Stress and Treatment Response in Puerto Rican Children With Asthma
Condition: Asthma in Children
MeSH terms: Asthma
Study type: Observational

Summary: 
      This study aims to first determine whether high child stress leads to reduced response to
      common treatmenIs for asthma (inhaled corticosteroids and short-acting bronchodilators), and
      then to identify DNA methylation differences leading to stress-induced treatment resistance
      among children with asthma.
    

Detailed description: 
      Puerto Rican (PR) and African American children share a disproportionate burden from asthma
      in the U.S. The investigators have demonstrated that in PR children, a variety of
      psychological stressors are associated with worse asthma outcomes. Puerto Rican children also
      have reduced response to bronchodilators (short-acting inhaled β2-agonists, the most commonly
      used medication for asthma worldwide). The investigators have recently shown that high child
      stress is associated with reduced response to short-acting inhaled β2-agonists
      (bronchodilator response or BDR) in PR and non-PR children with asthma, and our preliminary
      results also implicate genetic and epigenetic (DNA methylation) variation in genes involved
      in stress responses (e.g., ADCYAP1R1) on asthma and BDR. Moreover, external in vitro
      experiments show that high stress leads to reduced expression of the genes for the
      β2-adrenergic receptor (ADRB2) and the glucocorticoid receptor (NR3C1) in white blood cells
      of children with asthma. While it is known that stress reduces BDR, it is not known whether
      this can be prevented by treatment with inhaled corticosteroids (ICS), or whether stress
      reduces response to ICS in vivo. Moreover, the research community has very limited knowledge
      of the genetic or epigenetic mechanisms underlying treatment resistance in stressed children.
      On the basis of novel preliminary results, the investigators hypothesize that chronic stress
      reduces response to inhaled corticosteroids (ICS) and BDR in PR and African American children
      with asthma, and that these effects are mediated by altered methylation of genes regulating
      responses to stress, corticosteroids and BDR. To test this hypothesis, the investigators will
      first determine whether increased stress leads to reduced response to ICS or BDR (even after
      treatment with ICS) in 300 PR and African American children with asthma (Aim 1). The
      investigators will then test for association between high child stress and genome-wide DNA
      methylation in respiratory (nasal) epithelium in 550 Puerto Rican and African American
      children with asthma (Aim 2). Next, the investigators will examine whether methylation
      changes in the top 100 genes identified in Aim 2 are associated with response to ICS or BDR
      in 300 to 550 PR and African American children with asthma (Aim 3a). Finally, the
      investigators will assess the effects of methylation changes identified in Aim 3a on gene
      expression (Aim 3b). This proposal should determine whether and how psychosocial stress leads
      to reduced response to common treatments for asthma control (ICS) and relief of asthma
      symptoms (short-acting inhaled β2-agonists) in a high-risk group (Puerto Rican and African
      American children).
    

Intervention name(s): Inhaled corticosteroid (mometasone)
Intervention type(s): Drug
Intervention description(s): The investigators are not measuring the effect of the intervention (ICS), but rather the effect of stress (which is not being intervened on), and this is thus an observational study. The ICS is given to children with asthma in whom an ICS is clinically indicated
Other intervention name(s): Asmanex
Intervention MeSH terms: Mometasone Furoate
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        300 Puerto Rican and African American children with mild to moderate persistent asthma,
        ages 8 to 20 years. Of these children, 150 (all Puerto Rican) will be recruited in the
        metropolitan area of San Juan and Caguas (Puerto Rico), and 150 (all African American) will
        be recruited in Pittsburgh (PA).
      
Biospecimen description: 
      Nasal epithelial samples for DNA and RNA extraction
    
Keywords: Asthma; Children; Stress; Puerto Rican; Health disparities; Treatment response; African American