Quantitative CT Scoring for Local COPD Severity.

Chronic obstructive pulmonary disease (COPD) is complex, and its course is difficult to predict due to its diverse pathophysiology. Small airway disease (SAD), a key component of COPD and potential target for emerging therapeutics, may be reversible in mild COPD, but left unchecked, may worsen, leading to airway loss and emphysema. The dual nature of SAD complicates clinical management of COPD patients, necessitating more accurate monitoring methods.

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).

Quantitative Computed Tomography Measures of Lung Fibrosis and Outcomes in the National Lung Screening Trial.

Incidental features of interstitial lung disease (ILD) are commonly observed on chest computed tomography (CT) scans and are independently associated with poor outcomes. Although most studies to date have relied on qualitative assessments of ILD, quantitative imaging algorithms have the potential to effectively detect ILD and assist in risk stratification for population-based cohorts. To determine whether quantitative measures of ILD are associated with clinically relevant outcomes in the NLST (National Lung Screening Trial).

Metabolic Aging as an Increased Risk for Chronic Obstructive Pulmonary Disease.

Background/objectives: Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD.

Methods: Plasma from 5704 subjects from the Genetic Epidemiology of COPD study (COPDGene) and 2449 subjects from Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) were profiled using the Metabolon global metabolomics platform (1013 annotated metabolites). Post-bronchodilator spirometry measures of airflow obstruction (forced expiratory volume at one second (FEV)/forced vital capacity (FVC) < 0.

Associations between life-course FEV/FVC trajectories and respiratory symptoms up to middle age: analysis of data from two prospective cohort studies.

Background: Life-course lung function trajectories leading to airflow obstruction, as measured by impaired FEV/FVC (forced vital capacity), precede the onset of chronic obstructive pulmonary disease (COPD). We aimed to investigate whether individuals on impaired FEV/FVC trajectories have an increased burden of respiratory symptoms, including those who do not meet the spirometric criteria for COPD.

Methods: We analysed serial life-course data from two population-based cohort studies separately, which included respiratory symptoms and spirometry: the Tasmanian Longitudinal Health Study (TAHS, Australia) cohort was recruited at age 6-7 years and followed up until middle age (mean age 53 years; range 51-55); and the Coronary Artery Risk Development in Young Adults (CARDIA, USA) cohort was recruited at a mean age of 25 years (range 18-30) and followed up to a mean age of 55 years (range 47-64).

Temporal Exploration of Chronic Obstructive Pulmonary Disease Phenotypes: Insights from the COPDGene and SPIROMICS Cohorts.

Chronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships. Our primary objective was to create a map of COPD phenotypes and their connectivity using EPGA.

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.

Use of Pulmonary Rehabilitation after Chronic Obstructive Pulmonary Disease Hospitalization: An Analysis of Statewide Patient and Hospital Data.

Pulmonary rehabilitation (PR) is a clinically effective and cost-effective outpatient treatment for chronic obstructive pulmonary disease (COPD) that remains highly underused. Existing analyses of PR use patterns have been focused largely on patient characteristics, but hospital-level analysis is lacking and is needed to inform interventions aimed at improving use after COPD hospitalization. To evaluate PR use across hospitals after COPD hospitalization in the state of Michigan, with the goal of characterizing hospital-level variation and identifying the characteristics of high-performing hospitals.

Local heterogeneity of normal lung parenchyma and small airways disease are associated with COPD severity and progression.

Background: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline.

Plasma metabolomics and quantitative interstitial abnormalities in ever-smokers.

Background: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers.

Risk Factors for Chronic Obstructive Pulmonary Disease Exacerbations among Individuals without a History of Recent Exacerbations: A COPDGene Analysis.

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are detrimental events in the natural history of COPD, but the risk factors associated with future exacerbations in the absence of a history of recent exacerbations are not fully understood. To identify risk factors for COPD exacerbations among participants in the Genetic Epidemiology of COPD Study (COPDGene) without a history of exacerbation in the previous year. We identified participants with a smoking history enrolled in COPDGene who had COPD (defined as forced expiratory volume in 1 second [FEV]/forced vital capacity < 0.

Levels of Urinary Mercapturic Acids of Acrolein, Methacrolein, Crotonaldehyde, and Methyl Vinyl Ketone in Relationship to Chronic Obstructive Pulmonary Disease in Cigarette Smokers of the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Cigarette smoking is an established cause of chronic obstructive pulmonary disease (COPD). Numerous studies implicate acrolein, which occurs in relatively high concentrations in cigarette smoke and reacts readily with proteins, as one causative factor for COPD in smokers. Far less is known about the possible roles in COPD of the related α,β-unsaturated carbonyl compounds of cigarette smoke crotonaldehyde, methacrolein, and methyl vinyl ketone.

Topologic Parametric Response Mapping Identifies Tissue Subtypes Associated with Emphysema Progression.

Rationale And Objectives: Small airways disease (SAD) and emphysema are significant components of chronic obstructive pulmonary disease (COPD), a heterogenous disease where predicting progression is difficult. SAD, a principal cause of airflow obstruction in mild COPD, has been identified as a precursor to emphysema. Parametric Response Mapping (PRM) of chest computed tomography (CT) can help distinguish SAD from emphysema.

Quantitative CT of Normal Lung Parenchyma and Small Airways Disease Topologies are Associated With COPD Severity and Progression.

Objectives: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients, and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline.

A blood and bronchoalveolar lavage protein signature of rapid FEV decline in smoking-associated COPD.

Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights.

Changes in Lung Volumes with Spirometric Disease Progression in COPD.

Background: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear.

Methods: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.

Causes of and Clinical Features Associated with Death in Tobacco Cigarette Users by Lung Function Impairment.

Cigarette smoking contributes to the risk of death through different mechanisms. To determine how causes of and clinical features associated with death vary in tobacco cigarette users by lung function impairment. We stratified current and former tobacco cigarette users enrolled in Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) into normal spirometry, PRISm (Preserved Ratio Impaired Spirometry), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 COPD, and GOLD 3-4 COPD.

Machine learning for screening of at-risk, mild and moderate COPD patients at risk of FEV decline: results from COPDGene and SPIROMICS.

The purpose of this study was to train and validate machine learning models for predicting rapid decline of forced expiratory volume in 1 s (FEV) in individuals with a smoking history at-risk-for chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease (GOLD 0), or with mild-to-moderate (GOLD 1-2) COPD. We trained multiple models to predict rapid FEV decline using demographic, clinical and radiologic biomarker data. Training and internal validation data were obtained from the COPDGene study and prediction models were validated against the SPIROMICS cohort.