Bronchiolitis obliterans syndrome in chemical workers producing diacetyl for food flavorings

Am J Respir Crit Care Med. 2007 Sep 1;176(5):498-504. doi: 10.1164/rccm.200611-1620OC. Epub 2007 May 31.


Rationale: Workers in microwave popcorn plants are at risk of developing bronchiolitis obliterans associated with exposure to butter flavoring volatiles, including diacetyl.

Objectives: To investigate the risk of bronchiolitis obliterans for chemical workers producing diacetyl, with exposure to less complex mixtures of chemicals.

Methods: We interviewed and conducted spirometry on 175 of 196 workers from a chemical production plant that produced diacetyl between 1960 and 2003. We used all available historical exposure data to classify all workers into three exposure groups with varying exposure profiles to diacetyl, based on frequency and level of exposure.

Measurements and main results: Workers with fixed airway obstruction underwent further pulmonary function testing (including diffusing capacity and lung volumes) and paired inspiratory and expiratory high-resolution computed tomography studies. We identified three cases consistent with bronchiolitis obliterans syndrome with air trapping on high-resolution computed tomography of the lungs, in the highest exposure group of 102 process operators. Two of these cases were lifelong nonsmokers. Potential exposures included acetoin, diacetyl, acetaldehyde, and acetic acid, with diacetyl exposures in the range previously reported to be associated with fixed airway obstruction in the microwave popcorn industry.

Conclusions: Exposure to an agent during diacetyl production appears to be responsible for causing bronchiolitis obliterans syndrome in chemical process operators, consistent with the suspected role of diacetyl in downstream food production.

MeSH terms

  • Adult
  • Aged
  • Air Pollutants, Occupational / adverse effects*
  • Bronchiolitis Obliterans / chemically induced
  • Bronchiolitis Obliterans / epidemiology*
  • Bronchiolitis Obliterans / pathology
  • Diacetyl / adverse effects*
  • Female
  • Food Industry*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Netherlands
  • Occupational Exposure / analysis
  • Risk
  • Spirometry
  • Tomography, X-Ray Computed


  • Air Pollutants, Occupational
  • Diacetyl