Response to Muge Akpinar-Elci Letter to Editor re. Pierce et al., Diacetyl and 2,3-pentanedione exposures associated with cigarette smoking: implications for risk assessment of food and flavoring workers, Crit. Rev. Toxicol. 44(5):420–435, 2014

possible risk factor related to the work environment ” . As U.S. Supreme Court Justice Louis Brandeis noted when referring to the benefi ts of transparency, “ sunlight is said to be the best of disinfectants ” . Let us shed some sunlight onto the above claim. First, they failed to note that only three of their alleged nine cases of bronchiolitis obliterans underwent lung biopsy to allow for confi rmation of the suspected diagnosis. Of these, only one had fi ndings that supported a possible diagnosis of bronchiolitis obliterans. Second, although bronchiolitis obliterans is a fi xed obstructive disease, there was no diff erence in the prevalence of obstruction between the diacetyl-exposed workers versus controls in either of the Akpinar-Elci et al. (2005, 2006) studies of GML workers. Oddly, in neither study do they note that these fi ndings completely contradict those of Kreiss et al. (2002), who claimed to have observed a signifi cant relationship between diacetyl exposure and obstruction prevalence in workers at the same facility. Given the fact that Kreiss et al. (2002) is considered by Akpinar-Elci et al. to be a seminal study, failure to replicate the results of Kreiss et al. (2002) in their studies should warrant some mention in their papers. Similarly, in neither study do the authors inform the reader that in the original GML cohort (Kreiss et al. 2002), 57% of the cohort claimed to have had off -site (mostly farming-related) exposures to “ other possible causes of lung disease ” , including known inducers of bronchiolitis obliterans , such as nitrogen oxides (silo gas). Furthermore, the authors are mistaken in suggesting that had we “ more carefully ” reviewed the fi ndings of their analyses, our conclusions would have been diff erent. We have reviewed their studies at length, and believe that their claim of “ fi ndings that strongly indicate a relationship between occupational butter fl avoring exposure and respiratory diseases among popcorn production workers ” is desperately over-reaching. In fact, their To the Editor: My co-authors and I appreciate the opportunity to respond to the Letter to the Editor (Akpinar-Elci and Elci 2014) concerning our recent article (Pierce et al. 2014). Akpinar-Elci and Elci suggest that we “ falsely ” claimed that “ all of the cohorts evaluated had considerable smoking histories ” . To support their assertion, they off er a nonsequitur: of the nine alleged cases of bronchiolitis obliterans in their cohort, a majority (6/9) were current or former smokers. Unfortunately, they seem to have confused the terms “ cohort ” and “ case ” . To reiterate, all food/ fl avoring cohorts studied to date had a signifi cant fraction of current/former smokers, and indeed in the Akpinar-Elci et al. (2005, 2006) analyses of the Gilster-Mary Lee (GML) workers, nearly 50% of the study participants were current smokers. They also appear to believe that, because most of the alleged cases of bronchiolitis obliterans in their cohort (8/9) were not current smokers, then smoking was not a confounder in their study. They have unintentionally reinforced our point. Cigarette smoke contains high levels of diacetyl, therefore workers who smoke have much higher diacetyl exposures than the non-smoking food/fl avoring workers. More importantly, even though smokers arguably have the highest peak and cumulative diacetyl exposures of any defi nable cohort, smoking is not a risk factor for bronchiolitis obliterans . These observations argue against a relationship between diacetyl exposure and bronchiolitis obliteran s. Finally, they have confused “ controlling for the eff ects of smoking on respiratory function ” (which they did do) versus “ accounting for the relatively large diacetyl exposure from smoking when assessing the exposure-response relationship between diacetyl inhalation and respiratory function in food/fl avoring workers ” (which they certainly did not do). Akpinar-Elci and Elci claim that “ A cluster of such a rare disease as bronchiolitis obliterans indicates a http://informahealthcare.com/txc ISSN: 1040-8444 (print), 1547-6898 (electronic)