In response to the letter by Ernst and Suissa¹ published in the August edition of Thorax, the issue of incomplete ascertainment of vital status information in five of the seven trials included in the pooled analysis was discussed in the paper.² This would only make a meaningful impact on the overall results if patients in the inhaled corticosteroid group who withdrew were more likely to die than those patients who withdrew from the placebo arm of the trials. There is no material reason to believe that this would be the case. In the five trials with incomplete data on mortality, inhaled corticosteroids were effective in reducing all-cause mortality in patients with a forced expiratory volume in 1 second (FEV₁) of <60% of predicted (adjusted hazards ratio 0.69). In the two trials for which complete mortality data were available (ISOLDE and LHS-2), inhaled corticosteroids were just as effective in reducing mortality (adjusted hazard ratio 0.60), providing assurances that incomplete follow up data did not bias the overall findings.²

The seven trials largely recruited patients who had stable COPD and were free of life threatening co-morbidities at baseline because the end points of these studies were not mortality but were exacerbations or lung function. Not surprisingly, the overall mortality rate in the first 6–9 months was very low. However, with passage of time the mortality rate in the placebo arm increased, as would be expected given the natural history of COPD.³ In contrast, the mortality rate remained consistently low in the group that received inhaled corticosteroids, indicating a (protective) survival effect of these medications in COPD.

As pointed out in the paper, the cause-specific mortality data should be interpreted cautiously.² We relied on death certificates and/or monitoring reports to ascribe specific causes of deaths. However, in patients with COPD, such data may not be reliable.⁴

While we agree with Drs Ernst and Suissa¹ that inhaled corticosteroids may have salutary effects on the cardiovascular system, causation has not been fully established. There are some emerging data on the potential effects of inhaled corticosteroids on oncogenesis that should not be dismissed.^5,6 We agree with Drs Ernst and Suissa that our paper “raises more questions than it answers”. We hope that these questions stimulate more research in COPD which, in time, we believe will lead to novel discoveries of mechanisms and therapeutic compounds that will improve the health and health outcomes of patients with COPD across the world.