title: Multi-site placebo-controlled randomised clinical trial to assess protection following oral immunisation with inactivated non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Previous studies identified factors that modify response to an oral non-typeable Haemophilus influenzae (NTHi) vaccine in chronic obstructive pulmonary disease (COPD): severe COPD, moderate-severe exacerbations as end-point and a threshold prevalence of NTHi in the study population. More data are needed to confirm parameters that influence clinical outcomes.
  
  
  OBJECTIVE
  The primary aim was to determine the efficacy of an oral NTHi vaccine (HI-164OV) in reducing the rate of exacerbations requiring systemic corticosteroids or hospitalisation in COPD. Secondary aims included effect on the proportion of patients experiencing such exacerbations, severity of infections and quality of life (St George Respiratory Questionnaire for COPD patients (SGRQ-C)).
  
  
  METHODS
  This multi-centre, double-blind, placebo-controlled study was conducted at 21 Australian sites for 9 months in 2011.
  
  
  RESULTS
  Three-hundred and twenty subjects with COPD, FEV1 <60% predicted and ≥1 moderate-severe exacerbations in the previous 12 months were recruited. The primary and secondary end-points for the intention-to-treat population aged 40-88 years were not achieved, and only 5% of subjects had an H. influenzae-positive sputum sample. Subsequent exploratory analysis of patients <65 years (91 subjects) indicated protection with respect to the primary and most of the secondary end-points, with SGRQ-C symptom scores lower at 3 and 6 months.
  
  
  CONCLUSIONS
  Patients aged 40-88 years with moderate to severe COPD and low rates of H. influenzae-positive sputum were not protected against exacerbations by HI-1640V. Further studies are needed to confirm protection in subjects aged <65 years. Older age and low colonisation rates appear to affect adversely response to this vaccine.
authors.affiliation: Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: R L
authors.initials: RL
authors.lastname: Clancy
authors.affiliation: Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.|Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: M L
authors.initials: ML
authors.lastname: Dunkley
authors.affiliation: Datapharm Australia Pty Ltd, Sydney, New South Wales, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Sockler
authors.affiliation: Department of Respiratory and Sleep Medicine, Austin Hospital, Melbourne, Victoria, Australia.|Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: C F
authors.initials: CF
authors.lastname: McDonald
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D006193:Haemophilus influenzae; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000382:microbiology; D011788:Quality of Life; D012720:Severity of Illness Index; D013183:Sputum / Q000382:microbiology; D014611:Vaccination / Q000379:methods
chemical_list: D018073:Haemophilus Vaccines
keywords: COPD; immunisation; non-typeable H. influenzae; vaccine