Biomarkers to target antibiotic and systemic corticosteroid therapy in COPD exacerbations

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Chronic obstructive pulmonary disease (COPD) is a common chronic lung disease. Its prevalence is rising and it will become the third leading cause of death by 2020 (1). In the UK 900,000 people are diagnosed with COPD and it is likely that many more remain undiagnosed. COPD is a burden for sufferers and an enormous drain on health care provision with annual costs estimated at #492 million. The times when a patient?s condition worsens is known as an exacerbation and COPD exacerbations account for 15% of all medical admissions and can lead to death. The current treatment for COPD exacerbations is supportive care together with antibiotics and oral corticosteroids. The clinical response to treatment varies considerably and to date we have no robust well-validated measurements to direct therapy for COPD exacerbations. Importantly, the widespread use of antibiotic therapy is implicated as the major contributing factor leading to the recent increase in the ?Superbugs? MRSA and Clostridium difficile infection and oral corticosteroids complicate heart disease and diabetes. Therefore our current inability to target therapy for COPD exacerbations means that some patients with COPD are inappropriately treated and this places a vulnerable population at risk. Therefore there is a pressing need to target antibiotic and oral corticosteroid therapy for COPD exacerbations. In this proposal we shall invite 110 patients with COPD to enter a 1 year study in which we shall further assess mediators that can be measured in sputum and blood that are already known to closely relate to infections and inflammation. These mediators will be measured when patients are well and when they have an exacerbation. This will provide us with precise levels of the mediators of interest that can then be used to decide whether we treat patients with antibiotics, corticosteroids, both or neither. Indeed we shall use these measurements to direct treatment in a second 1 year intervention study that will include the same patients as for the first study. At exacerbations half of the patients will be treated according to standard care and the other half will have their treatment directed by the measurements derived from the first study. We anticipate that this will provide us with an opportunity to treat patients with COPD at times of exacerbations more effectively with a reduction in the total use of treatment without any detrimental effects.