PKU: Yahong Chen, MD, PhD UM: Steven K. Huang, MD

Transcription

1 DNA Methylation Changes Induced by Particulate Matter in Air Pollution Contributes to Chronic Airway Inflammation in Moderate-to-Severe Uncontrolled Asthma PKU: Yahong Chen, MD, PhD UM: Steven K. Huang, MD

2 Asthma Statistics Affects nearly 300 million people worldwide Expected to grow another 100 million by 2025 United States: 1 in 12 adults (8%) have asthma $56 billion in medical expenses, missed school and work China: Prevalence is only % Represents a 2-fold increase compared to 2002 Expected to continue to rise, lack of access

3 Background-Asthma burden 2013 AIM study-asia-pacific:asthma control rate is low Asthma control in the past 4 weeks(gina criteria) uncontrolled Partially controlled controlled % 7.6% Asia Pacific n=3630 Australia n=403 China n=402 Hongkong n=412 India n=400 Malaysia n=413 Signopore n=400 Korea n=400 Taiwan n=400 Tailand n=400 Thompson PJ, Salvi S, Lin J, et al. Insights, attitudes and perceptions about asthma and its treatment: findings from a multinational survey of patients from 8 Asia-Pacific countries and Hong Kong. Respirology. 2013;18(6):

4 Comparison of prevalence and severity of asthma worldwide

5 Background-Air pollution in asthma Traffic, construction, and industrial emissions are the major source of air pollution in Beijing Particulate matter (PM) is one type of air pollution PM levels in Beijing have reached as high as 700 µg/m 3 Average PM 10 level in China was 98 compared to 18, the average PM 10 level in the United States In 2013, the Air Quality Index (AQI) averaged a reading of in Beijing compared to 8.3 in Manhattan Most of the studies of pollution on asthma have been focused in Europe and North America

6 Background-DNA methylation and association with asthma Pollution is a risk factor for the development of asthma, and for exacerbations In utero exposure to smoke or air pollution increases the risk for the development of asthma in early childhood and adolescence Pollution has been associated with DNA methylation changes DNA methylation changes have been associated with asthma development Sofer et al. Epigenomics Apr;5(2): Yang and Schwartz, J Allergy Clin Immunol Dec;130(6): Tarantini et al. Environ Health Perspect Feb;117(2): It is unknown whether exposure to pollution induces further DNA methylation changes that might contribute to the increased severity and resistance to therapy of adults with more moderately severe, uncontrolled asthma.

7 Central Hypothesis Particulate matter in air pollution induces DNA methylation changes in the airways of adults with chronic asthma, thus increasing the frequency of exacerbations, and impairment in lung function associated with poorly controlled, moderate-to-severe disease Long-term Goal To understand both the epidemiologic and molecular mechanisms by which ambient air pollution affects asthma severity in China, and in particular, the molecular mechanisms that contribute to inflammation and airway remodeling in patients with uncontrolled moderate-tosevere disease

8 2 Study Aims Aim 1: Determine how longitudinal exposure to particulate matter contributes to both DNA methylation changes of specific genes and to worsening symptoms, decline in physiology, and increase in frequency of asthma exacerbations of adults with moderate-tosevere asthma in China. Aim 2: Determine the mechanism by which particulate matter alters the DNA methylation of key genes in bronchial epithelial cells

9 Study Design Prospective, Panel study 100 moderate-severe asthmatics, yo Non-smokers or ex-smokers who quit smoking for two years Patients who live in Haidian Excluded: current smokers, have COPD or other lung diseases baseline daily monthly At 6 months At 12 months demography Asthma control test (ACT) Exacerbation PFT Airway inflammation Air pollution monitor Blood sample The blood sampled from patients at different time points will be analyzed for global DNA methylation changes and DNA methylation changes of select genes

10 Study team PKU-YH. Chen,MD,PhD,Professor PI for several national grants Research interests: chronic airway inflammatory diseases Visiting scholar at U of M: U of M-SK. Huang, MD,Assistant Professor PI for NIH grants Research interests: DNA methylation in pulmonary diseases, especially in IPF and asthma

11 Key collaborators FR Deng,PhD,Associate Professor, School of Public Health,PKU Health effects of air pollution Stuart Batterman, PhD, Professor, Environmental Health Sciences, SPH, U of M EHS Environmental Exposures Core Leader Health effects of air pollution PKU CRI,U of M MICHR Study design, data analysis Anne Marie Scruggs,MS,Research technician DNA methylation, biostatistical analysis 11

12 Thanks!