title: Lung Function Trajectory in Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplant.
abstract: The natural history of lung function in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant is poorly characterized. Understanding the trajectory of lung function is necessary for prompt clinical recognition and treatment and also for the rational design of prospective studies.
  
  
  
  To describe the longitudinal trajectory of lung function parameters, including FEV1, in patients with BOS after hematopoietic cell transplant.
  
  
  
  Subjects with BOS defined by National Institutes of Health consensus guidelines criteria from a recent multicenter prospective trial of combination treatment with fluticasone, azithromycin and montelukast and a retrospective cohort from Fred Hutchinson Cancer Research Center were included. Longitudinal change in FEV1for each patient was calculated on the basis of available pulmonary function tests in three periods: pre-BOS, from BOS diagnosis to 6 months, and 6-18 months after diagnosis. The effect of treatment on FEV1trajectory was analyzed by univariate and multivariate linear regression. The Kaplan-Meier method was used to estimate survival.
  
  
  
  The FEV1percent predicted value at diagnosis was 46% (interquartile range, 35-57%) for trial participants and 53% (interquartile range, 41-64%) for the retrospective cohort. There was a concomitant mild reduction in FVC, as well as a marked reduction in forced expiratory flow, midexpiratory phase, at diagnosis. While there was individual heterogeneity, the overall FEV1trajectory was characterized by a marked decline within 6 months prior to BOS diagnosis, followed by stability of FEV1early after diagnosis and a slow rate of decline beyond 6 months. The effect of the trial medications on FEV1trajectory after BOS diagnosis was a mean rate of change of 0.92% predicted per month (95% confidence interval, -0.53 to 2.37) compared with the retrospective cohort, but this was not statistically significant. Two-year overall survival rates were 76% and 72% for the study participants and the retrospective cohort patients, respectively. Earlier time to diagnosis after hematopoietic cell transplant and severity of FVC at diagnosis were significantly associated with reduced survival.
  
  
  
  The FEV1trajectory in patients with BOS after hematopoietic cell transplant in a contemporary era of management follows a predominant pattern of rapid FEV1decline in the 6 months prior to diagnosis, followed by FEV1stabilization after diagnosis.
authors: 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|2 Pulmonary and Critical Care Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Guang-Shing
authors: 0000-0003-4324-9634
authors: GS
authors: Cheng
authors: 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Barry
authors: B
authors: Storer
authors: 2 Pulmonary and Critical Care Medicine, University of Washington School of Medicine, Seattle, Washington.|3 Gilead Sciences, Inc., Foster City, California.
authors: Jason W
authors: JW
authors: Chien
authors: 4 Division of Hematology/Oncology, Vanderbilt University, Nashville, Tennessee.
authors: Madan
authors: M
authors: Jagasia
authors: 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Jesse J
authors: JJ
authors: Hubbard
authors: 5 National Marrow Donor Program, Minneapolis, Minnesota.
authors: Linda
authors: L
authors: Burns
authors: 6 Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Vincent T
authors: VT
authors: Ho
authors: 7 Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, Florida.
authors: Joseph
authors: J
authors: Pidala
authors: 8 Division of Hematology/Oncology, Mayo Clinic-Scottsdale, Scottsdale, Arizona.
authors: Jeanne
authors: J
authors: Palmer
authors: 9 Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors: Laura
authors: L
authors: Johnston
authors: 10 Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Sebastian
authors: S
authors: Mayer
authors: 2 Pulmonary and Critical Care Medicine, University of Washington School of Medicine, Seattle, Washington.
authors: Kristina
authors: K
authors: Crothers
authors: 11 Division of Medicine and Oncology, Washington University, St. Louis, Missouri; and.
authors: Iskra
authors: I
authors: Pusic
authors: 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Stephanie J
authors: SJ
authors: Lee
authors: 12 Children's Research Institute, Children's National Health System, Washington, District of Columbia.
authors: Kirsten M
authors: KM
authors: Williams
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000627:therapeutic use; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000503:physiopathology*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use; D005541:Forced Expiratory Volume; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000209:etiology / Q000503:physiopathology*; D011446:Prospective Studies; D011804:Quinolines / Q000627:therapeutic use; D012189:Retrospective Studies; D013440:Sulfides; D015996:Survival Rate; D014481:United States; D055815:Young Adult
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D017963:Azithromycin; D000068298:Fluticasone; C093875:montelukast
keywords: FEV1 trajectory; bronchiolitis obliterans syndrome; hematopoietic cell transplantation; outcomes; pulmonary complications