Bronchiolitis Obliterans (BO; Obliterative Bronchiolitis)


Classification of Bronchiolar Disorders



Connective Tissue Disease

  • Eosinophilic Fasciitis (see Eosinophilic Fasciitis)
  • Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis)
    • Epidemiology: RA is the connective tissue disease most commonly associated with BO
      • RA-associated BO was originally thought to be associated with gold/penicillamine use -> however, the persistent incidence of RA-associated BO despite decreased use of these drugs suggests that RA itself is responsible
      • Peak Group: long-standing RA seropositive females in 40’s-50’s -> these cases may have rapid clinical progression
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus)
    • Epidemiology: only a few reported cases
  • Polydermatomyositis (see Polydermatomyositis)
    • Epidemiology: only a few reported cases

Post-Hematopoietic Stem Cell Transplant (HSCT) (Bone Marrow Transplant, BMT) (see Hematopoietic Stem Cell Transplant)

  • Epidemiology: BO is the most common non-infectious pulmonary complication following allogeneic BMT/SCT
    • Increasing Incidence: BO associated with BMT/SCT has increased in incidence over the last 30 yrs
    • Incidence: 5.5% in allogeneic BMT/SCT (incidence is 14% in subpopulation of patients with extrathoracic chronic graft vs host disease)
  • Risk Factors
    • Acute Graft vs Host Disease (GVHD) (see Graft vs Host Disease)
    • Busulfan Conditioning Regimen (see Busulfan)
    • Chronic Graft vs Host Disease (GVHD) (see Graft vs Host Disease): chronic GVHD occurs in 33% of long-term survivors of allo-BMT -> BO occurs in 10% of chronic GVHD cases
    • Factors Related to Transplant Type: there is an increased risk of BO with the use of peripheral blood stem cells
    • Gastroesophageal Reflux Disease (GERD) (see Gastroesophageal Reflux Disease)
    • Greater Degree of HLA Mismatch
    • Hypogammaglobulinemia (see Hypogammaglobulinemia)
    • Methotrexate (see Methotrexate): causes BO only in combination with chronic GVHD, not alone (methotrexate induces MHC expression, which are targets for T-cell in GVHD)
    • Older Age of Donor/Recipient
    • Tobacco Abuse (see Tobacco)
    • Underlying Hematologic Disease
    • Use of Graft vs Host Disease Prophylaxis (see Graft vs Host Disease): immunosuppression for GVHD increases viral infection risk
    • Viral Infection: viral infection occurs in 25-30% of post-SCT BO cases
  • Physiology: BO likely represents chronic graft vs host disease in the lung

Post-Heart-Lung or Lung Transplant (see Cardiac Transplant) and Lung Transplant)

  • Epidemiology
    • 10 Year Incidence: 70% of cases develop BO [MEDLINE]
    • Risk Related to Type of Immunosuppression: incidence of BO is lower with taccolimus, as compared to cyclosporine A [MEDLINE]
  • Physiology: related to chronic allograft rejection (associated with HLA locus mismatch)
    • Cofactors: PCP, CMV, altered mucociliary clearance, altered blood flow due to bronchial artery ligation, immunosuppression, and aspiration due to loss of cough)


  • Amiodarone (Cordarone) (see Amiodarone)
  • Carmustine (see Carmustine)
  • Gold (see Gold)
    • Epidemiology: unclear etiologic association (as cases occurred in RA patients that were treated with this drug)
  • Penicillamine (see Penicillamine)
    • Epidemiology: unclear etiologic association (as cases occurred in RA patients that were treated with this drug)
  • Topotecan (Hycamtin) (see Topotecan)

Toxic Fume Exposure

  • 2,3-Pentanedione (see 2,3-Pentanedione)
    • Epidemiology: used in manufacture of food flavorings
  • Ammonia Gas (see Ammonia)
  • Chlorine Inhalation (see Chlorine)
  • Chromic Acid Inhalation (see Chromic Acid)
  • Cocaine (see Cocaine)
  • Diacetyl (see Diacetyl)
    • Epidemiology
      • Diacetyl-Associated BO Cases Have Been Reported in Workers mManufacturing Butter Flavoring Used in Popcorn Processing Plants
      • Diacetyl is Also a Component (or is Used in the Manufacturing Process) of Buttered Popcorn/Chips, Candy, Butter, Ice Cream, Baked Goods, and Coffee Flavorings
  • Hydrogen Fluoride Inhalation (see Hydrogen Fluoride Gas)
  • Hydrogen Sulfide Inhalation (see Hydrogen Sulfide Gas)
    • Epidemiology: reports of hydrogen sulfide-associated BO date back to World War I (1914-1918) and the Iran-Iraq War (1980-1988), during which this agent was used
    • Clinical: acute chemical pneumonitis (chest tightness, dyspnea, massive hemoptysis) -> fibrous exudates and granulation tissue in bronchi/distal bronchioles -> eventual development of bronchiolitis obliterans
  • Nitrogen Oxides: used in fertilizer production (probably involved in silo-filler’s disease)
    • Nitrogen Dioxide Inhalation (see Nitrogen Dioxide)
      • Epidemiology: BO occurs in only 5% of cases
  • Ozone Inhalation (see Ozone)
  • Phosgene Gas Inhalation (see Phosgene Gas)
  • Smoke Inhalation (see Smoke Inhalation)
  • Sulfur Dioxide (see Sulfur Dioxide)
    • Epidemiology
      • Reports of US Soldiers from Iraq/Afghanistan with BO Who Were in Proximity to a Fire in a Sulfur Mine in 2003 (fire produced high ambient air levels of sulfur dioxide, a known cause of BO), exposure to dust storms, exposure to incinerated solid/human waste, and/or exposure to combat smoke (NEJM, 2011) [MEDLINE]
  • Sulfur Mustard Gas Inhalation (see Sulfur Mustard Gas)
    • Epidemiology
      • Reports of Sulfur Mustard-Associated BO Date Back to World War I (1914-1918) and the Iran-Iraq War (1980-1988), During Which this Agent was Used
    • Clinical: acute chemical pneumonitis (chest tightness, dyspnea, massive hemoptysis) -> fibrous exudates and granulation tissue in bronchi/distal bronchioles -> eventual development of bronchiolitis obliterans

Other Toxic Exposures

  • Fiberglass
  • Papaverine (see Papaverine)
    • Epidemiology: Sauropus Androgynus (Katuk) juice is used for weight loss
    • Physiology: papaverine is found in juice extracted from Sauropus Androgynus (Katuk)
    • Clinical: respiratory symptoms develop several weeks after ingestion


Idiopathic Bronchiolitis Obliterans

  • May Occur



Arterial Blood Gas (ABG) (see Arterial Blood Gas)

Chest X-Ray (see Chest X-Ray)

Chest CT (see Chest Computed Tomography)

High-Resolution-Chest CT (see High-Resolution Chest Computed Tomography)

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)

Bronchoscopy (see Bronchoscopy)

Video-Assisted Thoracoscopic Surgery (VATS) with Lung Biopsy (see Video-Assisted Thoracoscopic Surgery)

Clinical Presentations

General Comments

Toxic Fume Exposure-Associated Bronchiolitis Obliterans

Infection-Associated Bronchiolitis Obliterans

Connective Tissue Disease-Associated Bronchiolitis Obliterans

Bone Marrow/Stem Cell Transplant-Associated Bronchiolitis Obliterans

Heart-Lung/Lung Transplant-Associated Bronchiolitis Obliterans


Specific Treatment of Toxic Fume-Associated Bronchiolitis Obliterans

Specific Treatment of Bone Marrow Transplant/Stem Cell Transplant-Associated Bronchiolitis Obliterans

Specific Treatment of Heart-Lung/Lung Transplant-Associated Bronchiolitis Obliterans

Lung Transplantation (see Lung Transplant)


Epler-Colby Prognostic Classification (1983)



Toxin-Associated Bronchiolitis Obliterans

Transplant-Associated Bronchiolitis Obliterans