Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous condition and is likely to be initiated by many different forms of lung injury. Injury to the alveolar epithelium followed by aberrant repair is, however, recognised to be a central pathogenic mechanism in IPF.1 Histologically, there is evidence of epithelial cell hyperplasia and proliferation, particularly adjacent to fibroblastic foci, but also areas of epithelial apoptosis and denudation.2 In murine models of pulmonary fibrosis, inhibition of components of apoptotic signalling pathways abrogates both alveolar epithelial cell death and fibrosis. This has been achieved by treatment with caspase inhibitors or with antibody blockade of the Fas death receptor, these results being confirmed in mice deficient in murine Fas (lpr) or its ligand, gld.3 4 The mechanisms of epithelial cell apoptosis in human IPF are not clearly defined, although there is evidence that the Fas pathway may be upregulated resulting in caspase-dependent apoptosis.5 A recent paper has shown that apoptosis of epithelial cells derived from patients with IPF is specifically associated with markers of endoplasmic reticulum stress.6

In this issue of Thorax, Oikonomou and colleagues (see page 467) show that …