title: Pilot study exploring lung allograft surfactant protein A (SP-A) expression in association with lung transplant outcome.
abstract: Primary graft failure and chronic lung allograft dysfunction (CLAD) limit lung transplant long-term outcomes. Various lung diseases have been correlated with surfactant protein (SP) expression and polymorphisms. We sought to investigate the role of SP expression in lung allografts prior to implantation, in relation to posttransplant outcomes. The expression of SP-(A, B, C, D) mRNA was assayed in 42 allografts. Posttransplant assessments include pulmonary function tests, bronchoscopy, broncho-alveolar lavage fluid (BALF) and biopsies to determine allograft rejection. BALF was assayed for SP-A, SP-D in addition to cytokines IL-8, IL-12 and IL-2. The diagnosis of CLAD was evaluated 6 months after transplantation. Lung allografts with low SP-A mRNA expression prior to implantation reduced survival (Log-rank p < 0.0001). No association was noted for the other SPs. Allografts with low SP-A mRNA had greater IL-2 (p = 0.03) and IL-12 (p < 0.0001) in the BALF and a greater incidence of rejection episodes (p = 0.003). Levels of SP-A mRNA expression were associated with the SP-A2 polymorphisms (p = 0.015). Specifically, genotype 1A1A(0) was associated with lower SP-A mRNA expression (p < 0.05). Lung allografts with low levels of SP-A mRNA expression are associated with reduced survival. Lung allograft SP-A mRNA expression appears to be associated with SP-A gene polymorphisms.
authors.affiliation: Lung Transplant Program, Columbia University Medical Centre, New York, NY.
authors.forename: F
authors.initials: F
authors.lastname: D'Ovidio
authors.forename: H
authors.initials: H
authors.lastname: Kaneda
authors.forename: C
authors.initials: C
authors.lastname: Chaparro
authors.forename: M
authors.initials: M
authors.lastname: Mura
authors.forename: D
authors.initials: D
authors.lastname: Lederer
authors.forename: S
authors.initials: S
authors.lastname: Di Angelo
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: C
authors.initials: C
authors.lastname: Gutierrez
authors.forename: M
authors.initials: M
authors.lastname: Hutcheon
authors.forename: L G
authors.initials: LG
authors.lastname: Singer
authors.forename: T K
authors.initials: TK
authors.lastname: Waddell
authors.forename: J
authors.initials: J
authors.lastname: Floros
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008171:Lung Diseases / Q000601:surgery*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D011446:Prospective Studies; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger
keywords: Innate immunity; lung transplantation; polymorphism; surfactant protein A