Asthma, the most common chronic pediatric disease, affects over 7 million U.S. children. Despite effective treatment options, exacerbations from asthma account for substantial preventable morbidity and annual U.S. healthcare costs totaling more than $50 billion. Applications of the genetic knowledge resulting from the Human Genome Project are not yet available for asthma despite the immense potential that pharmacogenomics demonstrates for improving asthma care. Our preliminary studies suggest that focusing on age-dependent factors is likely to yield important indicators of asthma drug response that are applicable to children. We believe that specific genetic mechanisms regulating response to inhaled steroids and ?2-agonists differ between children and adults, and focusing on these differences will yield novel biologic findings that will allow response predictability and aid pediatric clinical care. Using ae-dependent biomarkers to predict asthma drug response carries tremendous promise to significantly improve asthma management by allowing clinicians to tailor asthma management to individual needs. This will result in less asthma suffering and huge cost-savings as the number of exacerbations from asthma will decrease. This study will elucidate response to the two most commonly used medications for asthma, inhaled steroids and ?2-agonists. This research employs existing genetic, genomic, and metabolomics data from clinical trial and real-life populations. Linking genetic variants to the therapeutic responses with additional information from genomics and metabolomics will provide insight into the biologic pathways that may be activated. By integrating and accounting for the interplay between genetics, genomics, and metabolomics, we will develop a comprehensive signature that predicts response to inhaled steroids and ?2-agonists. At the conclusion of this research, we expect to have identified genetic, genomic, and metabolomic indicators of child response to inhaled steroids and ?2-agonists. The results from the proposed study would provide an important opportunity to make prediction of asthma drug response a reality in clinical practice, and thus benefit very large numbers of patients, the healthcare industry, and society at large both domestically and globally. Knowledge gained from this research will advance the field of personalized medicine for pediatric asthma.
Applications of the genetic knowledge resulting from the Human Genome Project are not yet available for asthma despite the immense potential that pharmacogenomics demonstrates for improving asthma care. This research will link genetic variants to therapeutic responses with additional information from genomics and metabolomics to provide insight into the biologic pathways that may be drug-activated in an age- dependent method. Knowledge gained from this research will advance the field of personalized medicine for pediatric asthma through the creation of a prediction model.
| Kelly, R S; Sordillo, J E; Lasky-Su, J et al. (2018) Plasma metabolite profiles in children with current asthma. Clin Exp Allergy 48:1297-1304 |
| McGeachie, Michael J; Clemmer, George L; Hayete, Boris et al. (2018) Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator. J Allergy Clin Immunol 142:1479-1488.e12 |
| Carlson, Sonia; Borrell, Luisa N; Eng, Celeste et al. (2017) Self-reported racial/ethnic discrimination and bronchodilator response in African American youth with asthma. PLoS One 12:e0179091 |
