Measurement of Bronchial and Alveolar Nitric Oxide Production in Normal Children and Children with Asthma

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Abstract
Rationale: Airway inflammation is characteristic of asthma. Distal inflammation may be particularly important. Objective: To calculate alveolar nitric oxide (NO) concentration (Calv) and bronchial flux NO (JNO) in children. Methods: We measured Calv and JNO from the fractional exhaled NO (FeNO50) measured at multiple exhalation flow rates in 132 children (aged 4–18 yr) with known atopic status, medication, and asthma control. Measurements and Main Results: Of participants, 85% (112/132) completed all measurements. In 20 of 112, the result did not fit the linear model. Thus, JNO and Calv were assessed in 92 (70%) subjects. The median (range) values of asthmatic (n = 52), normal (n = 20), and nonasthmatic atopic (n = 20) children were as follows: FeNO50: 28.1 (4.3–190), 10.35 (3.3–29), 21.8 (8.7–69) ppb, respectively; JNO: 1,230 (204–9,236), 480 (196–1,913), 1,225 (486–4,119) pl/s, respectively; Calv: 2.22 (0.44–6.63), 1.63 (0.44–3), 1.21 (0.03–2.85) ppb, respectively. A reproducibility study in 18 other children gave intraclass correlation coefficients (single measures) of 0.99 (JNO) and 0.81 (Calv). JNO and Calv were higher in children with asthma than normal children (p = 0.0004 and p = 0.0002, respectively). Children with poorly controlled asthma (n = 27) had higher FeNO50 measurements than children with good symptom control (n = 25): Calv: mean (± SD), 3.17 ± 1.62 versus 2.26 ± 1.30 ppb, p = 0.03; JNO: mean (± SD), 2,634 ± 2,255 versus 1,193 ± 1,294 pl/s, p = 0.007, respectively. Conclusions: Measurement of JNO and Calv is feasible in 70% of school-age children. FeNO50 and JNO give the same information (r = 0.97, p < 0.0001), Calv is higher in asthmatic children than in normal children and is affected by asthma control, but not by atopy. Calv may possibly reflect alveolar inflammation in asthma.