Fleming, Margaret and Grant, Sarah (2019) COPDGene 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease. Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, 6 (5). pp. 384-399. ISSN 2372952X

Abstract

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 (CT) and clinical evidence of disease.
Using data from 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 8,784 current and former smokers who were participants in
COPDGene Phase 1. Using these four disease characteristics, eight categories of
subjects 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 GOLD criteria would diagnose 4,062 (46%) of the
8,784 study subjects with COPD. The proposed COPDGene 2019 diagnostic criteria
would add an additional 3,144 subjects. Under the new criteria, 82% of the 8,784 study
subjects 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% CI: 4.15-6.48) in those with all four
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.

Item Type:	Article
Date Deposited:	12 Sep 2020 00:45
Last Modified:	12 Sep 2020 00:45
URI:	https://oak.novartis.com/id/eprint/41392