Measurement of bronchial and alveolar nitric oxide production in normal children and children with asthma

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 UNO) 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;]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 (]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 JNO 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.