Bronchiolitis obliterans

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Bronchiolitis obliterans
Other namesObliterative bronchiolitis (OB),[1]
constrictive bronchiolitis (CB),[2]
bronchiolitis obliterans syndrome (BOS),
popcorn lung
High resolution CT scan showing bronchiolitis obliterans with ground glass opacification, air trapping and bronchial thickening[3]
SpecialtyPulmonology Edit this on Wikidata
SymptomsDry cough, shortness of breath, wheezing, feeling tired[1]
Usual onsetWorsens over weeks to months[4]
CausesToxic fumes, respiratory infections, connective tissue disorder, following a bone marrow or heart-lung transplant[1]
Diagnostic methodCT scan, pulmonary function tests, lung biopsy[1]
Differential diagnosisAsthma[5]
TreatmentCorticosteroids, immunosuppressive medication, lung transplant[1][4]
PrognosisOften poor[4]

Bronchiolitis obliterans (BO), also known as obliterative bronchiolitis and popcorn lung, is a disease that results in obstruction of the smallest airways of the lungs (bronchioles) due to inflammation.[1] Symptoms include a dry cough, shortness of breath, wheezing and feeling tired.[1] These symptoms generally get worse over weeks to months.[4] It is not related to cryptogenic organizing pneumonia, previously known as bronchiolitis obliterans organizing pneumonia.[4]

Causes include breathing in toxic fumes, respiratory infections, connective tissue disorder or complications following a bone marrow or heart-lung transplant.[1] Symptoms may not occur until two to eight weeks following toxic exposure or infection.[1] The underlying mechanism involves inflammation that results in scar tissue formation.[1] Diagnosis is by CT scan, pulmonary function tests or lung biopsy.[1] A chest X-ray is often normal.[4]

While the disease is not reversible, treatments can slow further worsening.[1] This may include the use of corticosteroids or immunosuppressive medication.[1] A lung transplant may be offered.[4] Outcomes are often poor, with most people dying in months to years.[4]

Bronchiolitis obliterans is rare in the general population.[4] 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.[4] The condition was first clearly described in 1981.[4] Prior descriptions occurred as early as 1956.[6]

Signs and symptoms[edit]

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 suddenly.[7][8]


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[citation needed]. It can also be present in patients with rheumatoid arthritis.[9] Certain orally administrated emergency medications, such as activated charcoal, have been known to cause it when aspirated.[10] The ingestion of large doses of papaverine in the vegetable Sauropus androgynus has caused it.[11] Additionally, the disorder may be idiopathic (without known cause).[12][13][14]

Industrial inhalants[edit]

There are many industrial inhalants that are known to cause various types of bronchiolitis, including bronchiolitis obliterans.[15]

Industrial workers who have presented with bronchiolitis:

  • nylon-flock workers[14]
  • workers who spray prints onto textiles with polyamide-amine dyes[14]
  • battery workers who are exposed to thionyl chloride fumes
  • workers at plants that use or manufacture flavorings, e.g. diacetyl butter-like flavoring [7][14][16]


Bronchiolitis obliterans may be caused by inhalation of airborne diacetyl, a chemical used to produce the artificial butter flavoring[17] 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".[18][19][20][21] It is also referred to as "flavorings-related lung disease".[22]

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 workplace.[22] 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 ppb.[21]

In 2007, a heavy consumer of microwaved popcorn was diagnosed by a doctor in Denver with "popcorn lung," the first known case involving a consumer.[23] 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 U.S. 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."[24] On 19 September 2012 a jury in U.S. District Court in Denver awarded $2.3 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 chain.[25][26][27]

On 27 August 2007, Weaver Popcorn Company of Indianapolis promised to replace the diacetyl butter flavor ingredient in Pop Weaver popcorn with another flavoring.[28]

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 blog.[29][30]

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 products.[31]

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.

A NIOSH peer-reviewed publication documents that, in laboratory studies, acute inhalation exposures to acetyl propionyl (2,3-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 diacetyl.[32]

Diacetyl is found in the vapor created by some electronic cigarette flavors, however the chemical is present in less than 1% the levels found in cigarette smoke, and cigarettes have been determined not to contribute to the disease.[33][34]

Burn pits[edit]

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 connection.[35][36]


Bronchiolitis obliterans is often misdiagnosed as asthma, COPD, or pneumonia.[22]

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 samples.[22]


Flavorings-related lung disease can be prevented with the use of engineering controls (e.g., exhaust hoods or closed systems), personal protective equipment, monitoring of potentially affected workers, worker education,[37] and by not using lung-disease-causing flavorings.


This disease is irreversible and severe cases often require a lung transplant.[22] 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 progression.[38] This has only been studied in patients who previously underwent hematopoietic stem cell transplantation.

See also[edit]


  1. ^ a b c d e f g h i j k l m "Bronchiolitis obliterans". GARD. 2012. Archived from the original on 21 January 2017. 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. doi:10.1016/S1092-9134(98)80026-9. PMID 9845757.
  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. Bibcode:2014PLoSO...998381X. doi:10.1371/journal.pone.0098381. PMC 4031120. PMID 24852165.
  4. ^ a b c d e f g h i j k l 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. doi:10.1055/s-0032-1325161. PMID 23001805.
  5. ^ Lockey, Richard F.; Ledford, Dennis K. (2014). Asthma: Comorbidities, Coexisting Conditions, and Differential Diagnosis. Oxford University Press. p. 111. ISBN 9780199918072. Archived from the original on 2017-09-08.
  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. Archived from the original on 2017-09-08.
  7. ^ a b Centers for Disease Control and Prevention (2002). Fixed obstructive lung disease in workers at a microwave popcorn factory (7th ed.).
  8. ^ "More than a cold". Archived from the original on 2016-09-15. Retrieved 2016-08-18.
  9. ^ Sam, Amir H.; James T.H. Teo (2010). Rapid Medicine. Wiley-Blackwell. ISBN 978-1-4051-8323-9.
  10. ^ Morrone, Nelson; Saito, Makoto; Bairral, Bruna Quaranta Lobão. "Activated charcoal bronchial aspiration". Jornal Brasileiro de Pneumologia. 38 (4): 533–534. doi:10.1590/S1806-37132012000400018. Archived from the original on 5 July 2015. Retrieved 23 January 2016.
  11. ^ Bunawan H, Bunawan SN, Baharum SN, Noor NM (2015). "Sauropus androgynus (L.) Merr. Induced Bronchiolitis Obliterans: From Botanical Studies to Toxicology". Evid Based Complement Alternat Med. 2015: 714158. doi:10.1155/2015/714158. PMC 4564651. PMID 26413127.
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  16. ^ California Department of Public Health Archived 2009-10-16 at the Wayback Machine
  17. ^ Harber P, Saechao K, Boomus C (2006). "Diacetyl-induced lung disease". Toxicol Rev. 25 (4): 261–272. doi:10.2165/00139709-200625040-00006. PMID 17288497.
  18. ^ "Preventing lung disease in workers who make or use flavorings". National Institute for Occupational Safety and Health. 2004. doi:10.26616/NIOSHPUB2004110. Archived from the original on 2006-07-18.
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  20. ^ Egilman, David (2007). "Popcorn Workers Lung" (PDF). Archived from the original (PDF) on 2007-09-27. Retrieved 2007-08-09.
  21. ^ 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. doi:10.1016/j.ccm.2012.09.002. PMC 3515663. PMID 23153608.
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  27. ^ "News Feed Researcher". Retrieved 18 December 2015.[permanent dead link]
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  35. ^ Archived 2013-12-31 at the Wayback Machine
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  38. ^ "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". Archived from the original on 4 March 2016. Retrieved 18 December 2015.

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