Dataset Information

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

ABSTRACT: Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.

SUBMITTER: Altman MC

PROVIDER: S-EPMC6472965 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

Altman Matthew C MC Gill Michelle A MA Whalen Elizabeth E Babineau Denise C DC Shao Baomei B Liu Andrew H AH Jepson Brett B Gruchalla Rebecca S RS O'Connor George T GT Pongracic Jacqueline A JA Kercsmar Carolyn M CM Khurana Hershey Gurjit K GK Zoratti Edward M EM Johnson Christine C CC Teach Stephen J SJ Kattan Meyer M Bacharier Leonard B LB Beigelman Avraham A Sigelman Steve M SM Presnell Scott S Gern James E JE Gergen Peter J PJ Wheatley Lisa M LM Togias Alkis A Busse William W WW Jackson Daniel J DJ

Nature immunology 20190408 5

Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among whi ...[more]

PMID: 30962590

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Project description:Changes in dietary patterns may partly explain the epidemic of asthma in industrialized countries. The objective of this study was to examine the relationship between dietary patterns and lung function and asthma exacerbations in Puerto Rican children. This is a case-control study of 678 Puerto Rican children (ages 6-14 years) in San Juan (Puerto Rico). All participants completed a respiratory health questionnaire and a 75-item food frequency questionnaire. Food items were aggregated into 7 groups: fruits, vegetables, grains, protein, dairy, fats, and sweets. Logistic regression was used to evaluate consumption frequency of each group and asthma. Based on the results, a dietary score was created [range from -2 (unhealthy diet: high consumption of dairy and sweets, low consumption of vegetables and grains) to 2 (healthy diet: high consumption of vegetables and grains and low consumption of dairy and sweet)]. Multivariable linear or logistic regression was used to assess the relationship between dietary score and lung function or asthma exacerbations. After adjustment for covariates, a healthier diet (each 1-point increment in dietary score) was associated with significantly higher %predicted forced expiratory volume in the first second (FEV1) and %predicted forced vital capacity (FVC) in control subjects. Dietary pattern alone was not associated with asthma exacerbations, but children with an unhealthy diet and vitamin D insufficiency (plasma 25(OH)D <30?ng/mL) had higher odds of ?1 severe asthma exacerbation [odds ratio (OR)?=?3.4, 95% confidence interval (CI)?=?1.5-7.5] or ?1 hospitalization due to asthma (OR?=?3.9, 95% CI?=?1.6-9.8, OR?=?3.4, 95% CI?=?1.5-7.5) than children who ate a healthy diet and were vitamin D sufficient. A healthy diet, with frequent consumption of vegetables and grains and low consumption of dairy products and sweets, was associated with higher lung function (as measured by FEV1 and FVC). Vitamin D insufficiency, together with an unhealthy diet, may have detrimental effects on asthma exacerbations in children.

Dataset Information

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

Publications

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

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