Silicosis Leung, Chi Chiu, Dr; Yu, Ignatius Tak Sun, Prof; Chen, Weihong, Prof
The Lancet (British edition),
05/2012, Letnik:
379, Številka:
9830
Journal Article
Recenzirano
Summary Silicosis is a fibrotic lung disease caused by inhalation of free crystalline silicon dioxide or silica. Occupational exposure to respirable crystalline silica dust particles occurs in many ...industries. Phagocytosis of crystalline silica in the lung causes lysosomal damage, activating the NALP3 inflammasome and triggering the inflammatory cascade with subsequent fibrosis. Impairment of lung function increases with disease progression, even after the patient is no longer exposed. Diagnosis of silicosis needs carefully documented records of occupational exposure and radiological features, with exclusion of other competing diagnoses. Mycobacterial diseases, airway obstruction, and lung cancer are associated with silica dust exposure. As yet, no curative treatment exists, but comprehensive management strategies help to improve quality of life and slow deterioration. Further efforts are needed for recognition and control of silica hazards, especially in developing countries.
Abstract Background Ageing is related to the risk of many diseases and is affected by genetic, epigenetic, and environmental factors. Exposure to the ubiquitous pollutant polycyclic aromatic ...hydrocarbons (PAHs) is known to cause health damage, but the relation between such exposure with methylation ageing has not been studied. We undertook an association analysis of exposure to PAHs and DNA methylation ageing, a novel and promising ageing marker. Methods We built a model of methylation age and defined two ageing indicators (ageing rate, calculated as ratio of methylation to chronological age; and Δage, calculated as methylation minus chronological age) on the basis of genome-wide methylation data of blood in five panels of Chinese individuals (N=596). Participants included 137 coke oven workers (aged 26–60 years) who were chronically and occupationally exposed to high levels of PAHs; 101 patients with acute coronary syndrome (aged 40–86 years) from Wuhan, China; 97 patients with this syndrome (aged 38–83 years) from Guangdong, China; 162 healthy individuals (aged 26–79 years) from Wuhan; and 99 healthy individuals (aged 37–80 years) from Zhuhai, China. Exposure to individual PAHs was assessed by ten urinary PAH metabolites. We examined the relations between PAH exposure and the two ageing indicators, and investigated the potential CpGs mediating the association. Written informed consent was obtained from all participants. Our study was approved by the ethics committee of Tongji Medical College, Wuhan, China. No study subjects were from clinical trials. Findings Coke oven workers, who were exposed to high levels of PAHs at work (mean nature-log-transformed total urinary PAHs −1·909 SD 0·461), had significant age acceleration (2·7% increase in ageing rate p=0·002 and 1·218-year increase in Δage p=0·01 compared with all other panels). Urinary 3-OH-phenanthrene and 9-OH-phenanthrene were independently and significantly associated with the two ageing indicators in our non-disease panels. One unit increase of nature-log-transformed 9-OH-phenanthrene was associated with a 1·8% increase (p=0·0029) in ageing rate and a 1·1-year increase (p=0·0002) in Δage, whereas for 3-OH-phenanthrene the increase was 1·3% (p=0·0050) for ageing rate and 0·57 year (p=0·0109) for Δage. Methylation at several ageing-related and PAH-related CpGs (annotated on ELOVL2 , KLHL35 , FHL2 , BOK , PDP1 , and OTUD7A ) was reported to mediate the effect of PAH exposure on methylation ageing. Interpretation Our study revealed a significant association between PAH exposure and accelerated methylation ageing. The importance of exposure-related ageing needs to be further investigated. Funding National Key Basic Research and Development Program, Natural National Scientific Foundation, the 111 Project, the Program for Changjiang Scholars, and Innovative Research Team Scholars.
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