An article published Online First coinciding with this week’s COPD special issue of The Lancet reports the findings of the UPLIFT study that shows that treatment with inhaled tiotropium at an earlier stage of COPD reduces decline of lung function. While there is confirmation of the effectiveness of drug therapy for COPD patients at advanced stages of disease, little evidence exists regarding starting treatment at earlier stages. However, the findings of this study suggest that treatment should begin at the earlier stage. The article is the work of Professor Marc Decramer, University Hospital, University of Leuven, Belgium, and collaborators.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) is a collaboration that includes WHO and the U.S. National Heart, Lung, and Blood Institute. It has set out guidelines for the various stages of COPD. The UPLIFT study investigated patients at all stages of the disease. But the authors in this paper did a pre-specified subgroup analysis of patients in particular at GOLD stage II which is considered moderate disease. Out of a total of 5,993 patients, 2,739 had GOLD stage II COPD at randomization, with an average age of 64 years. Pre-bronchodilator spirometry was done prior to administration of study drug in the morning of a clinic visit which is 24 hours after the last dose of study medication. Post-bronchodilator spirometry was performed after study drug and short-acting bronchodilators such as ipratropium and salbutamol. The patients had an average post-bronchodilator FEV1 volume of 1.63L, 59 percent of the predicted value. FEV1 is the forced expiratory volume in one second, which is the greatest volume of air that can be breathed out in the first second of a large breath. A total of 2,376 patients qualified for the final analysis from which 1,218 patients had received tiotropium and 1,158 received placebo over a period of four years.

Results indicated that the rate of decline of mean post-bronchodilator FEV1 per year was 12 percent lower in the tiotropium group than the placebo group (43 mL compared to 49 mL). The rate of decline of mean pre-bronchodilator FEV1 did not fluctuate notably between groups (35 mL compared to 37 mL per year). At all time points, patients given tiotropium were also found to have better health status. This was measured by questionnaire. The risk of an exacerbation or serious worsening of symptoms was reduced by 18 percent for patients who received tiotropium. In addition, the risk of a hospital admission due to an exacerbation fell by 26 percent for patients receiving tiotropium.

The authors write in conclusion: “In patients with GOLD stage II COPD, long-term treatment with tiotropium seemed to reduce the rate of decline of post-bronchodilator FEV1 and the risk of exacerbations. Since we also found that lung function and health-related quality of life were better in the tiotropium group than in the control group throughout the trial, treatment of COPD should begin in symptomatic patients with moderate disease.”

In an associated note, Dr Lisa Davies, Aintree Chest Centre, University Hospital Aintree, Liverpool, UK and Professor Peter M A Calverley, University of Liverpool, Liverpool, UK, comment: “As the UPLIFT investigators comment, there are still substantial numbers of symptomatic patients in GOLD stage II without a clinical diagnosis. Their data should encourage those developing plans for the early identification of COPD, which includes the UK Department of Health, that identifying such patients is indeed worthwhile and can provide the patient with better symptomatic control of their condition and improvements in their overall wellbeing.”

“Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial”
Marc Decramer, Bartolome Celli, Steven Kesten, Theodore Lystig, Sunil Mehra, Donald P Tashkin, for the UPLIFT investigators
DOI: 1016/S0140-6736(09)61298-8
The Lancet

Written by Stephanie Brunner (B.A.)