Longitudinal Imaging-Based Clusters in Former Smokers of the COPD Cohort Associate with Clinical Characteristics: The SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Purpose: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.
Patients and Methods: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers.
Results: COPD severities at baseline increased with increasing cluster number. Cluster 1 patients were an obese subgroup with rapid progression of functional small airway disease percentage (fSAD%) and emphysema percentage (Emph%). Cluster 2 exhibited a decrease of fSAD% and Emph%, an increase of tissue fraction at total lung capacity and airway narrowing over one year. Cluster 3 showed rapid expansion of Emph% and an attenuation of fSAD%. Cluster 4 demonstrated severe emphysema and fSAD and significant structural alterations at baseline with rapid progression of fSAD% over one year. Subjects with different progression patterns in the same cross-sectional cluster were identified by longitudinal clustering.
Conclusion: qCT imaging-based metrics at two visits for former smokers allow for the derivation of four statistically stable clusters associated with unique progression patterns and clinical characteristics. Use of baseline variables and their progression rates enables identification of longitudinal clusters, resulting in a refinement of cross-sectional clusters.
Competing Interests: Prof. Dr. Jiwoong Choi reported grants from Korea Environmental and Industrial Technology Institute, during the conduct of the study; Prof. Dr. Alejandro P Comellas reported grants from NIH, personal fees from GSK, personal fees from Astra Zeneca, outside the submitted work; Prof. Dr. John D Newell Jnr reported grants from NIH, personal fees, non-financial support, Paid Consultant Medical Advisor Shared Patent Holder Travel Expenses Honoraria from VIDA, Writing Book on Lung CT AI from Elsevier, during the conduct of the study; personal fees, non-financial support, Medical Advisor Paid Consultant Shared Patent Holder Travel Expenses Honoraria from VIDA, outside the submitted work; In addition, Prof. Dr. John D Newell Jnr has a patent VIDA issued, a patent Elsevier licensed; Prof. Dr. R Graham Barr reported grants from NIH, grants from COPD Foundation, during the conduct of the study; grants from NIH, outside the submitted work; Prof. Dr. Eugene Bleecker reported personal fees from AstraZeneca, personal fees MedImmune, personal fees from Boehringer Ingelheim, personal fees from Genentech, personal fees from Novartis, personal fees from Regeneron, personal fees from Sanofi Genzyme, personal fees from ALK-Abello, personal fees from Glaxo Smith Kline, personal fees from TEVA, outside the submitted work; Professor Christopher B Cooper reported personal fees from MGC Diagnostics, Chair, Clinical Events Committee from NUVAIRA, Global Medical Expert from GlaxoSmithKline, Chair, Clinical Events Committee from PulmonX, outside the submitted work; Prof. Dr. David Couper reported grants from NHLBI, grants from COPD Foundation, during the conduct of the study; Prof. Dr. Meilan Han reported personal fees from GSK, BI, AZ, Verona, Teva, Merck, grants from Sunovion, supply of study drug for clinical trial from Novartis, grants, personal fees from Sanofi, outside the submitted work; Prof. Dr. Nadia N Hansel reported grants, personal fees from AstraZeneca, personal fees from Mylan, grants from NIH, grants from COPD Foundation, grants, personal fees from GSK, grants, personal fees from Boehringer Ingelheim, during the conduct of the study; Prof. Dr. Eric C Kleerup reported grants from NIH, and Foundation for the NHLBI, non-financial support from GlaxoSmithKline, Supplied inhalers for PFT testing from Boehringer Ingelheim, during the conduct of the study; Prof. Dr. Fernando J Martinez reported grants, personal fees, non-financial support from AstraZeneca, Teleconference from Bayer, grants, personal fees, non-financial support from Boehringer Ingelheim, Advisory Board and Steering Committee from Chiesi, Advisory Board from Gala, grants, personal fees from GlaxoSmithKline, non-financial support from Novartis, non-financial support from Sanofi/Regeneron, Advisory Board from Sunovion, Teva, and Verona, during the conduct of the study; Prof. Dr. Robert Paine III reported grants from NHLBI, COPD Foundation, during the conduct of the study; grants from Department of Veterans Affairs, personal fees from Partner Therapeutics, outside the submitted work; Prof. Dr. Stephen I Rennard reported SR and was an employee of AstraZeneca from 2015 to 2019 and owns shares received as part of his compensation, personal fees from Bergenbio, Consultant from Verona Pharma, Consultant from NovoVentures, Consultant from GSK, outside the submitted work; Dr. Benjamin M Smith reported grants from NIH, during the conduct of the study; grants from CIHR, outside the submitted work; Prof. Dr. Prescott G Woodruff reported grants from NIH, COPD Foundation, during the conduct of the study; personal fees from Sanofi, Consulting from Regeneron, Consulting from Glenmark Pharmaceuticals, Consulting from Theravance, Consulting from GSK, Consulting from NGM Pharma, outside the submitted work; Prof. Dr. Eirc A Hoffman reported grants from NIH, during the conduct of the study; Founder and Shareholder from VIDA Diagnostics, outside the submitted work; The authors reported no other conflicts of interest in this work.
(© 2021 Zou et al.)