Popcorn lung and bronchiolitis obliterans: a critical appraisal

  • David Galbraith
  • David Weill
Short Communication



To perform a critical review of a series of journal articles and Health Hazard Evaluation Reports (HHER) by the National Institute for Occupational Safety and Health (NIOSH), where they have described the incidence of fixed obstructive pulmonary disease in a population of workers exposed to butter flavorings.


The clinical presentations, diagnostic modalities frequently employed and a review of the pertinent clinical literature are discussed for constrictive bronchiolitis and bronchiolitis obliterans with intraluminal polyps; two distinct forms of bronchiolitis obliterans (BO). An analysis of the NIOSH reports and scientific articles is provided, followed by suggestions for evaluating this public and occupational health concern moving forward.


Cases of lung disease in the food flavorings industry discussed in the literature have not been sufficiently documented to allow the conclusion that BO has been caused by diacetyl or butter flavoring. Further research is required to establish the causative agent(s).


The diagnosis of bronchiolitis obliterans should be reserved for those individuals who have diagnostic lung biopsy findings, obtained and interpreted by clinicians who are experienced with this complex disorder.


Bronchiolitis obliterans Butter flavoring Diacetyl Lung biopsy Popcorn lung 



American Thoracic Society


Bronchiolitis obliterans


Bronchiolitis obliterans organizing pneumonia


Bronchiolitis obliterans syndrome


Constrictive bronchiolitis


Centers for Disease Control and Prevention


California Department of Health Services


Cryptogenic organizing pneumonia


Chronic obstructive pulmonary disease


European Respiratory Society


Forced expiratory volume in one-second


Forced vital capacity


Health hazard evaluation report


High resolution computed tomography


International Society for Heart and Lung Transplant


National Health and Nutrition Examination Survey


National Institute of Occupational Safety and Health


Pulmonary function testing


Reactive airways dysfunction syndrome


Video-assisted thoracoscopic surgery



We would like to thank Dr. Mark Burton of the Jackson Pathology Group, affiliated with Jackson-Madison County General Hospital in Jackson, TN for his helpful suggestions during the drafting of this manuscript. Support for Dr. Galbraith’s time spent during the drafting of this manuscript was provided by his employer (ChemRisk) which received no funding to prepare this manuscript. Dr. Weill has not been compensated for his time.


  1. Akpinar-Elci M, Travis WD, Lynch DA et al (2004) Bronchiolitis obliterans syndrome in popcorn production plant workers. Eur Respir J 24:298–302PubMedCrossRefGoogle Scholar
  2. Akpinar-Elci M, Stemple KJ, Enright PL et al (2005) Induced sputum evaluation in microwave popcorn production workers. Chest 128:991–997PubMedCrossRefGoogle Scholar
  3. Akpinar-Elci M, Stemple KJ, Cinar-Elci O et al (2006) Exhaled nitric oxide measurement in workers in a microwave popcorn production plant. Int J Occup Environ Health 12:106–110PubMedGoogle Scholar
  4. Alleman T, Darcey DJ (2002) Case report: bronchiolitis obliterans organizing pneumonia in a spice process technician. Am Coll Occup Environ Med 44(3):215–216CrossRefGoogle Scholar
  5. Bergeron C, Boulet LP (2006) Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest 129:1068–1087PubMedCrossRefGoogle Scholar
  6. Bourke SJ, Dalphin JC, Boyd G et al (2001) Hypersensitivity pneumonitis: current concepts. Eur Respir J 18(Suppl 32):81–92Google Scholar
  7. Boylstein R, Piacitelli C, Grote A et al (2006) Diacetyl emissions and airborne dust from butter flavorings used in microwave popcorn production. J Occup Environ Hyg 3:530–535PubMedCrossRefGoogle Scholar
  8. Chan A, Allen R (2004) Bronchiolitis obliterans: an update. Curr Opin Pulm Med 10:133–141PubMedCrossRefGoogle Scholar
  9. Colby TV (1998) Bronchiolitis: pathologic considerations. Am J Clin Pathol 109:101–109PubMedGoogle Scholar
  10. Colby TV (2000) Surgical pathology of non-neoplastic lung disease. Mod Pathol 13(3):343–358PubMedCrossRefGoogle Scholar
  11. Colby TV, Myers JL (1992) Clinical and histologic spectrum of bronchiolitis obliterans, including bronchiolitis obliterans organizing pneumonia. Semin Respir Med. 13:119–133CrossRefGoogle Scholar
  12. Cordier JF (2002) Update on cryptogenic organising pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia). Swiss Med Wkly 132:588–591PubMedGoogle Scholar
  13. Cordier JF (2007) Challenges in pulmonary fibrosis—2: Bronchiolocentric fibrosis. Thorax 62(7):638–649PubMedCrossRefGoogle Scholar
  14. Epler GR (1995) Bronchiolitis obliterans organizing pneumonia. Sem Res Inf 10(2):65–77Google Scholar
  15. Epler GR (2001) Bronchiolitis obliterans organizing pneumonia. Arch Intern Med 161:158–164PubMedCrossRefGoogle Scholar
  16. Epler GR, Colby TV (1983) The spectrum of bronchiolitis obliterans. Chest 83(2):161–162PubMedCrossRefGoogle Scholar
  17. Epler GR, Colby TV, McLoud TC et al (1985) Bronchiolitis obliterans organizing pneumonia. N Engl J Med 312:152–158PubMedGoogle Scholar
  18. Estenne M, Maurer JR, Boehler A et al (2002) Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant 21:297–310PubMedCrossRefGoogle Scholar
  19. Fedan JS, Dowdy JA, Fedan KB et al (2006) Popcorn worker’s lung: in vitro exposure to diacetyl, an ingredient in microwave popcorn butter flavoring, increases reactivity to methacholine. Toxicol Appl Pharmacol (in press)Google Scholar
  20. Gaga M (2004) Fixed obstruction in severe asthma: not just a matter of time. Eur Respir J 24:8–10PubMedCrossRefGoogle Scholar
  21. Garg K, Lynch DA, Newell JD et al (1994) Proliferative and constrictive bronchiolitis: classification and radiologic features. Am J Radiol 162:803–808Google Scholar
  22. Gosink BB, Friedman PJ, Liebow AA (1973) Bronchiolitis obliterans: roentgenologic–pathologic correlation. Am J Roentgenol Radium Ther Nucl Med 117(4):816–832PubMedGoogle Scholar
  23. Hachem RR, Trulock EP (2004) Bronchiolitis obliterans syndrome: pathogenesis and management. Semin Thorac Cardiovasc Surg 16:350–355PubMedCrossRefGoogle Scholar
  24. Hansell DM (2001) Small airways diseases: detection and insights with computed tomography. Eur Respir J 17:1294–1313PubMedCrossRefGoogle Scholar
  25. Hansell DM, Rubens MB, Padley SPG et al (1997) Obliterative bronchiolitis: individual CT signs of small airways disease and functional correlation. Radiology 203:721–726PubMedGoogle Scholar
  26. Harrison R, Gelb A, Harber P (2006) Food flavoring workers with bronchiolitis obliterans following exposure to diacetyl—California. California Department of Health, May 15, 2006. Available at:
  27. Hayakawa H, Shirai M, Sato A et al (2002) Clinicopathological features of chronic hypersensitivity pneumonitis. Respirology 7:359–364PubMedCrossRefGoogle Scholar
  28. Hubbs AF, Battelli LA, Goldsmith WT et al (2002) Necrosis of nasal and airway epithelium in rats inhaling vapors of artificial butter flavoring. Toxicol Appl Pharmacol 185:128–135PubMedCrossRefGoogle Scholar
  29. Hubbs AF, Battelli LA, Mercer RR et al (2004) Inhalation toxicity of the flavoring agent, diacetyl (2,3-butanedione), in the upper respiratory tract of rats (Meeting abstract). Toxicol Sci 78(S1):438–439Google Scholar
  30. Janigan DT, Kilp T, Michael R et al (1997) Bronchiolitis obliterans in a man who used his wood-burning stove to burn synthetic construction materials. Can Med Assoc J 156:1171–1173Google Scholar
  31. Jensen SP, Lynch DA, Brown KK et al (2002) High resolution CT features of severe asthma and bronchiolitis obliterans. Clin Radiol 57:1078–1085PubMedCrossRefGoogle Scholar
  32. Kanwal R, Kullman G, Piacitelli C et al (2006) Evaluation of flavorings-related lung disease risk at six microwave popcorn plants. J Occup Environ Med 48(2):149–157PubMedCrossRefGoogle Scholar
  33. Khan MF, Kaphalia BS, Palafox A et al (1991) Heated linoleic acid anilide: toxicity and relevance to toxic oil syndrome. Toxicology 68:143–155PubMedCrossRefGoogle Scholar
  34. Kraft M, Mortenson RL, Colby TV et al (1993) Cryptogenic constrictive bronchiolitis: a clinicopathologic study. Am Rev Respir Dis 148:1093–1101PubMedGoogle Scholar
  35. Kreiss K, Gomaa A, Kullman G et al (2002) Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med 347(5):330–338PubMedCrossRefGoogle Scholar
  36. Lange W (1901) Uber eine eigenthumliche Erkrankung der kleinen Bronchien und Bronchiolen (Bronchitis et Bronchiolitis obliterans.). Dtsch Arch Klin Med 70:342–364Google Scholar
  37. Laohaburanakit P, Chan A, Allen RP (2003) Bronchiolitis obliterans. Clin Rev Allergy Immunol 25:259–274PubMedCrossRefGoogle Scholar
  38. Li X, Botts S, Morton D et al (2006) Oleic acid-associated bronchiolitis obliterans-organizing pneumonia in beagle dogs. Vet Pathol 43:183–185PubMedCrossRefGoogle Scholar
  39. Lynch DA (1993) Imaging of small airway diseases. Clin Chest Med 14:655–666Google Scholar
  40. Markopoulou KD, Cool CD, Elliot TL et al (2002) Obliterative bronchiolitis: varying presentations and clinicopathological correlation. Eur Respir J 19:20–30CrossRefGoogle Scholar
  41. Mobed K, Gold EB, Schenker MB (1992) Occupational health problems among migrant and seasonal farm workers. West J Med 157(3):367–373PubMedGoogle Scholar
  42. Muller NL, Miller RR (1995) Diseases of the bronchioles: CT and histopathologic findings. Radiology 196:3–12PubMedGoogle Scholar
  43. National Center for Health Statistics Analytic and reporting guidelines: the National Health and Nutrition Examination Survey. Centers for Disease Control, Washington DC, last updated December, 2005. Available at:
  44. Parmet AJ, Von Essen S (2002) Rapidly progressive, fixed airway obstructive disease in popcorn workers: a new occupational illness? J Occup Environ Med 44(3):216–218PubMedCrossRefGoogle Scholar
  45. NIOSH (2003a) Hazard Evaluation and Technical Assistance Report: Agrilink Foods Popcorn Plant, Ridgway, Illinois. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Publication #2002-0408-2915Google Scholar
  46. NIOSH (2003b) Hazard Evaluation and Technical Assistance Report: Nebraska Popcorn Corporation, Clearwater, Nebraska. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Publication #2002-0089Google Scholar
  47. NIOSH (2003c) Hazard Evaluation and Technical Assistance Report: B·K. Heuermann Popcorn Inc., Phillips, Nebraska. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Publication #2001-0517Google Scholar
  48. NIOSH (2003d) Aerosol Program Assessment Committee Report; April 7, 2003. Available at:
  49. NIOSH (2004a) Hazard Evaluation and Technical Assistance Report: American Popcorn Company, Sioux City, Iowa. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Publication #2001-0474-2943Google Scholar
  50. NIOSH (2004b) Hazard Evaluation and Technical Assistance Report: ConAgra Snack Foods, Marion, Ohio. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Publication #2003-0112-2949Google Scholar
  51. NIOSH (2006) Hazard Evaluation and Technical Assistance Report: Gilster-Mary Lee Corporation, Jasper, Missouri. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, NIOSH Publication #2000-0401-2991Google Scholar
  52. Paradis I (1998) Bronchiolitis obliterans: pathogenesis, prevention and management. S Soc Clin Inv 315(3):161–178Google Scholar
  53. Research Institute for Fragrance Materials (2006) Flavor or fragrance ingredient data sheet: diacetyl. CAS registry number 431-03-8. Available at:
  54. Roggli VL, Chiang A (1996) Constrictive bronchiolitis obliterans in Sauropus androgynus poisoning. J Toxicol Clin Toxicol 34(5):525–528PubMedCrossRefGoogle Scholar
  55. Ryu JH, Myers JL, Swensen SJ (2003) Bronchioloar disorders. Am J Respir Crit Care Med 168:1277–1292PubMedCrossRefGoogle Scholar
  56. Schenker MB (2005) Farming and asthma. Occup Environ Med 62:211–212PubMedCrossRefGoogle Scholar
  57. Sharma V, Shaaban AM, Berges G et al (2002) The radiological spectrum of small-airway diseases. Semin Ultrasound CT MR 23(4):339–351PubMedCrossRefGoogle Scholar
  58. Stern EJ, Swensen SJ, Hartman TE et al (1995) CT mosaic pattern of lung attenuation: distinguishing different causes. Am J Rad 165:813–816Google Scholar
  59. Turton CW, Williams G, Green M (1981) Cryptogenic obliterative bronchiolitis in adults. Thorax 36:805–810PubMedCrossRefGoogle Scholar
  60. Valentine VG, Robbins RC, Berry GJ et al (1996) Actuarial survival of heart-lung and bilateral sequential lung transplant recipients with obliterative bronchiolitis. J Heart Lung Transplant 15:371–383PubMedGoogle Scholar
  61. Verschakelen JA, Scheinbaum K, Bogaert AJ et al (1998) Expiratory CT in cigarette smokers: correlation between areas of decreased lung attenuation, pulmonary function tests and smoking history. Eur Radiol 8:1391–1399PubMedCrossRefGoogle Scholar
  62. Verleden GM, Dupont LJ, Van Raemdonck DE (2005) Is it bronchiolitis obliterans syndrome or is it chronic rejection: a reappraisal? Eur Respir J 25:221–224PubMedCrossRefGoogle Scholar
  63. Waitches GM, Stern EJ (2002) High resolution CT of peripheral airways diseases. Rad Clin N Am 40(1):21–29CrossRefGoogle Scholar
  64. Worthy SA, Muller NL, Hartman TE et al (1997) Mosaic attenuation pattern on thin-section CT scans of the lung: differentiation among infiltrative lung, airway and vascular diseases as a cause. Radiology 205:465–470PubMedGoogle Scholar
  65. Wright JL (1993) Inhalational lung injury causing bronchiolitis. Clin Chest Med 14(4):635–644PubMedGoogle Scholar
  66. Wright JL, Cagle P, Churg A et al (1992) State of the art: diseases of the small airways. Am Rev Respir Dis 146:240–262PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.ChemRisk, IncSan FranciscoUSA
  2. 2.Palo Alto Medical FoundationPalo AltoUSA
  3. 3.Division of Pulmonary and Critical Care MedicineStanford University Medical CenterStanfordUSA

Personalised recommendations