Focusing on diffuse (interstitial) lung disease: a rapidly evolving field

The diffuse (interstitial) lung diseases have attracted an unprecedented level of interest over the past 5 years. Statements from the American Thoracic Society/European Respiratory Society committees on idiopathic pulmonary fibrosis (IPF), sarcoidosis and the idiopathic interstitial pneumonias, and from the British Thoracic Society on diffuse parenchymal lung diseases [1–3] have defined the phenotype of the idio-pathic interstitial pneumonias more tightly than was previously the case. Much of the credit for this lies in the exploitation of high-resolution computed tomography to provide a three-dimensional anatomical display, with great precision, of the patterns of abnormality that occur in diffuse lung diseases [4]. Such precision has reinvigorated a molecular scientific approach, including molecular genetics, to gain an understanding of disease causation and progression. With a more precisely defined diffuse lung disease phenotype , it is now possible to apply high throughput, moderately fine mapping technologies to define genetic predisposition to disease and severity of disease. The more precise phenotype has also stimulated scientists to rethink concepts of pathogenesis, particularly with regard to IPF, and to re-explore the relative contributions of inflammation and fibrogenesis to this disease. This renaissance in scientific interest has stimulated the pharmaceutical industry into an unprecedented level of activity with regard to these diseases , with investment in phase II and phase III studies of novel therapeutic approaches in an attempt to improve the appalling outcome for the most lethal of the diffuse lung diseases – IPF. At least seven studies of IPF therapy have been completed, are proceeding or are at the planning stages. In this series of articles in volume 3 of Respiratory Research, we address a number of key areas of development , with a specific focus on genetic predisposition and the fibrogenesis versus inflammation debate in IPF. Iannuzzi et al. [5] discuss the power of genetic polymor-phism analysis. They stress the number of pitfalls that can be encountered and the need for careful study design, using clearly defined populations, appropriate controls and a judicious combination of family-based association studies (generally using genome marker strategies) with case–control candidate gene studies. With this approach, important strides can be taken in our understanding of a variety of lung diseases, particularly chronic beryllium disease, sarcoidosis and IPF. Seitzer et al. [6] and Pantelidis et al. [7] provide reviews of specific genetic targets. Seitzer et al. [6] discuss the loci on the short arm of chromosome 6, most specifically the class …