Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth.

Importance: T helper 2 (T2) cells and T helper 17 (T17) cells are CD4+ T cell subtypes involved in asthma. Characterizing asthma endotypes based on these cell types in diverse groups is important for developing effective therapies for youths with asthma.

Objective: To identify asthma endotypes in school-aged youths aged 6 to 20 years by examining the distribution and characteristics of transcriptomic profiles in nasal epithelium.

miRNAome-metabolome wide association study reveals effects of miRNA regulation in eosinophilia and airflow obstruction in childhood asthma.

Background: There are important inter-relationships between miRNAs and metabolites: alterations in miRNA expression can be induced by various metabolic stimuli, and miRNAs play a regulatory role in numerous cellular processes, impacting metabolism. While both specific miRNAs and metabolites have been identified for their role in childhood asthma, there has been no global assessment of the combined effect of miRNAs and the metabolome in childhood asthma.

Methods: We performed miRNAome-metabolome-wide association studies ('miR-metabo-WAS') in two childhood cohorts of asthma to evaluate the contemporaneous and persistent miRNA-metabolite associations: 1) Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (N = 1121); 2) the Childhood Asthma Management Program (CAMP) (N = 312 and N = 454).

Sociocultural Stressors and Asthma among Adults in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

Background: Hispanic/Latino adults commonly experience high psychosocial stress yet little is known about the pathways linking sociocultural stressors and asthma in this population.

Objective: Whether and how sociocultural stressors are associated with asthma in Hispanic/Latino adults.

Methods: Cross-sectional study of 4,759 adults aged 18 to 74 years who participated in the Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos.

Molecular group and correlation guided structural learning for multi-phenotype prediction.

We propose a supervised learning bioinformatics tool, Biological gRoup guIded muLtivariate muLtiple lIneAr regression with peNalizaTion (Brilliant), designed for feature selection and outcome prediction in genomic data with multi-phenotypic responses. Brilliant specifically incorporates genome and/or phenotype grouping structures, as well as phenotype correlation structures, in feature selection, effect estimation, and outcome prediction under a penalized multi-response linear regression model. Extensive simulations demonstrate its superior performance compared to competing methods.

Immunomodulatory metabolites in IgE-mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling.

Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.

Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.

Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward).

Circulating microRNAs associated with bronchodilator response in childhood asthma.

Background: Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.

MiR-107 and Its Association With House Dust Mite Sensitisation: Implications for Asthma.

Introduction: MicroRNAs (miRNAs) have been linked to allergic diseases but their effects on sensitisation to allergens in individuals with asthma are unknown. We aimed to identify miRNAs associated with house dust mite (HDM) sensitisation in childhood asthma.

Methods: Serum samples from 1126 children with asthma who participated in the Genetics of Asthma in Costa Rica Study (GACRS) were profiled for 304 miRNAs.

Identification of MicroRNAs in children with increased asthma bronchodilator usage in genetics of asthma in Costa Rica Study.

Introduction: Uncontrolled or severe asthma results in symptomatic usage of short-acting ß2-agonist (SABA) usage. MicroRNAs (miRNAs) are posttranslational regulators that can influence asthma biology. This study aims to identify miRNAs that are associated with increased SABA usage.

Access to Treatment for Chronic Obstructive Pulmonary Disease in the Americas: A Call for Action. A Joint Perspective from the Brazilian Thoracic Society, Canadian Thoracic Society, Latin American Thoracic Society, and the American Thoracic Society.

Chronic obstructive pulmonary disease (COPD) is a major public health problem in the Americas (a region of the world comprising North, Central, and South America), although there is substantial variation in disease prevalence, morbidity, and mortality between and within nations. Across the Americas, COPD disproportionately affects vulnerable populations, including minoritized populations and impoverished persons, who are more likely to be exposed to risk factors such as tobacco use, air pollution, infections such as tuberculosis, and biomass smoke, but less likely to have adequate healthcare access. Management of COPD can be challenging across the Americas, with some barriers being specific to certain countries and others shared across the United States, Canada, and Latin America.

The effects of violence and related stress on asthma.

In the United States, people living in deprived urban areas and persons in certain minoritized groups are often exposed to violence and affected with asthma, and epidemiologic studies have shown a link between exposure to violence (ETV) and asthma throughout the lifespan. Indeed, ETV at the individual, intrafamilial and community levels has been linked to asthma in children and adults. In this review, we discuss the evidence for a causal relation between ETV and asthma, emphasizing findings published in the last five years.

Nasal Epithelium Transcriptomics Predict Clinical Response to Elexacaftor/Tezacaftor/Ivacaftor.

Elexacaftor/tezacaftor/ivacaftor (ETI) has had a substantial positive impact for people living with cystic fibrosis (pwCF). However, there can be substantial variability in efficacy, and we lack adequate biomarkers to predict individual response. We thus aimed to identify transcriptomic profiles in nasal respiratory epithelium that predict clinical response to ETI treatment.

Long-Term PM Exposure and Upregulation of Expression in Nasal Epithelium from Youth with Asthma.

Background: Little is known about long-term PM exposure and airway epithelial gene expression.

Objective: To test for association between long-term PM exposure and nasal epithelial gene expression in youth with asthma.

Methods: Transcriptome-wide association study (TWAS) of long-term PM in nasal epithelium from youth aged 6-20 years in the: 1) Epigenetic Variation and Childhood Asthma in Puerto Ricans study (EVA-PR, n=182); 2) Vitamin D Kids Asthma Study (VDKA, n=58); and 3) Stress and Treatment Response in Puerto Rican and African American Children with Asthma study (STAR, n=81).

Metabolomics of IgE-Mediated Food Allergy and Oral Immunotherapy Outcomes based on Metabolomic Profiling.

Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.

Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multi-ethnic cohorts and responses to OIT.

Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N=384), a Costa Rican cohort of children with asthma (N=1040), and a peanut OIT trial (N=20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterwards).

Persistent cat ownership and asthma in a longitudinal study of Puerto Rican youth.

Background: Epidemiologic studies have reported conflicting findings for cat or dog exposure and childhood asthma. No study has evaluated whether persistent pet exposure from early life to school age is associated with asthma or allergic sensitization in youth.

Objective: To evaluate whether persistent ownership of a cat or a dog throughout childhood is associated with asthma in Puerto Rican youth, a group disproportionately affected with asthma.

Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation.

Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma.

Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma.

Background: Lung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants.

Methods: We utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n = 660).

Socioeconomic status, diet, and recurrent severe asthma exacerbations in Puerto Rican youth.

Background: Why Puerto Rican youths have higher rates of severe asthma exacerbations (SAEs) than their non-Hispanic White peers is unclear.

Objective: We aimed to identify risk factors associated with recurrent SAEs in Puerto Rican youths with asthma.

Methods: We performed cross-sectional and longitudinal analyses of recurrent SAEs in 209 Puerto Rican youths with asthma who participated in 2 cross-sectional studies approximately 5.