title: Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD.
abstract: BACKGROUND
  Radiographically confirmed pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been assessed to date.
  
  
  OBJECTIVE
  To determine the incidence of pneumonia, risk factors, and clinical attributes with inhaled fluticasone furoate (FF) in patients with COPD with an exacerbation history.
  
  
  METHODS
  Two replicate, 1-year, double-blind clinical trials enrolled subjects with COPD with moderate to very severe airflow limitation and at least one exacerbation within the prior year. Subjects were randomized 1:1:1:1 to receive inhaled once-daily vilanterol (VI) 25 μg or VI 25 μg combined with 50, 100, or 200 μg FF. Subjects were required to have a chest radiograph at screening and within 48 hours of any suspected pneumonia or exacerbation.
  
  
  RESULTS
  Among 3,255 randomized subjects, 205 pneumonia events occurred in 181 subjects. Chest imaging was available for 195 (95%) of these events. Chest radiographs were also obtained for 1,793 (70%) of the 2,545 moderate and severe exacerbations. For VI alone and the combination with 50, 100, or 200 μg FF, reported pneumonia incidence was 3, 6, 6, and 7%, respectively. However, for events with compatible parenchymal infiltrates, the respective incidences were 2, 4, 4, and 5%. Factors associated with at least a twofold increase in the risk of pneumonia with FF/VI treatment were being a current smoker, having prior pneumonia, body mass index <25 kg/m(2), and severe airflow limitation.
  
  
  CONCLUSIONS
  Radiographically confirmed pneumonia risk is increased with inhaled FF/VI, although at less than investigator-defined rates. Modifiable pneumonia risk factors should be considered when attempting to optimize COPD management. Clinical trial registered with www.clinicaltrials.gov (NCT01009463 [HZC102871]; NCT01017952 [HZC102970]).
authors.affiliation: 1 GSK, Research Triangle Park, North Carolina.
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.forename: Jean
authors.initials: J
authors.lastname: Bourbeau
authors.forename: Paul W
authors.initials: PW
authors.lastname: Jones
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.forename: Donald A
authors.initials: DA
authors.lastname: Mahler
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: Andrew
authors.initials: A
authors.lastname: Wachtel
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Frank
authors.initials: F
authors.lastname: Barnhart
authors.forename: Sally
authors.initials: S
authors.lastname: Lettis
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
mesh_terms: D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage*; D001592:Benzyl Alcohols / Q000008:administration & dosage*; D002722:Chlorobenzenes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014481:United States / Q000453:epidemiology
chemical_list: D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; C550468:vilanterol; C523187:fluticasone furoate
keywords: chronic obstructive pulmonary disease; corticosteroids; pneumonia