Evidence map›Paper›PMID 32946850›Full record

Observational studyChest2021

Distinguishing Smoking-Related Lung Disease Phenotypes Via Imaging and Molecular Features.

Ehab Billatos, Samuel Y Ash, Fenghai Duan, Ke Xu, Justin Romanoff, Helga Marques, Elizabeth Moses, MeiLan K Han, Elizabeth A Regan, Russell P Bowler and 19 more

3 registry-linked trialsOpen access · bronzeAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Chest, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00608764 active not recruitingnot on this map

Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene)

TypeobservationalSponsorBrigham and Women's HospitalRan2007 to 2028Enrolled10,718ConditionsPulmonary Disease, Chronic Obstructive, Emphysema, Bronchitis, Chronic
NCT01785342 completednot on this map

Detection of Early Lung Cancer Among Military Personnel Study 1 (DECAMP-1): Diagnosis and Surveillance of Indeterminate Pulmonary Nodules

TypeobservationalSponsorBoston UniversityRan2013 to 2022Enrolled489ConditionsLung CancerArmsBiosample and Imaging Collection
NCT02504697 active not recruitingnot on this map

Detection of Early Lung Cancer Among Military Personnel Study 2 (DECAMP-2): Screening of Patients With Early Stage Lung Cancer or at High Risk for Developing Lung Cancer

TypeobservationalSponsorBoston UniversityRan2011 to 2027Enrolled665ConditionsPulmonary DiseaseArmsBiosamples from airway and blood
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. COPD Phenotyping.Respiratory care · 2023
    Review
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 10 institutions in 1 country.

Ehab BillatosDepartment of Medicine, Section of Pulmonary and Critical Care Medicine, Boston University, Boston, MA; Department of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA. Electronic address: ebillato@bu.edu.
Samuel Y AshDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
Fenghai DuanDepartment of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, RI.
Ke XuDepartment of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA; Bioinformatics Program, Boston University College of Engineering, Boston, MA.
Justin RomanoffDepartment of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, RI.
Helga MarquesDepartment of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, RI.
Elizabeth MosesDepartment of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA.
MeiLan K HanDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI.
Elizabeth A ReganDepartment of Medicine, Division of Rheumatology, National Jewish Health, Denver, CO.
Russell P BowlerDepartment of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO.
Stefanie E MasonDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
Tracy J DoyleDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.
Rubén San José EstéparApplied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Boston, MA.
Ivan O RosasDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.
James C RossApplied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
Xiaohui XiaoDepartment of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA.
Hanqiao LiuDepartment of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA.
Gang LiuDepartment of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA.
Gauthaman SukumarDepartment of Anatomy, Physiology & Genetics, The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
Matthew WilkersonDepartment of Anatomy, Physiology & Genetics, The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
Clifton DalgardDepartment of Anatomy, Physiology & Genetics, The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD.
Christopher StevensonLung Cancer Initiative at Johnson & Johnson, New Brunswick, NJ.
Duncan WhitneyLung Cancer Initiative at Johnson & Johnson, New Brunswick, NJ.
Denise AberleDepartment of Radiology, University of California at Los Angeles, Los Angeles, CA.
Avrum SpiraDepartment of Medicine, Section of Pulmonary and Critical Care Medicine, Boston University, Boston, MA; Department of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA; Lung Cancer Initiative at Johnson & Johnson, New Brunswick, NJ.
Raúl San José EstéparApplied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA; Department of Radiology, Brigham and Women's Hospital, Boston, MA.
Marc E LenburgDepartment of Medicine, Section of Computational Biomedicine, Boston University, Boston, MA; Bioinformatics Program, Boston University College of Engineering, Boston, MA.
George R WashkoDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA; Applied Chest Imaging Laboratory, Brigham and Women's Hospital, Boston, MA.
DECAMP and COPDGene Investigators
Brigham and Women's Hospital · USBoston University · USBrown University · USJohnson & Johnson (United States) · USUniformed Services University of the Health Sciences · USHenry M. Jackson Foundation · USNational Jewish Health · USUniversity of California, Los Angeles · USUniversity of Colorado Denver · USUniversity of Michigan–Ann Arbor · US

Funding

ECOG-ACRIN NCORP Research Base - TMISTUG1CA189828 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer, MITCHELL D. SCHNALL · 2014 to 2026
$199.7M
Genetic Epidemiology of COPDU01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2007 to 2021
$56.9M
Metabolomic signatures of empysema and COPD progression in the COPDGene cohortR01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2012 to 2016
$31.1M
Respiratory Computational Discovery CoreP01HL114501 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHOI, MARY E · 2013 to 2025
$24.9M
BIOLOGY OF THE LUNG--MULTIDISCIPLINARY PROGRAMT32HL007035 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton, JOSEPH P MIZGERD · 1985 to 2026
$24.3M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
(2 of 2) Genetic Epidemiology of COPDR01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2012 to 2016
$18.9M
RESPIRATORY RESEARCHT32HL007633 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI George R Washko · 1985 to 2026
$14.9M
Integrated Molecular, Cellular, and Imaging Characterization of Screen-Detected Lung CancerU01CA196408 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ABERLE, DENISE R., DUBINETT, STEVEN M. · 2015 to 2021
$7.1M
The clinical impact of pulmonary vascular remodeling in smokersR01HL116473 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SAN JOSE ESTEPAR, RAUL, WASHKO, GEORGE R · 2013 to 2021
$5.0M
Molecular and Imaging Biomarkers for Early Lung Cancer Detection in the Setting of Indeterminate Pulmonary NodulesR01CA210360 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ABERLE, DENISE R., LENBURG, MARC ELLIOTT · 2016 to 2021
$3.1M
Prognostic Markers of Emphysema ProgressionR01HL149877 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SAN JOSE ESTEPAR, RAUL · 2020 to 2023
$2.8M
NCI NIH HHS R01 CA210360NCI NIH HHS U01 CA196408NCI NIH HHS UG1 CA189828NHLBI NIH HHS K08 HL145118NHLBI NIH HHS K23 HL119558NHLBI NIH HHS L30 HL134158NHLBI NIH HHS P01 HL114501NHLBI NIH HHS R01 HL089856NHLBI NIH HHS R01 HL089897NHLBI NIH HHS R01 HL107246NHLBI NIH HHS R01 HL116473NHLBI NIH HHS R01 HL122464NHLBI NIH HHS R01 HL149877NHLBI NIH HHS R21 HL140422NHLBI NIH HHS T32 HL007035NHLBI NIH HHS T32 HL007633NHLBI NIH HHS U01 HL089856NHLBI NIH HHS U01 HL089897
6 · The paper itself

Abstract

backgroundChronic tobacco smoke exposure results in a broad range of lung pathologies including emphysema, airway disease and parenchymal fibrosis as well as a multitude of extra-pulmonary comorbidities. Prior work using CT imaging has identified several clinically relevant subgroups of smoking related lung disease, but these investigations have generally lacked organ specific molecular correlates. RESEARCH QUESTION: Can CT imaging be used to identify clinical phenotypes of smoking related lung disease that have specific bronchial epithelial gene expression patterns to better understand disease pathogenesis? STUDY DESIGN AND

methodsUsing K-means clustering, we clustered participants from the COPDGene study (n = 5,273) based on CT imaging characteristics and then evaluated their clinical phenotypes. These clusters were replicated in the Detection of Early Lung Cancer Among Military Personnel (DECAMP) cohort (n = 360), and were further characterized using bronchial epithelial gene expression.

resultsThree clusters (preserved, interstitial predominant and emphysema predominant) were identified. Compared to the preserved cluster, the interstitial and emphysema clusters had worse lung function, exercise capacity and quality of life. In longitudinal follow-up, individuals from the emphysema group had greater declines in exercise capacity and lung function, more emphysema, more exacerbations, and higher mortality. Similarly, genes involved in inflammatory pathways (tumor necrosis factor-α, interferon-β) are more highly expressed in bronchial epithelial cells from individuals in the emphysema cluster, while genes associated with T-cell related biology are decreased in these samples. Samples from individuals in the interstitial cluster generally had intermediate levels of expression of these genes.

interpretationUsing quantitative CT imaging, we identified three groups of individuals in older ever-smokers that replicate in two cohorts. Airway gene expression differences between the three groups suggests increased levels of inflammation in the most severe clinical phenotype, possibly mediated by the tumor necrosis factor-α and interferon-β pathways. CLINICAL

trial registrationCOPDGene (NCT00608764), DECAMP-1 (NCT01785342), DECAMP-2 (NCT02504697).

Indexed as

Tomography, X-Ray ComputedAcademic Medical CentersAgedFemaleHospitals, VeteransHumansLongitudinal StudiesMaleMiddle AgedPhenotypePulmonary Disease, Chronic ObstructiveSmokingUnited Statesairway gene expressionCOPDdiagnostic imaginggene expressionimaginginterferon

Identifiers

PMID32946850
PMCPMC8039011
OpenAlexW3086561255

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.