**4. Role of systemic inflammation**

Inflammation associated with underlying lung disease may be partly responsible for the development of PH in hypoxic states. Inflammatory cells have been detected in local vascular structures in COPD patients, in addition to the evidence of systemic inflammation with raised inflammatory markers, such as CRP and TNF–α [29,30]. In rats exposed to hypoxia, alveolar macrophages play a critical role in the inflammatory process, with inflammation occurring in the presence of reduced alveolar PaO2 [31]. In alveolar macrophage-depleted conditions, systemic inflammation was not observed [32].
