Serial monitoring of exhaled nitric oxide in lung transplant recipients

Abstract

Background: Exhaled nitric oxide (FeNO), a marker of airway inflammation, is often elevated in lung transplant recipients (LTxRs) with acute rejection or infection. Isolated measurements in the setting of bronchiolitis obliterans syndrome have been variable. We sought to assess the utility of serial FeNO in predicting chronic allograft dysfunction or the presence of acute rejection or infection.

Methods: Eighty-six LTxRs underwent 325 serial FeNO measurements at an expiratory flow rate of 50 ml/s. The change in FeNO (ΔFeNO) between two measurements obtained during a stable state (ΔFeNO-SS) was compared with ΔFeNO, where the first measurement was taken during a stable state and the second during an unstable state (defined as a subsequent decline in FEV1 > 10% over 3 months [ΔFeNO-SU]) or an acute complication (acute rejection, lymphocytic bronchiolitis or acute infection [ΔFeNO-SAC]). The median follow-up time after the baseline FeNO was 10 (range 3 to 25) months.

Results: ΔFeNO-SS in 117 FeNO pairs was similar to ΔFeNO-SU in 26 pairs (2.1 ± 3 ppb vs 2.3 ± 4 ppb; p = 0.2). ΔFeNO-SAC in 17 pairs was markedly increased (27 ± 20 ppb; p < 0.001 vs ΔFeNO-SS). The area under the receiver-operating characteristic curve for ΔFeNO in detecting an acute complication was 0.93 (p < 0.001). By applying a cut-off of >10 ppb, the sensitivity and specificity was 82% and 100%, respectively, with positive and negative predictive values of 100% and 97.5%.

Conclusions: Changes in FeNO may serve as a useful adjunct in the detection of acute complications after lung transplantation. In this limited analysis, ΔFeNO was not predictive of a subsequent decline in allograft function.

Keywords: acute rejection; bronchiolitis obliterans syndrome; exhaled nitric oxide; infection; lung transplantations.