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Clustering-based COPD subtypes have distinct longitudinal outcomes and multi-omics biomarkers
Andrew Gregory1, Zhonghui Xu1, Katherine Pratte2
1Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
BMJ Open Respiratory Research
|August 23, 2022
Summary
Four chronic obstructive pulmonary disease (COPD) subtypes identified by k-means clustering show distinct progression patterns. These subtypes correlate with varying mortality risks and biomarker associations, highlighting their clinical relevance.
Area of Science:
- Pulmonary Medicine
- Genomics
- Proteomics
Background:
- Chronic obstructive pulmonary disease (COPD) progression is complex and influenced by multiple factors.
- Previous research identified four COPD subtypes using k-means clustering based on spirometry and chest imaging: relatively resistant smokers (RRS), mild upper lobe-predominant emphysema (ULE), airway-predominant disease (AD), and severe emphysema (SE).
Purpose of the Study:
- To investigate the associations of these four COPD subtypes with longitudinal health outcomes.
- To examine the relationship between COPD subtypes and blood transcriptomic and plasma proteomic biomarkers.
Main Methods:
- Analysis of 8266 participants from the COPDGene study (non-Hispanic white and African-American smokers).
- Linear regression used to assess cluster associations with 5-year changes in spirometry, radiology, gene expression, and protein levels.
- Cox-proportional hazard tests employed to evaluate cluster associations with exacerbations, comorbidities, and mortality.
Main Results:
- The SE cluster exhibited the most significant 5-year progression in FEV1 and emphysema, alongside the highest risks for exacerbations, cardiovascular disease, and mortality.
- The AD cluster showed the highest risk for diabetes.
- While only the SE cluster had elevated respiratory mortality, ULE, AD, and SE clusters were associated with increased all-cause mortality. Differential gene and protein expression, primarily linked to inflammation and immunity, was observed across subtypes.
Conclusions:
- The identified COPD subtypes exhibit differential disease progression, comorbidity risks, and mortality rates.
- These subtypes demonstrate distinct associations with transcriptomic and proteomic biomarkers, underscoring their biological and clinical significance.
- Further research is warranted to translate these subtype findings into clinical practice for personalized COPD management.
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