Am. J. Respir. Crit. Care Med., Volume 160, Number 6, December 1999, 2093-2099

In Stable Lung Transplant Recipients, Exhaled Nitric Oxide Levels Positively Correlate with Airway Neutrophilia and Bronchial Epithelial iNOS

ELI GABBAY, E. HAYDN WALTERS, BERNADETTE ORSIDA, HELEN WHITFORD, CHRISTOPHER WARD, TOM C. KOTSIMBOS, GREGORY I. SNELL, and TREVOR J. WILLIAMS

Department of Respiratory Medicine and Monash University Medical School, Alfred Hospital, Commercial Road, Prahran, Victoria, Australia

In conditions characterized by airway inflammation, exhaled nitric oxide (eNO) levels are increased. Variable degrees of airway inflammation are present in stable lung transplant recipients (LTR), and may lead to airway remodeling and chronic graft dysfunction. The hypothesis tested is that in stable LTR, eNO concentrations would reflect the expression of inducible (iNOS) (but not constitutive [cNOS] nitric oxide synthase) in the bronchial epithelium as well as the degree of airway inflammation. We determined eNO concentrations in 20 stable LTR, free of infection, rejection, or obliterative bronchiolitis (OB). At routine bronchoscopy, we measured the differential cell count on bronchoalveolar lavage (BAL) and a quantitative assessment of iNOS and cNOS expression in endobronchial biopsies by immunohistochemistry. Mean ± SEM eNO concentrations in stable LTR were not significantly different from control subjects (13 ± 0.7 ppb versus 14.2 ± 0.49; p = 0.42). Percent 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 bronchial epithelium and lamina propria contained abundant iNOS but cNOS was present only in the lamina propria. Using regression analysis, percent BAL neutrophils (r² = 0.82; p < 0.0001) and iNOS expression in the bronchial epithelium (r² = 0.75; p < 0.0001), but not in the lamina propria (r² = 0.16; p = 0.08), were positively predictive of eNO. There was an inverse relationship between cNOS and eNO. We conclude that eNO concentrations although normal for the group, still reflect the degree of airway inflammation in stable LTR. Epithelial iNOS appears to be the major source of eNO and expression of cNOS may be downregulated with increasing iNOS expression. Gabbay E, Walters EH, Orsida B, Whitford H, Ward C, Kotsimbos TC, Snell GI, Williams TJ. In stable lung transplant recipients, exhaled nitric oxide levels positively correlate with airway neutrophilia and bronchial epithelial iNOS.

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