Journal article
Disease Progression Modeling in Chronic Obstructive Pulmonary Disease
American journal of respiratory and critical care medicine, Vol.201(3), pp.294-302
02/01/2020
DOI: 10.1164/rccm.201908-1600OC
PMCID: PMC6999095
PMID: 31657634
Abstract
The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.
To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.
We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.
We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (
= 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway→Tissue" subtype (
= 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV
/FVC decline (
= -0.16 [
< 0.001] in the Tissue→Airway group;
= -0.14 [
= 0.011] in the Airway→Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.
We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."
Details
- Title: Subtitle
- Disease Progression Modeling in Chronic Obstructive Pulmonary Disease
- Creators
- Alexandra L Young - University College LondonFelix J S Bragman - University College LondonBojidar Rangelov - University College LondonMeiLan K Han - University of Michigan–Ann ArborCraig J Galbán - University of Michigan–Ann ArborDavid A Lynch - University of Colorado DenverDavid J Hawkes - University College LondonDaniel C Alexander - University College LondonJohn R Hurst - University College LondonCOPDGene Investigators
- Contributors
- Karin F Hoth (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.201(3), pp.294-302
- DOI
- 10.1164/rccm.201908-1600OC
- PMID
- 31657634
- PMCID
- PMC6999095
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Grant note
- U01 HL089856 / NHLBI NIH HHS MR/T027800/1 / Medical Research Council K08 HL141601 / NHLBI NIH HHS R01 HL139690 / NHLBI NIH HHS U01 HL089897 / NHLBI NIH HHS S10 OD018526 / NIH HHS
- Language
- English
- Date published
- 02/01/2020
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984293656802771
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