Podium Presentation in Room 2 on Thursday at 15:50 (Chair: Livia Eberlin / Anand Mehta)
Authors: Steven Booth MSc (1), Hyun-Kyoung Koo M.D (1), Aileen Hsieh (1), Dragoş M. Vasilescu Ph.D (1), Daniela Quail Ph.D (2), Yuhong Wei Ph.D (2), W. Mark Elliott Ph.D (1), Joel D. Cooper M.D (3), Ph.D, Peter D. Paré (1), M.D., James C. Hogg M.D (1), Tillie-Louise Hackett Ph.D (1).
Introduction: We have recently demonstrated that the smallest conducting airways, the terminal bronchioles, are the initial site of tissue injury in mild and moderate chronic obstructive pulmonary disease (COPD) patients prior to emphysematous destruction of the lung alveolar surface area. We aimed to investigate the alterations in the cellular microenvironment of mild and moderate COPD terminal bronchioles using in-situ, single cell imaging, and to determine how they might be targeted for therapeutic intervention.
Methods: This cross-sectional analysis used volumetric micro computed tomography imaging to identify terminal bronchioles for histological sectioning and imaging mass cytometry (IMC) to produce the first single cell atlas of the terminal bronchiole in a cohort of tissue samples obtained from the lungs of smokers with normal lung function (controls, n=10), and patients with mild (n=10), moderate (n=8), and very-severe (n=6) COPD.
Results: Using an unsupervised machine learning approach we performed in-situ, single cell profiling to establish a cellular atlas of 21 diverse cell types within the terminal bronchiole. We found that a number of innate and adaptive immune cells (monocytes, naïve T cells, CD8 T cells, B cells and plasmacytoid dendritic cells) were increased in the terminal bronchioles from mild and moderate COPD patients, while CD8 T cells and plasmacytoid dendritic cells were only elevated in very-severe COPD patients. Spatial cell neighborhood analysis demonstrated that innate and adaptive immune cells displayed increased interactions with other immune cells and with fibroblasts in the terminal bronchioles of mild and moderate COPD patients. In addition, M1 macrophages formed primarily aggregates within the parenchymal tissue, and B and T cells displayed a pattern of heterogeneous lymphoid infiltration around the entire wall of the terminal bronchioles in COPD patients.
Conclusion: Using precision mass cytometry imaging we provide evidence of an activated immune response with increased cross-talk between innate and adaptive immune cells within the terminal bronchioles of mild and moderate COPD patients, emphasizing the importance of early diagnosis and targeted therapeutics for small airways disease.
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