In stable lung transplant recipients, exhaled nitric oxide levels positively correlate with airway neutrophilia and bronchial epithelial iNOS

In conditions characterized by airway inflammation, exhaled nitric oxide (e NO) levels are increased. Variable degrees of airway inflammation are prese nt in stable lung transplant recipients (LTR), and may lead to airway remod eling and chronic graft dysfunction. The hypothesis tested is that in stabl e LTR, eNO concentrations would reflect the expression of inducible (iNOS) (but not constitutive [cNOS] nitric oxide synthase) in the bronchial epithe lium as well as the degree of airway inflammation. We determined eNO concen trations in 20 stable LTR, free of infection, rejection, or obliterative br onchiolitis (OB). At routine bronchoscopy, we measured the differential cel l count on bronchoalveolar lavage (BAL) and a quantitative assessment of iN OS and cNOS expression in endobronchial biopsies by immunohistochemistry. M ean +/- SEM eNO concentrations in stable LTR were not significantly differe nt from control subjects (13 +/- 0.7 ppb versus 14.2 +/- 0.49; p = 0.42). P ercent BAL neutrophils was 11.5 +/- 3.2 which was significantly higher than in a group of local control subjects (1.7 +/- 0.6; p < 0.001). The bronchi al epithelium and lamina propria contained abundant iNOS but cNOS was prese nt only in the lamina propria. Using regression analysis, percent BAL neutr ophils (r(2) = 0.82; p < 0.0001) and iNOS expression in the bronchial epith elium (r(2) = 0.75; p < 0.0001), but not in the lamina propria (r(2) = 0.16 ; p = 0.08), were positively predictive of eNO. There was an inverse relati onship between cNOS and eNO. We conclude that eNO concentrations although n ormal for the group, still reflect the degree of airway inflammation in sta ble LTR. Epithelial iNOS appears to be the major source of eNO and expressi on of cNOS may be downregulated with increasing iNOS expression.