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Disease Progression Modeling in Chronic Obstructive Pulmonary Disease
- Source :
- American Journal of Respiratory and Critical Care Medicine, 201, 3, pp. 294-302, Am J Respir Crit Care Med, American Journal of Respiratory and Critical Care Medicine, American Journal of Respiratory and Critical Care Medicine, 201, 294-302
- Publication Year :
- 2020
-
Abstract
- Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: 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.Methods: 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.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 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 FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 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.Conclusions: 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."
- Subjects :
- Pulmonary and Respiratory Medicine
Male
medicine.medical_specialty
Pulmonary disease
Critical Care and Intensive Care Medicine
Machine Learning
03 medical and health sciences
Pulmonary Disease, Chronic Obstructive
0302 clinical medicine
Internal medicine
medicine
Humans
030212 general & internal medicine
Aged
COPD
business.industry
Disease progression
Editorials
Original Articles
Middle Aged
Models, Theoretical
respiratory system
medicine.disease
respiratory tract diseases
030228 respiratory system
Disease Progression
Bronchitis
Female
Ct imaging
business
Tomography, X-Ray Computed
Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Subjects
Details
- ISSN :
- 1073449X
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine, 201, 3, pp. 294-302, Am J Respir Crit Care Med, American Journal of Respiratory and Critical Care Medicine, American Journal of Respiratory and Critical Care Medicine, 201, 294-302
- Accession number :
- edsair.doi.dedup.....a01d5a541d61561fcfd03951635c6234