The current physiological and HRCT results revealed differences in clinical characteristics between silicosis and asbestosis. Asbestosis had a longer latency than silicosis, suggesting that asbestos dust might have a slower pathogenic effect than silica dust. Pulmonary function values, including FVC and DLCO, were lower in the asbestosis group, and PaO2 and CPI also differed between the two groups. In terms of HRCT appearance, chest imaging showed small round shadows or progressive massive fibrosis in patients with silicosis, compared with irregular reticular abnormalities in the lower lobes with pleural thickening in patients with asbestosis.
These differences in the clinical characteristics and underlying mechanisms of silicosis and asbestosis groups warranted further study. We therefore performed a pilot study using LC-MS-based metabolomics to discriminate between silicosis and asbestosis and thus improve the precision of health care. Compared with healthy controls, 37 and 39 metabolites were differentially detected in the plasma of patients with silicosis and asbestosis, respectively, of which 22 occurred in both the silicosis and asbestosis groups. Lipids, amino acids and carnitines were the main metabolites associated with silicosis and asbestosis, and most of the differentially expressed metabolites were up-regulated, especially in patients with asbestosis. We also found that plasma metabolites may differentially expressed in silicosis and asbestosis patients according to the disease severity. The severity of silicosis or asbestosis varies, as do its plasma metabolites, some of which may be associated with disease severity.
Lipids are the components of cell membranes and are an essential human nutrient. In addition to their structural role in cell membranes, they are also involved in energy storage, signal transduction, enzyme activation, growth factors, antioxidants, signal recognition and immunity . A previous metobonomics study found that the sphingolipid metabolic pathway was down-regulated; the arginine pathway was up-regulated, and glycolysis, mitochondrial beta-oxidation and the tricarboxylic acid cycle were disrupted in lung tissue from patients with IPF . The energy consumption during lung structural remodeling may contribute to the pathogenesis of IPF. Excessive lipid metabolism in the present study indicated abnormal cellular energy metabolism inpatients with silicosis and asbestosis, suggesting similar metabonomic changes in non-IPF chronic lung fibrotic diseases. Pneumoconiosis involves lung inflammation caused by organic dust, and proteins, carbohydrates and especially lipids were elevatedin pulmonary edema fluid in acute respiratory distress syndrome, which is also an inflammatory condition . Lysophosphatidic acid (LPA) is produced by activated platelets and fibroblasts and was increased in damaged skin and fibrotic lung in various fibrosis models . The hydrolysis of lysophosphatidylcholine by lysophospholipase D/autotaxin represents one pathway for LPA synthesis. In the current study, lysophosphatidylcholine levels were significantly higher in patients with silicosis or asbestosis compared with healthy controls, and LPA levels were the highest in the asbestosis group. In addition, lipid mediators exert wide-ranging and sometimes opposing effects on multiple tissues. Compared with a healthy control group, bronchial lavage fluid levels of prostaglandin E2 were significantly increased in IPF patients, but there was no significant difference between the two groups in serum levels of prostaglandin E2 . In the present study, patients with asbestosis had more severe pulmonary dysfunction than those with silicosis due to the extensive lung fibrosis. The percentage of lipid up-regulation was also higher in the asbestosis compared with the silicosis group (84.62% vs 56.52%, P < 0.05), which may indicate the different levels of protective lipid metabolites.
Amino acids are the basic components of proteins and are required as raw materials for protein synthesis. They also participate in the formation of enzymes, hormones and some vitamins. Ornithine can also be converted to proline and hydroxyproline for collagen formation in fibrosis . Increased levels of creatine, putrescine, spermidine, 4-hydroxyproline and the proline-hydroxyproline dipeptide were found in fibrotic lung tissue from patients with IPF compared with normal lung tissue . Compared with the healthy controls, plasma levels of amino acids, including ornithine, creatine and hydroxyproline, were largely increased in patients with silicosis and asbestosis. Silicosis and asbestosis were characterized by similar changes in amino acid metabolism to IPF, possibly related to the fibrotic process. As for lipid metabolism, the effects of asbestos fibers on amino acid metabolism were more obvious than those of silica. Glutamate synthase levels were previously shown to be elevated in lung tissue from patients with pleural mesothelioma compared with adjacent normal tissues . Furthermore, L-type amino acid transporters were associated with tumors, and their expression was increased in tumor samples, while expression levels of amino acids differed among different tissues . In the current study, plasma levels of amino acids were up-regulated in both silicosis and asbestosis, especially in asbestosis. In addition to lung cancer, a prospective population-based study showed that asbestos exposure was also associated with other cancers, such as gastric and colon cancer . A chest HRCT study of patients with asbestosis found that subpleural dots and lines were close to the chest wall and located < 5 mm from the inner chest wall, which may indicate that asbestos fibers, unlike silica, may also potentially cause pleural mesothelioma .
Carnitines are amino acid-like substances involved in the metabolism of fat into energy. Carnitines promote the transport and oxidation of fatty acids and the utilization of carbohydrates and amino acids, improve body tolerance, prevent lactic acid accumulation, delay aging and have antioxidant properties. Carnitine levels were significantly decreased in lung tissue, and mitochondrial beta-oxidation was reduced in patients with IPF. In contrast to IPF, plasma carnitine levels were largely up-regulated in the current patients with silicosis and asbestosis (except for one carnitine in the silicosis group), compared with the healthy controls. Further studies are needed to determine if the increase in plasma carnitine levels in patients with silicosis and asbestosis is related to lipid metabolism or to the disease itself.
The present study had several limitations. First, there may have been some selection bias. The enrolled population was from a single medical center and was therefore not fully representative of patients with silicosis and asbestosis. Furthermore, all the enrolled patients were of Chinese Han ethnicity, which may overlook any potential ethnic or geographical effects. This potential inclusion bias might affect the validity of the results. More males were enrolled the study, indicating that men were more prone to silicosis for occupational reasons. Males are at increased risk of exposure to silica dust because they are more likely to be involved in manual labor, such as excavation and digging, polishing and buffing, and more men were therefore enrolled in the present study. Second, the average age of patients with asbestosis was older than that of those with silicosis. However, we previously reported that asbestosis had a longer latency than silicosis, and this discrepancy may therefore be related to the different latencies . Third, we did not include a group with exposure to dust without silicosis or asbestosis because the plants were no longer in operation. Finally, although the systemic metabolic profiling of silicosis and asbestosis is accessible and noninvasive, it may not fully represent the metabolic process of the lungs. Further research on metabolomics may include both plasma and lung tissue for analyzing.