**2.1 Traditional management of COPD**

Currently, the only intervention known to influence the loss of lung function is smoking cessation (Gold 2009). Besides treating symptoms and improving quality of life, the treatment focus includes prevention of future exacerbations, reduction of mortality and prevention of disease progression. Treatment for COPD falls into two categories: those medications which relieve symptoms of airflow limitations and those medications which control the underlying inflammation. As such, the current gold standard of treatment for COPD patients involves a step-up paradigm commencing with short-acting bronchodilators (either short-acting 2 agonists or antimuscarinic agents), then adding on long-acting bronchodilators again either long-acting 2 agonists (LABA) or long acting muscarinics, (LAMA) followed by inclusion of inhaled corticosteroids (ICS). Lastly, long term oxygen and possible surgical treatments are final treatment options. Typically, the most common treatment involves ICS/LABA class of drugs, but can also include methylxanthines (bronchodilator) and leukotriene antagonists (anti-inflammatory) (Hurst et al. 2010). The majority of novel treatments for COPD forecasted to launch prior to 2018, are in fact minimally differentiated from current options, with either being improved dosing or combining therapies such as combinations of LABA/LAMA.

Another dilemma is that although highly effective in asthma, ICS have provided little therapeutic benefit in COPD (Barnes 2006). In patients with severe COPD, histological analysis of their peripheral airways have shown an intense inflammatory response, despite treatment with high doses of ICS, suggesting steroid resistance (Hogg et al. 2004). Combinations of ICS and LABA have been shown to be more effective at reducing COPD exacerbations (Calverley et al. 2007) but have not been shown to statistically decrease mortality (Calverley et al. 2007) (Tashkin et al. 2008). ICS use has been associated with osteoporosis, glaucoma, cataracts and skin thinning (Giembycz &Field 2010) and increased risk of pneumonia in patients with COPD (Ernst et al. 2007). Even with the current and immediate future medications, there are clear unmet needs for more effective antiinflammatories in COPD both for reducing progression of the disease and reducing mortality.
