Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant

N Engl J Med. 2002 Aug 1;347(5):330-8. doi: 10.1056/NEJMoa020300.


Background: In May 2000, eight persons who had formerly worked at a microwave-popcorn production plant were reported to have severe bronchiolitis obliterans. No recognized cause was identified in the plant. Therefore, we medically evaluated current employees and assessed their occupational exposures.

Methods: Questionnaire responses and spirometric findings in participating workers were compared with data from the third National Health and Nutrition Examination Survey, after adjustment for age and smoking status. We evaluated the relation between exposures and health-related outcomes by analyzing the rates of symptoms and abnormalities according to current and cumulative exposure to diacetyl, the predominant ketone in artificial butter flavoring and in the air at the plant.

Results: Of the 135 current workers at the plant, 117 (87 percent) completed the questionnaire. These 117 workers had 2.6 times the expected rates of chronic cough and shortness of breath, according to comparisons with the national data, and twice the expected rates of physician-diagnosed asthma and chronic bronchitis. Overall, the workers had 3.3 times the expected rate of airway obstruction; those who had never smoked had 10.8 times the expected rate. Workers directly involved in the production of microwave popcorn had higher rates of shortness of breath on exertion and skin problems that had developed since they started work than workers in other parts of the plant. There was a strong relation between the quartile of estimated cumulative exposure to diacetyl and the frequency and extent of airway obstruction.

Conclusions: The excess rates of lung disease and lung-function abnormalities and the relation between exposure and outcomes in this working population indicate that they probably had occupational bronchiolitis obliterans caused by the inhalation of volatile butter-flavoring ingredients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bronchiolitis Obliterans / chemically induced*
  • Bronchiolitis Obliterans / epidemiology
  • Bronchiolitis Obliterans / physiopathology
  • Chronic Disease
  • Diacetyl / adverse effects*
  • Diacetyl / analysis
  • Female
  • Flavoring Agents / adverse effects*
  • Flavoring Agents / analysis
  • Food-Processing Industry*
  • Forced Expiratory Volume
  • Health Surveys
  • Humans
  • Male
  • Middle Aged
  • Occupational Diseases / chemically induced*
  • Occupational Diseases / epidemiology
  • Occupational Diseases / physiopathology
  • Occupational Exposure / adverse effects*
  • Occupational Exposure / analysis
  • Prevalence
  • Respiratory Sounds / etiology
  • Spirometry
  • Surveys and Questionnaires
  • Volatilization


  • Flavoring Agents
  • Diacetyl