title: Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial.
abstract: BACKGROUND
  Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides.
  
  
  METHODS
  We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ).
  
  
  RESULTS
  The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci.
  
  
  CONCLUSIONS
  Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. CLINICALTRIALS.GOV NUMBER: NCT00760838.
authors.affiliation: Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. guy.brusselle@ugent.be
authors.forename: Guy G
authors.initials: GG
authors.lastname: Brusselle
authors.forename: Christine
authors.initials: C
authors.lastname: Vanderstichele
authors.forename: Paul
authors.initials: P
authors.lastname: Jordens
authors.forename: René
authors.initials: R
authors.lastname: Deman
authors.forename: Hans
authors.initials: H
authors.lastname: Slabbynck
authors.forename: Veerle
authors.initials: V
authors.lastname: Ringoet
authors.forename: Geert
authors.initials: G
authors.lastname: Verleden
authors.forename: Ingel K
authors.initials: IK
authors.lastname: Demedts
authors.forename: Katia
authors.initials: K
authors.lastname: Verhamme
authors.forename: Anja
authors.initials: A
authors.lastname: Delporte
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Demeyere
authors.forename: Geert
authors.initials: G
authors.lastname: Claeys
authors.forename: Jerina
authors.initials: J
authors.lastname: Boelens
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Padalko
authors.forename: Johny
authors.initials: J
authors.lastname: Verschakelen
authors.forename: Georges
authors.initials: G
authors.lastname: Van Maele
authors.forename: Ellen
authors.initials: E
authors.lastname: Deschepper
authors.forename: Guy F P
authors.initials: GF
authors.lastname: Joos
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin