Computational deconvolution of cell type-specific gene expression in COPD and IPF lungs reveals disease severity associations.

Background: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n > 1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity.

B cell immune repertoire sequencing in tobacco cigarette smoking, vaping, and chronic obstructive pulmonary disease in the COPDGene cohort.

Rationale: Cigarette smoking (CS) impairs B cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B cell activity is unclear.

Objective: To examine B cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, dual-use, COPD-related outcomes, and demographic factors.

Development and validation of a mortality risk prediction model for chronic obstructive pulmonary disease: a cross-sectional study using probabilistic graphical modelling.

Background: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in patients with COPD can be important for disease management strategies. Although all-cause mortality predictors have been developed previously, limited research exists on factors directly affecting COPD-specific mortality.

Impact of Short-Term Diesel Exhaust Exposure on Prothrombotic Markers in Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Crossover Study.

Growing evidence suggests that air pollution exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) that is associated with an increased prothrombotic state and adverse cardiovascular outcomes. However, much of this work is based on observational data or human exposure studies involving younger participants. The biological causality and mechanism of air pollution-induced prothrombotic response in patients with COPD remain to be explored.

Sex-biased Regulation of Extracellular Matrix Genes in COPD.

Compared to men, women often develop COPD at an earlier age with worse respiratory symptoms despite lower smoking exposure. However, most preventive, and therapeutic strategies ignore biological sex differences in COPD. Our goal was to better understand sex-specific gene regulatory processes in lung tissue and the molecular basis for sex differences in COPD onset and severity.

Disentangling Predictors of COPD Mortality with Probabilistic Graphical Models.

Background-research Question: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in COPD patients can be important for disease management strategies. Although scores for all-cause mortality have been developed previously, there is limited research on factors that may directly affect COPD-specific mortality.

COPD Exposed to Air Pollution: A Path to Understand and Protect a Susceptible Population.

Topic Importance: Air pollution poses a risk to the respiratory health of individuals with COPD. Long- and short-term exposures to higher levels of particulate-rich air pollution are associated with increased COPD exacerbation, hospitalization, and mortality, collectively implicating air pollution as a cause of adverse COPD-related outcomes.

Review Findings: This review summarizes the evidence for COPD as a phenotype that confers susceptibility for adverse health outcomes in the face of common air pollution.

Blood-based Transcriptomic and Proteomic Biomarkers of Emphysema.

Emphysema is a chronic obstructive pulmonary disease phenotype with important prognostic implications. Identifying blood-based biomarkers of emphysema will facilitate early diagnosis and development of targeted therapies. To discover blood omics biomarkers for chest computed tomography-quantified emphysema and develop predictive biomarker panels.

Activation of CD8 T Cells in Chronic Obstructive Pulmonary Disease Lung.

Despite the importance of inflammation in chronic obstructive pulmonary disease (COPD), the immune cell landscape in the lung tissue of patients with mild-moderate disease has not been well characterized at the single-cell and molecular level. To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution. We performed single-cell transcriptomic, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD ( = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction ( = 5), end-stage COPD ( = 2), control ( = 6), or donors ( = 4).

Variants in transient receptor potential channels and toll-like receptors modify airway responses to allergen and air pollution: a randomized controlled response human exposure study.

Background: Environmental co-exposure to allergen and traffic-related air pollution is common globally and contributes to the exacerbation of respiratory diseases. Individual responses to environmental insults remain variable due to gene-environment interactions.

Objective: This study examined whether single nucleotide polymorphisms (SNPs) in lung cell surface receptor genes modifies lung function change and immune cell recruitment in allergen-sensitized individuals exposed to diesel exhaust (DE) and allergen.

Blood Gene Expression and Immune Cell Subtypes Associated with Chronic Obstructive Pulmonary Disease Exacerbations.

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPDs) are associated with a significant disease burden. Blood immune phenotyping may improve our understanding of a COPD endotype at increased risk of exacerbations. To determine the relationship between the transcriptome of circulating leukocytes and COPD exacerbations.

Lung adenocarcinoma promotion by air pollutants.

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development. Here we propose that environmental particulate matter measuring ≤2.

Exposure to diesel exhaust alters the functional metagenomic composition of the airway microbiome in former smokers.

The lung microbiome plays a crucial role in airway homeostasis, yet we know little about the effects of exposures such as air pollution therein. We conducted a controlled human exposure study to assess the impact of diesel exhaust (DE) on the human airway microbiome. Twenty-four participants (former smokers with mild to moderate COPD (N = 9), healthy former smokers (N = 7), and control healthy never smokers (N = 8)) were exposed to DE (300 μg/m PM) and filtered air (FA) for 2 h in a randomized order, separated by a 4-week washout.

Peroxisome proliferator-activated receptor gamma gene variants modify human airway and systemic responses to indoor dibutyl phthalate exposure.

Background: Single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptor gamma (PPAR-γ; gene: PPARG) and oxidative stress genes are associated with asthma risk. However, whether such variants modulate responses to dibutyl phthalate (DBP), a common plasticizer associated with increased asthma development, remains unknown. The purpose of this study is to investigate how SNPs in PPARG and oxidative stress genes, as represented by two separate genetic risk scores, modify the impact of DBP exposure on lung function and the airway and systemic response after an inhaled allergen challenge.

Effect of traffic-related air pollution on cough in adults with polymorphisms in several cough-related genes.

With prevalent global air pollution, individuals with certain genetic predispositions and sensitivities are at of higher risk of developing respiratory symptoms including chronic cough. Studies to date have relied on patient-filled questionnaires in epidemiological studies to evaluate the gene-by-environment interactions. In a controlled human exposure study, we evaluated whether genetic risk score (GRS) based on cough-related single-nucleotide polymorphisms (SNPs) are associated with a cough count over 24 h post-exposure to diesel exhaust (DE), a model for traffic-related air pollution.

Engineered plant control of associative nitrogen fixation.

Engineering N2-fixing symbioses between cereals and diazotrophic bacteria represents a promising strategy to sustainably deliver biologically fixed nitrogen (N) in agriculture. We previously developed novel transkingdom signaling between plants and bacteria, through plant production of the bacterial signal rhizopine, allowing control of bacterial gene expression in association with the plant. Here, we have developed both a homozygous rhizopine producing (RhiP) barley line and a hybrid rhizopine uptake system that conveys upon our model bacterium Azorhizobium caulinodans ORS571 (Ac) 103-fold improved sensitivity for rhizopine perception.