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Popcorn lung and bronchiolitis obliterans: a critical appraisal

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Abstract

Purpose

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.

Methods

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.

Findings

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).

Conclusion

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.

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Notes

  1. Although mixers at the Agrilink plant were exposed to 30 times less butter flavoring than was measured at Gilster, and there were only one-third the number of workers at the plant, the authors claimed to have generated just as many suspected cases of BO as Gilster (ten at Agrilink and nine at Gilster-Mary Lee) and even reported on more lung biopsies (six compared to three) (Kanwal et al. 2006). All of those initially biopsied at Agrilink were smokers, and only one of the biopsies was reported to show signs of constrictive bronchiolitis, and not one of the pathology reports was described (NIOSH 2003a). Combining this with the cases identified through the questionable spirometry data and other noninvasive studies, NIOSH claimed a total of ten workers “may have bronchiolitis obliterans” out of 41 studied (NIOSH 2003a).

  2. The findings have an associated P value of 0.8; that is, there is an 80% probability that the data could have occurred by chance.

  3. Examples include extrinsic allergic alveolitis, nonspecific interstitial pneumonia, follicular bronchiolitis and lymphocytic interstitial pneumonia.

Abbreviations

ATS:

American Thoracic Society

BO:

Bronchiolitis obliterans

BOOP:

Bronchiolitis obliterans organizing pneumonia

BOS:

Bronchiolitis obliterans syndrome

CB:

Constrictive bronchiolitis

CDC:

Centers for Disease Control and Prevention

CDHS:

California Department of Health Services

COP:

Cryptogenic organizing pneumonia

COPD:

Chronic obstructive pulmonary disease

ERS:

European Respiratory Society

FEV1:

Forced expiratory volume in one-second

FVC:

Forced vital capacity

HHER:

Health hazard evaluation report

HRCT:

High resolution computed tomography

ISHLT:

International Society for Heart and Lung Transplant

NHANES:

National Health and Nutrition Examination Survey

NIOSH:

National Institute of Occupational Safety and Health

PFT:

Pulmonary function testing

RADS:

Reactive airways dysfunction syndrome

VATS:

Video-assisted thoracoscopic surgery

References

  • Akpinar-Elci M, Travis WD, Lynch DA et al (2004) Bronchiolitis obliterans syndrome in popcorn production plant workers. Eur Respir J 24:298–302

    Article  PubMed  CAS  Google Scholar 

  • Akpinar-Elci M, Stemple KJ, Enright PL et al (2005) Induced sputum evaluation in microwave popcorn production workers. Chest 128:991–997

    Article  PubMed  Google Scholar 

  • 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 12:106–110

    PubMed  CAS  Google Scholar 

  • Alleman T, Darcey DJ (2002) Case report: bronchiolitis obliterans organizing pneumonia in a spice process technician. Am Coll Occup Environ Med 44(3):215–216

    Article  Google Scholar 

  • Bergeron C, Boulet LP (2006) Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest 129:1068–1087

    Article  PubMed  CAS  Google Scholar 

  • Bourke SJ, Dalphin JC, Boyd G et al (2001) Hypersensitivity pneumonitis: current concepts. Eur Respir J 18(Suppl 32):81–92

    Google Scholar 

  • 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 3:530–535

    Article  PubMed  CAS  Google Scholar 

  • Chan A, Allen R (2004) Bronchiolitis obliterans: an update. Curr Opin Pulm Med 10:133–141

    Article  PubMed  Google Scholar 

  • Colby TV (1998) Bronchiolitis: pathologic considerations. Am J Clin Pathol 109:101–109

    PubMed  CAS  Google Scholar 

  • Colby TV (2000) Surgical pathology of non-neoplastic lung disease. Mod Pathol 13(3):343–358

    Article  PubMed  CAS  Google Scholar 

  • Colby TV, Myers JL (1992) Clinical and histologic spectrum of bronchiolitis obliterans, including bronchiolitis obliterans organizing pneumonia. Semin Respir Med. 13:119–133

    Article  Google Scholar 

  • Cordier JF (2002) Update on cryptogenic organising pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia). Swiss Med Wkly 132:588–591

    PubMed  Google Scholar 

  • Cordier JF (2007) Challenges in pulmonary fibrosis—2: Bronchiolocentric fibrosis. Thorax 62(7):638–649

    Article  PubMed  Google Scholar 

  • Epler GR (1995) Bronchiolitis obliterans organizing pneumonia. Sem Res Inf 10(2):65–77

    CAS  Google Scholar 

  • Epler GR (2001) Bronchiolitis obliterans organizing pneumonia. Arch Intern Med 161:158–164

    Article  PubMed  CAS  Google Scholar 

  • Epler GR, Colby TV (1983) The spectrum of bronchiolitis obliterans. Chest 83(2):161–162

    Article  PubMed  CAS  Google Scholar 

  • Epler GR, Colby TV, McLoud TC et al (1985) Bronchiolitis obliterans organizing pneumonia. N Engl J Med 312:152–158

    PubMed  CAS  Google Scholar 

  • Estenne M, Maurer JR, Boehler A et al (2002) Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant 21:297–310

    Article  PubMed  Google Scholar 

  • 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)

  • Gaga M (2004) Fixed obstruction in severe asthma: not just a matter of time. Eur Respir J 24:8–10

    Article  PubMed  CAS  Google Scholar 

  • Garg K, Lynch DA, Newell JD et al (1994) Proliferative and constrictive bronchiolitis: classification and radiologic features. Am J Radiol 162:803–808

    CAS  Google Scholar 

  • Gosink BB, Friedman PJ, Liebow AA (1973) Bronchiolitis obliterans: roentgenologic–pathologic correlation. Am J Roentgenol Radium Ther Nucl Med 117(4):816–832

    PubMed  CAS  Google Scholar 

  • Hachem RR, Trulock EP (2004) Bronchiolitis obliterans syndrome: pathogenesis and management. Semin Thorac Cardiovasc Surg 16:350–355

    Article  PubMed  Google Scholar 

  • Hansell DM (2001) Small airways diseases: detection and insights with computed tomography. Eur Respir J 17:1294–1313

    Article  PubMed  CAS  Google Scholar 

  • Hansell DM, Rubens MB, Padley SPG et al (1997) Obliterative bronchiolitis: individual CT signs of small airways disease and functional correlation. Radiology 203:721–726

    PubMed  CAS  Google Scholar 

  • 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: http://www.capanet.org/pdfs/BO_cases_%20final_5_16_06.pdf

  • Hayakawa H, Shirai M, Sato A et al (2002) Clinicopathological features of chronic hypersensitivity pneumonitis. Respirology 7:359–364

    Article  PubMed  Google Scholar 

  • 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 185:128–135

    Article  PubMed  CAS  Google Scholar 

  • 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):438–439

    Google Scholar 

  • 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 156:1171–1173

    CAS  Google Scholar 

  • Jensen SP, Lynch DA, Brown KK et al (2002) High resolution CT features of severe asthma and bronchiolitis obliterans. Clin Radiol 57:1078–1085

    Article  PubMed  CAS  Google Scholar 

  • 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):149–157

    Article  PubMed  CAS  Google Scholar 

  • Khan MF, Kaphalia BS, Palafox A et al (1991) Heated linoleic acid anilide: toxicity and relevance to toxic oil syndrome. Toxicology 68:143–155

    Article  PubMed  CAS  Google Scholar 

  • Kraft M, Mortenson RL, Colby TV et al (1993) Cryptogenic constrictive bronchiolitis: a clinicopathologic study. Am Rev Respir Dis 148:1093–1101

    PubMed  CAS  Google Scholar 

  • 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):330–338

    Article  PubMed  Google Scholar 

  • Lange W (1901) Uber eine eigenthumliche Erkrankung der kleinen Bronchien und Bronchiolen (Bronchitis et Bronchiolitis obliterans.). Dtsch Arch Klin Med 70:342–364

    Google Scholar 

  • Laohaburanakit P, Chan A, Allen RP (2003) Bronchiolitis obliterans. Clin Rev Allergy Immunol 25:259–274

    Article  PubMed  Google Scholar 

  • Li X, Botts S, Morton D et al (2006) Oleic acid-associated bronchiolitis obliterans-organizing pneumonia in beagle dogs. Vet Pathol 43:183–185

    Article  PubMed  Google Scholar 

  • Lynch DA (1993) Imaging of small airway diseases. Clin Chest Med 14:655–666

    Google Scholar 

  • Markopoulou KD, Cool CD, Elliot TL et al (2002) Obliterative bronchiolitis: varying presentations and clinicopathological correlation. Eur Respir J 19:20–30

    Article  Google Scholar 

  • Mobed K, Gold EB, Schenker MB (1992) Occupational health problems among migrant and seasonal farm workers. West J Med 157(3):367–373

    PubMed  CAS  Google Scholar 

  • Muller NL, Miller RR (1995) Diseases of the bronchioles: CT and histopathologic findings. Radiology 196:3–12

    PubMed  CAS  Google Scholar 

  • 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: http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/nhanes_analytic_guidelines_dec_2005.pdf

  • 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):216–218

    Article  PubMed  CAS  Google Scholar 

  • 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 #2002-0408-2915

  • 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 #2002-0089

  • 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 #2001-0517

  • NIOSH (2003d) Aerosol Program Assessment Committee Report; April 7, 2003. Available at: http://www.cdc.gov/niosh/topics/aerosols/aerosols_gaps.html

  • 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 #2001-0474-2943

  • 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 #2003-0112-2949

  • 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 #2000-0401-2991

  • Paradis I (1998) Bronchiolitis obliterans: pathogenesis, prevention and management. S Soc Clin Inv 315(3):161–178

    CAS  Google Scholar 

  • Research Institute for Fragrance Materials (2006) Flavor or fragrance ingredient data sheet: diacetyl. CAS registry number 431-03-8. Available at: http://www.femaflavor.org/html/public/DiacetylFFIDS2006.pdf

  • Roggli VL, Chiang A (1996) Constrictive bronchiolitis obliterans in Sauropus androgynus poisoning. J Toxicol Clin Toxicol 34(5):525–528

    Article  PubMed  CAS  Google Scholar 

  • Ryu JH, Myers JL, Swensen SJ (2003) Bronchioloar disorders. Am J Respir Crit Care Med 168:1277–1292

    Article  PubMed  Google Scholar 

  • Schenker MB (2005) Farming and asthma. Occup Environ Med 62:211–212

    Article  PubMed  CAS  Google Scholar 

  • Sharma V, Shaaban AM, Berges G et al (2002) The radiological spectrum of small-airway diseases. Semin Ultrasound CT MR 23(4):339–351

    Article  PubMed  Google Scholar 

  • Stern EJ, Swensen SJ, Hartman TE et al (1995) CT mosaic pattern of lung attenuation: distinguishing different causes. Am J Rad 165:813–816

    CAS  Google Scholar 

  • Turton CW, Williams G, Green M (1981) Cryptogenic obliterative bronchiolitis in adults. Thorax 36:805–810

    Article  PubMed  CAS  Google Scholar 

  • 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 15:371–383

    PubMed  CAS  Google Scholar 

  • 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 8:1391–1399

    Article  PubMed  CAS  Google Scholar 

  • Verleden GM, Dupont LJ, Van Raemdonck DE (2005) Is it bronchiolitis obliterans syndrome or is it chronic rejection: a reappraisal? Eur Respir J 25:221–224

    Article  PubMed  CAS  Google Scholar 

  • Waitches GM, Stern EJ (2002) High resolution CT of peripheral airways diseases. Rad Clin N Am 40(1):21–29

    Article  Google Scholar 

  • 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 205:465–470

    PubMed  CAS  Google Scholar 

  • Wright JL (1993) Inhalational lung injury causing bronchiolitis. Clin Chest Med 14(4):635–644

    PubMed  CAS  Google Scholar 

  • Wright JL, Cagle P, Churg A et al (1992) State of the art: diseases of the small airways. Am Rev Respir Dis 146:240–262

    PubMed  CAS  Google Scholar 

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Acknowledgments

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.

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Correspondence to David Galbraith.

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Drs. Galbraith and Weill are consultants in litigation for companies that have produced butter flavorings and for companies that have been users of butter flavorings in their manufacturing processes where workers may have been exposed to flavorings. The research performed and opinions expressed are those of the authors.

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Galbraith, D., Weill, D. Popcorn lung and bronchiolitis obliterans: a critical appraisal. Int Arch Occup Environ Health 82, 407–416 (2009). https://doi.org/10.1007/s00420-008-0337-x

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