Biological markers and occupational lung disease: mineral dust-induced respiratory disorders.

There is a need for methods to monitor early adverse effects, exposure, and/or susceptibility of individual subjects due to occupational and environmental causes. This paper discusses the experimental origin, value, and validity of several biological indicators, termed biomarkers, that were used to study coal dust-induced respiratory disorders. The findings are presented in a framework to visualize problems and challenges when developing biomarkers. Taking the framework of mineral dust-induced lung disorders as an example, it is demonstrated how carefully designed follow-up studies are a prerequisite to test the validity and use of events often put forward as biomarkers. It is concluded from the data that serum type III procollagen is neither an exposure nor an (early) effect marker, antioxidant enzyme expression is related to the early inflammatory response after mineral dust inhalation, while the evidence is accumulating that tumor necrosis factor-alpha is a susceptibility marker for progression in mineral dust-induced lung fibrosis.