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Diacetyl and Bronchiolitis Obliterans

We read with interest the analysis by Dr. van Rooy and colleagues of the risk of developing bronchiolitis obliterans in workers involved in manufacturing flavoring ingredients (1). We comment as follows.

In their study, the fraction of suspected workers for fixed airway obstruction was 6 out of 196 workers being evaluated. This fraction was further reduced as two were not found to have disease. Of the remaining four, one worker refused to have high-resolution computed tomography; three were subsequently diagnosed with bronchiolitis obliterans syndrome, unverified by lung biopsy. The worker refusing computed tomography had a heavy smoking history.

Exposure to diacetyl for process operators only existed at the end of the production process, and none of the workers were exposed to the heated compound—a much different scenario than mixers in microwave popcorn facilities. In the only subject who actually underwent lung biopsy, the histology showed "no signs of constrictive bronchiolitis."

In a previously published abstract (2), van Rooy and coworkers reported "no clear relationship between lung function and cumulative exposure." The authors stated: "Estimated historic exposure levels are subject to considerable measurement error and it is likely that exposure misclassification obscured exposure–response relationships." If these were problems in 2006, their 2007 analysis should also be at risk for the same issues.

The authors believe that animal studies confirm airway injury with diacetyl vapor. What is not mentioned is that this damage was consistently noted by Hubbs and coworkers (3) to be tracheal and upper bronchial in location, not terminal bronchiolar and alveolar injury as seen in constrictive bronchiolitis.

van Rooy and coworkers do not discuss respiratory protection measures routinely employed by process operators. The "control measures" instituted in 2001 are not described, nor are any worker respiratory complaints that might be indicative of high exposures summarized. These basic facts are important for proper comparison with popcorn worker studies, and for understanding industrial hygiene and worker safety.

We applaud the efforts of van Rooy and coworkers to examine the incidence of lung disease in workers exposed to diacetyl and other chemical agents. Prevention of occupational lung disease is predicated on a clear understanding of risk factors, disease mechanism, and confounding variables, and we share their desire to protect workers from dangerous exposures. Unfortunately, it seems that their survey has done little to demonstrate an association between diacetyl exposure and the development of bronchiolitis obliterans.

David A. Galbraith

Palo Alto Medical Foundation
Palo Alto, California

David Weill

Stanford University School of Medicine
Stanford, California

FOOTNOTES

Conflict of Interest Statement: D.A.G. has been a consultant for Kerry Foods and Chemtura Corporation. D.W. has been a consultant for Chemtura.

REFERENCES

1. van Rooy FGBGJ, Rooyackers JM, Prokop M, Houba R, Smit LAM, Heederik DJJ. Bronchiolitis obliterans syndrome in chemical workers producing diacetyl for food flavorings. Am J Respir Crit Care Med 2007;176:498–504.[Abstract/Free Full Text]
2. van Rooy F, Houba R, Zaat V, Smit L, Rooyackers J, Heederik D. A case series of bronchiolitis obliterans syndrome in workers at a diacetyl production plant [abstract]. Eur Respir J 2006;28:462s.
3. Hubbs AF, Battelli LA, Goldsmith WT, Porter DW, Frazer D, Friend S, Swegler-Berry D, Mercer RR, Reynolds JS, Grote A, et al. Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring. Toxicol Appl Pharmacol 2002;185:128–135.[CrossRef][Medline]

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