Weston Ainsley
National Institute for Occupational Safety and Health, Morgantown, WV, USA.
IARC Sci Publ. 2011(163):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 remodelling 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 HLA-DPB11(E69) 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-DPB1(E69) 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.
与工作相关的呼吸道疾病影响着各个工业部门的人群，约占所有疾病和伤害死亡率的60%以及所有职业病死亡率的70%。有两种基本类型：间质性肺病，即尘肺病（如石棉沉着病、棉尘病、慢性铍病、煤工尘肺、矽肺、绒毛工肺和农民肺疾病），以及气道疾病，如与工作相关的或病情加重的哮喘、慢性阻塞性肺疾病和闭塞性细支气管炎（一种仅在10年前的某些食品生产中才被认识的疾病）。这些疾病发展的常见因素是接触粉尘、金属、过敏原和其他毒素，这些因素经常导致氧化损伤。作为反应，身体通过激活初级免疫反应基因（即通常会导致进一步氧化损伤的细胞因子）、生长因子和组织重塑蛋白来做出反应。这些过程中频繁出现的复杂失衡会导致疾病的发展。例如，组织基质金属蛋白酶可导致组织降解，如在煤工尘肺小结节的发展过程中，但通常基质金属蛋白酶的过度表达受血清蛋白抑制剂的控制。因此，这种平衡的破坏会导致不良的组织损伤。对这类肺病易感性的研究主要通过候选基因研究进行，这些研究通常规模较小，其结果往往难以证实。一个重要的例外是发现HLA-DPB11（E69）等位基因与慢性铍病和铍敏感性密切相关。虽然慢性铍病仅由接触铍引起，但HLA-DPB1（E69）的遗传在接触铍的工人中使患病风险增加了2至30倍。这些职业相关疾病中的大多数（如果不是全部的话）都是可以预防的；因此，令人不安的是，例如，21世纪美国煤工尘肺的发病率再次上升。
