tPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life-saving rescue therapy after a significant SM inhalation exposure incident.

Inhalation of powerful chemical agents, such as sulfur mustard (SM), can have debilitating pulmonary consequences, such as bronchiolitis obliterans (BO) and parenchymal fibrosis (PF). The underlying pathogenesis of disorders after SM inhalation is not clearly understood, resulting in a paucity of effective therapies. In this study, we evaluated the role of profibrotic pathways involving transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) in the development of BO and PF after SM inhalation injury using a rat model. Adult Sprague-Dawley rats were intubated and exposed to SM (1.0 mg/kg), then monitored daily for respiratory distress, oxygen saturation changes, and weight loss. Rats were killed at 7, 14, 21, or 28 days, and markers of injury were determined by histopathology; pulmonary function testing; and assessment of TGF-β, PDGF, and PAI-1 concentrations. Respiratory distress developed over time after SM inhalation, with progressive hypoxemia, respiratory distress, and weight loss. Histopathology confirmed the presence of both BO and PF, and both gradually worsened with time. Pulmonary function testing demonstrated a time-dependent increase in lung resistance, as well as a decrease in lung compliance. Concentrations of TGF-β, PDGF, and PAI-1 were elevated at 28 days in lung, BAL fluid, and/or plasma. Time-dependent development of BO and PF occurs in lungs of rats exposed to SM inhalation, and the elevated concentrations of TGF-β, PDGF, and PAI-1 suggest involvement of these profibrotic pathways in the aberrant remodeling after injury.

Pediatric asthma is a common chronic condition with wide-ranging implications for children's health, their families, and the health care system. The diagnosis may be relatively straightforward for the child with characteristic symptoms, triggers, and response to therapy, but there are other less common presentations that can make the diagnosis challenging. Diagnosing asthma in a toddler with recurrent wheezing can be particularly difficult. Treating asthma in a step-wise fashion usually reduces symptom frequency and improves asthma control. Asthma exacerbations and poor outcomes from acute exacerbations remain an area in which we have room for improvement. This article provides an overview of the diagnosis and management of childhood asthma for the primary care provider. [ Pediatr Ann. 2019;48(3):e103–e109.]

Neuroendocrine cell Hyperplasia of Infancy (NEHI) presents with tachypnea, retractions, hypoxemia, and often failure to thrive. The radiologic and physiologic findings in infants with NEHI have been well described with a distinct geographic pattern of ground-glass opacities on chest computerized tomography imaging and profound air-trapping on infant pulmonary function testing. Despite gradual improvement over time, unexplained exacerbation has been observed but not well characterized. We present physiological and radiological changes of increased air-trapping during acute exacerbations in two older children with NEHI who had previously experienced significant clinical improvement. These cases illustrate previously undescribed manifestations of NEHI in older children.

Summary Background Inhalation of sulfur mustard (SM) and SM analog, 2-chloroethyl ethyl sulfide (CEES), cause fibrinous cast formation that occludes the conducting airways, similar to children with Fontan physiology-induced plastic bronchitis. These airway casts cause significant mortality and morbidity, including hypoxemia and respiratory distress. Our hypothesis was that intratracheal heparin, a highly cost effective and easily preserved rescue therapy, could reverse morbidity and mortality induced by bronchial cast formation. Methods Sprague-Dawley rats were exposed to 7.5% CEES via nose-only aerosol inhalation to produce extensive cast formation and mortality. The rats were distributed into three groups: non-treated, phosphate-buffered saline (PBS)-treated, and heparin-treated groups. Morbidity was assessed with oxygen saturations and clinical distress. Blood and bronchoalveolar lavage fluid (BALF) were obtained for analysis, and lungs were fixed for airway microdissection to quantify the extent of airway cast formation. Results Heparin, given intratracheally improved survival (100%) when compared to non-treated (75%) and PBS-treated (90%) controls. Heparin-treated rats also had improved oxygen saturations, clinical distress and airway cast scores. Heparin-treated rats had increased thrombin clotting times, factor Xa inhibition and activated partial thromboplastin times, indicating systemic absorption of heparin. There were also increased red blood cells (RBCs) in the BALF in 2/6 heparin-treated rats compared to PBS-treated control rats. Conclusions Intratracheal heparin 1 hr after CEES inhalation improved survival, oxygenation, airway obstruction, and clinical distress. There was systemic absorption of heparin in rats treated intratracheally. Some rats had increased RBCs in BALF, suggesting a potential for intrapulmonary bleeding if used chronically after SM inhalation.

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.

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Introduction Mucolipidosis type II (MLII) is a lysosomal storage disease causing systemic deposition of mucopolysaccharides. We describe imaging and bronchoscopy findings not previously reported in the literature in a child with MLII. Case A 9‐year‐old with MLII s/p hematopoietic stem‐cell transplant (HSCT), bronchiectasis, and aspiration presented with recurrent respiratory illnesses. Bronchoscopy and chest computed tomography were performed, showing a saber‐sheath trachea with fixed narrowing and curvature. Discussion This case describes potentially life‐threatening airway distortion in MLII despite HSCT that cannot be ameliorated with tracheostomy. Etiology is unknown but likely due to abnormal deposition causing an immobile, stenotic airway and restricted thorax.