Stress and Bronchodilator Response in Children with Asthma
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Published on: November 4, 2010
John M Brehm1, Sima K Ramratnam1, Sze Man Tse2
11 Division of Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, and.
Insights
High child stress and anxiety-related gene ADCYAP1R1 are linked to reduced bronchodilator response (BDR) in children with asthma. This may be due to lower expression of the beta-2 adrenergic receptor (ADRB2) in stressed children.
Area of Science:
- Pediatric Asthma Research
- Genetics and Immunology
- Stress and Health
Background:
- Asthma morbidity is linked to stress in Puerto Ricans, who exhibit reduced bronchodilator response (BDR).
- Understanding genetic and environmental factors influencing BDR is crucial for asthma management.
Purpose of the Study:
- To investigate the association between stress, the ADCYAP1R1 gene, and BDR in children with asthma.
- To explore these relationships in both Puerto Rican and non-Puerto Rican children.
Main Methods:
- Cross-sectional study of 234 Puerto Rican children (ages 9-14) with asthma.
- Assessed child and maternal stress using validated questionnaires.
- Genotyped ADCYAP1R1 polymorphisms and performed replication analyses in additional cohorts.
Main Results:
- High child stress correlated with reduced BDR across three cohorts.
- Combined high child and maternal stress significantly lowered BDR by 10.2%.
- An ADCYAP1R1 polymorphism (rs34548976) was associated with reduced BDR and lower ADRB2 gene expression.
Conclusions:
- Childhood stress and ADCYAP1R1 gene variants are associated with diminished BDR in asthmatic children.
- Reduced ADRB2 expression in highly stressed children may explain the observed BDR reduction.
Rationale:
Stress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR).
Objectives:
To examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma.
Methods:
This was a cross-sectional study of stress and BDR (percent change in FEV1 after BD) in 234 PRs ages 9-14 years with asthma. We assessed child stress using the Checklist of Children's Distress Symptoms, and maternal stress using the Perceived Stress Scale. Replication analyses were conducted in two cohorts. Polymorphisms in ADCYAP1R1 were genotyped in our study and six replication studies. Multivariable models of stress and BDR were adjusted for age, sex, income, environmental tobacco smoke, and use of inhaled corticosteroids.
Measurements And Main Results:
High child stress was associated with reduced BDR in three cohorts. PR children who were highly stressed (upper quartile, Checklist of Children's Distress Symptoms) and whose mothers had high stress (upper quartile, Perceived Stress Scale) had a BDR that was 10.2% (95% confidence interval, 6.1-14.2%) lower than children who had neither high stress nor a highly stressed mother. A polymorphism in ADCYAP1R1 (rs34548976) was associated with reduced BDR. This single-nucleotide polymorphism is associated with reduced expression of the gene for the β2-adrenergic receptor (ADRB2) in CD4(+) lymphocytes of subjects with asthma, and it affects brain connectivity of the amygdala and the insula (a biomarker of anxiety).
Conclusions:
High child stress and an ADCYAP1R1 single-nucleotide polymorphism are associated with reduced BDR in children with asthma. This is likely caused by down-regulation of ADRB2 in highly stressed children.
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