title: Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial.
abstract: BACKGROUND
  Patients with chronic obstructive pulmonary disease (COPD) often have vitamin D deficiency, which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation. Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking. We therefore investigated whether vitamin D3 (colecalciferol) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections.
  
  
  METHODS
  We did a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practices and four Acute National Health Service Trust clinics in London, UK. Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block randomisation. Participants and study staff were masked to treatment assignment. Coprimary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection. Analysis was by intention to treat. A prespecified subgroup analysis was done to assess whether effects of the intervention on the coprimary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov, number NCT00977873.
  
  
  RESULTS
  240 patients were randomly allocated to the vitamin D3 group (n=122) and placebo group (n=118). Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation (adjusted hazard ratio 0·86, 95% CI 0·60-1·24, p=0·42) or time to first upper respiratory infection (0·95, 0·69-1·31, p=0·75). Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L (0·57, 0·35-0·92, p=0·021), but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L (1·45, 0·81-2·62, p=0·21; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status). Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection (pinteraction=0·41).
  
  
  CONCLUSIONS
  Vitamin D3 supplementation protected against moderate or severe exacerbation, but not upper respiratory infection, in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation.
  
  
  BACKGROUND
  UK National Institute for Health Research.
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK. Electronic address: a.martineau@qmul.ac.uk.
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Wai Yee
authors.initials: WY
authors.lastname: James
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hooper
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Barnes
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Jolliffe
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Greiller
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Kamrul
authors.initials: K
authors.lastname: Islam
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: McLaughlin
authors.affiliation: Homerton University Hospital, Homerton Row, London, UK.
authors.forename: Angshu
authors.initials: A
authors.lastname: Bhowmik
authors.affiliation: Homerton University Hospital, Homerton Row, London, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Timms
authors.affiliation: Homerton University Hospital, Homerton Row, London, UK.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Rajakulasingam
authors.affiliation: Homerton University Hospital, Homerton Row, London, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Rowe
authors.affiliation: Homerton University Hospital, Homerton Row, London, UK.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Venton
authors.affiliation: Queen's Hospital, Rom Valley Way, Romford, UK.
authors.forename: Aklak B
authors.initials: AB
authors.lastname: Choudhury
authors.affiliation: Royal London Hospital, Whitechapel Road, London, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Simcock
authors.affiliation: Royal London Hospital, Whitechapel Road, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Wilks
authors.affiliation: Royal London Hospital, Whitechapel Road, London, UK.
authors.forename: Amarjeet
authors.initials: A
authors.lastname: Degun
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Zia
authors.initials: Z
authors.lastname: Sadique
authors.affiliation: Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester, UK.
authors.forename: William R
authors.initials: WR
authors.lastname: Monteiro
authors.affiliation: Medical Research Council, Asthma UK Centre in Allergic Mechanisms in Asthma, King's College London, London, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Corrigan
authors.affiliation: Medical Research Council, Asthma UK Centre in Allergic Mechanisms in Asthma, King's College London, London, UK.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hawrylowicz
authors.affiliation: Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Asthma UK Centre for Applied Research, Blizard Institute, Queen Mary University of London, London, UK; Medical Research Council, Asthma UK Centre in Allergic Mechanisms in Asthma, King's College London, London, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Griffiths
mesh_terms: D000368:Aged; D002762:Cholecalciferol / Q000627:therapeutic use*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000150:complications / Q000178:diet therapy*; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000209:etiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000178:diet therapy; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D