Bone marrow characterization in COPD: a multi-level network analysis

Nuria Toledo-Pons, Guillaume Noell, Andreas Jahn, Amanda Iglesias, Maria Antonia Duran, Julio Iglesias, Angel Rios, Sergio Scrimini, Rosa Faner, Orlando Gigirey, Alvar Agustí, Borja G. Cosío

Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-β, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils.