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

Abstract

Rationale: Airway inflammation is characteristic of asthma. Distal inflammation may be particularly important. Objective: To calculate alveolar nitric oxide (NO) concentration (C_alv) and bronchial flux NO (J_NO) in children. Methods: We measured C_alv and J_NO 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, J_NO and C_alv 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; J_NO: 1,230 (204–9,236), 480 (196–1,913), 1,225 (486–4,119) pl/s, respectively; C_alv: 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 (J_NO) and 0.81 (C_alv). J_NO and C_alv 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): C_alv: mean (± SD), 3.17 ± 1.62 versus 2.26 ± 1.30 ppb, p = 0.03; J_NO: mean (± SD), 2,634 ± 2,255 versus 1,193 ± 1,294 pl/s, p = 0.007, respectively. Conclusions: Measurement of J_NO and C_alv is feasible in 70% of school-age children. FeNO₅₀ and J_NO give the same information (r = 0.97, p < 0.0001), C_alv is higher in asthmatic children than in normal children and is affected by asthma control, but not by atopy. C_alv may possibly reflect alveolar inflammation in asthma.