title: Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.
abstract: Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow-up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including "restrictive allograft syndrome (RAS)", "neutrophilic CLAD (nCLAD)" and "rapid decliners". At follow-up, 8 patients demonstrated ≥10% improvement in FEV1 , 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1 . Patients fulfilling criteria for "rapid decliners" (n=21, p=0.005), RAS (n=22, p=0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n=44, p=0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression-free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: M
authors: M
authors: Greer
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: M
authors: M
authors: Dierich
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: C
authors: C
authors: De Wall
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: H
authors: H
authors: Suhling
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: J
authors: J
authors: Rademacher
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: T
authors: T
authors: Welte
authors: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Germany.
authors: A
authors: A
authors: Haverich
authors: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Germany.
authors: G
authors: G
authors: Warnecke
authors: Department of Hematology, Hemostasis, Oncology and StemCell Transplantation, Hannover Medical School, Germany.
authors: P
authors: P
authors: Ivanyi
authors: Department of Hematology, Hemostasis, Oncology and StemCell Transplantation, Hannover Medical School, Germany.
authors: S
authors: S
authors: Buchholz
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: J
authors: J
authors: Gottlieb
authors: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors: T
authors: T
authors: Fuehner
mesh_terms: D000328:Adult; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology; D001989:Bronchiolitis Obliterans / Q000503:physiopathology / Q000628:therapy; D018893:Bronchoalveolar Lavage; D018572:Disease-Free Survival; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008027:Light; D008168:Lung / Q000503:physiopathology; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010641:Phenotype; D017893:Photopheresis; D055031:Primary Graft Dysfunction / Q000503:physiopathology / Q000517:prevention & control*; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin