Project description:Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)
Project description:Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)
Project description:The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT01969344) includes 2,771 subjects, aged 40-80 years with at least 20 pack-years of smoking. An additional 202 subjects were never smokers. Fasting blood drawn at the enrollment visit using a p100 tube. The first 649 subjects who returned for a 5-7 year visit (Visit 5) were selected for this study. The blood profiled were from the year 1 visit.
Project description:Plasma Metabolomic signatures of COPD in a SPIROMICS cohort The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT01969344) includes 2,771 subjects, aged 40-80 years with at least 20 pack-years of smoking. An additional 202 subjects were never smokers. Fasting blood drawn at the enrollment visit using a p100 tube. The first 648 subjects who returned for a 5-7 year visit (Visit 5) were selected for this study. The blood profiled were from the year 1 visit. This study is a duplicate of ST001639 (https://www.metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Study&StudyID=ST001639) but differs in analysis and contains batch normalized data using median metabolite values.
Project description:Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multicentre observational study of chronic obstructive pulmonary disease (COPD) designed to guide future development of therapies for COPD by providing robust criteria for subclassifying COPD participants into groups most likely to benefit from a given therapy during a clinical trial, and identifying biomarkers/phenotypes that can be used as intermediate outcomes to reliably predict clinical benefit during therapeutic trials. The goal is to enrol 3200 participants in four strata. Participants undergo a baseline visit and three annual follow-up examinations, with quarterly telephone calls. Adjudication of exacerbations and mortality will be undertaken.
Project description:BackgroundQuantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.MethodsAn imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration.ResultsWe derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema.ConclusionsQCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.
Project description:BackgroundClassification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.MethodsAmong the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers. Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%). Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter. We employed an unsupervised method for clustering.ResultsFour clusters were identified. Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema. Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations. Cluster 4 showed relatively low FEV1/FVC and high exacerbations. While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters.ConclusionsAssociation of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations.