The cause of ILD is unknown in about 65% of patients (table 1). However, in several conditions, there is increasing evidence of the involvement of exogenous factors. Sarcoidosis is attributed to the combination of a susceptible constitution and exposure to a still unknown agent (microorganisms, inorganic material, etc.), but for the moment there is no convincing evidence of the precise causative agent(s). High exposure to metals (including brass, lead and steel) and wood dust have been shown to be risk factors for IPF.
Exogenous causes are recognised in 35% of patients with ILD, especially organic material (causing EAA), inorganic material (leading to pneumoconiosis), drug reactions and infections.
To date, human genetic studies of ILD have largely centred on descriptions of associations between certain phenotypes and known genetic loci, especially loci involved in inflammation and fibrogenesis. In the past decade, molecular genetic technology has improved greatly and complete genome scanning is now possible. In the future, more comprehensive information is expected thanks to advances in the field of functional genomics, including complementary DNA micro-array schemes and genetic bioinformatics. As a result, powerful strategies are becoming available to increase the resolution of gene mapping, even in complex diseases such as ILD.