Bronchiolitis Obliterans

1. Post-infectious bronchiolitis obliterans can be diagnosed when the following criteria are met:

1) A history of severe acute lower respiratory tract infection;

2) Persistent respiratory symptoms related to airway obstruction lasting more than 6 weeks after infection, despite treatment with corticosteroids and bronchodilators;

3) HRCT findings such as mosaic perfusion, air trapping, and bronchiectasis;

4) Exclusion of other chronic respiratory diseases (e.g., asthma, bronchopulmonary dysplasia, primary ciliary dyskinesia, immunodeficiency, cystic fibrosis, chronic aspiration).

• Expiratory HRCT is the most sensitive imaging modality to reflect the extent of lung lesions. 
• Lung biopsy: The most definitive diagnostic method, but limited due to the patchy distribution 
• Pulmonary function tests: Helpful for long-term monitoring of lung function changes.

2-1. Bronchiolitis obliterans after hematopoietic stem cell transplantation 

In 2015, the U.S. National Institutes of Health (NIH) proposed diagnostic criteria for BOS without requiring histologic confirmation via lung biopsy. All four of the following conditions must be met for diagnosis:

1) Reduced FEV1/FVC ratio (<0.7 or below the 5th percentile of predicted);

2) Decline in FEV1 (<75% of predicted), with a decrease of ≥10% over two years; or, if FEV1 recovers after albuterol administration but remains ≤75% of predicted and declines ≥10% over two years;

3) Exclusion of respiratory infection by comprehensive testing;

4) At least one of the following supportive features:

•  Chest CT showing signs of bronchial wall thickening, air trapping, or bronchiectasis;
•  Pulmonary function tests indicating air trapping.

2-2 Bronchiolitis Obliterans after Lung Transplantation

According to the criteria proposed by the International Society of Heart and Lung Transplantation (ISHLT), BOS can be diagnosed in lung transplant recipients when there is a persistent decline in FEV1 without evidence of infection or other identifiable causes. Specifically, BOS is defined as:

1) A sustained ≥20% reduction in FEV1 compared to the baseline(where baseline is the average of the two highest post-transplant FEV1 values measured at least 3 weeks apart;

2) Accompanied by all of the following:

•  Reduced FEV1/FVC ratio (<0.7)
•  No evidence of restrictive lung disease
•  Absence of parenchymal or pleural fibrosis on chest CT

1. Post-infectious bronchiolitis obliterans (PIBO)

• No officially established treatment guidelines, but the need for anti-inflammatory therapy to prevent disease progression has been suggested. 
• Short-term high-dose intravenous corticosteroid therapy: The most commonly attempted treatment , however, the optimal timing, duration, and frequency remain unclear. 
• Macrolide
• The FAM regimen (Inhaled fluticasone, azithromycin, and montelukast), used in bronchiolitis obliterans following HSCT, has also been reported to be effective in PIBO.

2-1. Bronchiolitis obliterans after hematopoietic stem cell transplantation 

• The first stepis to ensure appropriate use of immunosuppressants. 
• A combination of high-dose intravenous corticosteroids and the FAM regimen (inhaled fluticasone, azithromycin, montelukast), which has shown favorable outcomes after three months of treatment 
• A combination therapy with inhaled corticosteroids and long-acting beta-2 agonists for mild to moderate cases 

2-2. Bronchiolitis Obliterans after Lung Transplantation

The first step is proper immunosuppressive therapy 

•    Tacrolimus has been associated with a lower incidence of bronchiolitis obliterans compared to cyclosporine

Azithromycin: The most commonly used agent, with 29–50% of patients showing improvement in FEV1

•   Recent ISHLT guidelines recommend its prophylactic use immediately after lung transplantation