A simple flow-driven method for online measurement of exhaled NO starting at the age of 4 to 5 years

NO is increased in exhaled air of asthmatic patients, and may be used as a marker of airway inflammation. The online method is a standardized technique for measuring exhaled nitric oxide (ENO). However, this method has proven difficult for some children, who may have trouble maintaining a constant expiratory flow. The aim of this study was to validate a modified technique for online ENO measurement that utilizes a flow regulator to overcome the patient problem of having to actively maintain a constant expiratory flow. We measured ENO levers with two methods in 105 asthmatic and 10 healthy subjects, comparing the standardized (ST) single-breath method with a modified single-breath, flow-driven (FD) method. With the ST method and visual monitoring, the subjects inhaled NO-free air to TLC, and exhaled with a target flow of 50 ml/s. With the FD method, the subjects exhaled from TLC and flow was kept constant (50 ml/s) by the operator, using a flow regulator. The subjects were divided into two groups, one consisting of children aged 4 to 8 yr (n = 74) and the other of children aged 9 to 16 yr (n = 41). In the group aged 4 to 8 yr, 38 children (51%) were unable to perform the ST method, whereas only five children (7%) failed to perform the FD technique. In the group aged 9 to 16 yr, only four children (10%) were unable to perform the ST maneuver, and all successfully performed the FD maneuver. The mean concentrations of ENO in the 73 children who performed both types of maneuver were similar (36.1 +/- 3.4 [mean +/- SEM] ppb with the ST method and 33.8 +/- 3.3 ppb with the FD technique, p = NS) and were highly correlated with one another (r = 0.99, p < 0.0007). ENO values were significantly higher in steroid-naive than in steroid-treated asthmatic children. In conclusion, we describe a modified online method for measuring ENO that is simple, does not require active cooperation to maintain a constant expiratory flow, and can be easily performed by children from 4 to 5 yr of age onward.