Strategies for treating idiopathic pulmonary fibrosis

Key Points Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia (IIP), a group of diseases of unknown cause that scar predominantly the gas-exchanging regions of the lungs — the alveoli. IPF is also the most lethal IIP, with a mortality rate which exceeds that of many cancers. The current paradigm of pathogenesis is an aberrant healing response to epithelial cell injury, which probably occurs in response to a combination of environmental insults and/or genetic predispositions. Prior to 2000, no studies of therapy had been undertaken that had provided clear evidence of efficacy. More recent, better designed studies have generally been disappointing, although there is some evidence for benefit either with a combination of prednisone, azathioprine and N -acetylcysteine or with pirfenidone. Novel initiatives that hold promise include the National Heart, Lung and Blood Institute's IPFnet, which aims to find effective therapy for early and late IPF; the use of expression arrays to identify pivotal targets; and the blockade of signalling pathways. Future strategies need to focus on the cause and the consequences of the epithelial cell injury, without which the fibrogenic response would not occur. Further studies of the consequences of aberrant protein production by alveolar type II cells owing to genetic variants and other causes may prove fruitful. Trial design, especially the issue of which end points are most meaningful, remains a challenge in IPF. However, the experiences of the past decade have resulted in considerable progress, particularly regarding the use of change in the lung volume measure, forced vital capacity, as a surrogate for the risk of mortality. Idiopathic pulmonary fibrosis (IPF) is a life-threatening chronic lung disease, for which no specific therapies have been approved. In this article, du Bois discusses the current understanding of the pathophysiology of IPF, the potential of agents under development and possible future therapeutic strategies. Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal diffuse fibrosing lung disease, with a mortality rate that exceeds that of many cancers. Recently, there have been many clinical trials of novel therapies for IPF. The results have mostly been disappointing, although two treatment approaches have shown some efficacy. This Review describes the difficulties of treating IPF and the approaches that have been tried or are in development, an