Previous descriptions of these microwave popcorn company workers documented cases of lung disease consistent with bronchiolitis obliterans, excessive spirometric obstruction, accelerated decline in FEV1
during employment, and diacetyl exposure-related health outcomes
. This mortality study now suggests that these workers experience an increase in COPD-associated deaths, compared to the U.S. population. Overall mortality was not statistically different from that predicted for the age, gender, and ethnic distribution of the worker cohort, which remains young with a median age of about 52 after about 11 years of mortality follow up.
Workers with an abnormal spirometric result ranged across the cohort from 12.3% in subcohort 2 to 33.5% in the former worker group of subcohort 1. This trend mirrors the average diacetyl exposure experienced in each group, with subcohort 2 workers experiencing the lowest average exposure, followed by current workers from 2000, and former workers.
Current workers from 2000 and 2001–2003 reported respiratory symptoms at lower rates compared to former workers. A majority of former workers reported being troubled by shortness of breath on exertion and usual cough. The rates for respiratory symptoms experienced by former workers and current workers tested in 2000 were higher than rates of abnormal spirometry results for these same groups. This trend has also been documented in biopsy-confirmed case series among mustard gas-exposed patients from the Iran-Iraq war, some U.S. soldiers returning from Iraq and Afghanistan, and other case series where many patients have normal spirometric results but report respiratory symptoms
An excess of COPD-associated mortality was found among the entire cohort and specifically among subcohort 1, which experienced higher exposure to diacetyl before the company introduced interventions. COPD decedents had somewhat shorter median tenure, lower cumulative diacetyl exposure and lower average diacetyl exposure compared to non-COPD decedents, but the combined decedent values were much higher than non-decedents. Diacetyl-associated lung function impairment has a short latency, and affected workers may drop out of the workforce before accumulating substantial cumulative exposure. The risk for bronchiolitis obliterans may be associated with short-term peak exposures to butter flavorings
, and average exposures may be more pertinent to risk than cumulative exposures. Perhaps, for these reasons, we did not find exposure-response relationships for COPD mortality among the decedents. However, criteria for a causal association of diacetyl with respiratory disease have been met in the body of scientific work in exposed workers and animal experiments
Finally, the COPD decedents who were tested had abnormal spirometry results, which have previously been associated with diacetyl exposure
. Additionally, even though rates of ever smoking in this cohort were higher (p
<0.0001) than the U.S. average during a similar time period (U.S. ever smoking prevalence was 45.6% in 1999–2001 and 43.3% in 2002–2004)
, two COPD decedents had never smoked, eliminating the most common cause of COPD mortality. These findings suggest that limiting diacetyl exposure might reduce COPD-associated mortality, supporting efforts to establish a recommended exposure limit.
Because only 38% of former workers participated in spirometry, we are unclear how representative our findings are of all workers who were employed prior to November 2000. Increased symptom rates, well out of proportion to their prevalences of ever-smoking, which were not statistically different, may have motivated the former workers' participation in NIOSH medical testing and may not have reflected the health of all former workers, the majority of whom could not be located or identified. We do not have information about participants' jobs or exposures following the 2000–2003 surveys. We are missing the underlying and contributing causes of death for one decedent outside of Missouri, and did not pursue locating the state holding the death certificate through the National Death Index. This decedent was a current worker in subcohort 1 and had reversible mild airway obstruction in 2000. Long-term follow up of this cohort using the National Death Index, which provides more complete but less timely death registration, will be necessary to improve estimates of excess COPD deaths.
Bronchiolitis obliterans is not recognized in the ICD-10 classification system, potentially resulting in misclassification of causes of death. Additionally, previous epidemiologic studies of this cohort describe workers with airways obstruction receiving physician diagnoses of chronic bronchitis and asthma prior to 2000
. U.S. mortality rates for NIOSH cause of death category Minor 66 ‘Chronic Obstructive Pulmonary Disease' (ICD-10 codes J40–J44) and/or ICD-10 code J44 specifically, may underestimate causes of deaths potentially related to occupational flavoring exposure, as well as include obstructive causes of respiratory death unlikely to be related to workplace exposures. However, no decedent had asthma as a multiple or underlying cause of death, suggesting that prior misclassification of diagnoses did not result in an underestimate of deaths that may have reflected occupational disease.
End stage bronchiolitis obliterans was written as the underlying cause of death of one decedent who was also one of the eight sentinel cases that brought bronchiolitis obliterans to public health attention. The physician of the other sentinel case decedent listed lung damage and COPD related to exposures to flavoring in the microwave popcorn production plant as contributing causes of death. Therefore, it is unclear if COPD (ICD-10 codes J40–J44), specifically ‘other chronic obstructive pulmonary disease’ (J44), accurately captures bronchiolitis obliterans mortality, and autopsy studies were not available to evaluate misclassification of causes of death.
Despite these limitations, our finding of excess standardized respiratory mortality, coded as COPD, documents that flavoring-related lung disease has potentially changed the causes of death in this comparatively young worker cohort, despite about one third of workers having left employment before enrollment or during follow-up. This is consistent with reports of many having been placed on lung transplant lists because of the severity of their physiologic abnormality 
although none of the cohort is known to have undergone lung transplant. Long-term follow up of this cohort will more accurately reflect the ultimate burden of respiratory disease, cardiovascular disease associated with abnormal spirometry, and overall mortality.
The 11-year respiratory mortality excess in this microwave popcorn worker cohort underscores the importance of controlling inhaled butter flavoring exposures in food and flavoring production. Certainly, subcohort 2 was spared COPD mortality to date, but previous characterization of the newly-hired members of the cohort documented some excessive decline in FEV1
on serial testing
that, if continued, will result in spirometric abnormality. Despite short tenures at the time of the 2000–2003 surveys, average exposures remained about two orders of magnitude above NIOSH's recommended exposure limit for diacetyl, with a median time weighted average exposure of 1.89 ppm, nearly three orders of magnitude over the proposed exposure limit
. Follow-up characterization of exposures in subcohort 2 may be advantageous in interpreting future mortality findings of these less-exposed workers in the cohort.