STANFORD EXPERIENCE WITH OBLITERATIVE BRONCHIOLITIS AFTER LUNG AND HEART-LUNG TRANSPLANTATION

Background. Obliterative bronchiolitis (OB) is the main chronic compli cation after heart-lung (HLTx) and lung transplantation (LTx), limitin g the long-term success of both transplant procedures. Methods. Since 1981, 135 HLTxs and 61 isolated LTxs were performed in 184 patients at Stanford University. Results. The overall prevalence of OB in patient s surviving longer than 3 months postoperatively was 64% after HLTx an d 68% after LTx. The actuarial freedom from OB was 72%, 51%, 44%, and 29% at 1, 2, 3, and 5 years, respectively, after HLTx and LTx. An anal ysis of potential risk factors revealed that the frequency and severit y of acute rejection episodes (p < 0.001) and the appearance of lympho cytic bronchiolitis on biopsy (p < 0.05) were significantly associated with the development of OB. With regard to diagnosis of OB, pulmonary function tests show early reductions of the forced expiratory flow be tween 25% and 75% of the forced vital capacity with subsequent decreas es in the forced expiratory volume in 1 second. The sensitivity of tra nsbronchial biopsies has increased to 71% since 1993. Current treatmen t consists of augmented immunosuppression. Concurrent acute rejection episodes or active OB on biopsy have been treated aggressively with hi gh-dose steroid pulses. Analysis of data from 73 patients with OB afte r HLTx and LTx revealed actuarial 1-, 3-, 5-, and 10-year survival of 89%, 71%, 44%, and 17% versus 86%, 77%, 63% and 56% in patients withou t OB (p < 0.05 by log-rank analysis). The main complication and cause of death in patients with OB was superimposed respiratory tract infect ion, which was treated aggressively. Conclusions. Early diagnosis of O B using pulmonary function tests or transbronchial biopsy is possible and important, because immediate treatment initiation has led to accep table survival rates, with nearly 50% of affected patients still alive 5 years after transplantation. Current experimental research on OB su ggests that immune injury is the main pathogenetic event of airway obl iteration in animal models; rapamycin and leflunomide are new immunosu ppressive agents that may have the potential to prevent and treat airw ay obliteration.