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Bronchiolitis obliterans

bronchiolitis obliterans, bronchiolitis obliterans prognosis
Bronchiolitis obliterans BO, informally known as popcorn lung, is a disease that results in obstruction of the smallest airways of the lungs bronchioles due to inflammation1 Symptoms include a dry cough, shortness of breath, wheezing, and feeling tired1 These symptoms generally get worse over weeks to months It is not related to organizing pneumonia4

Causes include breathing in toxic fumes, respiratory infections, connective tissue disorder, or following a bone marrow or heart-lung transplant Symptoms may not occur until two to eight weeks following toxic exposure or infection The underlying mechanism involves inflammation that results in scar tissue formation Diagnosis is by CT scan, pulmonary function tests, or lung biopsy1 A chest X-ray is often normal4

While the disease is not reversible treatments can slow further worsening This may include the use of corticosteroids or immunosuppressive medication1 A lung transplant may be tried Outcomes are often poor with most people dying in months to years4

Bronchiolitis obliterans is rare in the general population It affects about 75% of people by ten years following a lung transplant and up to 10% of people who have received a bone marrow transplant from someone else The condition was first clearly described in 19814 Prior descriptions occurred as early as 19566


  • 1 Signs and symptoms
  • 2 Cause
    • 21 Industrial inhalants
    • 22 Diacetyl
    • 23 Burn pits
  • 3 Diagnosis
  • 4 Prevention
  • 5 Treatment
  • 6 See also
  • 7 References
  • 8 External links

Signs and symptomsedit

Bronchiolitis obliterans is a lung disease characterized by fixed airway obstruction Inflammation and scarring occur in the airways of the lung, resulting in severe shortness of breath and dry cough

FEV1 forced expiratory volume in 1 second should be above 80% of predicted values to be considered normal Bronchiolitis obliterans reduces this to between 16% and 21%

Symptoms include: dry cough, shortness of breath and wheezing

The symptoms can start gradually, or severe symptoms can occur suddenly78


Bronchiolitis obliterans has many possible causes, including: collagen vascular disease, transplant rejection in organ transplant patients, viral infection respiratory syncytial virus, adenovirus, HIV, cytomegalovirus, Stevens-Johnson Syndrome, Pneumocystis pneumonia, drug reaction, aspiration and complications of prematurity bronchopulmonary dysplasia, and exposure to toxic fumes, including: diacetyl, sulfur dioxide, nitrogen dioxide, ammonia, chlorine, thionyl chloride, methyl isocyanate, hydrogen fluoride, hydrogen bromide, hydrogen chloride, hydrogen sulfide, phosgene, polyamide-amine dyes, mustard gas and ozone It can also be present in patients with rheumatoid arthritis9 Certain orally administrated emergency medications, such as activated charcoal, have been known to cause it when aspirated10 Additionally, the disorder may be idiopathic without known cause111213

Industrial inhalantsedit

There are many industrial inhalants that are known to cause various types of bronchiolitis, including bronchiolitis obliterans14

Industrial workers who have presented with bronchiolitis:

  • nylon-flock workers13
  • workers who spray prints onto textiles with polyamide-amine dyes13
  • battery workers who are exposed to thionyl chloride fumes
  • workers at plants that use or manufacture flavorings, eg diacetyl butter-like flavoring 71315



Bronchiolitis obliterans may be caused by inhalation of airborne diacetyl, a chemical used to produce the artificial butter flavoring16 in many foods such as candy and microwave popcorn and occurring naturally in wines This first came to public attention when eight former employees of the Gilster-Mary Lee popcorn plant in Jasper, Missouri, developed bronchiolitis obliterans In 2000, the Missouri Department of Health called in the National Institute for Occupational Safety and Health to make a determination of the cause, and to recommend safety measures After surveying the plant and each patient's medical history, NIOSH recommended respiratory protection for all workers in microwave popcorn production Due to this event, bronchiolitis obliterans began to be referred to in the popular media as "popcorn lung" or "popcorn workers lung"17181920 It is also referred to as "flavorings-related lung disease"21

Bronchiolitis obliterans caused by diacetyl inhalation begins with a cough, wheezing and dyspnea shortness of breath, and usually progresses slowly, but severe symptoms can develop without warning Other symptoms that appear in some workers include fever, weight loss, and night sweats Symptoms do not change when workers are away from the workplace21 CT images show bronchial wall thickening and trapped air Non-smokers may be at higher risk for this form of bronchiolitis obliterans The Occupational Safety and Health Administration OSHA recommended that diacetyl manufacturing companies regularly sample air in work environments, provide air purifying respirators, and engage in medical surveillance of at-risk workers In 2011, National Institute for Occupational Safety and Health proposed a recommended short-term exposure limit of 25 parts per billion ppb and a time weighted average exposure of 5 ppb20

In 2007 a heavy consumer of microwaved popcorn was diagnosed by a doctor in Denver with "popcorn lung," the first known case involving a consumer22 On 16 January 2008, it was announced that Wayne Watson, a Denver man who developed "popcorn lung" after inhaling fumes from microwaved popcorn, was suing the Kroger grocery store chain and its affiliates In the lawsuit, filed in US District Court, Watson's attorney claimed that the companies "failed to warn that preparing microwave popcorn in a microwave oven as intended and smelling the buttery aroma could expose the consumer to an inhalation hazard and a risk of lung injury"23 On 19 September 2012 a jury in US District Court in Denver awarded $23 million in actual damages and $5 million in punitive damages to Watson Defendants included Gilster-Mary Lee, the manufacturer; Kroger, and Kroger's subsidiary Dillons, owners of King Soopers & City Market, a Colorado regional supermarket chain242526

On 27 August 2007, Weaver Popcorn Company of Indianapolis promised to replace the diacetyl butter flavor ingredient in Pop Weaver popcorn with another flavoring27

In September 2007, Dr Cecile Rose, pulmonary specialist at Denver's National Jewish Health medical and research Center, warned federal agencies that consumers, not just flavoring or food factory workers, may be in danger of contracting bronchiolitis obliterans David Michaels, of the George Washington University School of Public Health, first published Rose's warning letter on his blog2829

On 4 September 2007, the Flavor and Extract Manufacturers recommended reduction of diacetyl in butter-like flavorings The next day ConAgra Foods announced that it would soon remove diacetyl from its popcorn products30

Diacetyl is approved by the Food and Drug Administration as a safe flavor ingredient, but there is evidence to suggest that inhalation in large amounts is dangerous There are currently no warnings from federal regulators about diacetyl

Diacetyl is found in the vapor created by some electronic cigarette flavours31

A NIOSH peer-reviewed publication documents that, in laboratory studies, acute inhalation exposures to acetyl propionyl2,3-pentanedione, one of the compounds with a buttery flavor and/or smell put forward as a safer alternative to diacetyl, cause airway epithelial damage that is as harmful as diacetyl32

Burn pitsedit

A new form of constrictive bronchiolitis is starting to present in Iraq and Afghanistan veterans It has been attributed to veterans being exposed to trash burn pits Veterans present with shortness of breath and other asthma like symptoms The only way to diagnose this condition is by doing a lung biopsy as chest x-rays and CT scans come back as normal The government still denies that there is any correlation between burn pits and health problems but the government has started an "Airborne Hazards and Open Burn Pit Registry" to begin tracking the health of veterans who were exposed to burn pits to see if there is a connection3334


Bronchiolitis obliterans is often misdiagnosed as asthma, chronic bronchitis, emphysema or pneumonia21

Several tests are often needed to correctly diagnose bronchiolitis obliterans, including chest x-rays, diffusing capacity of the lung tests DLCO, spirometry, lung volume tests, high-resolution CT HRCT, and lung biopsy Diffusing capacity of the lung DLCO tests are usually normal; people with early-stage BO are more likely to have normal DLCO Spirometry tests usually show fixed airway obstructions and sometimes restriction, where the lungs can't expand fully Lung volume tests may show hyperinflation excessive air in lungs caused by air trapping HRCT can also show air trapping when the person being scanned breathes out completely; it can also show thickening in the airway and haziness in the lungs Transthoracic lung biopsies are preferable for diagnosis of constrictive BO compared to transbronchial biopsies; regardless of the type of biopsy, a diagnosis may only be achieved by examination of multiple samples21


Flavorings-related lung disease can be prevented with the use of engineering controls eg exhaust hoods or closed systems, personal protective equipment, monitoring of potentially affected workers, worker education,35 and by not using lung-disease-causing flavorings


This disease is irreversible and severe cases often require a lung transplant21 Transplant recipients are at risk for re-developing the disease, as bronchiolitis obliterans is a common complication of chronic rejection Evaluation of interventions to prevent bronchiolitis obliterans relies on early detection of abnormal spirometry results or unusual decreases in repeated measurements

A multi-center study has shown the combination of inhaled fluticasone propionate, oral montelukast, and oral azithromycin may be able to stabilize the disease and slow disease progression36 This has only been studied in patients who previously underwent hematopoietic stem cell transplantation

See alsoedit

  • Diffuse panbronchiolitis


  1. ^ a b c d e f g h i "Bronchiolitis obliterans" GARD 2012 Retrieved 13 September 2016 
  2. ^ Schlesinger, C; Meyer, C; Veeraraghavan, S; Koss, M Jan 1998 "Constrictive obliterative bronchiolitis: diagnosis, etiology, and a critical review of the literature" Annals of Diagnostic Pathology 2 5: 321–334 PMID 9845757 doi:101016/S1092-91349880026-9 
  3. ^ Xie, BQ; Wang, W; Zhang, WQ; Guo, XH; Yang, MF; Wang, L; He, ZX; Tian, YQ 2014 "Ventilation/perfusion scintigraphy in children with post-infectious bronchiolitis obliterans: a pilot study" PLOS ONE 9 5: e98381 PMC 4031120  PMID 24852165 doi:101371/journalpone0098381 
  4. ^ a b c d e f g h Lynch JP, 3rd; Weigt, SS; DerHovanessian, A; Fishbein, MC; Gutierrez, A; Belperio, JA October 2012 "Obliterative constrictive bronchiolitis" Seminars in respiratory and critical care medicine 33 5: 509–32 PMID 23001805 doi:101055/s-0032-1325161 
  5. ^ Lockey, Richard F; Ledford, Dennis K 2014 Asthma: Comorbidities, Coexisting Conditions, and Differential Diagnosis Oxford University Press p 111 ISBN 9780199918072 
  6. ^ Gourtsoyiannis, Nicholas C; Ros, Pablo R 2005 Radiologic-Pathologic Correlations from Head to Toe: Understanding the Manifestations of Disease Springer Science & Business Media p 154 ISBN 9783540266648 
  7. ^ a b Centers for Disease Control and Prevention 2002 Fixed obstructive lung disease in workers at a microwave popcorn factory 7th ed 
  8. ^ https://wwwmorethanacoldcouk/about-bronchiolitis/symptoms-to-watch-out-for/
  9. ^ Sam, Amir H; James TH Teo 2010 Rapid Medicine Wiley-Blackwell ISBN 1-4051-8323-3 
  10. ^ "Activated charcoal bronchial aspiration" Retrieved 23 January 2016 
  11. ^ Brant & Helms 1999 Fundamentals of Diagnostic Radiology Baltimore: Williams & Wilkins ISBN 0-683-30093-8 
  12. ^ Webb; et al 2000 High Resolution CT of the Lung 3rd ed Philadelphia: Lippincott Williams & Wilkins ISBN 0-7817-0217-8 
  13. ^ a b c d Brown, Jay A "Haz-Map; Information on Hazardous Chemicals and Occupational Diseases" National Institutes of Health 
  14. ^ Colby, TV 1998 "Bronchiolitis, Pathologic Considerations" Am J Clin Pathology 109: 101–9 
  15. ^ California Department of Public Health
  16. ^ Harber P, Saechao K, Boomus C 2006 "Diacetyl-induced lung disease" Toxicol Rev 25 4: 261–272 PMID 17288497 doi:102165/00139709-200625040-00006 
  17. ^ "Preventing lung disease in workers who make or use flavorings" National Institute for Occupational Safety and Health 2004 
  18. ^ Schachter, E Neil 2002 "Popcorn Workers' Lung" New England Journal of Medicine 347 5: 360–1 doi:101056/nejme020064 
  19. ^ Egilman, David 2007 "Popcorn Workers Lung" PDF 
  20. ^ a b Sauler, Maor; Gulati, Mridu December 2012 "Newly Recognized Occupational and Environmental Causes of Chronic Terminal Airways and Parenchymal Lung Disease" Clinics in Chest Medicine 33 4: 667–680 PMC 3515663  PMID 23153608 doi:101016/jccm201209002 
  21. ^ a b c d e "CDC - Flavorings-Related Lung Disease - NIOSH Workplace Safety and Health Topic" wwwcdcgov Retrieved 15 October 2015 
  22. ^ Reuters New Report: FDA to probe popcorn link in man's lung disease
  23. ^ Man sues for "popcorn lung" by George Merritt, Associated Press Online edition Retrieved 29 April 2011
  24. ^ Mark Jaffe 21 September 2012 "Centennial man with "popcorn lung" disease gets $73 million award" The Denver Post Archived from the original on 22 September 2012 Retrieved 22 September 2012 
  25. ^ "Europe takes 'wait-and-see' stance on diacetyl flavouring" FoodNavigatorcom Retrieved 18 December 2015 
  26. ^ "News Feed Researcher" Retrieved 18 December 2015 
  27. ^ Weaver Popcorn Company Press Release: "Pop Weaver Introduces First Microwave Popcorn With Flavoring Containing No Diacetyl", 2007-08-27, hosted at PRNewswirecom ""Pop Weaver introduces first microwave popcorn with flavoring containing no diacetyl"" PDF Archived from the original PDF on 2007-09-28  216 KiB
  28. ^ Letter from Cecile Rose to US Food and Drug Administration Archived 2007-09-27 at the Wayback Machine, from wwwdefendingscienceorg
  29. ^ David Michaels 2007 Popcorn Lung Coming to Your Kitchen The FDA Doesn’t Want to Know, a blog post at thepumphandlewordpresscom
  30. ^ USA Today ConAgra to drop popcorn chemical linked to lung ailment
  31. ^ "Comments of the National Institute for Occupational Safety and Health to the Food and Drug Administration FDA in response to Establishment of a Public Docket; Electronic Cigarettes and the Public Health Workshop" PDF 5 August 2015 Retrieved 21 March 2017 
  32. ^ "CDC - Flavorings-Related Lung Disease: Exposures to Flavoring Chemicals - NIOSH Workplace Safety and Health Topic" Retrieved 18 December 2015 
  33. ^ http://wwwusmedicinecom/compendium/where-theres-smoke-dod-investigates-causes-of-deployment-related-pulmonary-symptoms-reported-by-troopshtml#UsH-jNJDvSs
  34. ^ Harrison Jacobs 5 November 2013 "Open-Air Burn Pits Leave Troops Sickly - Business Insider" Business Insider Retrieved 18 December 2015 
  35. ^ "CDC - Flavorings-Related Lung Disease: Exposure Control - NIOSH Workplace Safety and Health Topic" wwwcdcgov Retrieved 2015-10-22 
  36. ^ "Paper: Encouraging Results of a Phase II Trial of Inhaled Fluticasone Propionate, Azithromycin, and Montelukast FAM May Maintain Lung Function in Bronchiolitis Obliterans Syndrome BOS after Hematopoietic Cell Transplantation" Retrieved 18 December 2015 

External linksedit

  • ICD-10: J448, J684
  • ICD-9-CM: 4918
  • MeSH: D001989
  • DiseasesDB: 1704

  • King MS, Eisenberg R, Newman JH, et al July 2011 "Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan" N Engl J Med 365 3: 222–30 PMC 3296566  PMID 21774710 doi:101056/NEJMoa1101388 
  • Brown JA "Bronchiolitis obliterans" Haz-Map Information on Hazardous Chemicals and Occupational Diseases National Institutes of Health 
  • "NIOSH Alert: Preventing lung disease in workers who make or use flavorings" National Institute for Occupational Safety and Health 2004 
  • "Flavorings-Related Lung Disease" National Institute for Occupational Safety and Health 

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