Inhaled Tissue Plasminogen Activator for Acute Plastic Bronchitis

Inclusion Criteria (patients with plastic bronchitis):

• ≥ 5 years of age but ≤24 years of age and weigh at least 18.6 kg (41 lbs).
• Patients with CHD that have a history of PB with previous airway cast production and/or present with symptoms of an acute exacerbation (e.g., difficulty breathing, dyspnea) of PB that requires hospitalization. An acute exacerbation of PB is defined as either respiratory symptoms suspicious for airway cast formation and/or the expectoration of, or a bronchoscopy retrieved, fibrin PB cast.
• Patients without CHD that present with an acute exacerbation of PB, defined as the expectoration of, or a bronchoscopy retrieved, fibrin PB cast that causes acute respiratory distress (e.g., severe coughing, difficulty breathing, dyspnea) or a history of PB with pathologic evidence of fibrin airway cast production. Either a cast sample (at least ½ inch (~4cm)) or a pathology report that documents PB cast fibrin content must be submitted to the UM pathology core.
• Must be able to use a mouthpiece nebulizer.
• Informed consent (with parental if age ≥14 years) or assent for age ≥10 and /= 100th percentile or BMI > 30
• Known cystic fibrosis
• Currently receiving dornase-alfa and/or inhaled unfractionated or low molecular weight heparin and/or a direct acting oral anticoagulant (e.g., dabigatran, rivaroxaban)
• Inhaled unfractionated or low molecular weight heparin must be discontinued at least 72h. Inhaled dornase alfa should be discontinued no later than the time of the start of enrollment in the treatment phase. If the patient is receiving inhaled tPA, this regimen must be discontinued and transitioned to the inpatient dosing regimen (5mg Q6h) of study drug.
• Direct acting oral anticoagulants must be discontinued one week prior to the start of enrollment in the treatment phase.
• Protein losing enteropathy
• Liver dysfunction (defined as ≥ 3X the normal levels of one or both liver transaminases, AST and AST)
• Transaminase levels acquired within the last 9 months can be used to assess liver function. If previously normal and there is no clinical indication that liver function has worsened, the patient can be enrolled. If there are no transaminase values within the last 9 months, they need to be acquired as part of screening
• Need for concomitant intravenous or sub-cutaneous anti-coagulation with resulting anti- Xa levels > 0.5 (low molecular weight heparins) or > 0.3 (unfractionated heparin)
• International normalized ratio (INR) > 2.0 if not receiving warfarin
• Patients being actively treated for thrombosis
• Concomitant use of a thienopyridine class antiplatelet agent (e.g., clopidogrel)
• A platelet count of < 100, 000 platelets/µL
• A hematocrit <30%
• Gross hematuria on screening urinalysis
• Pregnant or lactating women (negative pregnancy test required for girls/women of childbearing potential at the time of inhaled tPA administration). All women of child- bearing potential must be willing to practice appropriate contraception throughout the study.
• Subjects who are known positive for, or are hospitalized with COVID-19 caused by the new coronavirus, SARS CoV-2, at the start of the treatment phase.
• Suspected or active concurrent infectious illness.

Inclusion Criteria for Healthy Controls

• Healthy children ≥ 5 years of age but ≤18 years of age with no other underlying concomitant illness or chronic medication use (with the exception of vitamin supplements)
• Weigh at least 18.6 kg (41 lbs)

Inclusion Criteria for Healthy non-PB Fontan Controls

• Children ≥ 5 years of age but ≤18 years of age with uncomplicated Fontan physiology with no history of PB, other Fontan-associated complications (e.g., hepatopathy, PLE), or other concomitant illnesses (e.g., asthma).
• Weigh at least 18.6 kg (41 lbs)

Inclusion Criteria for PLE Fontan Controls

• Children ≥ 5 years of age but ≤18 years of age with Fontan physiology, no history of PB and a diagnosis of PLE defined as clini