Asthma is a chronic inflammatory condition characterised by reversible airflow obstruction and airway hyperreactivity. The course of the illness may be punctuated by exacerbations resulting in deterioration in quality of life and, in some cases, days lost from school or work. That
asthma is common and increasingly prevalent magnifies the importance of any potential economic costs, and promoting
asthma control represents an important public health agenda. While lifestyle changes represent a valuable contribution in some patients, the majority of asthmatic patients require therapeutic intervention. The recognition of the role of
inflammation in the pathogenesis of
asthma has led to an emphasis on regular anti-inflammatory
therapy, of which inhaled
corticosteroid treatment remains the most superior. In selected patients, further improvements in
asthma control may be gained by the addition of regular inhaled long-acting beta(2)-adrenoceptor agonists or oral
leukotriene receptor antagonists to inhaled
corticosteroid therapy. However, a significant minority of patients with
asthma remain poorly controlled despite appropriate treatment, suggesting that additional
corticosteroid nonresponsive inflammatory pathways may be operative. Furthermore, some patients with
asthma display an accelerated decline in lung function, suggesting that active airway re-modeling is occurring. Such observations have focused attention on the potential to develop new
therapies which
complement existing treatments by targeting additional inflammatory pathways. The central role of
phosphodiesterase (PDE), and in particular the PDE4
enzyme, in the regulation of key inflammatory cells believed to be important in
asthma - including eosinophils, lymphocytes, neutrophils and airway smooth muscle - suggests that drugs designed to target this
enzyme will have the potential to deliver both bronchodilation and modulate the asthmatic inflammatory response. In vivo studies on individual inflammatory cells suggest that the effects are likely to be favorable in
asthma, and animal study models have provided proof of concept; however, first-generation PDE inhibitors have been poorly tolerated due to adverse effects. The development of second-generation agents such as
cilomilast and
roflumilast heralds a further opportunity to test the potential of these agents, although to date only a limited amount of data from human studies has been published, making it difficult to draw firm conclusions.