It is now over 10 years since the first edition of the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) consensus report was published [1]. In this decade, we have seen a large-scale and concerted effort by clinicians, academics, health care providers, governments, and the pharmaceutical industry to address the enormous unmet clinical need driven by chronic obstructive pulmonary disease (COPD). In that time, an array of international, national, and local COPD guidelines have been issued, but a consensus view on how to prevent, diagnose, and treat this highly prevalent condition is still evolving.
Despite considerable recent advances in treating COPD, the task ahead for all these agencies remains a very real one. COPD is still predicted to rise to fifth in overall global disease burden by 2020 [2] and, in many countries, it will become the leading cause of hospitalization during the winter months each year. In order to begin to address this enormous burden, it has been vital to raise the profile of the disease globally and to establish the real impact that COPD is having on patients and health services [3]. The drafting of evidence-based guidelines has also been key to this process by offering a straightforward and inclusive route to diagnosis and treatment for clinicians, contributing to a democratization of expertise that can offer real benefit to patients with COPD.
There are, however, some issues raised by the preeminence of practice guidelines that require reflection. First, the wheel of the guideline or consensus committee turns slowly—by necessity the process to draft, review, and issue these documents requires rigor and, therefore, time. On the date that a guideline is issued, it will often be 2 years behind emerging evidence and at renewal over 5 years behind the evidence base. Since guidelines are slow-moving but reliable beasts, clinicians must continue to make allowances and strive to keep updated. However, less apparent is an effect driven by the need to grade evidence and the resulting reliance on large, randomized, controlled trials. This may create a bias toward pharmaceutical interventions over lifestyle and behavioral techniques, which cannot command the same level of translational budget to deliver these studies. Simple cost-effective interventions, which are safe yet not grade A evidence-based, remain important considerations for clinicians who are often required to offer a pragmatic approach to treating COPD.
Any review of the evidence base that does exist will highlight that even with the recent combined efforts of academia and industry there remains a real need for new and more effective treatments for COPD. A key focus being a drug, which like smoking cessation, could significantly alter the natural history of the disease. Mechanistic studies have highlighted that pulmonary inflammation is a fundamental process in the pathology of disease, and thus the development of potent anti-inflammatory agents may offer some hope of long-standing patient benefit.
This issue of Hot Topics in Respiratory Medicine reviews the evidence for one such treatment: roflumilast. The development of phosphodiesterase enzyme 4 (PDE4) inhibition as a therapeutic target has arisen from careful mechanistic studies suggesting that the overexpression of this pathway in COPD is important. A series of large clinical trials have now been reported. Their findings, discussed in this article, conclude that this therapy offers additional benefit to currently prescribed inhaled therapies and that certain subgroups of patients with COPD demonstrated greater clinical benefit than did others. This not only highlights the heterogeneity of COPD, but also emphasizes the often ignored finding that the response to therapy is just as heterogeneous.
“Blockbuster,” multicentered, large, controlled trials that, while well-powered and appropriately designed, have often not shown significant evidence of overall effect in mixed COPD populations, have enabled, due to their size, subgroup analyses to be performed. Often frowned upon as “post hoc,” these have in fact identified key disease phenotypes that do and, just as importantly, do not respond to new treatments. This edition focuses on the implications of such stratification on new approaches to treatment. The discussion of bronchitic phenotype highlights a well-described clinical syndrome that may lead to more individualized treatment strategies for certain patients with COPD. The article by Anderson also highlights that in the era of disease-specific guidelines, COPD patients often carry a range of nonrespiratory comorbidities. New therapies for these are as relevant to the patient as treatments addressing pulmonary disease or its immediate complications, and so a personalized approach to therapy is again in vogue.
Overall, more work is needed—a greater understanding of this disease is necessary, as well as new, improved therapies and strategies for targeting these at the patients that will benefit most. Perhaps most challenging is the need to evolve a new approach to capturing the evidence of efficacy of emerging therapies in the new era of stratified medicine and the most effective ways of communicating this clearly and concisely to patients and practitioners alike.

REFERENCES

1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011. Available from: http://www.goldcopd.org/. Accessed June 10, 2012.

2. World Health Report. Geneva: World Health Organisation. Available from http://www.who.int/whr/2000/en. Accessed June 10, 2012.

3. British Lung Foundation. Invisible lives. COPD–finding the missing millions. Available from http://www.blf.org.uk. Accessed June 10, 2012.