| 1) For lung transplant recipients who have non-minimal acute cellular rejection (Grade ≥2) or lymphocytic bronchitis on transbronchial lung biopsy specimens, we suggest augmented immunosuppression with a course of systemic steroids to prevent the development of BOS (conditional recommendation, very low quality of evidence). Values and preferences: this recommendation places a high value on preventing a life-threatening complication of lung transplantation and a lower value on avoiding short-term adverse effects. Remarks: a typical course of systemic corticosteroids used to augment immunosuppression in adult recipients is intravenous methylprednisolone 1000 mg daily for 3 days (many centres use 10–15 mg·kg−1 per day for smaller patients). |
| 2) For lung transplant recipients who have clinically significant minimal acute cellular rejection (Grade A1) on transbronchial lung biopsy specimens, we suggest augmented immunosuppression with a course of systemic steroids to prevent the development of BOS if the finding of grade A1 acute cellular rejection is perceived to be clinically significant (conditional recommendation, very low quality of evidence). Values and preferences: this recommendation places a high value on preventing a life-threatening complication of lung transplantation and a lower value on avoiding short-term side-effects. Remarks: we consider Grade A1 acute cellular rejection to be clinically significant if it is associated with clinical findings, such as symptoms (e.g. dyspnoea, fatigue or new-onset cough) or objective measurements (e.g. decline in FEV1 or oxyhaemoglobin desaturation with ambulation), that suggest the presence of allograft dysfunction. A typical course of systemic steroids used to augment immunosuppression in adult recipients is intravenous methylprednisolone 1000 mg daily for 3 days (many centres use 10–15 mg·kg−1 per day for smaller patients). |
| 3) For lung transplant recipients who develop a decline in FEV1 consistent with the onset of BOS, we suggest that clinicians do not use long-term, high-dose corticosteroids (conditional recommendation, very low quality of evidence). Values and preferences: this recommendation places a high value on avoiding harmful effects due to ineffective therapies. Remarks: we define sustained administration of high-dose corticosteroid as ≥30 mg·day−1 of prednisone or an equivalent formulation. |
| 4) For lung transplant recipients who develop BOS while receiving chronic immunosuppression with a regimen that includes cyclosporine, we suggest switching the cyclosporine to tacrolimus (conditional recommendation, very low quality of evidence). Values and preferences: this recommendation places a higher value on mitigation of lung function decline and a lower value on avoiding nephrotoxicity and hyperglycaemia. Remarks: the conversion of cyclosporine to tacrolimus is generally performed by stopping cyclosporine and initiating tacrolimus while transiently increasing maintenance corticosteroid dosing until tacrolimus blood levels are ascertained to have reached the desired target range. The target for therapeutic trough blood levels of tacrolimus is generally considered to range from 5 to 15 ng·mL−1 for patients who are ≥18 years of age once a steady state has been attained. |
| 5) For lung transplant recipients who develop a decline in FEV1 consistent with the onset of BOS, we suggest a trial of azithromycin (conditional recommendation, very low quality of evidence). Values and preferences: this recommendation places a high value on preventing lung function deterioration and possibly reducing mortality, and a lower value on avoiding adverse effects. Remarks: azithromycin is generally administered orally at 250 mg per day for 5 days and then at 250 mg three times per week. We define a trial of azithromycin as treating continuously with azithromycin for a minimum of 3 months. Additionally, it is unclear 1) whether azithromycin should be continued long-term if a beneficial response is observed, or 2) whether it should be discontinued if lung function does not show improvement during follow-up clinical evaluation. |
| 6) For lung transplant recipients who develop a decline in FEV1 consistent with the onset of BOS and have confirmed GOR, we suggest referral to an experienced surgeon to be evaluated for potential fundoplication of the gastro-oesophageal junction (conditional recommendation, very low quality of evidence). Values and preferences: this recommendation places a high value on reducing the risk of lung function deterioration, and possibly mortality, and a lower value on avoiding surgical complications. Remarks: Nissen fundoplication has been more extensively studied than Toupet fundoplication; however, we have no reason to believe that one is superior to the other and feel that the choice of the surgical technique should remain at the surgeon’s discretion. |
| 7) For lung transplant recipients who have developed end-stage BOS refractory to other therapies, we recommend referral to a transplant surgeon to be evaluated for re-transplantation (conditional recommendation, very low quality of evidence). Values and preferences: this recommendation places a high value on avoiding surgical complications (e.g. mortality), recurrent BOS and resource utilisation. Remarks: the selection process for re-transplantation is the same as that used for first-time lung transplantation. |
BOS: bronchiolitis obliterans syndrome; FEV1: forced expiratory volume in 1 s; GOR: gastro-oesophageal reflux.