New pharmacological strategies for the treatment of pulmonary fibrosis

The treatment of pulmonary fibrosis continues to pose major difficulties. Idiopathic pulmonary fibrosis (IPF), the most prevalent chronic fibrosing lung disease, is a devastating condition that carries a prognosis worse than that of many cancers. Abnormalities in multiple pathways involved in wound healing and inflammation lead to the development of this condition. High doses of corticosteroids are now contraindicated in IPF, although they have a role in other fibrosing lung diseases. More effective treatments are urgently required and a number of novel candidate therapies have been put forward, based on animal and in vitro work. As in other complex disorders, it is likely that combinations of agents, rather than single treatments, will be needed. The principle of combination therapy was recently endorsed by the guidelines of the British Thoracic Society, which make a weak recommendation for a combination of prednisolone, azathioprine and N-acetylcysteine. However, enrolment of patients into trials of new therapies is considered to be ‘best current practice’ as this offers sufferers with IPF the chance to receive new agents that may be more effective than current treatments. In pulmonary fibrotic disorders other than IPF, anti-inflammatory therapy is broadly appropriate and benefits most patients, but a clear treatment strategy is essential. The art of management is to distinguish accurately between inherently stable fibrotic disease (with treatment not required), progressive predominantly fibrotic disease (with low-dose long-term treatment warranted to retard progression) and the presence of major associated inflammation (justifying initial high-dose treatment).