The Omics of Asthma
The term “omics” traditionally refers to the fields of genomics, proteomics, and/or metabolomics. Using these omics in childhood asthma may help predict outcomes later in life.
This was the topic of Juan C. Celedón's, MD, DrPh, session at the Celebration of Pediatric Pulmonology and Sleep 2019 meeting. Pulmonology Consultant caught up with Dr Celedón after his presentation.
Juan C. Celedón, MD, DrPh, is chief of service in the Division of Pediatric Pulmonology, Allergy, and Immunology and is the director of the Center for Environmental Health at the University of Pittsburgh.
CONSULTANT360: To start, can you give us an overview of your research and how it came about?
Dr Celedón: My research focuses on identifying genetic and environmental risk factors for airway diseases (asthma and chronic obstructive pulmonary disease [COPD]), particularly in ethnic minorities. Environmental exposures can increase the risk of asthma or COPD by affecting the human epigenome, and—ultimately—the expression of genes that cause or worsen these diseases. Studying epigenetics may help us understand the causes of a disease and predict disease risk.
C360: Which specific methylation profiles did you identify, and what are they associated with?
Dr Celedón: We studied methylation profiles in nasal epithelium because, in children, DNA methylation and gene expression in nasal epithelium are correlated with methylation and expression of bronchial epithelium. Abnormal integrity or function of the airway epithelium may allow injurious agents (eg, viruses, allergens, and pollutants) to penetrate beyond the epithelial barrier, interact with dendritic cells, and alter immune responses, which could be key to the development of allergic asthma in children.
Using DNA and RNA from nasal epithelium, we identified more than 2200 methylation signals that both affected gene expression and were significantly associated with atopy or atopic asthma in a study of 483 Puerto Rican children aged 9 to 20 years. Moreover, 28 of our top 30 signals for atopic asthma were replicated in two independent cohorts, one composed predominantly of African American children and another composed predominantly of European children. We then developed a panel of 30 methylation markers, which accurately classified or differentiated children with atopic asthma from non-atopic control subjects in all study cohorts.
C360: What do your results mean for clinical practice?
Dr Celedón: This provides “proof of concept” for developing nasal epithelial biomarkers to predict disease development, disease progression, and treatment response in future longitudinal studies of children and adults.
C360: What is the most common question you receive about your research? How do you respond?
Dr Celedón: Can this be used in clinical practice? The answer is “not yet,” but epigenetic and transcriptomic biomarkers of asthma should become a reality in clinical practice within the next few years.
C360: What else should our audience of pulmonologists know about your research?
Dr Celedón: Puerto Ricans and African Americans have the greatest burden from asthma of all ethnic groups in the United States. Studying these groups is important and should provide unique insights into the causes of asthma and, ultimately, better means of prevention, diagnosis, and treatment.
Forno E, Wang T, Qi C, et al. DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study [published online December 21, 2018]. Lancet Respir Med. https://doi.org/10.1016/S2213-2600(18)30466-1.