Low exhaled nitric oxide and a polymorphism in the NOSI gene is associated with acute chest syndrome

Abnormalities of nitric oxide metabolism have been implicated in the pathogenesis of acute chest syndrome in subjects with sickle cell anemia. It is not known whether exhaled nitric oxide levels (FENO) are abnormal in children with a history of the acute chest syndrome (ACS). We compared FENO, plasma nitric oxide metabolites (NOx), serum arginine and citrulline levels, and the number of AAT repeats in intron 20 of NOS I in subjects with sickle cell disease (SCID) and a history of at least one episode of ACS (ACS(+) n = 13), subjects with SCD and no prior history of ACS (ACS(-), n 7), and healthy children (HC, n = 6). Mean +/- SD FENO (ppb) was lower in ACS(+) than in ACS(-) and HC: (10.4 +/- 4.3 versus 23.4 +/- 6.1 [p = 0.002] and 30.4 +/- 15.8 [p = 0.0001], respectively). Plasma NOx (muM) were similar in all three groups (37.3 +/- 19.4, 33.0 +/- 13.2, 44.7 +/- 7.8, respectively). Arginine and citrulline levels ( muM) did not differ between ACS(+) and ACS(-) groups. Spirometric data revealed a mildly diminished FEV1 and FVC in ACS(+) that was statistically different from HC but not ACS(-): (FEV1 as % of predicted for ACS(+), ACS(-), and HC; 83 +/- 17 versus 87 +/- 16 versus 102 +/- 16, respectively, p < 0.05 between ACS(-) and HC). The level of FENO was significantly associated with the sum of AAT repeats in intron 20 of NOS I gene alleles. The correlation coefficient (r) was 0.62 (p < 0.005). We conclude that FENO levels are significantly reduced in subjects who have a history of ACS and that the FENO levels are significantly correlated with the number of NOS I AAT repeats. FENO is a sensitive marker and may be a predictor of ACS prone children.