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Background/Purpose As survival rates for patients with congenital diaphragmatic hernia (CDH) increase, long-term sequelae become increasingly prevalent. We present the outcomes of patients who underwent CDH repair at our institution and discuss standardization of follow-up care in our long-term multidisciplinary follow-up clinic. Methods A retrospective review of patients followed in multidisciplinary clinic after CDH repair at our institution from January 1, 2005 to December 1, 2020. Results A total of 193 patients met inclusion criteria, 73 females (37.8%) and 120 males (62.2%). Left-sided defects were most common (75.7%), followed by right-sided defects (20.7%). Median age at repair was 4 days (IQR 3–6) and 59.6% of all defects required patch repair. Median length of stay was 29 days (IQR 16.8–50.0). Median length of follow up was 49 months (IQR 17.8–95.3) with 25 patients followed for more than 12 years. Long-term outcomes included gastroesophageal reflux disease (42.0%), diaphragmatic hernia recurrence (10.9%), asthma (23.6%), neurodevelopmental delay (28.6%), attention deficit hyperactivity disorder (7.3%), autism (1.6%), chest wall deformity (15.5%), scoliosis (11.4%), and inguinal hernia (6.7%). Conclusion As survival of patients with CDH improves, long-term care must be continuously studied and fine-tuned to ensure appropriate surveillance and optimization of long-term outcomes.

INTRODUCTION Epidemiologic studies have found low/absence of atopy in obese asthmatic children, but the association or lack thereof of atopy with disease morbidity, including pulmonary function, in obese asthma is not well understood. We sought to define the association of atopy with pulmonary function in overweight/obese minority children with asthma. METHODS In a retrospective chart review of 200 predominantly minority children evaluated at an academic Pediatric Asthma Center over 5 years, we compared the prevalence of atopy, defined as ≥ 1 positive skin prick test or serum-specific immunoglobulin E quantification to environmental allergens, and its association with pulmonary function in overweight/obese (body mass index [BMI] > 85th percentile) (n = 99) to healthy-weight children (BMI, 5th-85th percentile for age) (n = 101). RESULTS In a cohort comprised of 47.5% Hispanics and 39.5% African Americans, 81% of overweight/obese and 74% of healthy-weight children were atopic. While atopic healthy-weight children had lower percent-predicted forced expiratory volume in the first second (FEV1 ) (93 ± 13.6 vs 107% ± 33.2%, P = .03) and lower percent-predicted forced vital capacity (FVC) (93% ± 12.2% vs 104% ± 16.1%, P = .01) as compared to nonatopic children, atopy was not associated with FEV1 (P = .7) or FVC (P = .17) in overweight/obese children. Adjusting for demographic and clinical variables, atopy was found to be an independent predictor of FEV1 and FVC in healthy-weight (β = -2.4, P = .07 and β = -1.7, P = .04, respectively) but not in overweight/obese children (β = .6, P = .5 and β = .8, P = .3). CONCLUSIONS Atopy is associated with lower lung function in healthy-weight asthmatics but not in overweight/obese asthmatics, supporting the role of nonallergic mechanisms in disease burden in pediatric obesity-related asthma.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Background Several underlying conditions have been associated with severe acute respiratory syndrome coronavirus 2 illness, but it remains unclear whether underlying asthma is associated with worse coronavirus disease 2019 (COVID-19) outcomes. Objective Given the high prevalence of asthma in the New York City area, our objective was to determine whether underlying asthma was associated with poor outcomes among hospitalized patients with severe COVID-19 compared with patients without asthma. Methods Electronic heath records were reviewed for 1298 sequential patients 65 years or younger without chronic obstructive pulmonary disease who were admitted to our hospital system with a confirmed positive severe acute respiratory syndrome coronavirus 2 test result. Results The overall prevalence of asthma among all hospitalized patients with COVID-19 was 12.6%, yet a higher prevalence (23.6%) was observed in the subset of 55 patients younger than 21 years. There was no significant difference in hospital length of stay, need for intubation, length of intubation, tracheostomy tube placement, hospital readmission, or mortality between patients with and without asthma. Observations between patients with and without asthma were similar when stratified by obesity, other comorbid conditions (ie, hypertension, hyperlipidemia, and diabetes), use of controller asthma medication, and absolute eosinophil count. Conclusions Among hospitalized patients 65 years or younger with severe COVID-19, asthma diagnosis was not associated with worse outcomes, regardless of age, obesity, or other high-risk comorbidities. Future population-based studies are needed to investigate the risk of developing COVID-19 among patients with asthma once universal testing becomes readily available., Graphical abstract

Background A relationship between adiposity and asthma has been described in some cohort studies, but little is known about trajectories of adiposity throughout early childhood among children at high risk for developing asthma in urban United States cities. Moreover, early life trajectories of adipokines that have metabolic and immunologic properties have not been comprehensively investigated. Objective Our objective was to characterize trajectories of adiposity in a longitudinal birth cohort of predominately Black and Latinx children (n = 418) using several different repeated measures including body mass index (BMI) z score, bioimpedance analysis, leptin, and adiponectin in the first 10 years of life. Methods In a longitudinal birth cohort of predominately Black and Latinx children, we used repeated annual measures of BMI, bioimpedance analysis (ie, percentage of body fat), leptin, and adiponectin to create trajectories across the first 10 years of life. Across those trajectories, we compared asthma diagnosis and multiple lung function outcomes, including spirometry, impulse oscillometry, and methacholine response. Results Three trajectories were observed for BMI z score, bioimpedance analysis, and leptin and 2 for adiponectin. There was no association between trajectories of BMI, percentage of body fat, leptin, or adipokine and asthma diagnosis or lung function (P > .05). Conclusions Trajectories of adiposity were not associated with asthma or lung function in children at high risk for developing asthma. Risk factors related to geography as well as social and demographic factors unique to specific populations could explain the lack of association and should be considered in obesity and asthma studies.

Rationale Pulmonary complications are the leading cause of morbidity and mortality in sickle cell disease (SCD) patients. Research in SCD has predominantly been conducted on African-Americans, and the disease burden of SCD in other races and ethnicities, including Hispanic patients, is not well characterized. Objective To compare pulmonary disease burden between Hispanic and non-Hispanic ethnic groups among children with SCD. Methods In a retrospective chart review on 566 SCD patients followed at the Children's Hospital at Montefiore, NY, we compared the pulmonary disease burden and disease management in Hispanic patients to their non-Hispanic counterparts. We also compared the contribution of demographic and clinical variables to acute chest syndrome (ACS), vaso-occlusive crisis (VOC), and hospitalizations for SCD related complications between the two ethnic groups. Results Hispanic patients had a greater proportion of ACS, and had lower forced expiratory volume (FEV1), forced vital capacity, and vital capacity, compared to non-Hispanics. Hispanic patients were more likely to be evaluated in pulmonary clinic and to be on inhaled corticosteroids, short-acting β agonizts, and leukotriene receptor antagonists. In addition, Hispanic children were more likely to be on hydroxyurea, and receive exchange transfusions. However, the association of asthma with the proportion of ACS did not differ between Hispanics and non-Hispanics. Conclusion Hispanic children with SCD had differences in their pulmonary function profile and received more pulmonary evaluations than non-Hispanic children.

ObjectiveTo investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).MethodsIn a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.ResultsLD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.ConclusionsA rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

Background Symptoms of pulmonary injury following lung irradiation may not manifest clinically in childhood. We performed comprehensive pulmonary evaluation of patients who had received lung irradiation for treatment of cancer. Materials and methods Patients underwent a focused history and physical examination, computed tomography of the chest, pulmonary function test, and cardiopulmonary exercise stress test (CPET). Health-related Quality of Life was also measured. Results Fourteen patients were recruited with median age of 16 years (range, 6 to 21 y). Median time from pulmonary radiation to testing was 5 years (range, 2 to 11 y). Five patients reported pulmonary symptoms. Twelve patients (85.7%) had at least 1 pulmonary function test abnormality. Nine patients demonstrated CPET abnormalities; 7 patients had abnormal pulmonary limitation to exercise, and 5 patients had exercise-induced bronchospasm. The pulmonary limitations included abnormal ventilatory response to exercise in 5 patients, and gas exchange abnormalities in 4 patients. Chest computed tomography demonstrated grade 1-2 radiation-induced lung changes in 4 patients, and grade 3 abnormalities in 1 patient. Conclusions Significant pulmonary dysfunction was observed in childhood cancer survivors who had received lung irradiation. CPET is feasible in childhood cancer survivors and can be valuable for assessment of pulmonary function and exercise capacity.

There are few studies measuring postoperative respiratory complications in obese children with obstructive sleep apnea (OSA) undergoing adenotonsillectomy (AT). These complications are further compounded by perioperative medications. Our objective was to study obese children with OSA for their respiratory characteristics and sleep architecture on the night of AT.This was a prospective study at a tertiary pediatric hospital between January 2009-February 2012. Twenty obese children between 8-17 years of age with OSA and adenotonsillar hypertrophy were recruited. Patients underwent baseline polysomnography (PSG) and AT with or without additional debulking procedures, followed by a second PSG on the night of surgery. Demographic and clinical variables, surgical details, perioperative anesthetics and analgesics, and PSG respiratory and sleep architecture parameters were recorded. Statistical tests included Pearson correlation coefficient for correlation between continuous variables and chi-square and Wilcoxon rank-sum tests for differences between groups.Baseline PSG showed OSA with mean obstructive apnea-hypopnea index (oAHI) 27.1 ± 22.9, SpOObese children undergoing AT for OSA are at increased risk for residual OSA on the night of surgery. Special considerations should be taken for postoperative monitoring and treatment of these children.A commentary on this article appears in this issue on page 775.

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease in the pediatric population. There are currently few cases documenting hemophagocytic lymphohistiocytosis as a cause for secondary PAP. We describe an ex-preterm child with secondary hemophagocytic lymphohistiocytosis, complicated by PAP and hypoxemic respiratory failure.

Bleomycin is associated with pulmonary toxic side effects including pneumonitis and pulmonary fibrosis. We evaluated the prevalence of long-term pulmonary function abnormalities in children receiving bleomycin therapy in the context of current chemotherapeutic regimens.A retrospective review of patients who received bleomycin between January 1999 and December 2011 was conducted. Abnormalities in the most recent pulmonary function test (PFT) at least 1 year after diagnosis were analyzed.Two-hundred and seven patients had received bleomycin. The results of PFT performed at least 1 year from diagnosis were available for 80 patients. Median time of follow up was 3.9 years (range 1.1-11.76 years). Median cumulative dose of bleomycin was 65 IU/m(2) (range 10-120). The most common diagnoses were Hodgkin lymphoma and germ cell tumor. At least one pulmonary function abnormality was present in 42 (52.5%) patients. When classified in groups, 22.5% patients had obstructive lung disease, 7.5% had restrictive lung disease, 28.8% had hyperinflation and 14% of patients had non-uniform distribution of ventilation. Non-Hispanic patients (OR 2.81) and children younger than 8 years (OR 4.14) had higher odds of having an abnormal PFT parameter. Very few patients had pulmonary symptoms.More than half the patients who received bleomycin had subclinical pulmonary dysfunction as evidenced by abnormalities in pulmonary function tests, although the incidence of clinical symptoms was low.

There is limited data on pulmonary function test (PFT) abnormalities in children treated with modern irradiation techniques. PFT abnormalities have not been correlated with the dose and volume of irradiation.A retrospective chart review of PFTs and clinical outcomes in children who received radiation therapy (RT) at Children's Hospital Los Angeles between 1999 and 2009 was performed. Radiation dose distribution to normal lung tissue was calculated.Forty-nine patients had PFTs available post-RT at a median time of 2.91 years (range, 0.01-8.28) from irradiation. Sixty-seven percent of patients had at least one PFT abnormality on their last available study. The most common abnormality was obstructive lung disease (24%) followed by hyperinflation (20%). Thoracic surgery prior to RT increased the odds of an abnormal FEV1, RV/TLC, and obstructive disease. The sex of the patient, age at the time of irradiation, and time of the PFT after irradiation did not have a significant association with abnormalities. The mean lung dose, maximum lung dose, and prescribed dose of radiation were significantly associated with the development of PFT abnormalities. The odds of developing an abnormal PFT increased with increase in the minimum threshold dose (V(dose)) of radiation, mostly above V(20).PFT abnormalities are common even when modern radiation techniques are used. A significant correlation between radiation parameters and PFT abnormalities was noted.

* ALT: : alanine aminotransferase AST: : aspartate aminotransferase BUN: : blood urea nitrogen CBC: : complete blood count CNS: : central nervous system CSF: : cerebrospinal fluid CT: : computed tomography ECG: : electrocardiography ED: : emergency department EEG: : electroencephalography ESR: : erythrocyte sedimentation rate GI: : gastrointestinal GU: : genitourinary Hct: : hematocrit Hgb: : hemoglobin MRI: : magnetic resonance imaging WBC: : white blood cell A 5-year-old boy is brought to the ED by emergency medical services in status epilepticus after a 3-day history of headaches. This morning he had a generalized tonic-clonic seizure, and paramedics administered lorazepam at his home. He continues to seize and requires a second dose of lorazepam on arrival to the ED. Once he is stabilized, a history is obtained from the parents. They describe the headaches as generalized, they start suddenly, and nothing seems to alleviate them. The headaches are not worse in the early morning and not associated with vomiting or vision changes. The boy has had no recent illnesses and has been eating well and acting well between the headaches. In the ED, his blood pressure is 137/106 mm Hg, heart rate is 109 beats/min, respiratory rate is 20 breaths/min, and temperature is 37.8°C. On physical examination, he is postictal but has no focal signs. All other physical findings, including on funduscopic examination, are normal. Results of laboratory evaluation, including CBC, basic metabolic panel, urinalysis, thyroid panel, complement assessment, antistreptolysin O titer, and cardiac enzymes, are within normal limits. CT scan of the brain also yields normal results, as does echocardiography. The patient is admitted to the intensive care unit. Further imaging studies reveal the diagnosis. A 13-year-old previously healthy competitive gymnast collapses while climbing a rope during practice. She exhibits cyanosis and apnea, and cardiopulmonary resuscitation is started immediately. An automated external defibrillator is connected by emergency personnel. The monitor shows a shockable rhythm (Fig. 1), and she is defibrillated once. Thereafter, she develops agonal respirations and sinus tachycardia. She remains unresponsive, has a Glasgow Coma Scale score of 5, and is endotracheally intubated. She has no history of fainting in the past, and her family history is negative for any sudden cardiac deaths, arrhythmias, or …