title: Prospective, longitudinal study of plastic bronchitis cast pathology and responsiveness to tissue plasminogen activator.
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.
authors.affiliation: Department of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Heath
authors.forename: Shelley
authors.initials: S
authors.lastname: Ling
authors.forename: Jennifer
authors.initials: J
authors.lastname: Racz
authors.forename: Gerta
authors.initials: G
authors.lastname: Mane
authors.forename: Lindsay
authors.initials: L
authors.lastname: Schmidt
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Myers
authors.forename: Wan C
authors.initials: WC
authors.lastname: Tsai
authors.forename: Regine L
authors.initials: RL
authors.lastname: Caruthers
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Hirsch
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Stringer
mesh_terms: D000280:Administration, Inhalation; D001980:Bronchi / Q000473:pathology*; D001991:Bronchitis / Q000188:drug therapy* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D016612:Paraffin Embedding; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D005343:Fibrinolytic Agents; D005337:Fibrin; D010959:Tissue Plasminogen Activator