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Comparison of measured exhaled nitric oxide at varying flow rates
  1. D Menzies,
  2. T Fardon,
  3. P Burns,
  4. B J Lipworth
  1. Asthma & Allergy Research Group, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
  1. Correspondence to:
    Dr D Menzies
    Asthma & Allergy Research Group, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK;

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Altered levels of exhaled nitric oxide (FeNO) have been well documented in a number of conditions, although it is in asthma that this phenomenon has been most extensively investigated.1 Raised FeNO levels in patients with asthma have been correlated not only with other markers of airway inflammation (including induced sputum eosinophil count), but also with airway hyperresponsiveness and response to inhaled corticosteroids.2 Furthermore, the detection of a raised FeNO level has been shown to have a positive predictive value of up to 95% for the diagnosis of asthma.3

A number of factors can influence the production and measurement of FeNO including airway calibre, caffeine, smoking and, in particular, respiratory flow rate. A standardised flow rate of 50 ml/s has recently been adopted by both the European Respiratory Society and the American Thoracic Society; however, to date, there has been a discrepancy in the rates used by clinicians and researchers worldwide.4 The Logan LR 2000 chemiluminescence analyser (Logan Research Ltd, UK) uses a mouth flow rate of 250 ml/s to measure FeNO while the Niox® Nitric Oxide Analyzer (Aerocrine AB, Sweden) uses a flow rate of 50 ml/s. Both analysers use online measurements to calculate FeNO, express the results in parts per billion (ppb), and have similar accuracies.

Few data are available to allow direct comparison between the two analysers and hence flow rates. This can make comparison of studies using the different methods difficult. We have prospectively analysed the FeNO from asthmatic (n = 63) and non-asthmatic (n = 29) adult patients with both devices in a head to head fashion. The geometric mean for the FeNO using the Niox analyser was 25.6 (95% CI 24.4 to 26.8) ppb for asthmatics and 16.8 (95% CI 15.6 to 18.0) ppb for non-asthmatics (p<0.01). With the Logan LR 2000 the values were 6.8 (95% CI 5.6 to 8.0) ppb in asthmatics and 4.4 (95% CI 3.1 to 5.7) ppb in non-asthmatics (p<0.01). The pooled data from the Niox and Logan LR 2000 were found to be closely correlated to one another (r2 = 0.62, p<0.001). Altman-Bland plots of the data obtained support the suggestion that there is a high level of agreement between the two methods (fig 1). This agreement is retained when subgroup analysis of asthmatics and non-asthmatics is performed. The slightly better discrimination between asthmatics and non-asthmatics at lower flow rates (shown by the well separated confidence intervals) may be partly because of the improved FeNO plateau at this rate.

Figure 1

 Comparison of eNO values with the Niox and Logan analysers

These results suggest that data obtained using either flow rate are valid, and the methods demonstrate a strong degree of correlation. This is an important confirmatory analysis as it facilitates comparison of results obtained by the two techniques, both previously and in ongoing clinical trials using flow rates which differ from that recently recommended.


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