Usefulness of Exhaled Nitric Oxide to Guide Risk Stratification for Bronchiolitis Obliterans Syndrome After Lung Transplantation

Abstract

The aim of this study was to assess fractional exhaled nitric oxide (FeNO) for the early diagnosis of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). 611 FeNO measurements in 166 consecutive patients were classified depending on BOS stage at the time of assessment and course during minimum follow-up of 3 months: (1) stable non-BOS, (2) unstable non-BOS, (3) stable BOS and (4) unstable BOS. Unstable course was defined as new onset of BOS≥1 or progression of BOS. FeNO before unstable course was significantly increased in comparison to their stable counterparts (non-BOS: 28.9 ± 1.2 ppb, n = 40 vs. 16.4 ± 0.8 ppb, n = 131 and BOS: 32.5 ± 1.3 ppb, n = 35 vs. 15.3 ± 0.8 ppb, n = 26; p = 0.01 each). Average time from FeNO reading to onset of deterioration was 117 ± 9 days in non-BOS and 136 ± 9 days in BOS patients. The positive and negative predictive value of FeNO >20 ppb for BOS was 69.0% and 96.9%, respectively. Serial measurements demonstrated significantly lower mean individual variation in stable recipients as compared to stable patients switching to unstable course (3.2 ± 0.3 ppb vs. 12.7 ± 1.4 ppb, p = 0.02). In particular, the excellent negative predictive value of persistently low FeNO readings for future BOS make FeNO assessments a useful tool for continuous risk stratification after LTX.