Context

Although bronchodilators are the first-line maintenance treatment for chronic obstructive pulmonary disease (COPD), we still ignore what their real role is in treating obstructed asymptomatic patients.1 For this reason it is still not well established if we must use long-acting bronchodilators in all patients with COPD. This is a critical issue because many patients suffering from COPD do not complain about the classic disturbing symptoms of COPD such as cough, sputum and dyspnoea, despite the present of a mild and even moderate airflow obstruction as measured by spirometry.2 ,3

Findings

The annual decline rate in FEV₁ measured after bronchodilator use was significantly (p=0.006) higher in the placebo group (51 ± 6  mL   per year) than in the tiotropium group (29±5 mL per year), with a difference of 22 mL (95% CI 6 to 37). However, the declined in trough FEV₁was rather similar in the two groups with a difference of 15mL per year (95% CI, -1 to 31) that was not statistically significant (p=0.06). Adjustment for potential cofounders such as smoking status, per cent of the predicted FEV₁ value at baseline, age, sex, hospitalisation, GOLD stage and body mass index did not change the pattern of acute differences among the groups. In addition, the rate of exacerbations per year was lower in the tiotropium group than in the than placebo (0.27 vs 0.50 episodes per patient-year; risk ratio, 0.53; 95% CI 0.39 to 0.73; p<0.001). However, the difference between groups in the annual decline rate in the post-bronchodilator FEV₁ was significant (P=0.03) only in patients with a CAT score <10 (milder disease) but not in those with a CAT score of ≥10 (more severe disease) (p=0.07).

Commentary

There in solid evidence that the annual decline rate in FEV₁ is greater in patients with mild-moderate (GOLD stage 1 and 2) COPD than in those with more severe disease (GOLD 3 and 4),5 with statistically significant association between exacerbations of COPD and an excess annual decline in FEV₁, especially in mild COPD.6 On the other hand, it should be avoided as far as possible that patients become symptomatic because if symptomatic, they have a more rapid decline in lung function, a lower health-related quality of life and increased health utilisation compared with asymptomatic individuals.7

The results of this study suggest that therapy with tiotropium might modify the course of COPD if started very early in its initial stages, mainly in relatively asymptomatic patients, those with a CAT score <10. In our opinion it is very interesting that tiotropium not only slowed the loss of FEV₁ but also reduced the risk of COPD exacerbations in these patients, although we must point out that this is not really new information. Actually, there is evidence generated by a post-hoc sub-analysis from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study that GOLD stage 2 patients with post-bronchodilator FEV₁ ≥60% predicted (60-78% range) treated with tiotropium had a lower loss in FEV₁ and a reduced risk of exacerbations .8 However, it is likely that tiotropium does not reduce the decline in lung function if COPD patients with an FEV₁≥ 70% are currently taking other classes of respiratory drugs.9

Implications for practice

To establish the real impact of an early treatment with tiotropium on the evolution of COPD, it is necessary to assess what is its actual benefit in patients suffering from mild (GOLD 1) COPD, mainly if they report the classic symptoms of COPD and exacerbations. It remains also to be established whether the observed benefits change over time. Therefore, much longer studies are needed than those currently available in the literature.