title: Everolimus alters the bronchoalveolar lavage and endobronchial biopsy immunologic profile post-human lung transplantation.
abstract: Everolimus has recently shown promise in terms of short- and long-term clinical lung transplant outcomes. This study aims to determine the altered lung allograft cellular and cytokine mileau when everolimus is substituted for azathioprine (AZA). Twenty-three stable lung transplantation (LTx) recipients were randomized in a double-blinded study to receive everolimus (13) or AZA (10) plus standard cyclosporine/prednisolone. Bronchoalveolar lavage (BAL) and endobronchial biopsies (EBB) were performed on three occasions (T(0)-T(2)) to elucidate cellular and cytokine profiles via immunocytochemistry, immunohistology and enzyme-linked immunosorbent assay (ELISA) techniques. There were no group differences for demographics or clinical events throughout the study nor baseline cellular/cytokine differences. BAL lymphocyte percentage fell in the AZA group by T(2) (p = 0.05). BAL and EBB CD4 measures significantly declined in the everolimus group by T(2) (p < 0.05). EBB neutrophils rose significantly in the AZA group, with a fall in the everolimus group resulting in a significant difference at T(2) (p = 0.01). In conclusion, everolimus has contributed to potentially important differences in BAL and EBB cellular profiles.
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Australia. g.snell@alfred.org.au
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Snell
authors.forename: Bronwyn J
authors.initials: BJ
authors.lastname: Levvey
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Bernadette
authors.initials: B
authors.lastname: Orsida
authors.forename: Lucas
authors.initials: L
authors.lastname: Law
authors.forename: Helen M
authors.initials: HM
authors.lastname: Whitford
authors.forename: Tom C
authors.initials: TC
authors.lastname: Kotsimbos
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Williams
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000276:immunology / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011183:Postoperative Complications; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D010919:Placebos; D000068338:Everolimus; D001379:Azathioprine; D020123:Sirolimus