RT Journal Article
SR Electronic
T1 Clustering-based COPD subtypes have distinct longitudinal outcomes and multi-omics biomarkers
JF BMJ Open Respiratory Research
JO BMJ Open Resp Res
FD British Thoracic Society
SP e001182
DO 10.1136/bmjresp-2021-001182
VO 9
IS 1
A1 Andrew Gregory
A1 Zhonghui Xu
A1 Katherine Pratte
A1 Sool Lee
A1 Congjian Liu
A1 Robert Chase
A1 Jeong Yun
A1 Aabida Saferali
A1 Craig P Hersh
A1 Russell Bowler
A1 Edwin Silverman
A1 Peter J Castaldi
A1 Adel Boueiz
YR 2022
UL http://bmjopenrespres.bmj.com/content/9/1/e001182.abstract
AB Introduction Chronic obstructive pulmonary disease (COPD) can progress across several domains, complicating the identification of the determinants of disease progression. In our previous work, we applied k-means clustering to spirometric and chest radiological measures to identify four COPD-related subtypes: ‘relatively resistant smokers (RRS)’, ‘mild upper lobe-predominant emphysema (ULE)’, ‘airway-predominant disease (AD)’ and ‘severe emphysema (SE)’. In the current study, we examined the associations of these subtypes to longitudinal COPD-related health measures as well as blood transcriptomic and plasma proteomic biomarkers.Methods We included 8266 non-Hispanic white and African-American smokers from the COPDGene study. We used linear regression to investigate cluster associations to 5-year prospective changes in spirometric and radiological measures and to gene expression and protein levels. We used Cox-proportional hazard test to test for cluster associations to prospective exacerbations, comorbidities and mortality.Results The RRS, ULE, AD and SE clusters represented 39%, 15%, 26% and 20% of the studied cohort at baseline, respectively. The SE cluster had the greatest 5-year FEV1 (forced expiratory volume in 1 s) and emphysema progression, and the highest risks of exacerbations, cardiovascular disease and mortality. The AD cluster had the highest diabetes risk. After adjustments, only the SE cluster had an elevated respiratory mortality risk, while the ULE, AD and SE clusters had elevated all-cause mortality risks. These clusters also demonstrated differential protein and gene expression biomarker associations, mostly related to inflammatory and immune processes.Conclusion COPD k-means subtypes demonstrate varying rates of disease progression, prospective comorbidities, mortality and associations to transcriptomic and proteomic biomarkers. These findings emphasise the clinical and biological relevance of these subtypes, which call for more study for translation into clinical practice.Trail registration number NCT00608764.Data are available in a public, open access repository.