Stress and Bronchodilator Response in Children with Asthma

Brehm, John M.; Ramratnam, Sima; Tse, Sze Man; Croteau‐Chonka, Damien C.; Pino-Yanes, María; Rosas‐Salazar, Christian; Litonjua, Augusto A.; Raby, Benjamin A.; Boutaoui, Nadia; Han, Y.-Y.; Chen, Wei; Forno, Erick; Marsland, Anna L.; Nugent, Nicole R.; Eng, Celeste; Colón-Semidey, Angel; Alvarez, María; Acosta‐Pérez, Edna; Spear, Melissa L.; Martínez, Fernando D.; Avila, Lydiana; Weiss, Scott T.; Soto-Quirós, Manuel E.; Ober, Carole; Nicolae, Dan L.; Barnes, Kathleen C.; Lemanske, Robert F.; Strunk, Robert C.; Liu, Andy; London, Stephanie J.; Gilliland, Frank D.; Sleiman, Patrick; March, Michael; Hákonarson, Hákon; Duan, Qing; Kolls, Jay; Fritz, Gregory K.; Hu, Donglei; Fani, Negar; Stevens, Jennifer; Almli, Lynn M.; Burchard, Esteban G.; Shin, Jaemin; McQuaid, Elizabeth L.; Ressler, Kerry J.; Canino, Glorisa; Celedón, Juan C.

doi:10.1164/rccm.201501-0037oc

Cited by 94 publications

(69 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The Asthma BRIDGE dataset, which has been described previously (9,14,15), comprises a cohort of subjects selected from the EVE asthma genetics consortium (16). Additional detail on subject ascertainment is presented in the METHODS section of the online supplement.…”

Section: Methodsmentioning

confidence: 99%

“…Using clinical phenotype data available in Asthma BRIDGE and in CAMP, we developed two composite scores summarizing self-reported asthma control in the preceding 6 months (chronic, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 7 days (acute, 0-28), respectively, each modeled on the ACT questionnaire (11), where higher scores indicate worse asthma control. Based on the medians of the corresponding phenotypic distributions, optimal chronic asthma control was defined as a score less than or equal to six in BRIDGE WB and moderately suboptimal asthma control was defined as a score less than or equal to 11 in BRIDGE CD4 ( Figure 2).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Croteau‐Chonka¹,

Qiu²,

Martínez

et al. 2017

Am J Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

Rationale: Maintaining optimal symptom control remains the primary objective of asthma treatment. Better understanding of the biologic underpinnings of asthma control may lead to the development of improved clinical and pharmaceutical approaches.Objectives: To identify molecular pathways and interrelated genes whose differential expression was associated with asthma control.Methods: We performed gene set enrichment analyses of asthma control in 1,170 adults with asthma, each with gene expression data derived from either whole blood (WB) or unstimulated CD4 1 T lymphocytes (CD4), and a self-reported asthma control score representing either the preceding 6 months (chronic) or 7 days (acute). Our study comprised a discovery WB cohort (n = 245, chronic) and three independent, nonoverlapping replication cohorts: a second WB set (n = 448, acute) and two CD4 sets (n = 300, chronic; n = 77, acute). Measurements and Main Results:In the WB discovery cohort, we found significant overrepresentation of genes associated with asthma control in 1,106 gene sets from the Molecular Signatures Database (false discovery rate, ,5%). Of these, 583 (53%) replicated in at least one replication cohort (false discovery rate, ,25%). Suboptimal control was associated with signatures of eosinophilic and granulocytic inflammatory signals, whereas optimal control signatures were enriched for immature lymphocytic patterns. These signatures included two related biologic processes related to activation by TREM-1 (triggering receptor expressed on myeloid cells 1) and lipopolysaccharide. Conclusions:Together, these results demonstrate the existence of specific, reproducible transcriptomic components in blood that vary with degree of asthma control and implicate a novel biologic target (TREM-1).

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Croteau‐Chonka¹,

Qiu²,

Martínez

et al. 2017

Am J Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…As part of a case-control study of asthma in Puerto Rican subjects, we recruited 1,127 children (618 with asthma and 509 without asthma) living in San Juan, Puerto Rico, and Hartford, Connecticut (the HPR cohort). Details on subject recruitment and study procedures were reported previously (15,(23)(24)(25). A total of 147 children with dysanapsis (79 with and 69 without asthma) and 236 control subjects (120 with and 116 without asthma) and complete data were included in this analysis.…”

Section: Study Populationsmentioning

confidence: 99%

Obesity and Airway Dysanapsis in Children with and without Asthma

Forno

Weiner

Mullen

et al. 2017

Am J Respir Crit Care Med

Self Cite

196

137

View full text Add to dashboard Cite

Rationale: For unclear reasons, obese children with asthma have higher morbidity and reduced response to inhaled corticosteroids.Objectives: To assess whether childhood obesity is associated with airway dysanapsis (an incongruence between the growth of the lungs and the airways) and whether dysanapsis is associated with asthma morbidity.Methods: We examined the relationship between obesity and dysanapsis in six cohorts of children with and without asthma, as well as the relationship between dysanapsis and clinical outcomes in children with asthma. Adjusted odds ratios (ORs) were calculated for each cohort and in a combined analysis of all cohorts; longitudinal analyses were also performed for cohorts with available data. Hazard ratios (HRs) for clinical outcomes were calculated for children with asthma in the Childhood Asthma Management Program.Measurements and Main Results: Being overweight or obese was associated with dysanapsis in both the cross-sectional (OR, 1.95; 95% confidence interval [CI], 1.62-2.35 [for overweight/obese compared with normal weight children]) and the longitudinal (OR, 4.31; 95% CI, 2.99-6.22 [for children who were overweight/obese at all visits compared with normal weight children]) analyses. Dysanapsis was associated with greater lung volumes (FVC, vital capacity, and total lung capacity) and lesser flows (FEV 1 and forced expiratory flow, midexpiratory phase), and with indicators of ventilation inhomogeneity and anisotropic lung and airway growth. Among overweight/obese children with asthma, dysanapsis was associated with severe disease exacerbations (HR, 1.95; 95% CI, 1.38-2.75) and use of systemic steroids (HR, 3.22; 95% CI, 2.02-5.14).Conclusions: Obesity is associated with airway dysanapsis in children. Dysanapsis is associated with increased morbidity among obese children with asthma and may partly explain their reduced response to inhaled corticosteroids.

show abstract

“…The mechanisms that underlie the relationship between psychological symptoms and asthma remain unclear (19). We recently found that anxiety symptoms are associated with greater perceived dyspnea intensity in asthma during bronchoconstriction (16); and that depression and high stress were associated with reduced bronchodilator response (20,21), and altered pattern of inflammation (22), which could be involved in therapy resistance. The relationship between psychological disturbance and asthma control needs further study.…”

Section: Discussionmentioning

confidence: 99%

Severe and uncontrolled asthma in China: a cross-sectional survey from the Australasian Severe Asthma Network

Wang¹,

Wang²,

Gibson³

et al. 2017

J. Thorac. Dis.

View full text Add to dashboard Cite

Background: Severe asthma is largely unexplored in the Chinese population. Patients with asthma underwent systematic evaluation, by investigating the characteristics of uncontrolled asthma and of asthma treated with three different controller therapies. Methods: This multi-centre, real-world study was conducted from March 2014 to September 2015. Adults with stable asthma underwent assessment of medication use, asthma control, quality of life, psychological symptoms, work productivity and activity impairment, bronchodilator response and sputum induction. Results: Participants (n=379) had a mean (SD) age of 47.4 (14.0) years, and 57.0% were female. There were 14.8% (n=56) of patients receiving treatment with Step 4/5 as severe asthma, but only 13 (3.4%) met ERS/ATS severe refractory asthma criteria. The patients with severe asthma usually used triple controller therapy: ICS/LABA, additional leukotriene modifier or theophylline, and reported better asthma control.Two fifths of patients (n=147) had uncontrolled asthma, with worse symptoms, psychological symptoms (both Conclusions: Although there is a relatively low proportion of severe refractory asthma based on ERS/ATS criteria, two of five patients with asthma in China are uncontrolled, displaying more psychological symptoms and reduced work productivity. Substantial gain in asthma control is obtained by triple controller therapy and this may be a promising therapeutic option for persistent asthma.

show abstract

Stress and Bronchodilator Response in Children with Asthma

Cited by 94 publications

References 61 publications

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Obesity and Airway Dysanapsis in Children with and without Asthma

Severe and uncontrolled asthma in China: a cross-sectional survey from the Australasian Severe Asthma Network

Contact Info

Product

Resources

About