Kreiss Kathleen
Division of Respiratory Health, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown WV, United States.
Toxicology. 2017 Aug 1;388:48-54. doi: 10.1016/j.tox.2016.06.009. Epub 2016 Jun 17.
For half of the 30-odd years that diacetyl-exposed workers have developed disabling lung disease, obliterative bronchiolitis was unrecognized as an occupational risk. Delays in its recognition as an occupational lung disease are attributable to the absence of a work-related temporal pattern of symptoms; failure to recognize clusters of cases; complexity of exposure environments; and absence of epidemiologic characterization of workforces giving rise to case clusters. Few physicians are familiar with this rare disease, and motivation to investigate the unknown requires familiarity with what is known and what is anomalous. In pursuit of the previously undescribed risk, investigators benefited greatly from multi-disciplinary collaboration, in this case including physicians, epidemiologists, environmental scientists, toxicologists, industry representatives, and worker advocates. In the 15 years since obliterative bronchiolitis was described in microwave popcorn workers, α-dicarbonyl-related lung disease has been found in flavoring manufacturing workers, other food production workers, diacetyl manufacturing workers, and coffee production workers, alongside case reports in other industries. Within the field of occupational health, impacts include new ventures in public health surveillance, attention to spirometry quality for serial measurements, identifying other indolent causes of obliterative bronchiolitis apart from accidental over-exposures, and broadening the spectrum of diagnostic abnormalities in the disease. Within toxicology, impacts include new attention to appropriate animal models of obliterative bronchiolitis, pertinence of computational fluid dynamic-physiologically based pharmacokinetic modeling, and contributions to mechanistic understanding of respiratory epithelial necrosis, airway fibrosis, and central nervous system effects. In these continuing efforts, collaboration between laboratory scientists, clinicians, occupational public health practitioners in government and industry, and employers remains critical for improving the health of workers inhaling volatile α-dicarbonyl compounds.
在接触二乙酰的工人罹患致残性肺部疾病的30多年里,有一半时间闭塞性细支气管炎都未被视为职业风险。其被认定为职业性肺病的时间之所以推迟,是因为缺乏与工作相关的症状时间模式;未能识别病例群;接触环境复杂;以及缺乏对引发病例群的劳动力进行流行病学特征描述。很少有医生熟悉这种罕见疾病,而调查未知情况的动力需要熟悉已知情况和异常情况。为了探寻此前未被描述的风险,研究人员从多学科合作中受益匪浅,在这个案例中,合作人员包括医生、流行病学家、环境科学家、毒理学家、行业代表和工人权益倡导者。自从在微波爆米花工人中描述了闭塞性细支气管炎后的15年里,在调味剂制造工人、其他食品生产工人、二乙酰制造工人和咖啡生产工人中发现了与α-二羰基相关的肺病,其他行业也有病例报告。在职业健康领域,影响包括公共卫生监测方面的新举措、关注连续测量的肺活量测定质量、识别除意外过度接触之外闭塞性细支气管炎的其他隐匿病因,以及拓宽该疾病诊断异常的范围。在毒理学领域,影响包括重新关注闭塞性细支气管炎合适的动物模型、计算流体动力学-基于生理学的药代动力学模型的相关性,以及对呼吸上皮坏死、气道纤维化和中枢神经系统影响的机制理解做出贡献。在这些持续的努力中,实验室科学家、临床医生、政府和行业的职业公共卫生从业者以及雇主之间的合作对于改善吸入挥发性α-二羰基化合物的工人的健康仍然至关重要。