Detection of Bronchiolitis Obliterans Syndrome Following Pediatric Hematopoietic Stem Cell Transplantation. An Official American Thoracic Society Clinical Practice Guideline.

BACKGROUND: Many children undergo allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for the treatment of malignant and non-malignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common non-infectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent National Institutes of Health workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. METHODS: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of post-HSCT BOS in children. Systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. RESULTS: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. CONCLUSIONS: This document provides an evidence-based approach to detection of post-HSCT BOS in children, while also highlighting considerations for implementation of each recommendation. Further, the document describes important areas for future research.

Diagnosis of Post-Hematopoietic Stem Cell Transplantation Bronchiolitis Obliterans Syndrome in Children: Time for a Rethink?

Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT. Unfortunately, during the development of a recent American Thoracic Society (ATS) Clinical Practice Guideline on this topic, it became apparent that the NIH criteria have significant limitations in the pediatric population, leading to late diagnosis of BOS. Specific limitations include use of an outdated pulmonary function testing reference equation, a reliance on spirometry, use of a fixed forced expiratory volume in 1 second (FEV1) threshold, focus on obstructive defects defined by FEV1/vital capacity, and failure to acknowledge that BOS and infection can coexist. In this review, we summarize the evidence regarding the limitations of the current criteria. We also suggest potential evidence-based ideas for improving these criteria. Finally, we highlight a new proposed criteria for post-HSCT BOS in children that were developed by the authors of the recently published ATS clinical practice guideline, along with a pathway forward for improving timely diagnosis of BOS in children post-HSCT.

Pediatric Pulmonology 2023 year in review: Rare and diffuse lung disease.

The field of pediatric rare and diffuse lung disease continues its maturation as research advances the understanding of diagnosis and treatment of children's interstitial lung disease, noncystic fibrosis bronchiectasis, and primary ciliary dyskinesia. The rarity and breadth of these conditions make them challenging to study, yet we continue to make progress in our understanding of pathophysiology, genotype/phenotype relationships, and treatment. Papers published on these topics in Pediatric Pulmonology and other journals in 2023 describe the power of multicenter cooperation and patient registries, enhance our understanding of pathophysiology and genotype/phenotype relationships, and report progress in treatments. In this review, we hope to increase awareness and knowledge of these conditions and to inspire future research.

Improved tracheostomy-dependent patient outcomes after implementation of the Pediatric Resident Education in Pulmonary (PREP) Boot Camp.

INTRODUCTION: Children with tracheostomies are high risk for morbidity and mortality. Pediatric resident physicians are not routinely taught skills to care for this vulnerable patient population. Few reports link educational interventions to improved patient outcomes. This study evaluates the impact of an intensive educational training program on pediatric residents' observed skills and tracheostomy-dependent patient outcomes. METHODS: Pediatric post-graduate year 2 (PGY2) resident physicians rotating through the inpatient pediatric pulmonology month at Children's Hospital Colorado July 2018-2019 participated in the Pediatric Resident Education in Pulmonary (PREP) Boot Camp, an intensive educational program with an interactive lecture and simulation experience on patients with tracheostomy-dependence. PGY2s who partook in PREP and PGY3s who rotated before PREP initiation were invited to be studied. Primary outcomes included: (1) resident skills assessed by direct observation during simulation encounters and (2) rates of intensive care unit (ICU) transfers in tracheostomy-dependent patients following acute events before and after introduction of PREP. We hypothesized that increased education would enhance resident skills and improve patient outcomes by decreasing the rate of ICU transfers. RESULTS: PGY2 residents retained skills learned during PREP up to 11 months following initial participation, and significantly outperformed their PGY3 counterparts. There was a significant decrease in ICU transfer rate in patients with tracheostomies admitted to the pulmonary team during the 19 months following initiation of PREP. CONCLUSIONS: Enhanced early education may improve resident physicians' ability to care for complex patients with tracheostomies and could improve outcomes in this high-risk population.

Pediatric Pulmonology 2022 year in review: Rare and diffuse lung disease.

The field of rare and diffuse pediatric lung disease continues to evolve and expand rapidly as clinicians and researchers make advancements in the diagnosis and treatment of children's interstitial and diffuse lung disease, non-cystic fibrosis bronchiectasis, and primary ciliary dyskinesia. Papers published on these topics in Pediatric Pulmonology and other journals in 2022 describe newly recognized disorders, elucidate disease mechanisms and courses, explore potential biomarkers, and assess novel treatments. In this review, we will discuss these important advancements and place them in the context of existing literature.

The US national registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort.

INTRODUCTION: 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. METHODS: 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. RESULTS: We report the study design and selected 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, 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%). CONCLUSION: This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

Pediatric pulmonology 2021 year in review: Rare and diffuse lung disease.

The field of rare and diffuse pediatric lung disease is experiencing rapid progress as diagnostic and therapeutic options continue to expand. In this annual review, we discuss manuscripts published in Pediatric Pulmonology in 2021 in (1) children's interstitial and diffuse lung disease, (2) congenital airway and lung malformations, and (3) noncystic fibrosis bronchiectasis including primary ciliary dyskinesia. These include case reports, descriptive cohorts, trials of therapies, animal model studies, and review articles. The results are put into the context of other literature in the field. Each furthers the field in important ways, while also highlighting the continued need for further studies.

How we approach pediatric congenital chylous effusions and ascites.

Congenital lymphatic leak may develop in patients with maldeveloped lymphatics and result in life-threatening fluid and electrolyte imbalance, protein deficiency, and immunodeficiency. Rapid diagnosis and therapy are necessary to prevent these complications; however, the field lacks clinical trials to support standardized diagnostic treatment guidelines. We present our current multidisciplinary approach to the diagnosis and management of congenital lymphatic leak including chylous pleural effusions and ascites. Depending on the rate of lymphatic leak, therapy can range from observation with nutritional modifications to surgical and interventional procedures aimed to reduce lymphatic drainage. Modalities to image central and peripheral lymphatics have advanced considerably. Genetic variants and subsequent targets that drive lymphatic maldevelopment have expanded the repertoire of possible pharmacotherapeutic options.

High-Altitude Pulmonary Edema in Colorado Children: A Cross-Sectional Survey and Retrospective Review.

Kelly, Timothy D., Maxene Meier, Jason P. Weinman, Dunbar Ivy, John T. Brinton, and Deborah R. Liptzin. High-altitude pulmonary edema in Colorado children: a cross-sectional survey and retrospective review. High Alt Med Biol. 23:119-124, 2022. Introduction: Few studies of high-altitude pulmonary edema (HAPE) are specific to the pediatric population. The purpose of this investigation was to further characterize the radiographic patterns of pediatric HAPE, and to better understand ongoing risk following an initial pediatric HAPE episode. Methods: This study uses both a retrospective chart review and cross-sectional survey. Pediatric patients with HAPE at a single quaternary referral center in the Rocky Mountain Region were identified between the years 2013 and 2020. Patients were eligible if they presented with a clinical diagnosis of HAPE and had a viewable chest radiograph (CXR). Surveys were sent to eligible patients/families to gather additional information relating to family history, puberty, and HAPE recurrence. Results: Forty-two individuals met criteria for clinical diagnosis of HAPE with a viewable CXR. A majority of CXRs (24/42, 57.1%) demonstrated predominant right-sided involvement. Similarly, 24 CXRs (24/42, 57.1%) demonstrated predominant upper lobe involvement. Twenty-one (21/42, 50%) surveys were completed. A minority of individuals went on to experience at least one other HAPE episode (8/19, 42.1%). Conclusion: The most common radiographic pattern seen in pediatric HAPE is pulmonary edema that favors the right lung and upper lobes. After an initial HAPE presentation, some children will experience additional HAPE episodes.

Pulmonary surveillance in pediatric hematopoietic stem cell transplant: A multinational multidisciplinary survey.

BACKGROUND: Hematopoietic Stem Cell Transplant (HSCT) is an established treatment for malignant and non-malignant conditions and pulmonary disease is a leading cause of late term morbidity and mortality. Accurate and early detection of pulmonary complications is a critical step in improving long term outcomes. Existing guidelines for surveillance of pulmonary complications post-HSCT contain conflicting recommendations. AIM: To determine the breadth of current practice in monitoring for pulmonary complications of pediatric HSCT. METHODS: An institutional review board approved, online, anonymous multiple-choice survey was distributed to HSCT and pulmonary physicians from the United States of America and Australasia using the REDcap platform. The survey was developed by members of the American Thoracic Society Working Group on Complications of Childhood Cancer, and was designed to assess patient management and service design. RESULTS: A total of 40 (34.8%) responses were received. The majority (62.5%) were pulmonologists, and 82.5% were from the United States of America. In all, 67.5% reported having a protocol for monitoring pulmonary complications and 50.0% reported adhering "well" or "very well" to protocols. Pulmonary function tests (PFTs) most commonly involved spirometry and diffusion capacity for carbon monoxide. The frequency of PFTs varied depending on time post-HSCT and presence of complications. In all, 55.0% reported a set threshold for a clinically significant change in PFT. CONCLUSIONS: These results illustrate current variation in surveillance for pulmonary complications of pediatric HSCT. The results of this survey will inform development of future guidelines for monitoring of pulmonary complications after pediatric HSCT.

Fibrin airway cast obstruction: Experience, classification, and treatment guideline from Denver.

BACKGROUND AND OBJECTIVES: Plastic bronchitis (PB) is a condition characterized by the formation of thick airway casts leading to acute and often life-threatening airway obstruction. PB occurs mainly in pediatric patients with congenital heart disease (CHO) who have undergone staged surgical palliation (Glenn, Fontan), but can also occur after chemical inhalation, H1N1, severe COVID-19, sickle cell disease, severe asthma, and other diseases. Mortality risk from PB can be up to 40%-60%, and no treatment guideline exist. The objectives herein are to develop a standardized evaluation, classification, and treatment guideline for PB patients presenting with tracheobronchial casts, based on our experience with PB at the Children's Hospital of Colorado in Denver. METHODS: We describe 11 patients with CHO-associated PB (post-Fontan [n = 9], pre-Fontan [n = 2]) who presented with their initial episodes. We utilized histopathological analysis of tracheobronchial casts to guide treatment in these patients, utilizing our hospital-wide guideline document and classification system. RESULTS: We found that 100% of post-Fontan PB patients had fibrinous airway casts, while pre-Fontan PB casts were fibrinous only in one of two patients (50%). Utilizing histopathology as a guide to therapy, PB patients with fibrin airway casts were treated with airway-delivered fibrinolytics and anticoagulants, as well as aggressive airway clearance and other supportive care measures. These therapies resulted in successful cast resolution and improved survival in post-Fontan PB patients. CONCLUSION: We have shown an improved outcome in PB patients whose treatment plan was based on Denver's PB classification schema and standardized treatment guideline based on tracheobronchial cast histopathology.

Vaping and diffuse alveolar hemorrhage: All EVALI is not created equal.

E-cigarette, or vaping product, use associated lung injury (EVALI) refers to respiratory illness in patients with recent vaping and no signs of infection or underlying illness. EVALI can cause severe acute respiratory distress syndrome and death. A spectrum of diagnoses can fit the description of EVALI since it relies heavily on nonspecific, radiographic findings. We present a rare case of EVALI in which a patient with a history of vaping presented with acute hypoxemia and was diagnosed with diffuse alveolar hemorrhage (DAH). The mechanism of injury of DAH due to vaping is unknown, and further research into the topic is required.