Molecular epidemiology: principles and practices. Rothman N, Hainaut P, Schulte P, Smith M, Boffetta P, Perera F, eds., Lyon, France: International Agency for Research on Cancer, IARC Scientific Publication, No 163, 2012 Jul; :387-405
Work-related respiratory diseases affect people in every industrial sector, constituting approximately 60% of all disease and injury mortality and 70% of all occupational disease mortality. There are two basic types: interstitial lung diseases, that is the pneumoconioses (asbestosis, byssinosis, chronic beryllium disease, coal workers' pneumoconiosis (CWP), silicosis, flock workers' lung, and farmers' lung disease), and airways diseases, such as work-related or exacerbated asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans (a disease that was recognized in the production of certain foods only 10 years ago). Common factors in the development of these diseases are exposures to dusts, metals, allergens and other toxins, which frequently cause oxidative damage. In response, the body reacts by activating primary immune response genes (i.e. cytokines that often lead to further oxidative damage), growth factors and tissue remodeling proteins. Frequently, complex imbalances in these processes contribute to the development of disease. For example, tissue matrix metalloproteases can cause the degradation of tissue, as in the development of CWP small profusions, but usually overexpression of matrix metalloproteases is controlled by serum protein inhibitors. Thus, disruption of such a balance can lead to adverse tissue damage. Susceptibility to these types of lung disease has been investigated largely through candidate gene studies, which have been characteristically small, often providing findings that have been difficult to corroborate. An important exception to this has been the finding that the HLADPB1E69 allele is closely associated with chronic beryllium disease and beryllium sensitivity. Although chronic beryllium disease is only caused by exposure to beryllium, inheritance of HLA-DPB1E69 carries an increased risk of between two and 30-fold in beryllium exposed workers. Most, if not all, of these occupationally related diseases are preventable; therefore, it is disturbing that rates of CWP, for example, are again increasing in the United States in the 21st century.