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

Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London; Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom

Correspondence and requests for reprints should be addressed to Emmanouil Paraskakis, M.D., Ph.D., Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. E-mail: paraskakis{at}edu.med.uoc.gr

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.

Key Words: airway monitoring • exhaled • pulmonary