Description of the condition
"Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease, which is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and co-morbidities contribute to the overall severity in individual patients" (GOLD 2015). It is estimated that 65 million people worldwide have moderate to severe COPD (WHO 2015). While mortality from cancer, heart disease and stroke has decreased, mortality from COPD has increased by 102% (Jemal 2005). It is predicted that COPD will be the fourth leading cause of death in the year 2030 (Mathers 2006). A systematic review of population studies of COPD estimated prevalence of 9% to 10% in adults over 40 years of age (Halbert 2006). A Burden of Obstructive Lung Disease Initiative (BOLD) (Buist 2005) study estimated the population prevalence of GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 2 or higher COPD at 8.5% to 22.2% across 12 international cities and observed significant variation in prevalence across sites (Buist 2007). The Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study reported a crude prevalence rate of GOLD stage 1 or higher COPD of 9.7% to 19.7% across five South American cities (Menezes 2005). In a prevalence study In Austria, at least one-quarter of the population over 40 years of age had irreversible airway obstruction (Schirnhofer 2007). In the United States, the estimated economic cost of COPD and asthma combined is $68 billion (NHLBI 2012).
Exacerbations of COPD are responsible for the largest portion of the COPD burden on the healthcare system (Strassels 2001). The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines a COPD exacerbation as "an acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication" (GOLD 2015). Acute exacerbations are associated with worse quality of life (Barnes 2013), increased hospitalisations (Mullerova 2014) and increased mortality (Seemungal 2008). Several interventions are available to prevent exacerbations, including smoking cessation, pulmonary rehabilitation and disease management programmes; patient education; pneumococcal and influenza vaccinations; and use of long-acting bronchodilators, inhaled corticosteroids, phosphodiesterase 4 inhibitors, antioxidants, mucolytic agents and antibiotics (Qureshi 2014). The effect of these interventions on exacerbation frequency is limited, with pharmacological interventions leading to a 14% to 35% reduction (Han 2011). Although smoking cessation has been shown to modify the accelerated rate of decline in lung function that is the hallmark of COPD (Godtfredsen 2008), this remains to be proven for any of the existing pharmacological interventions (GOLD 2015). The importance of finding treatments that can have this kind of impact cannot be overstated.
Chronic obstructive pulmonary disease is increasingly considered a multi-system disease involving pulmonary and systemic inflammation (Young 2013). The lung inflammatory response comprises increased concentrations of pro-inflammatory cytokines, as well as innate and adaptive immune cells (Sinden 2010). A systematic review found that people with COPD had raised levels of several inflammatory markers, including interleukin-6 (IL-6) and C-reactive protein (CRP), indicating the presence of persistent systemic inflammation (Gan 2004). Pulmonary and systemic inflammation is thought to be central to symptoms, exacerbations and mortality (Young 2009). In addition, many patients with COPD have multiple co-morbidities, particularly those who are elderly (Clini 2013).