In the present network model shown in Fig 1, M1, DC, Th1, CD8+T and Th17 cells along with their corresponding cytokines, TNF-α, IL-6, IL-12, IFN-γ, and IL-17 form multiple proinflammatory pathways, whereas M2, Th2 and Treg cells with the associated cytokines, IL-4, TGF-β, and IL-10, form anti-inflammatory/regulatory pathways. The inflammatory and anti-inflammatory/regulatory pathways are interlinked with each other through several nodes representing molecular mediators such as IL-6, TGF-β and IL-10 (Fig 1). These pathways eventually converge at the TD node that represents the tissue damage. Here, we focus on the immunologic aspects of COPD and the TD node is highly coarse-grained, involving neutrophil-induced tissue damage, epithelial and endothelial cell injury and extracellular matrix degradation etc. As discussed above, for example, M1 produces chemokines to recruit neutrophils (not shown in Fig 1) for the release of neutrophil elastase and ROS, contributing to TD. The representation of this process is included indirectly in the M1→TD motif shown in Fig 1. In addition, while M1 secretes MMPs to cause TD, TD also produces EFs to recruit monocytes for generating M1. This process is represented in the M1→TD→M1 positive feedback loop where MMPs and EFs are included indirectly (Fig 1). As TD is the major feature of CODP in the lung parenchyma, the dynamics of TD is used to characterize the progression of COPD in this work.