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Prospective, Longitudinal Study of Plastic Bronchitis Cast Pathology and Responsiveness to Tissue Plasminogen Activator

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Abstract

Plastic bronchitis (PB) is a rare disease that often occurs in patients with congenital heart disease (CHD) who have undergone staged single-ventricle palliation. It is characterized by the formation of rubbery “casts” in the airways. PB treatment frequently includes inhaled tissue plasminogen activator (tPA). However, the efficacy of tPA to reduce cast burden is unknown. This is further complicated by our lack of knowledge of cast composition. We obtained spontaneously expectorated PB casts from children (n = 4) with CHD and one adult patient with idiopathic PB. Pathological assessment was made from paraffin-preserved samples. Casts were treated with phosphate-buffered saline (PBS) or tPA. Cast response to tPA was assessed by changes in cast weight and the production of fibrin d-dimer. Independent of dose, tPA reduced cast weight compared with PBS-treatment (P = 0.001) and increased d-dimer levels. Histological staining showed that PB casts from all patients were composed of fibrin and contained notable numbers of lymphocytes. Cast composition did not change over time. Collectively, these data support that in our PB patients, casts are composed of fibrin and are responsive to tPA treatment. This makes inhaled tPA a potentially viable option for symptomatic relief of PB while we work to unravel the complexity of PB pathogenesis.

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References

  1. Barber BJ, Burch GH, Tripple D, Balaji S (2004) Resolution of plastic bronchitis with atrial pacing in a patient with fontan physiology. Pediatr Cardiol 25:73–76

    Article  PubMed  CAS  Google Scholar 

  2. Brogan TV, Finn LS, Pyskaty DJ Jr, Redding GJ, Ricker D, Inglis A, Gibson RL (2002) Plastic bronchitis in children: a case series and review of the medical literature. Pediatr Pulmonol 34:482–487

    Article  PubMed  Google Scholar 

  3. Buk SJ (1984) Simultaneous demonstration of connective tissue elastica and fibrin by a combined Verhoeff’s elastic-Martius-scarlet-blue trichrome stain. Stain Technol 59:1–5

    PubMed  CAS  Google Scholar 

  4. Chaudhari M, Stumper O (2004) Plastic bronchitis after Fontan operation: treatment with stent fenestration of the Fontan circuit. Heart 90:801

    Article  PubMed  CAS  Google Scholar 

  5. Chu EK, Cheng J, Foley JS, Mecham BH, Owen CA, Haley KJ, Mariani TJ, Kohane IS, Tschumperlin DJ, Drazen JM (2006) Induction of the plasminogen activator system by mechanical stimulation of human bronchial epithelial cells. Am J Respir Cell Mol Biol 35:628–638

    Article  PubMed  CAS  Google Scholar 

  6. Collen D, Lijnen HR (1986) The fibrinolytic system in man. Crit Rev Oncol Hematol 4:249–301

    Article  PubMed  CAS  Google Scholar 

  7. Costello JM, Steinhorn D, McColley S, Gerber ME, Kumar SP (2002) Treatment of plastic bronchitis in a Fontan patient with tissue plasminogen activator: a case report and review of the literature. Pediatrics 109:e67

    Article  PubMed  Google Scholar 

  8. DiCindio S, Theroux M, Costarino AT Jr, Cook S, O’Reilly R (2004) Plastic bronchitis: a case report. Paediatr Anaesth 14:520–523

    Article  PubMed  Google Scholar 

  9. Do TB, Chu JM, Berdjis F, Anas NG (2009) Fontan patient with plastic bronchitis treated successfully using aerosolized tissue plasminogen activator: a case report and review of the literature. Pediatr Cardiol 30:352–355

    Article  PubMed  Google Scholar 

  10. Dunn JS, Nayar R, Campos J, Hybertson BM, Zhou Y, Manning MC, Repine JE, Stringer KA (2005) Feasibility of tissue plasminogen activator formulated for pulmonary delivery. Pharm Res 22:1700–1707

    Article  PubMed  CAS  Google Scholar 

  11. Goldberg DJ, Dodds K, Rychik J (2010) Rare problems associated with the Fontan circulation. Cardiol Young 20:113–119

    Article  PubMed  Google Scholar 

  12. Goo HW, Jhang WK, Kim YH, Ko JK, Park IS, Park JJ, Yun TJ, Seo DM (2008) CT findings of plastic bronchitis in children after a Fontan operation. Pediatr Radiol 38:989–993

    Article  PubMed  Google Scholar 

  13. Griffiths ER, Kaza AK, Wyler von Ballmoos MC, Loyola H, Valente AM, Blume ED, del Nido P (2009) Evaluating failing Fontans for heart transplantation: predictors of death. Ann Thorac Surg 88:558–563 discussion 563–564

    Article  PubMed  Google Scholar 

  14. Hoylaerts M, Rijken DC, Lijnen HR, Collen D (1982) Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 257:2912–2919

    PubMed  CAS  Google Scholar 

  15. Lackowski NP, Pitzer JE, Tobias M, Van Rheen Z, Nayar R, Mosharaff M, Stringer KA (2010) Safety of prolonged, repeated administration of a pulmonary formulation of tissue plasminogen activator in mice. Pulmon Pharmacol Ther 23:107–114

    Article  CAS  Google Scholar 

  16. Madsen P, Shah SA, Rubin BK (2005) Plastic bronchitis: new insights and a classification scheme. Paediatr Respir Rev 6:292–300

    Article  PubMed  Google Scholar 

  17. Nishiuma T, Sisson TH, Subbotina N, Simon RH (2004) Localization of plasminogen activator activity within normal and injured lungs by in situ zymography. Am J Respir Cell Mol Biol 31:552–558

    Article  PubMed  CAS  Google Scholar 

  18. Onoue Y, Adachi Y, Ichida F, Miyawaki T (2003) Effective use of corticosteroid in a child with life-threatening plastic bronchitis after Fontan operation. Pediatr Int 45:107–109

    Article  PubMed  Google Scholar 

  19. Park JY, Elshami AA, Kang DS, Jung TH (1996) Plastic bronchitis. Eur Respir J 9:612–614

    Article  PubMed  CAS  Google Scholar 

  20. Peleg U, Schwartz S, Sirota G, Hochman I, Cohen D, Picard E (2005) Persistent plastic bronchitis in a child after cardiac surgery. Israel Med Assoc J 7:122–124

    Google Scholar 

  21. Preciado D, Verghese S, Choi S (2010) Aggressive bronchoscopic management of plastic bronchitis. Int J Pediatr Otorhinolaryngol 74:820–822

    Article  PubMed  Google Scholar 

  22. Quasney MW, Orman K, Thompson J, Ring JC, Salim M, Schoumacher RA, Watson D, Novick W, Deitcher SR, Joyner R (2000) Plastic bronchitis occurring late after the Fontan procedure: treatment with aerosolized urokinase. Crit Care Med 28:2107–2111

    Article  PubMed  CAS  Google Scholar 

  23. Setzer N, Malvezzi L, McBride W (2001) “Plastic bronchitis” complicating recovery from congenital heart surgery. J Pediatr 138:605

    Article  PubMed  CAS  Google Scholar 

  24. Shah SS, Drinkwater DC, Christian KG (2006) Plastic bronchitis: is thoracic duct ligation a real surgical option? Ann Thorac Surg 81:2281–2283

    Article  PubMed  Google Scholar 

  25. Stringer KA, Tobias M, Dunn JS, Campos J, Van Rheen Z, Mosharraf M, Nayar R (2008) Accelerated dosing frequency of a pulmonary formulation of tissue plasminogen activator is well-tolerated in mice. Clin Exp Pharmacol Physiol 35:1454–1460

    PubMed  CAS  Google Scholar 

  26. Suenson E, Lutzen O, Thorsen S (1984) Initial plasmin-degradation of fibrin as the basis of a positive feed-back mechanism in fibrinolysis. Eur J Biochem 140:513–522

    Article  PubMed  CAS  Google Scholar 

  27. Tzifa A, Robards M, Simpson JM (2005) Plastic bronchitis; a serious complication of the Fontan operation. Int J Cardiol 101:513–514

    Article  PubMed  CAS  Google Scholar 

  28. Wakeham MK, Van Bergen AH, Torero LE, Akhter J (2005) Long-term treatment of plastic bronchitis with aerosolized tissue plasminogen activator in a Fontan patient. Pediatr Crit Care Med 6:76–78

    Article  PubMed  Google Scholar 

  29. Zaccagni HJ, Kirchner L, Brownlee J, Bloom K (2008) A case of plastic bronchitis presenting 9 years after fontan. Pediatr Cardiol 29:157–159

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by the National Institute of Child Health and Human Development (NICHD) grant No. R15 HD065594. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the National Institutes of Health. This study was presented, in part, at the NIH Conference on Clinical Research for Rare Diseases, Bethesda, MD; September 21, 2010 and the American Thoracic Society Meeting, Denver, CO; May 13–18, 2011.

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Authors and Affiliations

  1. Department of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA

    Lauren Heath, Shelley Ling, Jennifer Racz, Gerta Mane & Kathleen A. Stringer

  2. Division of Anatomic Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA

    Lindsay Schmidt & Jeffrey L. Myers

  3. Division of Pediatric Pulmonology, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, 48109, USA

    Wan C. Tsai

  4. Department of Pharmacy, University of Michigan Hospitals and Health Centers, University of Michigan, Ann Arbor, MI, 48109, USA

    Regine L. Caruthers

  5. Department of Surgery, Division of Pediatric Cardiac Surgery, University of Michigan Health System, Ann Arbor, MI, 48109, USA

    Jennifer C. Hirsch

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  1. Lauren Heath
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  2. Shelley Ling
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  3. Jennifer Racz
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  4. Gerta Mane
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  5. Lindsay Schmidt
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  6. Jeffrey L. Myers
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  7. Wan C. Tsai
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  8. Regine L. Caruthers
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  9. Jennifer C. Hirsch
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  10. Kathleen A. Stringer
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Corresponding author

Correspondence to Kathleen A. Stringer.

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Heath, L., Ling, S., Racz, J. et al. Prospective, Longitudinal Study of Plastic Bronchitis Cast Pathology and Responsiveness to Tissue Plasminogen Activator. Pediatr Cardiol 32, 1182–1189 (2011). https://doi.org/10.1007/s00246-011-0058-x

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  • DOI: https://doi.org/10.1007/s00246-011-0058-x

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