What causes bronchiolitis obliterans syndrome (chronic rejection) following lung transplantation?

Updated: Aug 19, 2019
  • Author: Bryan A Whitson, MD, PhD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Bronchiolitis obliterans syndrome (chronic rejection)

The incidence of bronchiolitis obliterans syndrome (BOS) is highest after the first year following lung transplantation. However, the risk of BOS increases to 60-80% 5-10 years after the lung transplantation procedure. It is the most important complication that adversely affects the long-term survival of graft recipients.

Symptoms occur secondary to the airflow obstruction that progresses over time. These patients develop exertional dyspnea, a nonproductive cough, wheezing, and/or low-grade fever. Although the symptoms resemble bronchial asthma, the limited response to bronchodilator and corticosteroid therapy makes these ineffective.

BOS has a variable course. The disease may be progressive, it may plateau, or it may progress gradually in a stepwise fashion. Therefore, early detection of this complication is paramount. Obliterative bronchiolitis is staged according to the level of airflow obstruction as measured by FEV1. Four stages are described, based on severity, from grade 0 to grade III, as follows:

  • Stage 0 – FEV1 greater than 80% of baseline

  • Stage I – FEV1 66-80% of baseline

  • Stage II – FEV1 51-65% of baseline

  • Stage III – FEV1 50% or less of baseline

Pathologically, bronchiolar inflammation and narrowing of the lumen are present, and bronchiectasis is present in larger airways. The active lesions demonstrate lymphocytic inflammation and the formation of granulation tissue. Fibrotic tissue compromises the airway lumen in a constrictive fashion. In advanced stages, collagen is deposited and fibrosis of the bronchiolar wall can cause occlusion of the lumen.

The pathogenesis of BOS may be initiated by alloimmune and infectious inflammation of bronchiolar structures, followed by a fibroproliferative response. Diagnosis is confirmed by high-resolution computed tomography (HRCT) scans and a complete battery of pulmonary function tests. HRCT scans demonstrate bronchiectasis, thickening of septal lines, hyperlucency, peribronchial and perivascular infiltrates, and mosaic attenuation of lung parenchyma. Because of the air trapped in different regions of the lung, the mosaic pattern is most prominent during expiratory images.

Pulmonary function tests reveal expiratory airflow obstruction. A decrement of at least 20% in the FEV1 and FEV1 -to-FVC ratio occurs. The diffusing capacity of lung volumes generally is maintained or may decrease slightly.

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