Machine learning assisted immune profiling of COPD identifies a unique emphysema subtype independent of GOLD stage
Chronic obstructive pulmonary disease (COPD) is a severe, progressive, and heterogeneous disease with a poor outcome. Inflammation plays a central role in disease pathogenesis; however, the interplay between immune changes and disease heterogeneity has been difficult to unravel. We performed a multilevel immunoinflammatory characterization of patients with COPD using flow cytometry, cytokine profiling, single-cell, or spatial transcriptomics in combination with machine learning algorithms. Our cross-cohort analysis demonstrated shared skewing of immune profiles in COPD lungs toward adaptive immune cells. We furthermore identified a subgroup of patients with COPD with a distinct immune profile, characterized by increased antigen-presenting cells, mast cells, and CD8<sup>+</sup> cells, and circulating IL-1β, IFN-β, and GM-CSF, that were associated with increased emphysema severity and decreased gas exchange parameters independent of their GOLD-stage. Our findings suggest that unbiased immune profiling can refine disease classification and reveal inflammation-driven disease subtypes with potential relevance for prognosis and treatment strategies.
Authors
- Diana Schnoegl (ORCID: https://orcid.org/0009-0004-9633-8299)
- Robab Breyer‐Kohansal (ORCID: https://orcid.org/0000-0001-5850-5923)
- Vasile Foris (ORCID: https://orcid.org/0000-0002-8863-0298)
- Grażyna Kwapiszewska (ORCID: https://orcid.org/0000-0003-0518-9079)
- Slaven Crnković (ORCID: https://orcid.org/0000-0002-0820-3318)
- Leigh M. Marsh (ORCID: https://orcid.org/0000-0002-1754-9249)
- Konrad Höetzenecker (ORCID: https://orcid.org/0000-0001-6775-7460)
- Gregor Gorkiewicz (ORCID: https://orcid.org/0000-0003-1149-4782)
- Katarina Zeder (ORCID: https://orcid.org/0000-0002-8415-727X)
- Francesca Polverino (ORCID: https://orcid.org/0000-0001-9686-5698)
- Katharina Jandl (ORCID: https://orcid.org/0000-0002-7892-6618)
- Ayse Ceren Mutgan (ORCID: https://orcid.org/0000-0003-4981-3646)
- Panja Maria Boehm
- Ayu Hutami Syarif
- Natalie Bordag (ORCID: https://orcid.org/0000-0002-9505-6271)
- Juergen Gindlhuber (ORCID: https://orcid.org/0000-0002-6155-5208)
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Baylor College of Medicine (US)
- Medical University of Graz (AT)
- Klinik Hietzing (AT)
- Ludwig Boltzmann Institute for Lung Vascular Research (AT)
- Austrian Institute for Health Technology Assessment GmbH (AT)
- Nawi Graz (AT)
- Cardio-Pulmonary Institute (DE)
- University of Maryland, College Park (US)
- Medical University of Vienna (AT)
Publication Details
- Journal
- iScience
- Published
- 2025-06-19
- DOI
- https://doi.org/10.1016/j.isci.2025.112966
- Primary Topic
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00