiatric/mental health disorder, 9 had prolonged coagulation profile (prothrombin time, partial thromboplastin time, and/or International Normalized Ratio), and 11 had elevated inflammatory markers. Eight needed respiratory support. All 12 were negative for SARS-CoV-2 PCR. Four were tested for IgG antibodies and were negative. As these cases were admitted to rule out COVID infection, initial treatment included hydroxychloroquine. Steroids were started only after SARS-CoV-2 PCR was shown to be negative. Urine tetrahydrocannabinol was positive in all cases. Chest X-ray and computed tomography findings showed ground glass opacities. CONCLUSIONS: Clinical and radiological features are similar in both EVALI and SARS-CoV-2 infection. Inflammatory markers are elevated in both conditions. A detailed social and substance use history in patients presenting with "typical" COVID pneumonia like illness is important. EVALI should be ruled in early to start the appropriate treatment. Given the ongoing pandemic, pediatricians and other health-care providers need to be aware of other conditions that can masquerade as SARS-CoV-2.

Vascular endothelial growth factor levels and bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) regulate both vasculogenesis, the development of blood vessels from precursor cells, and angiogenesis, the formation of blood vessels from preexisting vessels. In the fetal lung, high-affinity receptors for VEGF are expressed mainly in alveolar epithelial cells and myocytes, suggesting a paracrine role for VEGF in modulating activities in adjacent vascular endothelium. Previous studies have shown that vascular growth is impaired in bronchopulmonary dysplasia (BPD). OBJECTIVE: The goal of this study was to examine tracheal (T-VEGF) and gastric (G-VEGF) levels in premature infants in the first and third day of life and examine if these levels were associated with the development of BPD. DESIGN/METHODS: Tracheal aspirates from intubated infants and gastric samples from others were obtained on postnatal days 1 (D1) and 3 (D3) from 43 preterm infants (<2000 g birth weight, ≤34 wks gestation). VEGF was quantified by a VEGF Elisa Kit. Demographic, clinical, and pulmonary outcome data were collected including information on respiratory support (oxygenation index (OI) and ventilatory index (VI)) and on the development of BPD, determined at 36 weeks PMA using NICHD criteria. RESULTS: The mean birth weight was 1060 ± 379 g and gestational age 27.5 ± 2.8 wks. BPD was diagnosed in 26 infants who were less mature than the 17 controls without BPD. Day 1 and day 3T-VEGF concentrations did not correlate, but day 3 levels correlated with gestational age (r = 0.75, p < .05). BPD infants, characterized by longer ventilator, CPAP and oxygen days, had day 1T-VEGF levels similar to control infants (126.6 ± 194.7 vs. 149.7 ± 333.2 pg/ml) but day 3 levels were significantly lower (168.9 ± 218.8 vs. 1041.6 ± 676.7 pg/ml). Day 1G-VEGF levels reflected tracheal samples, trending lower in BPD infants. Mode of delivery, race, sex, antenatal steroid administration, chorioamnionitis, sepsis, or growth restriction did not impact VEGF levels. However, lower VEGF levels were associated with a lower VI and lower OI: Day 3 OI correlated with day 3T-VEGF (r = 0.72, p > .05), albeit not significantly. T-VEGF increased from day 1 to day 3 in controls and decreased in BPD infants. There was no relationship between oxygen, CPAP and ventilator days and day 1 or day 3T-VEGF levels. CONCLUSIONS: BPD may be associated with low-serum VEGF levels during the first week of life. This finding is likely related to decreased expression in the lungs of the less mature infants, who are at the highest risk for BPD.

Sleep disorders in children with asthma.

Asthma and sleep disorders are both common in childhood, and often co-exist in the same child. Moreover, studies have shown that in many children the rate of one is influenced by the other. Sleep disorders can be classified into six different groups-insomnia, hypersomnia, parasomnia, movement disorders, circadian disorders, and sleep-related breathing disorders. Children with asthma often present with complaints of insomnia with poor sleep quality, difficulty falling asleep and sleep disruptions. These complains are often associated with asthma control. They may also complain of daytime sleepiness and have higher rates of parasomnias, such as night terrors and nocturnal enuresis when compared with their healthy peers. Whether movement and circadian disorders are also more prevalent in children with asthma is less clear. Finally, there is a complex bidirectional interaction between sleep-related breathing disorders and asthma: poor sleep and sleep disorders may worsen asthma, and asthma, particularly when it is poorly controlled, may impair sleep. In the current review we examine the association of each of the sleep disorders with asthma and review the common pathophysiological pathways. We hope to convince the reader that appropriate management of asthma must include inquiries into the patient's sleep, and vice versa.

An overview of noninvasive ventilation in cystic fibrosis.

Noninvasive ventilation (NIV) use was initially reported in cystic fibrosis (CF) in 1991 as a bridge to lung transplantation, and over the decades, the use of NIV has increased in the CF population. Individuals with CF are prone to various physiologic changes as lung function worsens, and they benefit from NIV for advanced lung disease. As life expectancy in CF has been increasing due to advances such as highly effective modulator therapy, people with CF may also benefit from NIV for other diagnosis beyond advanced lung disease. NIV can improve gas exchange, quality of sleep, exercise tolerance, and augment airway clearance in CF. CF providers can readily become comfortable with this therapeutic modality. In this review, we will summarize the physiologic basis for NIV use in CF, describe indications for initiation, and discuss how to order and monitor patients on NIV. We will discuss aspects unique to people with CF and the use of NIV, as well as suggestions on how to reduce risks such as infection. We hope that this serves as a resource for CF providers, in particular those who do not have dedicated training in sleep medicine as we all continue to care for the CF patient population.

Analysis of polysomnogram findings in children with concurrent obstructive and central sleep apnea.

OBJECTIVE: Increasing evidence suggests overlap in mechanisms of obstructive and central sleep apnea. Our objective was to compare the patient characteristics and polysomnographic findings of children with concurrent obstructive and central sleep apnea (obstructive sleep apnea + central sleep apnea [OSA + CSA]), to those with OSA only. METHODS: A retrospective case series of polysomnogram (PSG) from 30 June 2013 to 30 June 2018 of patients 18 years and younger was performed. PSG parameters were analyzed per standard protocol. There were two groups, OSA only group and OSA + CSA group. OSA + CSA was subdivided into groups of central apnea index (CAI) ≤5, and CAI >5. Differences in the age, sex, body mass index (BMI) percentile, prevalence of medical conditions, and PSG parameters between OSA only and OSA + CSA were assessed for statistical significance. RESULTS: The mean age of the OSA only group was 8.2 years, significantly higher than that of the OSA + CSA group, 5.0 years, P < .00001. The proportion of underweight, normal weight, overweight, and obese patients according to BMI percentiles was not statistically significantly different between the two groups, P > .05. Most common comorbidity in the two groups was pulmonary conditions, which included asthma. Of the PSG parameters, arousals due to respiratory events and obstructive apnea hypopnea index of all OSA + CSA groups were significantly higher than those of the OSA only group, P < .05. Rapid eye movement (REM) sleep was significantly higher in total OSA + CSA group and OSA + CSA subgroup with CAI ≤5, P < .05, compared to OSA only. CONCLUSION: Children with concurrent OSA + CSA are younger, but there appears to be no difference in BMI percentiles between OSA only and OSA + CSA. Compared to OSA only group, children with concurrent OSA + CSA have significantly different sleep architecture-higher REM %-and experience significantly higher respiratory arousals and obstructive events, especially in the subgroup with CAI >5. There appears to be overlap in mechanisms of CSA and OSA in this cohort. LEVEL OF EVIDENCE: 4.

The effect of the indoor environment on wheeze- and sleep-related symptoms in young Indian children.

BACKGROUND: Environmental exposures have a significant effect on respiratory and sleep symptoms in young children. Although the effect of air pollution on the respiratory symptoms in young children is well-established, less is known about the effect of household environmental characteristics and practices on wheeze and sleep concerns. AIMS: The aim of this pilot study is to explore the association between household environmental characteristics and practices with the symptoms of wheezing and sleep concerns in the past year in a convenience sample of young Indian children. MATERIALS AND METHODS: A detailed questionnaire about the child's home environment and respiratory and sleep symptoms was administered to the caregivers of 190 outpatients aged between 6 months and 5 years old at a teaching hospital. RESULTS: Indoor environmental characteristics and cleaning techniques were analyzed for the association with wheeze and sleep disorders. Half (50%) of the cohort had the symptoms of wheezing and 21% had occasional or frequent sleep concerns. Sleeping with a stuffed toy was significantly associated with both wheezing and sleep concerns (P = 0.05). CONCLUSIONS: : Sleeping with a stuffed toy was a risk factor for wheeze and a risk factor for sleep disorders independent of wheeze.

Sleep-disordered breathing in cystic fibrosis.

Sleep-disordered breathing (SBD) is an under recognized comorbidity in the cystic fibrosis (CF) population across the lifespan. Nocturnal hypoxemia, obstructive sleep apnea, and nocturnal hypoventilation are respiratory abnormalities that occur commonly during sleep in patients with lung disease, and have deleterious consequences to the quality of life in people with CF. Effective screening for these abnormalities is needed to allow for timely initiation of treatment, which has been reported to be efficacious. Lack of treatment leads to worsened pulmonary, cardiovascular, and metabolic outcomes in patients. In this review, we give an overview of SBD for the CF clinician, including prevalence, treatment, and suggestions for future research. We strongly encourage the CF community to incorporate evaluation for SBD in CF clinical care so that outcomes for the subset of the CF patients with comorbid SBD improve.

Comparison of particulate matter exposure estimates in young children from personal sampling equipment and a robotic sampler.

Accurate characterization of particulate matter (PM) exposure in young children is difficult, because personal samplers are often too heavy, bulky or impractical to be used. The Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler was developed to help address this problem. In this study, we measured inhalable PM exposures in 2-year-olds via a lightweight personal sampler worn in a small backpack and evaluated the use of a robotic sampler with an identical sampling train for estimating PM exposure in this age group. PM mass concentrations measured by the personal sampler ranged from 100 to almost 1,200 µg/m3, with a median value of 331 µg/m3. PM concentrations measured by PIPER were considerably lower, ranging from 14 to 513 µg/m3 with a median value of 56 µg/m3. Floor cleaning habits and activity patterns of the 2-year-olds varied widely by home; vigorous play and recent floor cleaning were most associated with higher personal exposure. Our findings highlight the need for additional characterization of children's activity patterns and their effect on personal exposures.

Use of a Robotic Sampler (PIPER) for Evaluation of Particulate Matter Exposure and Eczema in Preschoolers.

While the association of eczema with asthma is well recognized, little research has focused on the potential role of inhalable exposures and eczema. While indoor air quality is important in the development of respiratory disease as children in the U.S. spend the majority of their time indoors, relatively little research has focused on correlated non-respiratory conditions. This study examined the relationship between particulate matter (PM) exposures in preschool age children and major correlates of asthma, such as wheeze and eczema. Air sampling was carried out using a robotic (PIPER) child-sampling surrogate. This study enrolled 128 participants, 57 male and 71 female children. Ages ranged from 3 to 58 months with the mean age of 29.3 months. A comparison of subjects with and without eczema showed a difference in the natural log (ln) of PM collected from the PIPER air sampling (p = 0.049). PIPER's sampling observed an association between the ln PM concentrations and eczema, but not an association with wheezing history in pre-school children. Our findings are consistent with the hypothesis of the role of the microenvironment in mediating atopic dermatitis, which is one of the predictors of persistent asthma. Our findings also support the use of PIPER in its ability to model and sample the microenvironment of young children.

Evaluation of particle resuspension in young children's breathing zone using stationary and robotic (PIPER) aerosol samplers.

Development of asthma in young children may be associated with high exposure to particulate matter (PM). However, typical stationary samplers may not represent the personal exposure of children ages 3 and younger since they may not detect particles resuspended from the floor as children play, thus reducing our ability to correlate exposure and disease etiology. To address this, an autonomous robot, the Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler, was developed to simulate the movements of children as they play on the floor. PIPER and a stationary sampler took simultaneous measurements of particle number concentration in six size channels using an optical particle counter and inhalable PM on filters in 65 homes in New Jersey, USA. To study particle resuspension, for each sampler we calculated the ratio of particle concentration measured while PIPER was moving to the average concentration of particles measured during a reference period when PIPER remained still. For all investigated particle sizes, higher particle resuspension was observed by PIPER compared to the stationary sampler. In 71% of carpeted homes a more significant (at the α = 0.05 level) resuspension of particles larger than 2.5 µm was observed by PIPER compared to the stationary sampler. Typically, particles larger than 2.5 µm were resuspended more efficiently than smaller particles, over both carpeted and bare floors. Additionally, in carpeted homes estimations of PM10 mass from the particle number concentrations measured on PIPER while it was moving were on average a factor of 1.54 higher compared to reference period when PIPER was not moving. For comparison, the stationary sampler measured an increase of PM2.5 mass by a factor of only 1.08 when PIPER was moving compared to a reference period. This demonstrates that PIPER is able to resuspend particles through movement, and provide a better characterization of the resuspended particles than stationary samplers. Accurate measurement of resuspended PM will improve estimates of children's total PM exposure.

Improved exposure characterization with robotic (PIPER) sampling and association with children's respiratory symptoms, asthma and eczema.

Particulate matter (PM) and its constituents are recognized risk factors for the development of respiratory symptoms and illness in children. Most measurements of exposure have relied upon stationary indoor monitors (SIMs), overlooking the role of resuspended PM. To improve exposure characterization to resuspended aerosol PM, a recently developed methodology has been employed. The goal of this study was to characterize the resuspendable fraction of house dust and early childhood exposures to PM and its constituents in the child's home and compare conventional SIM and the Pre-toddler Inhalable Particulate Environmental Robotic (PIPER), an innovative mobile sampler. The study seeks to demonstrate that PIPER provides a more relevant estimate of exposure from inhalable particulate matter through improved correlation with respiratory symptoms in young children. Seventy-five households with children between 3 and 59 months of age were recruited from clinics in central New Jersey. Demographic information, and responses to a health questionnaire based upon that used by the International Study of Allergies and Asthma in Childhood (ISAAC), and household data were collected. Household exposures to inhalable PM (PM100) and endotoxin were determined with simultaneous SIM and mobile (PIPER) sampling. Univariate and multivariate analyses were carried out. History of wheeze ("recent" (<1 year) and "ever"), cough, asthma and eczema was evaluated. Multivariate analysis models included PM100 and endotoxin levels by tertiles of exposure. Risk of asthma for the highest tertile of PM100, as measured by PIPER (odds ratio=4.2; 95% confidence interval 0.7-24.0), was compared with measurements by SIM (odds ratio=0.7; 95% confidence interval 0.2-2.6). Measurements of PM and its constituents with PIPER are more strongly associated with asthma, eczema and wheeze compared with measurements using SIMs. Application of this methodology may provide useful insights into early childhood exposures related to the etiology of childhood illnesses associated with inhalation exposures.

Sleep architecture and behavioral abnormalities in children and adolescents.

OBJECTIVE: To investigate the association between sleep disordered breathing (SDB) and parent report of attention and behavioral problems in children, as well as the association between sleep stage duration and measures of child functioning in a clinically referred sample. METHODS: A chart review was conducted of 95 children with clinical history of SDB who completed an overnight polysomnography study in a pediatric sleep laboratory. Child functioning was assessed at the time of the sleep study by parent report on the Child Behavior Checklist (CBCL). The apnea hypopnea index was used as a measure of SDB severity. RESULTS: The apnea hypopnea index was associated with externalizing behavior, but not attention problems on the CBCL. In children 2-3 years old, stage 4 sleep duration was associated with externalizing behavior. In children 4-16 years old, REM sleep duration was associated with externalizing behavior. CONCLUSIONS: Children with increased SDB severity may be at greater risk for behavioral problems. Differences between the association of sleep stages and externalizing behavior in toddlers compared with older children suggests possible developmental differences in the association between sleep and behavior.

Obstructive sleep apnea and history of asthma in snoring children.

Asthma has been identified as a possible risk factor for Obstructive Sleep Apnea (OSA) in children. It is not known whether parent-reported asthma increases the likelihood of the diagnosis of OSA in snoring children. We hypothesized that snoring children with asthma are more likely to have OSA than snoring children without asthma. This study is a 1-year retrospective review of polysomnogram and questionnaire data collected on 236 patients referred to the University of Maryland Pediatric Sleep laboratory for evaluation of snoring. Of the 236 patients, 58% (137/236) were boys, and 79% (173/219 reporting race) were African-American (AA). The age at referral was 7.2 +/- 3.7 years (mean +/- S.D.). Mean body mass index (BMI) percentile was 73.4 +/- 32.3%, with 43.2% (54/125) >95th percentile. A history of asthma was reported by 31.4% (74/236); no subject was symptomatic on the night of the study. We found no increased risk for polysomnographically diagnosed OSA for asthmatics. To the contrary, by logistic regression analysis, a parent/guardian report of asthma decreased the odds of having OSA by 34% (p = 0.027), controlling for individual and socioeconomic factors and assessment results. Polysomnographic (PSG) differences between asthmatic and non-asthmatic children were found in only the arousal index (11.0 vs.9.3 +/- 6.5/h, p = 0.099) and total sleep time (337.1 +/- 64.3 vs. 347 +/- 65.2 min, p = 0.1) In a referral-based group of predominantly AA inner-city snoring children, asymptomatic asthma decreased the likelihood of OSA.