Post-transplant changes in exhaled nitric oxide (eNO) of pulmonary transplant recipients and the influence of mycophenolate (MMF)

Abstract

The role of eNO in lung transplantation has emerged as a useful marker for allograft airway inflammation. eNO is produced by nitric oxide synthases including iNOS. This enzyme isoform is inhibited by Mycophenolate (MMF) in endothelial cells (Senda, 1995, Transplantation). It is not known if MMF can inhibit human respiratory epithelial iNOS. We therefore assessed the changes in eNO post-transplant and compared differences in eNO and lung function between patients treated with MMF and azathioprine (AZA). Methods; 28 lung transplant recipients entered into a randomised multi-centre trial of MMF vs. AZA were followed over 1 year. Single breath eNO was measured by chemi-luminescence within the first 10 days post op, 1 month and then at 3 monthly intervals as was lung function. We used a Logan LR 2000; a clinically significant intra-patient change is 2-3ppb using this method. 16 received MMF and 12 AZA (14 females and 14 males). There were no baseline differences in the eNO between MMF and AZA groups. There was a significantly lower first eNO (within 10 days of transplant) than at 1 month, 3 months and 6 months that was clinically and statistically significant (paired t-test); difference of means 3ppb p=0.002, 3 ppb p=0.002, 2.5 ppb p=0.001 respectively. There were no statistical nor clinically significant differences in eNO between any of the other time-points. There were no differences in FEV1 between MMF and AZA groups at any time point. eNO levels are depressed in the immediate post-transplant period but rise to baseline levels by one month possibly reflecting changes in immunosuppressant regimens. Researchers assessing eNO in pulmonary transplant recipients should not use early post-op eNO levels to establish a patients baseline. Treatment with MMF does not appear to reduce eNO levels or improve lung function at 1 year in pulmonary transplant recipients as compared to those treated with AZA. The long term follow up of these patients and the rates of chronic rejection are however awaited with interest.