Decoding the Enigmatic Causes of Asthma
The most common serious chronic disease in infants and children, asthma is caused by many factors, including genetics and ethnicity, environment, diet, stress and more. Today, researchers are in the early stages of understanding these causes, and their precise relationship to pediatric asthma. Pulmonologist and genetic epidemiologist Juan C. Celedón, MD, DrPH, and his team have taken a leadership role in the identification of genetic factors and environmental exposures that influence the development of asthma and chronic obstructive pulmonary disease (COPD), particularly in ethnic minorities.
Dr. Celedón’s team first identified MMP12 and TSLP as susceptibility genes for asthma- or COPD-phenotypes in humans, while also showing that racial ancestry partly explains marked differences in the burden of asthma and COPD between Puerto Ricans and Mexicans – the Hispanic paradox. Moreover, Dr. Celedón’s group first reported that genetic and epigenetic variation in a susceptibility gene for post-traumatic stress disorder (ADCYAP1R1) is associated with asthma, and that exposure to violence is associated with both ADCYAP1R1methylation and asthma. They then showed that both psychosocial stress and a genetic variant in ADCYAP1R1 are associated with reduced response to short-acting bronchodilators in children with or at risk for asthma. Based on that work, Dr. Celedón’s team is now examining whether changes in DNA methylation and gene expression induced by violence or stress lead to asthma or reduced response to treatment for asthma in minority children.
Dr. Celedón’s research team also first showed that low vitamin D levels are associated with severe asthma attacks in school-aged children. They are now conducting a National Institutes of Health-funded clinical trial of vitamin D to prevent severe asthma attacks in childhood.