Associations of aeroallergen testing with reduced oral corticosteroid bursts among adults with asthma.

Background: Aeroallergen testing can improve precision care for persistent asthma. How testing benefits diverse populations of adults with asthma and the importance of the aeroallergen sensitization and test modality used remain poorly understood.

Objective: We evaluated whether aeroallergen testing was associated with a reduction in oral corticosteroid (OCS) bursts.

Influences of quality of maternal care and environmental enrichment on associative memory function in rats with early life lead exposure.

Introduction: Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure.

Racial differences in odds of asthma exacerbations among Aspergillus fumigatus-sensitized adults with asthma.

Background: Allergic sensitization to mold is a risk factor for poor asthma outcomes, but whether it accounts for disparities in asthma outcomes according to race or socioeconomic status is not well-studied.

Objective: To identify factors associated with allergic sensitization to molds and evaluate associations of sensitization to molds with asthma exacerbations after stratifying by race.

Methods: We conducted a retrospective cohort study of adults with asthma who had an outpatient visit to a large health system between January 1, 2017 and June 30, 2023 and received aeroallergen testing to Aspergillus fumigatus, Penicillium, Alternaria, and Cladosporium.

Aldo-keto reductase (AKR) superfamily website and database: An update.

The aldo-keto reductase (AKR) superfamily is a large family of proteins found across the kingdoms of life. Shared features of the family include 1) structural similarities such as an (α/β)-barrel structure, disordered loop structure, cofactor binding site, and a catalytic tetrad, and 2) the ability to catalyze the nicotinamide adenine dinucleotide (phosphate) reduced (NAD(P)H)-dependent reduction of a carbonyl group. A criteria of family membership is that the protein must have a measured function, and thus, genomic sequences suggesting the transcription of potential AKR proteins are considered pseudo-members until evidence of a functionally expressed protein is available.

Clarifying Chronic Obstructive Pulmonary Disease Genetic Associations Observed in Biobanks via Mediation Analysis of Smoking.

Varying case definitions of COPD have heterogenous genetic risk profiles, potentially reflective of disease subtypes or classification bias (e.g., smokers more likely to be diagnosed with COPD).

Benefits of Aeroallergen Testing on Oral Corticosteroid Bursts in Adults with Asthma.

Background: Aeroallergen testing can improve precision care for persistent asthma and is recommended by the U.S. clinical guidelines.

Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells.

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood.

Factors associated with aeroallergen testing among adults with asthma in a large health system.

Background: Aeroallergen testing informs precision care for adults with asthma, yet the epidemiology of testing in this population remains poorly understood.

Objective: We sought to identify factors associated with receiving aeroallergen testing, the results of these tests, and subsequent reductions in exacerbation measures among adults with asthma.

Methods: We used electronic health record data to conduct a retrospective, observational cohort study of 30,775 adults with asthma who had an office visit with a primary care provider or an asthma specialist from January 1, 2017, to August 26, 2022.

Genetic Variation and Sensory Perception of a Pediatric Formulation of Ibuprofen: Can a Medicine Taste Too Good for Some?

There is wide variation in how individuals perceive the chemosensory attributes of liquid formulations of ibuprofen, encompassing both adults and children. To understand personal variation in the taste and chemesthesis properties of this medicine, and how to measure it, our first scientific strategy centered on utilizing trained adult panelists, due to the complex and time-consuming psychophysical tasks needed at this initial stage. We conducted a double-blind cohort study in which panelists underwent whole-genome-wide genotyping and psychophysically evaluated an over-the-counter pediatric medicine containing ibuprofen.

Improving Genetic Association Studies with a Novel Methodology that Unveils the Hidden Complexity of All-Cause Heart Failure.

Motivation: Genome-Wide Association Studies (GWAS) commonly assume phenotypic and genetic homogeneity that is not present in complex conditions. We designed Transformative Regression Analysis of Combined Effects (TRACE), a GWAS methodology that better accounts for clinical phenotype heterogeneity and identifies gene-by-environment (GxE) interactions. We demonstrated with UK Biobank (UKB) data that TRACE increased the variance explained in All-Cause Heart Failure (AHF) via the discovery of novel single nucleotide polymorphism (SNP) and SNP-by-environment (i.

Building Career Paths for Ph.D., Basic and Translational Scientists in Clinical Departments in the United States: An Official American Thoracic Society Workshop Report.

To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units.

Linking Ambient NO2 Pollution Measures with Electronic Health Record Data to Study Asthma Exacerbations.

Electronic health record (EHR)-derived data can be linked to geospatially distributed socioeconomic and environmental factors to conduct large-scale epidemiologic studies. Ambient NO2 is a known environmental risk factor for asthma. However, health exposure studies often rely on data from geographically sparse regulatory monitors that may not reflect true individual exposure.

Factors Associated With Asthma Biologic Prescribing and Primary Adherence Among Adults in a Large Health System.

Background: The availability of asthma biologics may not benefit all patients equally.

Objective: We sought to identify patient characteristics associated with asthma biologic prescribing, primary adherence, and effectiveness.

Methods: A retrospective, observational cohort study of 9,147 adults with asthma who established care with a Penn Medicine asthma subspecialist was conducted using Electronic Health Record data from January 1, 2016, to October 18, 2021.

Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness.

Obesity increases asthma prevalence and severity. However, the underlying mechanisms are poorly understood, and consequently, therapeutic options for asthma patients with obesity remain limited. Here we report that cholecystokinin-a metabolic hormone best known for its role in signaling satiation and fat metabolism-is increased in the lungs of obese mice and that pharmacological blockade of cholecystokinin A receptor signaling reduces obesity-associated airway hyperresponsiveness.

CEBPD modulates the airway smooth muscle transcriptomic response to glucocorticoids.

Background: CCAAT/Enhancer Binding Protein D (CEBPD), a pleiotropic glucocorticoid-responsive transcription factor, modulates inflammatory responses. Of relevance to asthma, expression of CEBPD in airway smooth muscle (ASM) increases with glucocorticoid exposure. We sought to characterize CEBPD-mediated transcriptomic responses to glucocorticoid exposure in ASM by measuring changes observed after knockdown of CEBPD and its impact on asthma-related ASM function.

Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness.

Variability in response to short-acting β-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities.

REALGAR: a web app of integrated respiratory omics data.

Motivation: In the post genome-wide association study (GWAS) era, omics techniques have characterized information beyond genomic variants to include cell and tissue type-specific gene transcription, transcription factor binding sites, expression quantitative trait loci (eQTL) and many other biological layers. Analysis of omics data and its integration has in turn improved the functional interpretation of disease-associated genetic variants. Over 170 000 transcriptomic and epigenomic datasets corresponding to studies of various cell and tissue types under specific disease, treatment and exposure conditions are available in the Gene Expression Omnibus resource.

Neighborhood Characteristics and COVID-19 Incidence and Mortality in Southeastern Pennsylvania.

The COVID-19 pandemic has differentially impacted people according to their race/ethnicity, socioeconomic status, and preexisting conditions. Public health surveillance efforts, especially those occurring early in the pandemic, did not gather nor report adequate individual-level demographic information to identify these differences, and thus, neighborhood-level characteristics were used to note striking disparities in the US. We sought to determine whether risk factors associated with COVID-19 incidence and mortality in five Southeastern Pennsylvania counties could be better understood by using neighborhood-level demographic data augmented with health, socioeconomic, and environmental characteristics derived from publicly available sources.

Skin fibroblast metabolomic profiling reveals that lipid dysfunction predicts the severity of Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a triplet guanine-adenine-adenine (GAA) repeat expansion in intron 1 of the FXN gene, which leads to decreased levels of the frataxin protein. Frataxin is involved in the formation of iron-sulfur (Fe-S) cluster prosthetic groups for various metabolic enzymes. To provide a better understanding of the metabolic status of patients with FRDA, here we used patient-derived fibroblast cells as a surrogate tissue for metabolic and lipidomic profiling by liquid chromatography-high resolution mass spectrometry.

Epinephrine evokes shortening of human airway smooth muscle cells following β adrenergic receptor desensitization.

Epinephrine (EPI), an endogenous catecholamine involved in the body's fight-or-flight responses to stress, activates α-adrenergic receptors (αARs) expressed on various organs to evoke a wide range of physiological functions, including vasoconstriction. In the smooth muscle of human bronchi, however, the functional role of EPI on αARs remains controversial. Classically, evidence suggests that EPI promotes bronchodilation by stimulating β-adrenergic receptors (βARs).

Consolidated Environmental and Social Data Facilitates Neighborhood-Level Health Studies in Philadelphia.

A wide range of datasets containing geographically distributed measures of the environment and social factors is currently available, and as low-cost sensors and other devices become increasingly used, the volume of these data will continue to grow. Because such factors influence many health outcomes, researchers with varied interests often repeat tasks related to gathering and preparing these data for studies. We created Sensor-based Analysis of Pollution in the Philadelphia Region with Information on Neighborhoods and the Environment (SAPPHIRINE), offered as a web application and package, to integrate pollution, crime, social disadvantage, and traffic data relevant to investigators, citizen scientists, and policy makers in the Greater Philadelphia Area.

Gene-Based Analysis Reveals Sex-Specific Genetic Risk Factors of COPD.

Sex-specific differences have been noted among people with chronic obstructive pulmonary disease (COPD), but whether these differences are attributable to genetic variation is poorly understood. The availability of large biobanks with deeply phenotyped subjects such as the UK Biobank enables the investigation of sex-specific genetic associations that may provide new insights into COPD risk factors. We performed sex-stratified genome-wide association studies (GWAS) of COPD (male: 12,958 cases and 95,631 controls; female: 11,311 cases and 123,714 controls) and found that while most associations were shared between sexes, several regions had sex-specific contributions, including respiratory viral infection-related loci in/near C5orf56 and PELI1.