What is the management approach for bronchiolitis obliterans in children?

Management of Bronchiolitis Obliterans in Children

The management of bronchiolitis obliterans (BO) in children requires a multidisciplinary approach in specialized centers, focusing on early detection through standardized surveillance protocols and supportive care, as there is currently no curative treatment available. 1, 2

Types and Etiology

Bronchiolitis obliterans in children can be categorized into three main types:

1. Post-infectious BO (PIBO) - Most common in children

   • Common infectious agents:
     • Adenovirus (most common)
     • Mycoplasma pneumoniae
     • Respiratory syncytial virus (RSV)
     • Parainfluenza virus
     • Influenza viruses 3, 4

2. Post-hematopoietic stem cell transplantation (HSCT) BO

   • Associated with chronic graft-versus-host disease 1

3. Post-lung transplantation BO

Diagnostic Approach

Clinical Presentation

• Persistent wheezing of varying severity (100% of cases)
• Chronic cough (92%)
• Exercise intolerance (85%)
• Shortness of breath (81%)
• Chest retractions (77%)
• Wheezy phlegm (62%)
• Persistent crackles (38%)
• Cyanosis (12%) 3

Diagnostic Testing

1. Pulmonary Function Testing

   • For children who can perform spirometry:
     • Evidence of fixed airflow obstruction
     • Reduced FEV1 (<75% predicted)
     • Air trapping (increased RV/TLC ratio) 1

2. Imaging

   • High-Resolution CT (HRCT) - Gold standard imaging

     • Air trapping on expiratory views
     • Mosaic perfusion pattern ("Westemark sign")
     • Bronchial wall thickening
     • Bronchiectasis
     • Patchy ground-glass opacities 3, 4

   • Chest X-ray

     • Limited utility (may show hyperinflation)
     • Often appears as bronchopneumonia (38%) 3

3. Laboratory Testing

   • ANCA testing (P-ANCA positive in ~53%, C-ANCA in ~42% of cases) 3
   • Microbiological studies to identify causative pathogens

4. Lung Biopsy

   • Considered gold standard for diagnosis
   • Reserved for cases where diagnosis is uncertain
   • Shows fibrosis and obliteration of small airways 2, 5

Diagnostic Criteria for Post-HSCT BO

For children who can perform spirometry:

• FEV1 <75% predicted
• FEV1/FVC ratio <0.7
• Evidence of air trapping on expiratory CT
• Lung clearance index >8.0
• History of cGVHD in another organ
• Persistence after treatment of any identified infection 1

Management Approach

Pharmacological Interventions

1. Corticosteroids

   • Oral corticosteroids are the cornerstone of treatment
   • Used to reduce airway inflammation 3, 4

2. Macrolide Antibiotics

   • Low-dose azithromycin for long-term use
   • Anti-inflammatory and immunomodulatory effects
   • May improve clinical condition in approximately 50% of patients 3, 4

3. Bronchodilators

   • Trial of bronchodilators to assess response
   • May provide symptomatic relief in some patients 6

Supportive Care

1. Respiratory Support

   • Supplemental oxygen for hypoxemia (SpO₂ <90%)
   • High-flow nasal cannula for worsening respiratory distress 6

2. Airway Clearance

   • Chest physiotherapy
   • Nasal suctioning to clear secretions 6

3. Nutritional Support

   • Ensure adequate hydration and nutrition

4. Prevention of Infections

   • Vaccination (including annual influenza)
   • Hand hygiene
   • Avoiding exposure to tobacco smoke 6

Monitoring and Follow-up

1. Regular Pulmonary Function Testing

   • Every 3 months in the first year
   • Every 3-6 months in the second year
   • Every 6 months between 2-3 years
   • Yearly after 3 years (up to 10 years) 1

2. Surveillance HRCT

   • Periodic imaging to assess disease progression

3. Assessment of Response to Therapy

   • Monitor for improvement in symptoms
   • Average time to symptom improvement: 7.1 ± 4.8 days 3

Prognosis

• PIBO generally has a chronic, non-progressive course
• Post-HSCT BO can have devastating impacts including:
  • Prolonged hospitalizations
  • Reduced quality of life
  • Need for supplemental oxygen
  • Increased mortality 1, 7

Advanced Interventions

• Lung Transplantation
  • Consider for progressive disease unresponsive to medical therapy
  • Treatment of choice in severe cases 5

Special Considerations

• Children with history of allergic rhinitis have increased risk for recurrent wheezing
• Close monitoring for development of asthma in children with history of BO 6
• Personalized surveillance plans should be developed based on individual risk profiles 1

Research Needs

• Earlier detection strategies
• Identification of biomarkers in BAL fluid
• Development of pathobiology-based treatments
• Personalized approaches to screening and management 1