Accuracy of exhaled nitric oxide measurements for the diagnosis of bronchiolitis obliterans syndrome after lung transplantation

Abstract

Background: Exhaled nitric oxide (eNO) is increased in patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation. However, the accuracy of eNO measurements in diagnosing BOS is unknown.

Methods: Thirty-two lung-transplant patients were included. Their immunosuppressive regimen consisted of cyclosporin A (tacrolimus), azathioprine (mycophenolate mofetil), and oral but no inhaled steroids. eNO levels and spirometry were prospectively followed until 2 years after transplantation or until the patient developed BOS.

Results: Thirteen patients (group A) developed BOS (607 +/- 158 days after transplantation). Their mean eNO level at that time was 24.3 +/- 13.2 parts per billion (ppb), whereas the eNO value in the stable patients at 2 years (group B) was 11.4 +/- 4.9 ppb, P=0.0054. All group A patients had an eNO of 15 or greater ppb. Seven patients of group B also had an eNO of 15 or greater ppb, resulting in a test accuracy for the diagnosis of BOS of 0.78. However, considering only those patients who had two consecutive measurements (3-6 weeks apart) of eNO 15 or greater ppb during the months preceding the diagnosis of BOS or in the whole 2-year evaluation period, only 3 of 19 patients in group B (false-positives) but 12 of 13 in group A (1 false-negative) now fulfilled that criteria, which became positive at a mean of 263 +/- 169 days before the diagnosis of BOS was met, based on the forced expiratory volume in 1 second criteria. This increased the accuracy to 0.88.

Conclusion: Measurements of eNO appear to be an accurate test for the early diagnosis of BOS.