Personalized therapeutic approaches for asthma

Differences in host susceptibility and environmental exposures result in significant heterogeneity in asthma clinical expression, natural evolution, and response to treatment. These differences are influenced by many factors including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, many of which are modified by environmental and allergic exposures. The complex and multiple characteristics that interact in asthma development and progression pose significant challenges for personalized management. This review aims to guide the clinician in its management decisions by reviewing each of the components important in developing this therapeutic paradigm and by providing several integrated goals for precision or personalized medicine for asthma. Biologic characteristics of asthma in relation to the genomics, exposome, and hypersensitivity reactions (allergic responsiveness) resulting in asthma diathesis are discussed. Further insights including the use of targeted biologics and allergen immunotherapy are provided, while discussing the importance of targeting the epithelium, mucus production, airway smooth muscle, and small airways. We examine the value of multivariate cluster analyses as a new paradigm that can inform treatment decisions and the potential of adaptive trial design to evaluate known and novel predictive biomarkers and characterize disease heterogeneity.