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Adherence to inhaled therapy, mortality and hospital admission in COPD
  1. J Vestbo1,2,
  2. J A Anderson3,
  3. P M A Calverley4,
  4. B Celli5,
  5. G T Ferguson6,
  6. C Jenkins7,
  7. K Knobil8,
  8. L R Willits3,
  9. J C Yates8,
  10. P W Jones9
  1. 1
    Respiratory Medicine Research Group, University of Manchester, Manchester, UK
  2. 2
    Department of Cardiology and Respiratory Medicine, Hvidovre Hospital and Faculty of Health Sciences, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark
  3. 3
    Respiratory Medicine Development Centre, GlaxoSmithKline, Middlesex, UK
  4. 4
    Clinical Science Centre, University Hospital Aintree, Liverpool, UK
  5. 5
    Tufts University School of Medicine, Boston, Massachusetts, USA
  6. 6
    Pulmonary Research Institute of Southeast Michigan, Michigan, USA
  7. 7
    Woolcock Institute of Medical Research, Sydney, Australia
  8. 8
    Respiratory Medicine Development Centre, GlaxoSmithKline, Research Triangle Park, North Carolina, USA
  9. 9
    St George’s, University of London, London, UK
  1. Correspondence to Professor J Vestbo, Respiratory Medicine Research Group, ERC Building, 2nd Floor, University Hospital of South Manchester NHS Foundation Trust, Southmoor Road, Manchester M23 9LT, UK; jorgen.vestbo{at}


Background: Little is known about adherence to inhaled medication in chronic obstructive pulmonary disease (COPD) and the impact on mortality and morbidity.

Methods: Data on drug adherence from a randomised double-blind trial comparing inhaled salmeterol 50 μg + fluticasone propionate 500 μg twice daily with placebo and each drug individually in 6112 patients with moderate to severe COPD over 3 years in the TORCH study were used. All-cause mortality and exacerbations leading to hospital admission were primary and secondary end points. The study of adherence was not specified a priori as an ancillary study.

Results: Of the 4880 patients (79.8%) with good adherence defined as >80% use of study medication, 11.3% died compared with 26.4% of the 1232 patients (20.2%) with poor adherence. The annual rates of hospital admission for exacerbations were 0.15 and 0.27, respectively. The association between adherence and mortality remained unchanged and statistically significant after adjusting for other factors related to prognosis (hazard ratio 0.40 (95% CI 0.35 to 0.46), p<0.001). The association was even stronger when analysing on-treatment deaths only. Similarly, the association between adherence and hospital admission remained unchanged and significant in a multivariate analysis (rate ratio 0.58 (95% CI 0.44 to 0.73, p<0.001). The association between increased adherence and improved mortality and reduction in hospital admission was independent of study treatment. The effect of treatment was more pronounced in patients with good adherence than in those with poor adherence.

Conclusion: Adherence to inhaled medication is significantly associated with reduced risk of death and admission to hospital due to exacerbations in COPD. Further research is needed to understand these strong associations.

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  • See Editorial, p 922

  • ▸ Additional information is published online only at

  • Funding The study was sponsored by GlaxoSmithKline. A Steering Committee comprising six academics and three representatives of the sponsor developed the original study design and concept, the plan for studying effects of adherence, approved the statistical plan, had full access to the data and was responsible for decisions with regard to publication. The study sponsor did not place any restrictions with regard to statements made in the final paper.

  • Competing interests JV, PC, BC, GF, CJ and PJ have received fees from pharmaceutical companies, including GlaxoSmithKline, for speaking at meetings and participating in advisory board meetings. JV, PC, BC, GF, CJ and PJ have received support for research from pharmaceutical companies, including GlaxoSmithKline. JV’s wife was an employee of GlaxoSmithKline until 2004. JA, JY, KK and LW are all GlaxoSmithKline employees and shareholders of GlaxoSmithKline.

  • Ethics approval All patients gave informed consent and the study was approved by ethical review boards and conducted in accordance with the Declaration of Helsinki.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

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