+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      ICS and COPD: Time to clear the air

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          The debate about what constitutes the correct treatment for COPD has recently intensified.1 This discussion has grumbled on ever since the first multicenter trials using inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) such as the European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP) and Inhaled Steroids in Obstructive Lung Disease (ISOLDE) were published in the late 1990’s and the results of trials such as TORCH (TOwards a Revolution in COPD Health) using combination products has only added to the confusion. Complex debate predominantly pertaining to statistical methodology has muddied the waters. Concepts such as immortal time bias and selection bias introducing regression to the mean are often too difficult to grasp for the average reader. However, some of the methodological flaws identified by Suissa and colleagues2 are much easier to understand and solutions to these are potentially at hand. Firstly, it is clear trials investigating the effects of ICS on COPD may in fact be trials predominantly examining the effects of ICS withdrawal. It is not sufficient to state a treatment works simply because patients deteriorate when that treatment is withdrawn. Re-analysis of all data such that treatment effects are stratified according to pre-use of ICS is easy to do as all the data is there, as Suissa eloquently showed in his re-working of the OPTIMAL trial data.3 Even though most of the ICS/COPD trials have approximately 50% of subjects on ICS at randomization, some have a much lower rate, such as in Szfranski and colleagues4 (26%) and this may not necessarily skew the overall conclusions of the trial(s). Secondly, when assessing the impact of combination treatments it is imperative to present the correct 2 × 2 factorial analysis such that the impact of each individual component can be assessed as Suissa performed for TORCH.2 Thus it becomes clear the effect on mortality may be entirely long-acting β-agonists (LABA) dependant. The issue of systemic side effects and pneumonia in COPD patients treated with high doses of ICS over long periods also needs further careful evaluation. It would be disingenuous of us to suggest ICS have no place in the management of COPD. We know a proportion of patients benefit from their bronchoprotective effect and that this subset of patients with COPD has a higher mortality risk.5 ICS are also indicated in the patients with more reversible COPD who probably suffer from concomitant asthma. It is time that some fundamental issues are addressed. We strongly urge the pharmaceutical industry to re-analyze the underlying data and demystify at least some of the methodological smog.

          Related collections

          Most cited references 5

          • Record: found
          • Abstract: found
          • Article: not found

          Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.

          The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.
            • Record: found
            • Abstract: found
            • Article: not found

            Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial.

            Treatment of moderate or severe chronic obstructive pulmonary disease (COPD) with combinations of inhaled corticosteroids, long-acting beta-agonists, and long-acting anticholinergic bronchodilators is common but unstudied. To determine whether combining tiotropium with salmeterol or fluticasone-salmeterol improves clinical outcomes in adults with moderate to severe COPD compared with tiotropium alone. Randomized, double-blind, placebo-controlled trial conducted from October 2003 to January 2006. 27 academic and community medical centers in Canada. 449 patients with moderate or severe COPD. 1 year of treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol. The primary end point was the proportion of patients who experienced an exacerbation of COPD that required treatment with systemic steroids or antibiotics. The proportion of patients in the tiotropium plus placebo group who experienced an exacerbation (62.8%) did not differ from that in the tiotropium plus salmeterol group (64.8%; difference, -2.0 percentage points [95% CI, -12.8 to 8.8 percentage points]) or in the tiotropium plus fluticasone-salmeterol group (60.0%; difference, 2.8 percentage points [CI, -8.2 to 13.8 percentage points]). In sensitivity analyses, the point estimates and 95% confidence bounds shifted in the direction favoring tiotropium plus salmeterol and tiotropium plus fluticasone-salmeterol. Tiotropium plus fluticasone-salmeterol improved lung function (P = 0.049) and disease-specific quality of life (P = 0.01) and reduced the number of hospitalizations for COPD exacerbation (incidence rate ratio, 0.53 [CI, 0.33 to 0.86]) and all-cause hospitalizations (incidence rate ratio, 0.67 [CI, 0.45 to 0.99]) compared with tiotropium plus placebo. In contrast, tiotropium plus salmeterol did not statistically improve lung function or hospitalization rates compared with tiotropium plus placebo. More than 40% of patients who received tiotropium plus placebo and tiotropium plus salmeterol discontinued therapy prematurely, and many crossed over to treatment with open-label inhaled steroids or long-acting beta-agonists. Addition of fluticasone-salmeterol to tiotropium therapy did not statistically influence rates of COPD exacerbation but did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD. International Standard Randomised Controlled Trial registration number: ISRCTN29870041.
              • Record: found
              • Abstract: not found
              • Article: not found

              Inhaled corticosteroids in COPD: the case against.


                Author and article information

                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                3 August 2009
                : 4
                : 289-290
                Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK
                Author notes
                Correspondence: Paul A Ford, Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK, Tel +44 1753 636458, Fax +44 1753 636460, Email
                © 2009 Ford et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Guest Editorial

                Respiratory medicine


                Comment on this article