Diagnosing Type 2 Inflammation in COPD: Comparison of Blood and Sputum Eosinophil Assessment in the University of California Los Angeles COPD Phenotyping Study.

Background: COPD phenotyping is an approach for developing tailored therapies. The eosinophilic phenotype is associated with exacerbation risk and response to specific treatments. This study evaluates the relationship between sputum and blood eosinophilia, hypothesizing that sputum eosinophil percentage (SpE%) better reflects disease severity and exacerbation risk than blood eosinophil counts (BEC).

Light Convolutional Neural Network to Detect Chronic Obstructive Pulmonary Disease (COPDxNet): A Multicenter Model Development and External Validation Study.

Background: Approximately 70% of adults with chronic obstructive pulmonary disease (COPD) remain undiagnosed. Opportunistic screening using chest computed tomography (CT) scans, commonly acquired in clinical practice, may be used to improve COPD detection through simple, clinically applicable deep-learning models. We developed a lightweight, convolutional neural network (COPDxNet) that utilizes minimally processed chest CT scans to detect COPD.

Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study.

Background: Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets.

Thioquinazolinones as Antituberculosis Agents Targeting Phosphopantetheinyl Transferase.

The essential mycobacterial enzyme phosphopantetheinyl transferase (PptT) is a potential target for antituberculosis drugs. We here report the identification of (pyridin-3-ylmethyl)-substituted thioquinazolinones as hits in a screen against PptT and a structure-activity relationship (SAR) study of the chemotype. The resulting thioquinazolinones exert on-target whole-cell activity against in axenic culture and in macrophages with efficacy comparable to that of clinically used antituberculosis drugs.

Association of Lung Quantitative CT Scan Textures With Systemic Inflammation and Mortality in COPD.

Background: COPD is characterized by persistent inflammation that is responsible for remodeling the bronchovascular bundles (BVBs), which may lead to poor quality of life. Quantitative CT (QCT) scan textures of the lung can capture local disease patterns of inflammation and related respiratory morbidity.

Research Question: Are BVB textures, obtained from the adaptive multiple feature method, associated with systemic inflammation, morbidity, and mortality in COPD?

Study Design And Methods: We analyzed data from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS; n = 2,981) and the Genetic Epidemiology of COPD (COPDGene) study (n = 10,305).

Characteristics Associated with Lung Function Trajectories: An Analysis of the SPIROMICS Cohort.

Discovering the biological basis of progression in chronic obstructive pulmonary disease (COPD), especially of rapid decline (RD) in forced expiratory volume in 1 second, is essential to the development of precision therapies. First, we sought to define baseline characteristics of RD (⩾100 ml/yr), relative to participants with stable-to-improved (S/I) status or with intermediate decline (D)-categories based on spirometric data from the Framingham Offspring cohort. Second, we sought to examine these categories as predictors of longitudinal COPD outcomes, adjusting for baseline characteristics.

Deep Learning Estimation of Small Airway Disease from Inspiratory Chest Computed Tomography: Clinical Validation, Repeatability, and Associations with Adverse Clinical Outcomes in Chronic Obstructive Pulmonary Disease.

Quantifying functional small airway disease (fSAD) requires additional expiratory computed tomography (CT) scans, limiting clinical applicability. Artificial intelligence (AI) could enable fSAD quantification from chest CT scans at total lung capacity (TLC) alone (fSAD). To evaluate an AI model for estimating fSAD, compare it with dual-volume parametric response mapping fSAD (fSAD), and assess its clinical associations and repeatability in chronic obstructive pulmonary disease (COPD).

Longitudinal Outcomes in Pi*MZ Alpha-1 Antitrypsin-Deficient Individuals with Tobacco Smoking History from the SPIROMICS Cohort.

Reliable data about the natural history of lung function decline in alpha-1 antitrypsin (AAT)-deficient Pi*MZ heterozygotes is largely missing. We hypothesized that, in adults with a tobacco smoking history, lung function deteriorates faster in Pi*MZ compared with the Pi*MM genotype. We identified 1,856 Pi*MM and 79 Pi*MZ participants with ⩾20 pack-years tobacco smoking history from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) cohort by DNA sequencing and followed them over a median of 4.

MRI-assessed Dynamic Hyperinflation Induced by Tachypnea in Chronic Obstructive Pulmonary Disease: The SPIROMICS-HF Study.

Purpose To assess the repeatability of real-time cine pulmonary MRI measures of metronome-paced tachypnea (MPT)-induced dynamic hyperinflation and its relationship with chronic obstructive pulmonary disease (COPD) severity. Materials and Methods SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) (ClinicalTrials.gov identifier no.

Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes.

Among tobacco-exposed persons with preserved spirometry (TEPSs), we previously demonstrated that different lung volume indices-specifically, elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity to TLC (FRC/TLC)-identify different lung disease characteristics in the COPDGene cohort. We sought to determine differential disease characteristics and trajectories associated with lung volume indices among TEPSs in the SPIROMICS cohort. We categorized TEPSs ( = 814) by tertiles (low, intermediate, and high) of TLC or residual volume-to-TLC ratio (RV/TLC) derived from baseline computed tomography images and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]) versus high RV/TLC without high TLC ([RV/TLC]).

Duration and Frequency of Spirometry Needed to Accurately Reflect Annualized Change of FEV in Chronic Obstructive Pulmonary Disease.

The slope of decline in forced expiratory volume in 1 second (FEV) is commonly used to reflect the rate of disease progression for descriptive studies and therapeutic trials in chronic obstructive pulmonary disease (COPD). The frequency and duration of spirometric testing needed to report the true slope are unknown. We sought to define the minimum frequency and follow-up duration needed to accurately describe the annualized rate of FEV change among patients with moderate to very severe COPD.

Dynamic and prognostic proteomic associations with FEV decline in chronic obstructive pulmonary disease.

Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.

Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression.

Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung.

Association of bronchial disease on CT imaging and clinical definitions of chronic bronchitis in a single-center COPD phenotyping study.

Introduction: Chronic Bronchitis (CB) represents a phenotype of chronic obstructive pulmonary disease (COPD). While several definitions have been used for diagnosis, the relationship between clinical definitions and radiologic assessment of bronchial disease (BD) has not been well studied. The aim of this study was to evaluate the relationship between three clinical definitions of CB and radiographic findings of BD in spirometry-defined COPD patients.

Association of Ground-Glass Opacities with Systemic Inflammation and Progression of Emphysema.

Ground-glass opacities (GGOs) in the absence of interstitial lung disease are understudied. To assess the association of GGOs with white blood cells (WBCs) and progression of quantified chest computed tomography emphysema. We analyzed data of participants in the SPIROMICS study (Subpopulations and Intermediate Outcome Measures in COPD Study).

Vessel and Airway Characteristics in One-Year Computed Tomography-defined Rapid Emphysema Progression: SPIROMICS.

Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <-950 Hounsfield units) progression. Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0-3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs;  = 188, 1-year ΔEI > 1%), nonprogressors ( = 301, 1-year ΔEI ± 0.

The Effect of Chronic Altitude Exposure on Chronic Obstructive Pulmonary Disease Outcomes in the SPIROMICS Cohort: An Observational Cohort Study.

Individuals with chronic obstructive pulmonary disease (COPD) have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. Does residence at higher altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, and mortality? From the SPIROMICS (Subpopulation and Intermediate Outcome Measures in COPD Study) cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation ( = 1,367) versus above 4,000 ft (1,219 m) elevation ( = 288).

Redirecting raltitrexed from cancer cell thymidylate synthase to phosphopantetheinyl transferase.

There is a compelling need to find drugs active against (). 4'-Phosphopantetheinyl transferase (PptT) is an essential enzyme in that has attracted interest as a potential drug target. We optimized a PptT assay, used it to screen 422,740 compounds, and identified raltitrexed, an antineoplastic antimetabolite, as the most potent PptT inhibitor yet reported.

LungViT: Ensembling Cascade of Texture Sensitive Hierarchical Vision Transformers for Cross-Volume Chest CT Image-to-Image Translation.

Chest computed tomography (CT) at inspiration is often complemented by an expiratory CT to identify peripheral airways disease. Additionally, co-registered inspiratory-expiratory volumes can be used to derive various markers of lung function. Expiratory CT scans, however, may not be acquired due to dose or scan time considerations or may be inadequate due to motion or insufficient exhale; leading to a missed opportunity to evaluate underlying small airways disease.