How is bronchiolitis obliterans syndrome (chronic rejection) following lung transplantation prevented and treated?

Updated: Aug 19, 2019
  • Author: Bryan A Whitson, MD, PhD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Prevention and treatment of bronchiolitis obliterans

Acute rejection is a major risk factor for BOS. Therefore, prevention of acute rejection likely leads to a decreased incidence of obliterative bronchiolitis. Some centers perform surveillance transbronchial biopsies during the first 2 years following transplantation. When the biopsies demonstrate acute rejection of grade A2 or higher, patients are treated with intensified immunosuppression. CMV infection also may be a risk factor for the development of obliterative bronchiolitis. Therefore, preventing CMV infection by transfusing CMV-negative blood products and using prophylactic ganciclovir may reduce the incidence of this devastating disease.

Early detection of BOS in a preclinical stage is ideal so that aggressive attempts can be made to prevent a fully developed syndrome. However, to date, no particular marker to indicate obliterative bronchiolitis, either from the peripheral blood or bronchoalveolar lavage fluid, has predicted a risk for this disease.

The treatment for established BOS has not proven to be effective. [54] The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society have published a clinical practice guideline on the diagnosis and management of BOS. All the treatment recommendations in the guideline are conditional, as the supporting evidence is of very low quality. The recommendations are as follows [55] :

  • Switching from cyclosporine to tacrolimus for long-term immunosuppression

  • A trial of azithromycin

  • Consideration of antireflux surgery, for patients with confirmed gastroesophageal reflux

  • Re-transplantation, for end-stage BOS refractory to all other therapies

The guidelines suggest not using sustained high-dose systemic corticosteroids (≥ 30 mg/day of prednisone or the equivalent) for the treatment of BOS, given the lack of proven benefit and the potential for serious adverse effects.

The guidelines note that beneficial effects have been reported for approximately 35–40% of lung transplant recipients treated with azithromycin, especially patients with BAL neutrophilia. Azithromycin is given orally at 250 mg per day for 5 days and then 250 mg three times per week, for a minimum of 3 months. It is unclear whether azithromycin should be continued long-term in patients who show a beneficial response.


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