Recognizing occupational effects of diacetyl: What can we learn from this history?

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.