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Chronic Obstr Pulm Dis. 2019 Nov;6(5):384-399. doi: 10.15326/jcopdf.6.5.2019.0149.

COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.

Author information

1
Cleveland Clinic Lerner College of Medicine of Case Western Reserve School of Medicine, Cleveland, Ohio.
2
National Jewish Health, Denver, Colorado.
3
University of Texas Health, San Antonio.
4
University of Colorado at Denver.
5
Columbia University, New York.
6
Johns Hopkins University, Baltimore, Maryland.
7
University of Pittsburgh, Pittsburgh, Pennsylvania.
8
Brigham and Women's Hospital, Boston, Massachusetts.
9
University of Alabama at Birmingham.
10
University of Arizona Health Sciences, Tucson.
11
VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
12
Baylor College of Medicine, Houston, Texas.
13
Los Angeles Biomedical Research Institute at Harbor- University of California Los Angeles Medical Center, Torrance.
14
Thirona, Nijmegen, The Netherlands.
15
University of Iowa, Iowa City.
16
University of California at San Diego.
17
COPD Foundation, Washington, DC.
18
Temple University, Philadelphia, Pennsylvania.
19
Ann Arbor VA Medical Center, Ann Arbor, Michigan.
20
Northeastern University, Boston, Massachusetts.
21
Novartis Institute for Biomedical Research, Cambridge, Massachusetts.
22
Morehouse School of Medicine, Atlanta, Georgia.
23
Hôpital Foch, Suresnes, France.
24
University of Michigan, Ann Arbor.
25
Boehringer Ingelheim, Biberach an der Riss, Germany.
26
University of British Columbia, Vancouver, Canada.
27
University of Colorado Anschutz Medical Campus, Aurora.
28
University of California-San Diego, La Jolla.
29
Kangwon National University, Chuncheon, Korea.
30
Boehringer-Ingelheim, Ingelheim, Germany.
31
Harvard Medical School, Boston, Massachusetts.
32
Duke University Health, Durham, North Carolina.
33
Weill-Cornell Medicine, New York City, New York.
34
Minnesota Health Partners, St. Paul.
35
AstraZeneca, Denver, Colorado.
36
University of Washington, Seattle.
37
VIDA Diagnostics, Inc, Coralville, Iowa.
38
University of Florence, Florence, Italy.
39
AstraZeneca, Cambridge, United Kingdom.
40
University of Nebraska Medical Center, Omaha.
41
Reliant Medical Group, Worcester, Massachusetts.
42
University of Leeds, Leeds, United Kingdom.
43
GlaxoSmithKline, Research Triangle Park, North Carolina.
44
GlaxoSmithKline, Collegeville, Pennsylvania.
45
COPD Foundation, Miami, Florida, † deceased.
46
VA Boston Healthcare System, Jamaica Plain, Massachusetts.
47
Minneapolis VA, Minneapolis, Minnesota.

Abstract

Background:

Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality.

Methods:

Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined.

Results:

Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics.

Conclusions:

A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00608764.

KEYWORDS:

COPD Genetic Epidemiology study,preserved ratio-impaired spirometry,COPD diagnosis; COPD diagnosis; COPDGene; GOLD; Global initiative for chronic Obstructive Lung Dis; PRISm; chronic obstructive pulmonary disease; copd; preserved ratio-impaired spirometry; spirometry

PMID:
31710793
DOI:
10.15326/jcopdf.6.5.2019.0149
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Conflict of interest statement

The COPDGene® study is funded by National Heart, Lung, and Blood Institute grants U01 HL089897 and U01 HL089856. The COPDGene® study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee comprised of AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion. While some individual authors of this manuscript were employed by one of the listed funders at the time the work of this study was conducted, these employment relationships did not constitute undue influence by funders. These funders have had no official role in the collection, management, analysis and interpretation of the data or design and conduct of the study. All authors have completed a Conflict of Interest form, disclosing any real or apparent financial relationships including receiving royalties, honoraria or fees for consulting, lectures, speakers’ bureaus, continuing education, medical advisory boards or expert testimony; receipt of grants; travel reimbursement; direct employment compensation. These disclosure forms have been filed with the Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation Editorial Office and are available for review, upon request, at COPDC@njhealth.org.

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