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Updated: Mar 28, 2026
Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Extended nitric oxide analysis may improve personalized anti-inflammatory treatment in asthmatic children with
A Thornadtsson1, A H Neerincx, M Högman
1Respiratory, Allergy and Sleep Research, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Centre for Clinical Research, Uppsala University/Region Gävleborg, Uppsala, Sweden.
Insights
Exhaled nitric oxide (F(E)NO) levels in children with asthma can indicate eosinophilic inflammation. Extended NO analysis may help personalize inhaled corticosteroid treatment by assessing airway wall content (CawNO).
Area of Science:
- Pediatric Pulmonology
- Respiratory Medicine
- Biomarkers
Background:
- Elevated exhaled nitric oxide (F(E)NO) is a hallmark of asthma, particularly eosinophilic inflammation.
- Clinical guidelines suggest F(E)NO thresholds to guide anti-inflammatory treatment, specifically inhaled corticosteroids (ICS).
- The interpretation of intermediate F(E)NO levels requires further investigation in pediatric asthma.
Purpose of the Study:
- To evaluate a clinical practice guideline for F(E)NO interpretation in asthmatic children.
- To investigate the utility of extended nitric oxide analysis, including airway wall content (CawNO), in a pediatric asthma cohort.
- To determine if CawNO can refine treatment decisions for children with intermediate F(E)NO levels.
Main Methods:
- Thirty-seven asthmatic children provided exhaled breath samples for offline nitric oxide (NO) measurement.
- Extended NO analysis using the Högman-Meriläinen algorithm (HMA) was performed at three flow rates to estimate alveolar concentration (C(A)NO), diffusion rate (D(aw)NO), and airway wall content (CawNO).
- Measured F(E)NO at 50 ml/s (F(E)NO50) was compared with HMA-estimated F(E)NO50, with data excluded if the difference exceeded 5 ppb.
Main Results:
- Children with F(E)NO50 > 35 ppb (n=10) showed elevated CawNO (140 ppb) and reported allergies.
- Children with F(E)NO50 < 20 ppb (n=5) had no known allergies and lower CawNO (32 ppb).
- Among children with intermediate F(E)NO50 (20-35 ppb, n=13), eight had elevated CawNO (108 ppb), suggesting potential for ICS benefit, while five had values comparable to healthy children.
Conclusions:
- Extended NO analysis, particularly CawNO, shows clinical potential for personalizing F(E)NO target values in pediatric asthma monitoring.
- Considering CawNO may help identify children with intermediate F(E)NO50 who could benefit from adjusted inhaled corticosteroid therapy.
- This approach may improve treatment efficacy by tailoring anti-inflammatory strategies based on individual airway inflammation markers.
Abstract:
Exhaled nitric oxide (F(E)NO) is elevated in asthma, and a clinical practice guideline has been published with recommendations for anti-inflammatory treatment. It summarizes that a F(E)NO at an expiratory flow rate of 50 ml s(-1) (F(E)NO50) above 35 ppb in children indicates eosinophilic inflammation, and the most likely response is to use inhaled corticosteroids. Intermediate F(E)NO50 between 20-35 ppb should be interpreted cautiously. The aim of the study was to investigate this guideline in a small group of asthmatic children. Thirty-seven asthmatic children; 23 boys and 14 girls, visited the outpatient clinic, and provided exhaled breath samples for offline NO measurement. These samples were analysed with chemiluminescence techniques. Three flow rates, namely 16, 90 and 230 ml s(-1) were used for the extended NO analysis (Högman-Meriläinen algorithm, HMA) to estimate the alveolar concentration (C(A)NO), diffusion rate of the airway wall (D(aw)NO) and airway wall content (C(aw)NO). For accuracy of the HMA, the estimated value of F(E)NO at 50 ml s(-1) (F(E)NO50) was compared with measured F(E)NO50. In nine children the difference was more than 5 ppb and the data were therefore excluded. Five children with F(E)NO50 <20 ppb had no known allergy and their F(E)NO50 geometrical mean (25th; 75th percentile) was 11 (10;14) and CawNO was 32 (20;43) ppb. Ten children with F(E)NO50 > 35 ppb had an allergy and had F(E)NO50 of 56 (47;60) ppb and C(aw)NO of 140 (121;172) ppb. Thirteen children with allergies, with intermediate F(E)NO50, had F(E)NO50 of 27 (25;30) ppb with a wide range of C(aw)NO. In five of these children, values were comparable to healthy children, 44 (43;50) ppb while eight children had elevated C(aw)NO values of 108 (95;129) ppb. Our data indicate the clinical potential use of extended NO analysis to determine the personal target value of F(E)NO50 for monitoring the treatment outcome. Furthermore, for children with intermediate F(E)NO50 more than half of them could possibly benefit from an adjustment of inhaled corticosteroids if the C(aw)NO value was considered.
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