Pulmonary Hypertension and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disabling disease of the lung parenchyma, characterized by progressive accumulation of scar tissue and myofibroblast activation after repetitive epithelial microinjury. The therapeutic options are limited, and patients usually die within a few years after diagnosis. Pulmonary hypertension (PH) in IPF has been increasingly recognized as a condition with relevance for the overall prognosis. Treatment trials are being designed, but to be effective, it is crucial to better understand the pathobiology of PH in IPF: the traditional concept, that hypoxic vasoconstriction and accumulation of scar tissue are mainly responsible for the development of PH in IPF, has been challenged. Recent studies, including our own in vivo research, suggest that the underlying pathobiology is much more complex, and includes a complicated interaction of epithelial cells, fibroblasts, and vascular cells. This interaction seems to be regulated by a large variety of angiogenesis promoters and inhibitors, as well as growth factors. Central components seem to be endothelial apoptosis and growth factor-induced remodeling of the pulmonary artery wall. The present review gives a conceptual overview about known and putative mechanisms that are involved in the development of PH in IPF. This report summarizes currently available therapeutic options, and also translates experimental research to discuss potential novel biomarkers and therapeutic strategies derived from new concepts in pathogenesis.