Alveolar concentration and bronchial flux of nitric oxide: Two linear modeling methods evaluated in children and adolescents with allergic rhinitis and atopic asthma

Objective Alveolar concentration (C A NO) and bronchial flux (J aw NO) of nitric oxide (NO) characterize the contributions of peripheral and proximal airways to exhaled NO. Both parameters can be estimated using a two‐compartment model if the fraction of NO in orally exhaled air (FE NO ) is measured at multiple constant expiratory flow rates (V). The aim of this study was to evaluate how departures from linearity influence the estimates of C A NO and J aw NO obtained with the help of linear regression analysis of the relationships between FE NO and 1/V (method P), and between the NO output (V NO  = FE NO  × V) and V (method T). Furthermore, differences between patients with atopic asthma (AA) and allergic rhinitis (AR) and between methods P and T were assessed. Design Measurements of FE NO were performed with a chemiluminiscence analyzer at five levels of V ranging from 50 to 250 ml/sec in school children and adolescents with mild to moderate‐severe AA treated by inhaled corticosteroids (N = 42) and AR (N = 20). Results Violation of the linearity condition at V ≤ 100 ml/sec caused shifts between methods with regard to the partition of exhaled NO into alveolar (C A NO: P > T) and bronchial (J aw NO: T > P) components. Both methods gave similar results in the linear range of 150–250 ml/sec: The mean ratios P/T and limits of agreement calculated in AA and AR patients were 1.03 (0.49–1.56) and 1.07 (0.55–1.59) for C A NO and 1.03 (0.73–1.33) and 0.99 (0.90–1.10) for J aw NO, respectively. No significant differences between AA and AR were found in C A NO and J aw NO calculated in the linear range by the T method {medians (inter‐quartile ranges): 1.7 ppb (0.9–3.9) vs. 2.3 ppb (0.8–3.7), P  = 0.91; 1,800 pl/sec (950–3,560) vs. 1,180 pl/sec (639–1,950), P  = 0.061}. However, the flow‐dependency of the estimates was markedly higher in AA than in AR patients: C A NO was decreased 2.8‐fold vs. 1.5‐fold and J aw NO was increased 1.5‐fold vs. 1.2‐fold in the linear range as compared to the range of 50–250 ml/sec. In both groups, the median standard errors (SE) of the J aw NO estimates were similar for the metods P and T and small (<15%) regardless of the range for expiratory flows. The precision of C A NO estimates was less in all ranges. For both methods, the SE of the estimates obtained in the range of 150–250 ml/sec exceeded 50% in asthmatics and 30% in AR patients, respectively. The results show that FE NO has to be measured at several expiratory flows ≥100 ml/sec for the accurate estimation of C A NO and J aw NO using linear methods P and T in children and adolescents with AA and AR. A stepwise procedure for detecting nonlinearity and evaluating the quality of FE NO measurements is suggested. Pediatr Pulmonol. 2012. 47:1070–1079. © 2012 Wiley Periodicals, Inc.