We were greatly dismayed by Pierce et al.’ s report on the associations between exposure to Diacetyl and 2,3-pentanedione and cigarette smoking (Pierce et al. 2014). It stated that “ Diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. ” Based on this finding, the authors suggested that “ previous claims of a significant exposure – response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all the cohorts evaluated had considerable smoking histories. 

Akpinar-Elci, Muge

Elci, Omur Cinar

English

Old Dominion University

Old Dominion UniversityODU Digital CommonsCenter for Global Health Publications Center for Global Health2014Re: Pierce et al. Diacetyl and 2,3-PentanedioneExposures Associated with Cigarette Smoking:Implications for Risk Assessment of Food andFlavoring Workers Crit Rev Toxicol, 2014; 44(5):420-435Muge Akpinar-ElciOld Dominion University, makpinar@odu.eduOmur Cinar ElciFollow this and additional works at: https://digitalcommons.odu.edu/globalhealth_pubsPart of the Toxicology CommonsThis Letter to the Editor is brought to you for free and open access by the Center for Global Health at ODU Digital Commons. It has been accepted forinclusion in Center for Global Health Publications by an authorized administrator of ODU Digital Commons. For more information, please contactdigitalcommons@odu.edu.Repository CitationAkpinar-Elci, Muge and Elci, Omur Cinar, "Re: Pierce et al. Diacetyl and 2,3-Pentanedione Exposures Associated with CigaretteSmoking: Implications for Risk Assessment of Food and Flavoring Workers Crit Rev Toxicol, 2014; 44(5): 420-435" (2014). Centerfor Global Health Publications. 4.https://digitalcommons.odu.edu/globalhealth_pubs/4Original Publication CitationAkpinar-Elci, M., & Elci, O. C. (2014). 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, 2014; 44(5): 420-435. Critical Reviews in Toxicology,44(7), 638-639. doi:10.3109/10408444.2014.930092 Address for correspondence: Muge Akpinar-Elci, MD, MPH, Center for Global Health, College of Health Sciences, Old Dominion University, Health Science Bldg, Room 3133, Norfolk VA 23529, USA. Tel:    757-683-5270. Fax:    757-683-5336. E-mail: makpinar@odu.edu  History  Received  3  April  2014 Accepted  28  May  2014 popcorn workers, we controlled for possible confounding eff ects of smoking, age, and gender. In one of these two studies, we investigated whether exhaled nitric oxide (FE NO ) levels were associated with exposure, respiratory symptoms, or airways obstruction (Akpinar-Elci et  al. 2006). A ques-tionnaire, spirometry, and FE NO measurements were com-pleted by 135 workers — 52.6% of whom were nonsmokers. Workers, who were current smokers, had signifi cantly lower FE NO levels when compared with nonsmokers ( p    0.01). FE NO levels were also low in the high-exposure group compared with those of the low-exposure group ( p    0.05). When we excluded smokers, FE NO levels were still lower in the high-exposure group than those in either the healthy control group or the low exposure group. A low FE NO level is not a normal fi nding and has been associated with lung diseases other than asthma such as primary pulmonary hypertension, COPD, cystic fi brosis, and ciliary dyski-nesia. (Chatkin et  al. 1999, Clini et  al. 2000, Kharitonov and Barnes 2001) Although a FE NO increase or decrease depends on the outcome of exposure, previous studies have shown that changes in FE NO depend on the type of exposure. Kim et  al. reported an inverse exposure – response between the FE NO and metal exposure in boilermakers similar to our results: Occupational exposure was associated with a sig-nifi cant decrease in FE NO (Kim et al. 2003a, b).  Our other study evaluated the association between airway infl ammation markers from induced sputum and popcorn fl avoring agent exposure among 81 workers (of whom 53.1% were nonsmokers). (Akpinar-Elci et  al. 2005) Because current smoking is known to aff ect cell count, we adjusted our analysis of associations between exposures, symptoms, lung function, and airways infl ammation for smoking status. We calculated the smoking-adjusted odds ratios (ORs) to assess relationships  To the Editor:  We were greatly dismayed by Pierce et  al. ’ s report on the associations between exposure to Diacetyl and 2,3-pentanedione and cigarette smoking (Pierce et  al. 2014). It stated that  “ Diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/fl avoring workers who smoke. ” Based on this fi nding, the authors suggested that  “ previous claims of a signifi cant exposure – response relationship between diacetyl inhalation and respiratory disease in food/fl avoring workers were confounded because none of the investigations consid-ered or quantifi ed the non-occupational diacetyl exposure from cigarette smoke, yet all the cohorts evaluated had considerable smoking histories. ”  Regretfully, the authors misrepresented cases of Bronchi-olitis obliterans among the microwave popcorn production workers, who were exposed to artifi cial butter fl avoring. Pierce et  al. ’ s claim that  “ all of the cohorts evaluated had con-siderable smoking histories ” is false. Our study documented the sentinel cases and clearly stated that of the nine cases only one of the workers was a current smoker (Akpinar-Elci et  al. 2004). Three (33.3%) of the remaining eight workers had never smoked. The remaining fi ve (55.6%) sentinel cases were former smokers. Regardless of any clinical, toxicologi-cal, or exposure analysis, basic principles of epidemiology highlight the importance of identifying such unusual disease clusters among workers in the same plant. A cluster of such a rare disease as Bronchiolitis obliterans indicates a possible causal factor related to the work environment and/or occupa-tional exposures.  Pierce et  al. also included our two epidemiological stud-ies in their review. Throughout our occupational health and infl ammatory markers investigation among the microwave http://informahealthcare.com/txcISSN: 1040-8444 (print), 1547-6898 (electronic) LET TER TO THE EDITOR  Re: Pierce et  al. Diacetyl and 2,3-pentanedione exposures associated with cigarette smoking: implications for risk assessment of food and fl avoring workers Crit Rev Toxicol, 2014; 44(5):420 – 435  Microwave popcorn production workers and smoking  Muge  Akpinar-Elci 1  and  Omur Cinar  Elci 2  1 Center for Global Health, College of Health Sciences, Old Dominion University, Norfolk, VA, USA and  2 Department of Public Health and Preventive Medicine, School of Medicine, St. George ’ s University, WI, Grenada Crit Rev Toxicol, 2014; 44(7): 638–639© 2014 Informa Healthcare USA, Inc. DOI: 10.3109/10408444.2014.930092Letter to the Editor 639DOI 10.3109/10408444.2014.930092among various symptoms or worker characteristics and high sputum cell counts. In this study, absolute neutrophil counts were higher in nonsmoking popcorn production workers com-pared to a nonsmoking healthy external control group. Even after controlling for smoking, the relationship between high exposure to fl avoring agents and neutrophilic infl ammation remained signifi cant.  Therefore, it is important to note that:  Eight of nine sentinel cases and a signifi cant portion 1. of workers who participated in our studies were non-smokers.  All of our analyses have been carefully controlled for 2. confounds with age, gender, and smoking.  Besides all these observations, nonsmoker workers dem-3. onstrated cyto-pathological changes, which are signs and symptoms of a suspected occupational exposure to butter fl avoring agents.  We would have expected Pierce et  al. to have reviewed our observations more carefully and to have noted our fi ndings that strongly indicate a relationship between occupational butter fl avoring exposure and respiratory diseases among popcorn production workers. When we conducted our research, we adhered to basic ethical principles that dic-tate objectivity and fairness in evaluating the scientifi c evidence. These principles have been summarized in the Hippocratic Oath as  “ primum non nocere ” :  “ First, do no harm ” . We believe that failing to practice this oath raises questions regarding the validity of scientifi c conclusions. We are aware that the conclusions that we published might have a signifi cant impact on human health, which we all aim to protect.  Declaration of interest  Neither author ever off ered testimony during any regula-tory proceeding concerning fl avoring agents nor was an expert witness in any related litigation. Each author com-pleted research on fl avoring during his/her employment at The National Institute for Occupational Safety and Health (NIOSH). The authors have sole responsibility for this letter. They do not have any confl icts of interest to declare.  References  Akpinar-Elci  M ,  Travis  WD ,  Lynch  DA ,  Kreiss  K .  (2004) .  Bronchiolitis obliterans syndrome in popcorn production plant workers .  Eur Respir J , 24 ,  298 – 302 .  Akpinar-Elci  M ,  Stemple  KJ ,  Enright  P ,  Fahy  JV ,  Bledsoe  TA ,  Kreiss  K ,  Weissman  DN .  (2005) .  Induced sputum evaluation in microwave popcorn production workers .  Chest ,  128 ,  991 – 7 .  Akpinar-Elci  M ,  Stemple  KJ ,  Elci  OC ,  Dweik  RA ,  Kreiss  K ,  Enright  P .  (2006) .  Exhaled nitric oxide measurement in microwave popcorn production plant workers .  Int J Occup Environ Health ,  12 ,  106 – 10 .  Chatkin  JM ,  Ansarin  K ,  Silkoff   PE ,  McClean  P ,  Gutierrez  C ,  Zamel  N ,  Chapman  KR .  (1999) .  Exhaled nitric oxide as a noninvasive assessment of chronic cough .  Am J Respir Crit Care Med ,  159 ,  1810 – 3 .  Clini  E ,  Bianchi  L ,  Vitacca  M ,  Porta  R ,  Foglio  K ,  Ambrosino  N .  (2000) .  Exhaled nitric oxide and exercise in stable COPD patients .  Chest ,  117 ,  702 – 7 .  Kharitonov  SA ,  Barnes  PJ .  (2001) .  Exhaled markers of pulmonary disease .  Am J Respir Crit Care Med ,  163 ,  1693 – 722 .  Kim  JY ,  Hauser  R ,  Wand  MP ,  Herrick  RF ,  Amarasiriwardena  CJ ,  Christiani  DC .  (2003a) .  The association of expired nitric oxide with occupational particulate metal exposure .  Environ Res ,  93 ,  158 – 66 .  Kim  JY ,  Wand  MP ,  Hauser  R ,  Mukherjee  S ,  Herrick  RF ,  Christiani  DC .  (2003b) .  Association of expired nitric oxide with occupational particulate exposure .  Environ Health Perspect ,  111 ,  676 – 80 .  Pierce  JS ,  Abelmann  A ,  Spicer  JL ,  Adams  RE ,  Finley  B .  (2014) .  Diacetyl and 2,3-pentanedione exposures associated with cigarette smoking: implications for risk assessment of food and fl avoring workers .  Crit Rev Toxicol ,  44 ,  420 – 35 . 

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, 2014; 44(5): 420-435

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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, 2014; 44(5): 420-435

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