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Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children’s Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders. This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform. We report the study design and some elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy (NEHI), with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%). This Registry is the largest longitudinal chILD cohort in the U.S. to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

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.

OBJECTIVE: Cardiopulmonary exercise testing (CPET) is used prior to bariatric surgery in adolescents with obesity to assess surgical risk factors. Lack of normative equations for peak oxygen consumption (pVO2) for this population limits CPET interpretation. We aimed to use lean body weight (LBW) to predict pVO and developed novel predictive equations for use in this population. METHODS: 446 participants with obesity ages 9-20 underwent CPET prior to bariatric surgery from January 1, 2006 to December 31, 2019. Bioelectrical impedance analysis helped calculate LBW. Achieving peak heart rate > 90% predicted and RER of >1.1 were considered satisfactory effort. RESULTS: 107 CPET studies (29%) were satisfactory. Mean weight was 127 ± 21 kg, and BF% 49.7 ± 6.8, and LBW 63 ± 10, kg. Mean pVO was 22.2 ± 3.2 mL/kg/min. The mean pVO using LBW was 44.8 ± 8.7 mL/kg/min. Total body weight (TBW) estimated pVO to be 50.7 ± 7.0 % predicted[(1)](#ref-0001), while LBW estimated it at 102.3 ± 17.6 % predicted. Linear regression yielded reference equations pVO =1571.6+12.2*TBW (males) and pVO2=1301.8+10.6*TBW (females). CONCLUSION: When pVO is corrected for LBW, adolescents with obesity demonstrate normal pVO . A novel set of equations were developed to predict absolute pVO using TBW.

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.

Cheyne-Stokes respiration is a pattern of alternating central apnea and hyperpnea. It is well described in adults with congestive heart failure, but not in children. We report the case of a 17-year-old boy whose systolic heart failure was complicated by Cheyne-Stokes respiration. He was given supportive therapy until heart transplant, after which his Cheyne-Stokes respiration clinically resolved. Clinicians should be aware of this uncommon condition in pediatric and adolescent patients who have advanced heart failure and irregular breathing.

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 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 novel candidate CDH genes based on de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 cases and 11,220 ancestry-matched population controls 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 familial cases. Approximately 3% of our CDH cohort was heterozygous with ultra-rare predicted damaging variants in LONP1 who 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 and have reduced lung growth and branching that may at least partially explain 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.

Rationale: Asthma is a common comorbid condition in sickle cell disease (SCD). However, obstructive lung disease is prevalent in SCD, independent of a diagnosis of asthma. It is speculated that the heightened state of inflammation in SCD, involving pathways distinct from allergic asthma, may underlie the SCD-specific obstructive disease. Objective: The objective of the study was to compare airway and systemic inflammatory markers between SCD patients with pulmonary manifestations and patients with allergic asthma, and correlate the discriminating inflammatory markers with clinical measures of pulmonary disease. Materials and Methods: In a pilot translational study conducted at the Children's Hospital at Montefiore, 15 patients with SCD, and history of asthma, airway obstruction, or airway hyper-reactivity, and 15 control patients with allergic asthma 6–21 years of age were recruited. Inflammatory markers, including peripheral blood T helper cell subsets, serum and exhaled breath condensate (EBC) cytokines and chemokines of the Th-1/Th-17, Th-2, and monocytic pathways, and serum cysteinyl leukotrienes B4 (LTB4), were quantified, compared between the study groups, and correlated with atopic sensitization, pulmonary function tests, and markers of hemolysis. Results: White blood cells (P

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/Purpose: Short-term outcomes of congenital diaphragmatic hernia (CDH) are well described. We present the long-term outcomes and co-morbidities found in patients who underwent CDH repair at our institution. Methods: We conducted a retrospective review of all patients from 2004 – 2019 who underwent repair of CDH with survival to discharge. Means and percentages were used …

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

OBJECTIVE The purpose of the study was to assess mortality in an infant population receiving sildenafil. METHODS A retrospective review of hospitalized infants at Children's Hospital Los Angeles who received sildenafil between 2008 and 2012 was conducted. Patient characteristics, comorbidities, and treatment characteristics were analyzed. Primary outcome was mortality at discharge. Sildenafil dosage ranges were based on the Sildenafil in Treatment-Naïve Children, Aged 1–17 Years, With Pulmonary Arterial Hypertension trial and were categorized as small (7.5 mg/kg/day). RESULTS A total of 147 infants were studied. A total of 82% of patients had severe pulmonary hypertension. Our data revealed 29% mortality at discharge. Mortality increased with increasing sildenafil dosage: 14% (small), 19% (medium), 49% (large), and 90% (very large). On multivariate analysis of sildenafil dosage, other pulmonary hypertension therapies, presence of persistent cardiac shunts, and duration of sildenafil, odds of dying were significantly higher with combined high and very high sildenafil dosage groups compared with combined low and medium dosage groups (OR, 13.2; CI, 4.4–39.5; p < 0.0001). CONCLUSION Sildenafil was given to critically ill infants with multiple risk factors for mortality. Although higher doses cannot be causally related to mortality, there appears to be no added benefit by escalating the sildenafil dose.

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.

Introduction: Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare pulmonary disorders. Our objectives are to advance knowledge on clinical features, management, and outcomes of this population. Methods: The Children’s Interstitial and Diffuse Lung Disease Research Network (ChILDRN) established a longitudinal observational study in 2016 using a national platform for single IRB reliance agreements with 13 participating sites across the United States. Results: 254 subjects have been enrolled to date. Specific chILD diagnoses and clinical characteristics are summarized in Table 1. Overall mean age at study enrollment was 101±73 months. Identified morbidity included home oxygen supplementation in 71% at any time and 44% with ongoing requirement. Failure to thrive was noted in 53%. 46% of subjects had undergone lung biopsy; genetic studies were used in diagnosis for 23%. Pulmonary function abnormalities varied based on disease subgroup. Conclusions: The first multicenter prospective study of chILD in the U.S. indicates substantial morbidity with variable phenotypes in different forms of chILD. This cohort provides a framework for future longitudinal studies focused on elucidation of the genetic and molecular underpinnings of these disorders, development of targeted therapies, and optimization of supportive care.

BACKGROUND Airway involvement in patients with sickle cell disease (SCD) involves recurrent episodes of acute chest syndrome (ACS), co-existent asthma, lower airway obstruction (LAO), or airway hyper-responsiveness/ bronchodilator response (AHR/BDR). With increased recognition that sickle cell (SC) airway inflammation may be distinct from asthma, our aim was to study regional and individual practices among pediatric pulmonologists and elucidate the patient characteristics that determine the diagnosis of asthma or SC airway inflammation. METHODS A cross-sectional web-based survey including 6 case scenarios on diagnosis and management of pulmonary manifestations of pediatric SC airway disease was conducted. The case scenarios, combined different risk factors for airway inflammation: history of recurrent ACS, atopy, family history of asthma, LAO, or AHR/BDR, with possible responses including - diagnosis of asthma, SC airway inflammation, both or neither. RESULTS Of the 130 responses, 83 were complete. "Asthma" was diagnosed when LAO (OR, 7.96 [4.28, 14.79]; p

A 17-year-old male with history of neuromyelitis optica and seizures presented to the pulmonology clinic for evaluation of recurrent pneumonias. He had received rituximab for the past 6 years. Over the past 2 years, he experienced four episodes of pneumonia. In between these episodes, he would improve briefly but continued to have daily cough that was productive with yellow phlegm. He also had recurrent rhinitis and sinusitis despite multiple antibiotic courses. Review of chest X-rays revealed localized right middle lobe and right lower lobe infiltrates. An extensive workup was performed, including computed tomography (CT) of the chest and bronchoscopy to rule out congenital lesions of the right lung and foreign body aspiration. Chest CT showed right lower lobe bronchiectasis. Flexible bronchoscopy with bronchoalveolar lavage showed normal anatomy with thick mucus secretions in the right lower lobe. Immunologic evaluation was performed and revealed low levels of immunoglobulin (Ig)-G, IgM, and IgA, which had declined since initiation of rituximab. Lymphocyte subset testing was remarkable for low cluster of differentiation (CD)-19. He was referred to allergy and immunology and was initiated on immunoglobulin-replacement therapy (IGRT) for acquired hypogammaglobulinemia secondary to rituximab. There was marked clinical improvement after initiation of IGRT.

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.

Asthma and sickle cell disease (SCD) are common chronic conditions in children of African ancestry that are characterized by cough, wheeze, and obstructive patterns on pulmonary function. Pulmonary function testing in children with SCD has estimated a prevalence of obstructive lung disease ranging from 13% to 57%, and airway hyper-responsiveness of up to 77%, independent of a diagnosis of asthma. Asthma co-existing with SCD is associated with increased risk of acute chest syndrome (ACS), respiratory symptoms, pain episodes, and death. However, there are inherent differences in the pathophysiology of SCD and asthma. While classic allergic asthma in the general population is associated with a T-helper 2 cell (Th-2 cells) pattern of cell inflammation, increased IgE levels and often positive allergy testing, inflammation in SCD is associated with different inflammatory pathways, involving neutrophilic and monocytic pathways, which have been explored to a limited extent in mouse models and with a dearth of human studies. The current review summarizes the existent literature on sickle cell related airway inflammation and its cross roads with allergic asthma-related inflammation, and discusses the importance of further elucidating and understanding these common and divergent inflammatory pathways in human studies to facilitate development of targeted therapy for children with SCD and pulmonary morbidity.

Background 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. Methods 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. Results 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/m2 (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. Conclusions 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. Pediatr Blood Cancer 2014;61:1679–1684. © 2014 Wiley Periodicals, Inc.

Summary Background 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. Methods 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. Results 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 (Vdose) of radiation, mostly above V20. Conclusion PFT abnormalities are common even when modern radiation techniques are used. A significant correlation between radiation parameters and PFT abnormalities was noted. Pediatr Pulmonol. 2015; 50:596–603. © 2014 Wiley Periodicals, Inc.

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.

We report a case of a young boy with recurrent episodes of syncope at elevated altitude. While not conforming to common presentations of altitude sickness, the differential diagnoses and possible etiologies are discussed.

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.

A 3-month-old baby was diagnosed with obstructive sleep apnea (OSA) on polysomnography (PSG) with a high apnea hypopnea index (AHI). On further investigations he was found to have a vallecular cyst that was successfully treated. We discuss the clinical presentation of vallecular cysts and the importance of polysomnography in identifying this rare condition.

Varicella (chickenpox), a common childhood infection caused by the varicella-zoster virus, is self-limiting and usually benign. Although atypical manifestations of the virus are occasionally seen, it rarely presents with cardiovascular sequelae. Cardiovascular complications of varicella can include pericarditis, myocarditis, or endocarditis. Herein, we report the case of a 17-year-old boy who had varicella infection and severe chest pain. Examination revealed atypical electrocardiographic findings of pericarditis and remarkably elevated cardiac biomarker levels: peak cardiac troponin I, 37.2 ng/mL; total creatine kinase, 1,209 U/L; and creatine kinase-MB fraction, 133.6 ng/mL. After results of coronary angiography reliably excluded ischemia and myocardial infarction, the diagnosis was varicella myopericarditis. The patient was placed on a medical regimen during and after 5 days of hospitalization. In 2 weeks, he was asymptomatic, and at 6 months, he was doing well and had normal electrocardiographic and echocardiographic results.To our knowledge, cardiac enzyme elevations to these levels have not been reported in cases of cardiovascular sequelae of varicella. We discuss the diagnostic challenges of this atypical case and suggest that clinicians be aware that varicella disease is most often, but not always, benign.

* 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 …

Current therapy for acute lymphoblastic leukemia have resulted in cure rates over 80%. Relapses occur most frequently in the bone marrow. We report the unusual case of a young man who presented with an isolated kidney relapse after maintaining remission from acute lymphoblastic leukemia for over 6 years. Sites of extramedullary relapse and a review of the literature are discussed.