Bronchiolitis Obliterans

Bronchiolitis obliterans is an obstructive lung disease triggered by a bronchiolar injury, which leads to inflammatory fibrosis and narrowing of the distal bronchioles. The triggering bronchiolar injury is often due to inhalation of a noxious substance, infection, or drug toxicity. Bronchiolitis obliterans is also associated with rheumatic disease and is an important complication to recognize following a lung or hematopoietic stem-cell transplant. Following bronchiolar injury, there is an abnormal fibroproliferation within the bronchioles, which results in small-airway obstruction. Patients present with a persistent progressive cough and dyspnea. Diagnosis is usually made based on pulmonary function tests (showing a non-reversible obstructive pattern, air trapping, and decreased gas exchange) and high-resolution CT (showing air trapping and bronchial-wall thickening). Management involves supportive care, bronchodilators, glucocorticoids, and/or macrolide antibiotics. Immunosuppressive therapy is usually increased in patients who have undergone transplantation, and retransplantation may be required if the condition worsens.

Last update:

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Definition and Epidemiology


  • Bronchiolitis obliterans
    • An obstructive lung disease triggered by bronchiolar injury, leading to inflammatory fibrosis and narrowing of the distal bronchioles
    • Leads to dyspnea and ↓ airflow that is not reversible by bronchodilators
    • Bronchiolitis obliterans syndrome (BOS)
      • When the condition occurs after a lung transplant or hematopoietic stem-cell transplant
      • Considered a form of allograft rejection
  • Conditions representing entities separate from bronchiolitis obliterans:
    • Acute bronchiolitis: 
      • An intense inflammatory process in the small bronchioles
      • Common in young children, rare in adults
      • Most often caused by the respiratory syncytial virus (RSV)
    • Cryptogenic organizing pneumonia:
      • Previously referred to as bronchiolitis obliterans organizing pneumonia
      • A diffuse interstitial lung disease affecting the bronchioles and alveoli


  • Rare in individuals who have not undergone a transplant
  • > 50% of patients who have undergone lung transplant develop BOS by 5 years


Small airway injuries that trigger bronchiolitis obliterans can result from inhalation, infections, drug exposure, lung inflammation due to a rheumatic process, or chronic transplant rejection.

  • Inhalational injury:
    • Toxic fumes and gases:
      • Nitrogen oxides
      • Ammonia
      • Chlorine
      • Welding fumes
      • Sulfur mustard gas
    • Electronic cigarettes
    • Nicotine aerosols
    • Volatile organic compounds
    • Heavy metals and mineral dusts
    • Popcorn flavoring (diacetyl)
  • Infections:
    • RSV
    • Adenovirus
    • Mycoplasma pneumoniae
    • HIV
  • Drug exposure:
    • Busulfan
    • Gold
    • Penicillamine
  • Rheumatic disease → lung inflammation:
    • Rheumatoid arthritis
    • Systemic lupus erythematosus
  • Transplant → graft-versus-host disease:
    • Lung transplant
    • Hematopoietic stem-cell transplant

Pathophysiology and Clinical Presentation


Injury to the distal bronchioles results in inflammation. A dysregulated immune response then leads to fibroproliferation and narrowing of these small airways and decreases airflow.

  • Process: 
    • Injury to the bronchiolar epithelium (terminal and respiratory bronchioles) → inflammation of the bronchioles and adjacent alveoli → fibrosis (abnormal) instead of normal repair
    • Overall effect is narrowing or obliteration of the small airways leading to:
      • Obstruction
      • Air trapping
      • ↓ Gas exchange
  • In patients who have undergone a transplant, airway injury is caused by:
    • Microvascular insufficiency
    • Alloimmune responses
    • GERD with microaspiration
Bronchiolitis pathophysiology

Bronchiolitis pathophysiology:
The image on the left represents the structure of a normal bronchiole. The image on the right represents changes occurring in bronchiolitis obliterans. Injury to the distal bronchioles results in inflammation of the bronchioles and adjacent alveoli. Fibrosis occurs (which is abnormal) instead of normal repair. There is mucus buildup, tightening and hypertrophy of the bronchial smooth muscles followed by narrowing of the small airways.

Image by Lecturio.

Clinical presentation

Bronchiolitis obliterans should be suspected in patients with slowly progressive dyspnea and cough, especially when the presentation is otherwise atypical for asthma or chronic obstructive pulmonary disease (COPD).

  • Dyspnea
  • Cough:
    • Persistent (as opposed to episodic-like asthma)
    • Progressive, slowly developing over weeks to months
    • Sputum may or may not be present
  • Potential exam findings:
    • Tachypnea
    • ↓ Breath sounds
    • Prolonged expiratory phase while breathing
    • Crackles and/or wheezing


The diagnosis of bronchiolitis obliterans is usually made based on history, pulmonary function test, imaging, and biopsy findings.

Pulmonary tests

  • Lung tests include:
    • Spirometry:
      • Measures the volume of inhaled and exhaled air
      • Usually performed before and after administration of bronchodilators → determines the degree of reversible airflow obstruction
    • Diffusion capacity:
      • Measures the transfer of gas into the blood
      • A low concentration of carbon monoxide in the inhaled air is absorbed by hemoglobin in RBCs.
    • Helpful in diagnosing multiple lung conditions
  • Important definitions and acronyms:
    • Total lung capacity (TLC): total volume of air in lungs at the end of a maximal inspiration
    • Forced expiratory volume in the 1st second (FEV1)
    • Forced vital capacity (FVC): total forced exhaled volume
    • Residual volume (RV): volume remaining after maximal exhalation
    • Functional residual capacity (FRC): volume remaining at the end of a tidal volume breath
    • Diffusing capacity of the lungs for carbon monoxide (DLCO): reflects the lung’s ability to transfer inhaled gas across the alveolar-capillary membrane 
  • Obstruction versus restriction:
    • Restriction pattern: 
      • ↓ TLC and FVC
      • Think: “the lungs can’t expand (restriction) → ↓ volumes moving in and out”
      • Example: interstitial lung disease
    • Obstruction pattern: 
      • ↓ FEV1/FVC ratio
      • Think: “The lungs can expand and contract, but the air moves slowly (obstruction).”
      • Examples: asthma, COPD, and bronchiolitis
Interpretation of pulmonary function tests

Algorithm for interpretation of pulmonary function tests:
FEV1: forced expiratory volume in the 1st second
FVC: forced vital capacity (total forced exhaled volume)
DLCO: diffusing capacity of the lungs for carbon monoxide (reflects the lung’s ability to transfer inhaled gas across the alveolar-capillary membrane)
COPD: chronic obstructive pulmonary disease
ILD: interstitial lung disease

Image by Lecturio.

Bronchiolitis obliterans

  • Non-reversible airflow obstruction: ↓ FEV1
  • Evidence of air trapping: ↑ RV and FRC
  • Possible hyperinflation: ↑ TLC
  • Impaired gas exchange: ↓ DLCO
  • May be normal: 
    • There are a large number of bronchioles.
    • A high percentage needs to be affected before spirometry changes are seen.

Other diagnostic tests

  • Chest X-ray:
    • Usually normal
    • May show: 
      • ↑ Bronchial-wall thickening
      • Hyperinflation
  • High-resolution CT (HRCT):
    • Bronchial-wall thickening: branching linear opacities
    • Ground-glass opacity in a mosaic pattern
  • Bronchoscopy:
    • Rarely required for clinical diagnosis
    • Findings are usually nonspecific.
    • Used when other causes of airflow obstruction are suspected:
      • Endobronchial tumors
      • Sarcoidosis
      • Infections leading to lung damage
  • Lung biopsy:
    • Required for definitive diagnosis (although a clinical diagnosis can often be made without a biopsy)
    • Surgical (over transbronchial) specimen preferred
    • Histopathology:
      • Hypertrophy of the bronchiolar smooth muscle
      • Peribronchiolar inflammatory infiltrates
      • Bronchiolar mucus accumulation 
      • Fibrosis and obliteration of bronchioles (by submucosal scarring)
HRCT in bronchiolitis obliterans

High-resolution CT (HRCT) in bronchiolitis obliterans:
The HRCT at expiration demonstrates a mosaic-attenuation pattern that results from air trapping.

Image: “Mimics in chest disease: interstitial opacities” by Oikonomou A, Prassopoulos P. License: Public Domain, cropped by Lecturio.


Bronchiolitis obliterans is often progressive and refractory to therapy; thus, management is often supportive, symptom driven, and based on the etiology.

General management

  • Remove any offending agents.
  • Smoking cessation
  • Updated vaccination against influenza and pneumococcus
  • Treat GERD:
    • Proton pump inhibitors
    • Histamine-2 receptor antagonists
  • Symptom relief:
    • Cough suppressants:
      • Dextromethorphan
      • Codeine
    • Inhaled bronchodilators
  • Supplemental oxygen if needed to maintain oxygen saturation ≥ 89%
  • Consider a trial (3‒6 months) of macrolide antibiotics: 
    • Options:
      • Azithromycin
      • Erythromycin
      • Clarithromycin
    • Not formally studied in patients who have not undergone a transplant
    • Limited evidence suggests that there may be some benefits.
  • Consider a trial (4‒6 weeks) of glucocorticoids in patients with:
    • Rheumatic disease
    • Coexisting asthma

Management in patients who have undergone transplant

  • Increase immune suppression:
    • Tacrolimus
    • Cyclosporine
    • Mycophenolate mofetil
    • Prednisone
  • Evidence shows improvement in lung function (in patients who have undergone post-hematopoietic stem-cell transplant) and are on the following therapy:
    • Fluticasone (inhaled corticosteroid)
    • Montelukast (oral leukotriene receptor antagonist)
    • Azithromycin (oral macrolide antibiotic)
  • Consider retransplantation when BOS is severe.

Differential Diagnosis

  • Asthma: a condition of bronchial hyperresponsiveness and chronic airway inflammation that leads to intermittent airflow obstruction. Asthma typically presents with intermittent dyspnea, cough, and wheezing in response to a variety of stimuli. Asthma is diagnosed based on history and spirometry, which shows a reduced FEV1/FVC ratio (obstruction) that is reversible with bronchodilators (unlike bronchiolitis obliterans which is not reversible). Management involves avoiding triggers, and the use of bronchodilators and glucocorticoids.
  • COPD: an obstructive lung disease due to inflammation resulting from chronic exposure to noxious particles or gas (usually smoking). Subtypes include emphysema, chronic bronchitis, and chronic obstructive asthma. Both small airways and parenchyma can be affected. Spirometry usually shows non-reversible or only partially reversible obstruction (reduced FEV1/FVC ratio). Management involves smoking cessation and treatment with long-acting bronchodilators.
  • Bronchiectasis: an abnormal dilatation of the bronchi with destruction and thickening of the bronchial walls. Bronchiectasis is triggered by chronic or recurrent infections in the setting of impaired airway drainage or obstruction, and is characterized by a chronic cough, dyspnea, and daily sputum production. Bronchiectasis is a condition affecting the large airways, whereas bronchiolitis obliterans affects the small airways. Diagnosis is usually confirmed with a chest CT showing bronchial-wall thickening and large-airway dilatation.
  • Hypersensitivity pneumonitis: an interstitial lung disease characterized by an abnormal immune reaction within the pulmonary parenchyma in response to an inhaled substance. The inciting agents are often related to agricultural dust or microorganisms associated with farming, animal handling, and ventilation and construction work. Patients present with a productive cough, dyspnea, fatigue, and weight loss. Diagnosis involves characteristic findings on HRCT, and lymphocytosis on broncho-alveolar lavage.


  1. Bronchiolitis: Causes, symptoms and treatments (n.d.). Retrieved March 19, 2021, from
  2. King, T. (2020). Overview of bronchiolar disorders in adults. In Hollingsworth, H. (Ed.). UpToDate. Retrieved February 11, 2021, from
  3. McCormack, M. (2020). Overview of pulmonary function testing in adults. In Hollingsworth, H. (Ed.). UpToDate. Retrieved February 11, 2021, from
  4. Krishna, R., Anjum, F. (2020). Bronchiolitis obliterans. In Oliver, T. (Ed.). StatPearls. Retrieved February 11, 2021, from

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.