Brehm John M, Ramratnam Sima K, Tse Sze Man, Croteau-Chonka Damien C, Pino-Yanes Maria, Rosas-Salazar Christian, Litonjua Augusto A, Raby Benjamin A, Boutaoui Nadia, Han Yueh-Ying, Chen Wei, Forno Erick, Marsland Anna L, Nugent Nicole R, Eng Celeste, Colón-Semidey Angel, Alvarez María, Acosta-Pérez Edna, Spear Melissa L, Martinez Fernando D, Avila Lydiana, Weiss Scott T, Soto-Quiros Manuel, Ober Carole, Nicolae Dan L, Barnes Kathleen C, Lemanske Robert F, Strunk Robert C, Liu Andrew, London Stephanie J, Gilliland Frank, Sleiman Patrick, March Michael, Hakonarson Hakon, Duan Qing Ling, Kolls Jay K, Fritz Gregory K, Hu Donglei, Fani Negar, Stevens Jennifer S, Almli Lynn M, Burchard Esteban G, Shin Jaemin, McQuaid Elizabeth L, Ressler Kerry, Canino Glorisa, Celedón Juan C
1 Division of Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, and.
2 Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Respir Crit Care Med. 2015 Jul 1;192(1):47-56. doi: 10.1164/rccm.201501-0037OC.
Stress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR).
To examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma.
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.
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).
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.
压力与波多黎各人（PR）的哮喘发病率相关，而他们的支气管扩张剂反应（BDR）有所降低。
研究压力和/或一种调节焦虑的基因（ADCYAP1R1）是否与PR和非PR哮喘儿童的BDR相关。
这是一项对234名9至14岁患有哮喘的PR进行压力与BDR（支气管扩张后第一秒用力呼气量[FEV1]的变化百分比）的横断面研究。我们使用儿童苦恼症状清单评估儿童压力，使用感知压力量表评估母亲压力。在两个队列中进行了重复分析。在我们的研究和六项重复研究中对ADCYAP1R1的多态性进行了基因分型。压力与BDR的多变量模型针对年龄、性别、收入、环境烟草烟雾和吸入性糖皮质激素的使用进行了调整。
在三个队列中，儿童高压力与BDR降低相关。压力高（儿童苦恼症状清单上四分位数）且母亲压力高（感知压力量表上四分位数）的PR儿童的BDR比既无高压力儿童也无高压力母亲的儿童低10.2%（95%置信区间，6.1 - 14.2%）。ADCYAP1R1中的一种多态性（rs34548976）与BDR降低相关。这种单核苷酸多态性与哮喘患者CD4(+)淋巴细胞中β2 - 肾上腺素能受体（ADRB2）基因的表达降低相关，并且它影响杏仁核和脑岛的脑连接性（焦虑的生物标志物）。
儿童高压力和ADCYAP1R1单核苷酸多态性与哮喘儿童的BDR降低相关。这可能是由于高压力儿童中ADRB2的下调所致。
