Eur Respir J 2005; 26:359-360
Copyright ©ERS Journals Ltd 2005
From the authors
J. E. Brussee1,
H. A. Smit1,
B. Brunekreef2 and
J. C. de Jongste3
1 Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment, Bilthoven, 2 Institute for Risk Assessment Sciences, Utrecht University, Utrecht, 3 Dept of Paediatrics, Division of Respiratory Medicine, Sophia's Children's Hospital, Erasmus University Medical Centre, Rotterdam, the Netherlands.
We would like to thank S. Turner for his interest in our work, and we are pleased to comment on the methodological issues raised.
The first issue deals with the reproducibility of the fraction of exhaled nitric oxide (FeNO) measurement within a child. In our study 1, we observed a good correlation between the first and the second FeNO measurements from the children (Spearman r = 0.73; p<0.001). Also, in the majority of the children, the mean difference between the duplicate FeNO measurements was <5 ppb (89%), whereas, in a small minority of children, the difference was >10 ppb (2%; fig. 1
). To find a reasonable balance between the reproducibility of the measurement on the one hand, and the maintenance of sufficient numbers of children on the other hand, we chose to include all children for whom the difference between the duplicate FeNO measurements was within 10 ppb. Separate analyses of children for whom the duplicate measurements were within 5 ppb produced similar results. For example, in the total study population, the geometric mean FeNO values in ppb (95% confidence interval) for children with and without a doctor's diagnosis of asthma were 9.4 (7.6–11.7) and 7.6 (7.3–8.0), respectively (p = 0.06), instead of 10.0 (8.3–12.1) and 7.9 (7.5–8.2), respectively (p<0.05), when duplicate samples were within 10 ppb from each other. With respect to atopy, these numbers were 9.1 (8.0–10.4) and 7.4 (7.0–7.9), respectively (p<0.05), for samples within 5 ppb, and 9.4 (8.4–10.5) and 7.7 (7.2–8.1), respectively (p<0.05), for samples within 10 ppb. So, when more stringent criteria were applied, the FeNO values were not more discriminative between children with and without asthma or atopy.
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Fig. 1— Bland Altman plot of the agreement between the duplicate fraction of exhaled nitric oxide (FeNO) measurements, indicating the mean difference between the duplicate FeNO measurements ( ) and the mean difference ±2SD (-----). The open and solid circles indicate the children for whom the difference between duplicate FeNO measurements was <10 ppb or >10 ppb, respectively. The x-axis is logarithmic.
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With respect to the ambient nitric oxide values, we have examined their effect on exhaled nitric oxide. Since there was no significant influence of ambient nitric oxide levels <20 ppb on the fraction of exhaled nitric oxide values in our study population (figs 2 and 3), we decided to include all children with ambient nitric oxide levels <20 ppb in the analyses. When the analyses were repeated, including only those children for whom the ambient nitric oxide values were <10 ppb, similar results were observed.
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Fig. 2— The influence of ambient nitric oxide (NO) levels on the fraction of exhaled nitric oxide (FeNO) values in the study population. The x-axis is logarithmic.
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Fig. 3— The influence of ambient nitric oxide (NO) levels <20 ppb on the fraction of exhaled nitric oxide (FeNO) levels in the study population.
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REFERENCES
- Brussee JE, Smit HA, Kerkhof M, et al. Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopy. Eur Respir J 2005;25:455–461.[Abstract/Free Full Text]
