Low exhaled nitric oxide and a polymorphism in the NOS I 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 (FE(NO)) are abnormal in children with a history of the acute chest syndrome (ACS). We compared FE(NO), plasma nitric oxide metabolites (NO(x)), serum arginine and citrulline levels, and the number of AAT repeats in intron 20 of NOS I in subjects with sickle cell disease (SCD) 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 FE(NO) (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 NO(x) (microM) were similar in all three groups (37.3 +/- 19.4, 33.0 +/- 13.2, 44.7 +/- 7.8, respectively). Arginine and citrulline levels (microM) did not differ between ACS(+) and ACS(-) groups. Spirometric data revealed a mildly diminished FEV(1) and FVC in ACS(+) that was statistically different from HC but not ACS(-): (FEV(1) 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 FE(NO) 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 FE(NO) levels are significantly reduced in subjects who have a history of ACS and that the FE(NO) levels are significantly correlated with the number of NOS I AAT repeats. FE(NO) is a sensitive marker and may be a predictor of ACS prone children.

Exhaled nitric oxide as an indicator of severity of asthmatic inflammation.

Traditional assessment of severity of asthma relies on an evaluation of signs and symptoms and pulmonary function tests. These pulmonary function tests, such as peak expiratory flow rates, forced vital capacity, and forced expiratory flow rates, are indirect measures of airway caliber only, and not inflammation. Since asthma is an inflammatory disease, a measure of the degree of inflammation would be helpful in quantitating severity and titrating of anti-inflammatory therapy. A noninvasive method for measuring pulmonary inflammation would therefore be helpful to assist the emergency physician in initial treatment and assist in titration of anti-inflammatory therapy during repeat visits. Exhaled nitric oxide (NO) assays are convenient and practical and may fulfill this role. In this review, we discuss the role of NO in asthmatic inflammation and the role that exhaled NO values may play in the emergency management of asthma.

FE(NO): relationship to exhalation rates and online versus bag collection in healthy adolescents.

Measurement of exhaled nitric oxide (FE(NO)) is a noninvasive and practical method for assessing airway inflammation. We conducted this investigation to determine the most appropriate flow rate for FE(NO) measurement and to obtain normal values for FE(NO). We determined which expiratory flow was easy to sustain, generated reproducible values, and provided good correlation between offline and online measurements. Thirty-two healthy subjects (15- 18 yr old) underwent spirometry and FE(NO) measurements, using a chemiluminescent NO analyzer at expiratory flow rates of 46, 31, 23, 15, 10, 7, 5, and 4 ml/s. The major findings were as follows: (1) FE(NO) increased as flow rates decreased, with strong correlation between FE(NO) values and flow rates at the four highest flows (0. 85- 0.93, p < 0.001); (2) there were no significant differences and good agreement between offline bag and online FE(NO) values for the four highest flows (p < 0.09-0.83); (3) online FE(NO) values increased with age 15-17 yr at all flow rates, but decreased at age 18 yr; and (4) using multiple regression, significant predictors of FE(NO) were flow, body surface area, age, and FEF(25-75). On the basis of these results, we provide FE(NO) values for healthy adolescents and propose that the ideal flow rate for children is between 30 and 50 ml/s.