Increase in Alveolar Nitric Oxide in the Presence of Symptoms in Childhood Asthma. Part 4

One approach, described by Tsoukias and George, takes advantage of the fact that the relationship between Q NO and V appears to be linear above a threshold of 50 mL/s. The second approach, described by Silkoff and colleagues, is based on the nonlinear relationship observed between (Qno and V (< 50 mL/s), which gives additional information on the proximal airway characteristics of the QNO.

Both the linear and the nonlinear models allow characterizing distal (18th generation and beyond) and proximal airway (Qno by lower airways. It can be assumed that such models can be used in children due to similar physiologic characteristics as in adults; along this line, a study has demonstrated similar value for FAno in healthy children than previously reported in healthy adults.

Linear Model for Flow Rates > 50 mL/s

Simultaneously measured FEno and V values were used to calculate QNO as follows:

Qno = FEno X V X 0.06

where QNO is expressed in nanoliters per minute, FEno in parts per billion (ppb), and V in milliliters per second (0.06 is a unit correcting factor).

The calculated QNO was represented as a function of flow rate. Least-square linear regression was performed for flow rates > 50 mL/s. In this range of flows, lumenal NO concentration can be considered as negligible compared to airway wall concentration, so that the proximal airway (Qno is maximal and constant, whatever the flow rate. Tsoukias and George have shown that the slope of this linear relationship is representative of the constant FAno, and the intercept at zero flow of the Qbr,maxNO. At least two measurements at different ranges of V are necessary to determine FAno and Qbr,maxNO by this way. The knowledge of the relationship allows to calculate FEno at different V rates, which are computed as follows:

FeNO (V) = FAno + Qbr,maxNo/(V X 0.06) where V is the chosen V rate.

We have previously shown that the height of the subject influences Qbr,maxNO, and consequently exhaled NO, probably by affecting the size of airways. Consequently, it was important to ensure that the three groups of patients were comparable regarding their height. Moreover, the healthy group of children allowed to test whether their height similarly affected Qbr,maxNO than demonstrated in healthy adults.

Nonlinear Model With Flow Piates < 60 mL/s

When at least one low flow (40 to 60 mL/s) and one very low flow (< 40 mL/s) were computed, FAno, NO concentration in the airway wall (Cw,no), and proximal airway NO diffusing capacity (Dno) can be computed as described by Silkoff and colleagues:

FEno = Cw,no X (1 – e-DNO/v) + FAno X e-Dno/V

where e is exponential, and V is expiratory flow rate. The parameters of the model were calculated by using the solver function in Excel 97 software (Microsoft; Redmond, WA) to minimize the sum of the square residual values for FEno.