Use of Aerosolized Tissue Plasminogen Activator in the Treatment of Plastic Bronchitis

Lubcke, Nicole; Nussbaum, Vicki M; Schroth, Mary K.

doi:10.1345/aph.1r690

Cited by 14 publications

(12 citation statements)

References 13 publications

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“…Our experience is in agreement with several small case-reports suggesting that t-PA is a safe and effective treatment of plastic bronchitis after Fontan [1,2,20,21]. Our preferred dose of 4 mg inhaled 2–4 times daily has been effective in reducing cast burden and allowing outpatient management of symptoms in several patients in our series.…”

Section: Commentsupporting

confidence: 91%

“…Plastic bronchitis may resolve after surgical or catheter-based interventions to improve hemodynamics or after cardiac transplantation [12]. Additionally, aerosolized tissue plasminogen activator (t-PA) is an important treatment option that may decrease cast burden and improve clinical symptoms in patients with plastic bronchitis after Fontan [1,2,20,21]. …”

Section: Introductionmentioning

confidence: 99%

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A Multifaceted Approach to the Management of Plastic Bronchitis After Cavopulmonary Palliation

Avitabile¹,

Goldberg²,

Dodds³

et al. 2014

The Annals of Thoracic Surgery

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Background Plastic bronchitis is a rare, potentially life-threatening complication after Fontan operation. Hemodynamic alterations (elevated central venous pressure and low cardiac output) likely contribute to the formation of tracheobronchial casts composed of inflammatory debris, mucin, and fibrin. Pathologic studies of cast composition support medical treatment with fibrinolytics such as inhaled tissue plasminogen activator (t-PA). Methods Retrospective case series of medical, surgical, and catheter-based management of patients with plastic bronchitis after cavopulmonary palliation. Results Fourteen patients (86% male, 93% white) were included. Median age at Fontan operation was 2.7 years (range 1.2–4.1) with median interval to plastic bronchitis presentation of 1.5 years (9 days–15.4 years). Cast composition was available for 11 patients (79%) and included fibrin deposits in 7. All patients were treated with pulmonary vasodilators. Thirteen patients (93%) were treated with inhaled t-PA. Hemodynamically significant lesions in the Fontan pathway were addressed via catheter-based (n=9) and surgical (n=3) interventions. Three patients (21%) underwent heart transplantation. Median length of follow-up was 2.7 years (0.6–8.7). Symptoms improved such that six of thirteen (46%) patients were weaned off t-PA. Rare or episodic casts are successfully managed with outpatient t-PA in the majority of other patients. Of the 3 patients who underwent heart transplant, two are asymptomatic and one has recurrent casts in the setting of elevated filling pressures and rejection. Conclusions A systematic step-wise algorithm, which includes optimization of hemodynamics, aggressive pulmonary vasodilation and inhaled t-PA, is an effective treatment strategy for patients with plastic bronchitis after cavopulmonary connection.

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Section: Commentsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

A Multifaceted Approach to the Management of Plastic Bronchitis After Cavopulmonary Palliation

Avitabile¹,

Goldberg²,

Dodds³

et al. 2014

The Annals of Thoracic Surgery

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“…The use of both nebulised dornase-α (DNase) and tissue plasminogen activator (t-PA) has been reported for the management of chylous bronchial casts 2. Due to coexistent dual antiplatelet therapy following drug-eluting coronary arterial stent implantation, we initially examined in vitro efficacy.…”

mentioning

confidence: 99%

A lesson in plasticity: a 74-year-old man with plastic bronchitis

Donovan

Marino

Shah

et al. 2017

Thorax

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“…Inhalation of nebulized tPA has therapeutic potential as a treatment for the rare, pediatric illness, PB (5–9). However, very little is known about the transport of tPA following delivery into the airways.…”

Section: Discussionmentioning

confidence: 99%

“…Inhaled nebulized tPA (alteplase, Genentech, South San Francisco, CA, USA) is often clinically used off-label to treat acute exacerbations of PB (5–9). tPA is a serine protease that degrades fibrin via the activation of plasminogen which yields plasmin and is used therapeutically to dissolve thrombus associated with MI, pulmonary embolism, and AIS (10–12).…”

Section: Introductionmentioning

confidence: 99%

A Role for Low Density Lipoprotein Receptor-Related Protein 1 in the Cellular Uptake of Tissue Plasminogen Activator in the Lungs

et al. 2015

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Purpose To gain knowledge of lung clearance mechanisms of inhaled tissue plasminogen activator (tPA). Methods Using an in vivo mouse model and ex vivo murine whole organ cell suspensions, we examined the capability of the lungs to utilize LRP1 receptor-mediated endocytosis (RME) for the uptake of exogenous tPA with and without an LRP1 inhibitor, receptor associated protein (RAP), and quantitatively compared it to the liver. We also used a novel imaging technique to assess the amount LRP1 in sections of mouse liver and lung. Results Following intratracheal administration, tPA concentrations in the BALF declined over time following two-compartment pharmacokinetics suggestive of RME clearance mechanism. Ex vivo studies showed that lung and liver cells are similarly capable of tPA uptake via LRP1 RME which was reduced by ~50% by RAP. The comparable lung and liver uptake of tPA is likely due to equivalent amounts of LRP1 of which there was an abundance of LRP1 in alveolar epithelium. Conclusions Our findings indicate that LRP1 RME is a candidate clearance mechanism for inhaled tPA which has implications for the development of safe and effective dosing regimens of inhaled tPA for the treatment of plastic bronchitis and other fibrin-inflammatory airway diseases in which inhaled tPA may have utility.

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Use of Aerosolized Tissue Plasminogen Activator in the Treatment of Plastic Bronchitis

Abstract: t-PA can be nebulized and inhaled for successful inhibition of bronchial cast formation. More information to determine the most effective dose and duration of therapy is needed to effectively improve the lives of people with plastic bronchitis.

Cited by 14 publications

References 13 publications

A Multifaceted Approach to the Management of Plastic Bronchitis After Cavopulmonary Palliation

A Multifaceted Approach to the Management of Plastic Bronchitis After Cavopulmonary Palliation

A lesson in plasticity: a 74-year-old man with plastic bronchitis

A Role for Low Density Lipoprotein Receptor-Related Protein 1 in the Cellular Uptake of Tissue Plasminogen Activator in the Lungs

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