Work-Related Lung Diseases Ainsley Weston
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UNIT 5. APPLICATION OF BIOMARKERS TO DISEASE CHAPTER 21. Work-related lung diseases Ainsley Weston Summary Work-related respiratory diseases dusts, metals, allergens and other disease has been investigated largely affect people in every industrial toxins, which frequently cause through candidate gene studies, sector, constituting approximately oxidative damage. In response, the which have been characteristically 60% of all disease and injury body reacts by activating primary small, often providing findings that mortality and 70% of all occupational immune response genes (i.e. have been difficult to corroborate. disease mortality. There are two cytokines that often lead to further An important exception to this has basic types: interstitial lung diseases, oxidative damage), growth factors been the finding that the HLA- that is the pneumoconioses and tissue remodelling proteins. DPB1E69 allele is closely associated (asbestosis, byssinosis, chronic Frequently, complex imbalances in with chronic beryllium disease beryllium disease, coal workers’ these processes contribute to the and beryllium sensitivity. Although pneumoconiosis (CWP), silicosis, development of disease. For example, chronic beryllium disease is only flock workers’ lung, and farmers’ tissue matrix metalloproteases caused by exposure to beryllium, lung disease), and airways diseases, can cause the degradation of inheritance of HLA-DPB1E69 carries such as work-related or exacerbated tissue, as in the development an increased risk of between two- asthma, chronic obstructive of CWP small profusions, but and 30-fold in beryllium exposed pulmonary disease and bronchiolitis usually overexpression of matrix workers. Most, if not all, of these obliterans (a disease that was metalloproteases is controlled by occupationally related diseases recognized in the production of serum protein inhibitors. Thus, are preventable; therefore, it is certain foods only 10 years ago). disruption of such a balance can disturbing that rates of CWP, for Common factors in the development lead to adverse tissue damage. example, are again increasing in the of these diseases are exposures to Susceptibility to these types of lung United States in the 21st century. UNIT 5 CHAPTER 21 CHAPTER Unit 5 • Chapter 21. Work-related lung diseases 387 Introduction or asthma attack in the previous tremolite, actinolite and anthophyllite, 12 months (7). A 2003 statement are collectively known as asbestos. Excluding lung cancer, which is by the American Thoracic Society Asbestos mineral fibres are flame- thought to account for 10 000–12 estimated that 15% of COPD and and heat resistant, pliable, strong, 000 occupationally-related deaths adult asthma cases were work- refractory to corrosive chemicals, annually in the United States related, with a conservative annual and provide insulation. Therefore (1), and infectious diseases like estimated cost of nearly $7 billion in asbestos has been used as a tuberculosis and histoplasmosis the USA alone (8). building material to insulate buildings which may be work-related, several An emerging area that thus far from heat and protect against fire work-related lung diseases have has not been explored in terms (it has been especially important been identified. These have been of molecular epidemiology is that in the shipbuilding industry), in broadly divided into two types: of engineered nanotechnology. fabric to make protective suits, as a interstitial lung diseases that are Nanoparticles and nanomaterials brake liner (e.g. in automobiles and typified by the pneumoconioses have diverse applications (e.g. drug railroad rolling stock) and for engine (asbestosis, byssinosis, chronic delivery, electronics and cosmetics); gaskets, and in making filters (e.g. in beryllium disease, coal workers’ however, their large surface area the chemical industry). pneumoconiosis, silicosis, flock to volume and respirable nature Although known and used for workers’ lung and farmers’ lung suggest that they may pose a its fire resistant properties as early disease), and airways diseases risk of lung disease. Studies in as 3000 B.C., asbestos started like asthma, chronic obstructive rodents have shown the potential to become widely used in the pulmonary disease (COPD) and of nanomaterials to cause oxidative mid- to late-nineteenth century bronchiolitis obliterans. Work- stress, inflammation, and fibrosis (10). Asbestos-associated fibrosis related respiratory diseases are a (9). (asbestosis) was described in the problem of major magnitude. They In the last three decades, with 1920s, and mesothelioma (a very cut across all industrial sectors, the expansion of the emerging field rare cancer of the mesothelium, constituting ~60% of all disease of molecular epidemiology, several an epithelial lining of the serous and injury mortality and ~70% of all genetic susceptibility factors for cavities: thorax and peritoneum) and occupational disease mortality (2). work-related lung diseases and lung cancer were linked to asbestos Even though the capability has biomarkers of exposure and effect exposure in the 1960s (11). Thus, existed for many years to prevent have been recognized. The majority asbestosis, mesothelioma (almost pneumoconioses (e.g. silicosis, coal of these findings took clues from exclusively associated with asbestos workers’ pneumoconiosis (CWP) physiological or pathobiological exposure) and asbestos-associated and asbestosis), they still cause or observations, and in some cases lung cancer are diseases frequently contribute to more than 2500 deaths genetic linkage analysis, and applied found in workers employed or per year in the United States (3). them to candidate gene investigations formerly employed in construction, The threat of other interstitial lung in molecular epidemiological shipbuilding, mining, manufacturing diseases, such as chronic beryllium association studies. Though these and heat and frost insulation. disease in beryllium metal extraction, types of studies may help to identify Fibrous particles generally have production and processing, or high risk subpopulations, their a large length to diameter aspect; hypersensitivity pneumonitis in current utility is most valuable in asbestos fibres are generally those exposed to metal working understanding disease mechanisms considered to have a length to fluids, are also important concerns and developing better laboratory diameter ratio of at least 3:1. in specific industries (4,5). models of disease. Respirable fibrous particles have Airways diseases, such as an effective aerodynamic diameter asthma and COPD, are important Interstitial lung diseases that more closely resembles particle occupational problems. In 2004, diameter than length. Thus, long, 11.4 million adults (aged ≥ 18) in Asbestosis, asbestos- narrow fibres can reach the alveoli. the USA were estimated to have related lung cancer and Fibrous asbestos particles can exert COPD (6). In the interval from mesothelioma their biological effects in several 1997–1999, an estimated 7.4 million ways. Physiological attempts by people in the United States (aged ≥ Several mineral fibres, including the body to remove asbestos 15) reported an episode of asthma chrysotile, amosite, crocidolite, fibres from the deep lung may 388 result in “frustrated phagocytosis” = 51 ± 23 µl/L) in BALF and ELF, induced in human peripheral blood by macrophages that engulf long, respectively. Among 12 persons with mononuclear cells in vivo by silica, narrow fibres. These macrophages no X-ray evidence of abnormalities, but not by chrysotile asbestos (20). then disgorge digestive enzymes only two were positive, and both of Asbestosis progression has been and other cytological materials these had levels of PICP of less than monitored by X-ray analysis; the potentially leading to inflammation, 3 µl/L and 200 µl/L in BALF and ELF, radiographic changes (International fibrosis and malignancy. It has also respectively. Data for N-terminal Labour Office (ILO) classified) been proposed that the mineral propeptide of type 3 procollagen over 2–10 years were correlated fibres themselves can promote did not support it as a marker of with a large series of biomarkers: oxidative damage provoked by asbestosis. These results are adenosine deaminase, α-1- Fenton chemistry and the release of supportive of PICP as a biomarker antitrypsin, angiotensin-converting iron in the form of Fe3+ (12). for asbestosis; however, PICP has enzyme (ACE), β-2-microglobulin, Several approaches have been been associated with several other β-N -acetylglucosaminidase, taken to assess potential biomarkers fibrotic and chronic inflammatory carcinoembryonic antigen (CEA), of asbestosis. A major pathway is conditions (e.g. idiopathic fibrosing complement components (C3 and thought to be mediated through alveolitis (15), sarcoidosis (16) and C4), erythrocyte sedimentation macromolecular and chromosomal myocardial fibrosis (17)). PICP has rate (ESR), ferritin, fibronectin, damage resulting from reactive also been implicated in bone growth and lysozyme (21). Radiographic − oxygen species (ROS) (e.g. O2 , and bone metastasis (18). Thus, changes, which ranged from ILO 1/1 • HO , ONOO, NO2, NO3) formed in whereas PICP appears to be a good to ILO 2/2 (at an average of 0.4 minor the processes described above (13). biomarker of asbestosis, it is not ILO categories per year), were seen Because fibrosis and inflammation entirely specific. in 32 of 85 patients (OR = 1.54; 95% are major components of the Leukocyte glycoproteins (cluster CI = 0.96–2.47).