title: Budesonide/Formoterol for bronchiolitis obliterans after hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects.
  
  
  OBJECTIVE
  To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account.
  
  
  RESULTS
  At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment.
  
  
  CONCLUSIONS
  Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registered with www.clinicaltrials.gov (NCT00624754).
authors.affiliation: 1 Service de Pneumologie.
authors.forename: Anne
authors.initials: A
authors.lastname: Bergeron
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Karine
authors.initials: K
authors.lastname: Chagnon
authors.forename: Cendrine
authors.initials: C
authors.lastname: Godet
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bergot
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dominique
authors.forename: Thierry
authors.initials: T
authors.lastname: de Revel
authors.forename: Karine
authors.initials: K
authors.lastname: Juvin
authors.forename: Natacha
authors.initials: N
authors.lastname: Maillard
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.forename: Nathalie
authors.initials: N
authors.lastname: Contentin
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Tazi
mesh_terms: D000328:Adult; D001989:Bronchiolitis Obliterans / Q000628:therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use*; D004311:Double-Blind Method; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate
keywords: inhaled long-acting bronchodilator and steroids; lung chronic graft-versus-host disease; obstructive lung disease