Current and emerging therapies for the management of chronic inflammation in asthma.

The pathophysiology of asthma, current treatment guidelines, and emerging immunomodulating treatments are reviewed. Asthma is a chronic disease of inflammation, which left untreated, may result in irreversible lung damage. Inhaled antigens elicit a T-helper cell type-2 response, leading to the production of immunoglobulin E (IgE) and eosinophil sensitization. Eosinophil infiltration into the airway is thought to play an important role in chronic inflammation and increases several weeks before an acute exacerbation in moderate to severe asthma. The updated guidelines from the National Asthma Education and Prevention Program and the National Institutes of Health focus on the use of daily antiinflammatory treatment in patients with persistent asthma. Inhaled corticosteroid (ICS) therapy remains the cornerstone for controlling mild and moderate asthma, but when used in higher doses for moderate-to-severe asthma it may cause long-term adverse effects, including osteoporosis and glaucoma. Step-up therapy should be the combination of a long-acting beta-agonist (LABA) and an ICS. Leukotriene modifiers may provide additional symptom control in patients with moderate to severe asthma but have not been shown to be as cost-effective as monotherapy. Newer entities focus on direct immune modulation and include monoclonal antibodies targeting various inflammatory-response receptors (IgE, interleukin [IL]-2, IL-4, and IL-5). Phosphodiesterase-4 (PDE-4) inhibitors may be effective for chronic obstructive pulmonary disease, but have not delivered consistent results for controlling asthma. Cytokine-receptor antagonists and leukocyte-suppressing antiinflammatory drugs (LSAIDs) are currently under investigation and have yielded promising preliminary results as alternatives for the treatment of asthma. Current and emerging therapies for the management of chronic inflammation in asthma include ICSs, LABAs, leukotriene modifiers, monoclonal antibodies, PDE-4 inhibitors, cytokine-receptor antagonists, and LSAIDs.