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Asthma is the most common chronic disease among children. In the U.S., asthma prevalence is highest among Puerto Ricans (36.5%), intermediate among African Americans (13.4%), and lowest in Whites (7.6%) and Mexicans (7.5%). Asthma mortality is 3- to 5-fold higher in Puerto Ricans and African Americans compared to Mexican Americans and Whites. Disturbingly, Americans with the highest asthma prevalence and death rate have the lowest drug response to asthma therapies. Unfortunately, minority children also have the highest exposure to tobacco.
Inhaled corticosteroids (ICS) are a mainstay of asthma treatment. Minority children with asthma have worse asthma-related outcomes even with high use of ICS. Children with asthma who are exposed to tobacco smoke have poor drug response to ICS, suggesting that smoke exposure negatively impacts ICS therapeutic efficacy. African American children have among the highest levels of secondhand tobacco smoke (SHS) exposure and Puerto Rican women have the highest rates of smoking during pregnancy. In addition, in utero tobacco smoke exposure (IUS) is associated with increased asthma risk and morbidity. Some racial/ethnic groups are more susceptible than others to developing asthma following early-life exposure to tobacco smoke.
Differences in asthma risk may be partially explained by environmental factors. Genetic risk factors, racial/ethnic-specific differences in tobacco exposure and metabolism, and their interaction, may explain the excess asthma morbidity and mortality among minority children. Few studies have examined the effects of tobacco exposure on ICS drug response in children with asthma. In addition, there are no published data on the impact of genetic risk factors and tobacco exposure on ICS treatment outcomes in minority children with asthma.
We propose a comprehensive study of the impact of tobacco exposure on ICS drug response in minority children. We will investigate (1) the clinical factors associated with asthma-related traits and poor ICS drug response among minority children exposed to tobacco, (2) how the genetic makeup of individuals interacts with tobacco smoke exposure to elicit a poor ICS response, and (3) how tobacco exposure changes the way an individual’s genome influences the response to ICS therapy. This proposal fills a void in our understanding of the complex molecular responses to tobacco exposure and how that leads to ICS drug resistance in minority children with asthma. | 