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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.
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.
The coronavirus disease 2019 (COVID‐19) pandemic has caused respiratory failure and associated mortality in numbers that have overwhelmed global health systems. Thrombotic coagulopathy is present in nearly three quarters of patients with COVID‐19 admitted to the intensive care unit, and both the clinical picture and pathologic findings are consistent with microvascular occlusive phenomena being a major contributor to their unique form of respiratory failure. Numerous studies are ongoing focusing on anticytokine therapies, antibiotics, and antiviral agents, but none to date have focused on treating the underlying thrombotic coagulopathy in an effort to improve respiratory failure in COVID‐19. There are animal data and a previous human trial demonstrating a survival advantage with fibrinolytic therapy to treat acute respiratory distress syndrome. Here, we review the extant and emerging literature on the relationship between thrombotic coagulopathy and pulmonary failure in the context of COVID‐19 and present the scientific rationale for consideration of targeting the coagulation and fibrinolytic systems to improve pulmonary function in these patients.
Background The coronavirus disease 2019 (COVID‐19) pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non–COVID‐19) demonstrated improvement in pulmonary function in patients ARDS using fibrinolytic therapy. A follow‐up trial using the widely available tissue‐type plasminogen activator (t‐PA) alteplase is now needed to assess optimal dosing and safety in this critically ill patient population. Objective To describe the design and rationale of a phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID‐19–induced ARDS. Patients/Methods A rapidly adaptive, pragmatic, open‐label, randomized, controlled, phase IIa clinical trial will be conducted with 3 groups: intravenous alteplase 50 mg, intravenous alteplase 100 mg, and control (standard‐of‐care). Inclusion criteria are known/suspected COVID‐19 infection with PaO2/FiO2 ratio <150 mm Hg for > 4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50 mg or 100 mg followed by heparin infusion for systemic anticoagulation, with alteplase redosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results The primary outcome is improvement in PaO2/FiO2 at 48 hours after randomization. Other outcomes include ventilator‐ and intensive care unit–free days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifty eligible patients will be enrolled in a rapidly adaptive, modified stepped‐wedge design with 4 looks at the data. Conclusion Findings will provide timely information on the safety, efficacy, and optimal dosing of t‐PA to treat moderate/severe COVID‐19–induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).
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