IL-13 in asthma and allergic disease: Asthma phenotypes and targeted therapies

Decades of research in animal models have provided abundant evidence to show that IL-13 is a key TH2 cytokine that directs many of the important features of airway inflammation and remodeling in patients with allergic asthma. Several promising focused therapies for asthma that target the IL-13/IL-4/signal transducer and activator of transcription 6 pathway are in development, including anti–IL-13 mAbs and IL-4 receptor antagonists. The efficacy of these new potential asthma therapies depends on the responsiveness of patients. However, an understanding of how IL-13–directed therapies might benefit asthmatic patients is confounded by the complex heterogeneity of the disease. Recent efforts to classify subphenotypes of asthma have focused on sputum cellular inflammation profiles, as well as cluster analyses of clinical variables and molecular and genetic signatures. Researchers and clinicians can now evaluate biomarkers of TH2-driven airway inflammation in asthmatic patients, such as serum IgE levels, sputum eosinophil counts, fraction of exhaled nitric oxide levels, and serum periostin levels, to aid decision making in clinical trials and drug development and to identify subsets of patients who might benefit from therapies. Although it is unlikely that these therapies will benefit all asthmatic patients with this heterogeneous disease, advances in understanding asthma subphenotypes in relation to clinical variables and TH2 cytokine responses offer the opportunity to improve the efficacy and safety of proposed therapies for asthma.