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We read with great interest the paper by Gelb and colleagues1 who suggest that peripheral airway/alveolar nitric oxide (NO) concentration after correction for axial NO back-diffusion (CalvNOcorrected) is normal during asthma exacerbation (with a hypothesis of an incidence of >30% of its increase). If one admits that an exacerbation constitutes the ultimate expression of loss of asthma control, their results are in line with ours demonstrating that CalvNOcorrected is not a marker of asthma control.2 Nevertheless, some of their patients with an exacerbation had an increase in CalvNOcorrected since one can see in their figure 5 that almost 20% of their patients are above the 95th percentile of healthy subjects (∼7 ppb). The small size of their cohort (n=15) is an obvious limitation that is acknowledged by the authors.
We therefore reanalysed the results of our multicentre trial2 to evaluate the prevalence of increased CalvNOcorrected. When using an upper normal limit of 7 ppb for CalvNOcorrected (that corresponds approximately to their upper normal value1), the prevalence of its increase is 23% (41/175) in our population of adults and children with asthma. In our study we further demonstrated a negative relationship between CalvNOcorrected and mid forced expiratory flow (FEF25–75%), which may suggest that peripheral NO could be associated with airway remodelling.2 This latter result was in line with the demonstration that peripheral airway/alveolar NO concentration (without correction for axial NO back-diffusion) correlated with FEF25–75% in children with refractory asthma.3 Puckett and colleagues recently suggested that children with asthma with increased CalvNOcorrected (46/179, 26%) had significantly worse asthma control and morbidity.4 Overall, all these results emphasise that peripheral airway/alveolar NO concentration, after correction for axial NO back-diffusion, can be increased in some patients with asthma (∼25%). Whether peripheral NO helps to identify a specific ‘phenotype’ of asthma which may be more closely linked to severity than to control warrants further studies.
Gelb and colleagues also show that 2/15 subjects with an exacerbation had normal exhaled NO values.1 Similarly, we have previously shown in a multicentre trial that patients with acute asthma admitted to the emergency department can have normal exhaled NO levels (2/65 patients in our study).5
In conclusion, the clinical usefulness of techniques to discriminate NO gas exchange between large central airways and peripheral smaller airways/alveolar compartments in patients with asthma remains to be established, and the factors governing the increase in exhaled NO remain partly determined.
Competing interests CD has received a free NO analyser (ENDONO 8000) from SERES (Aix en Provence, France) for the development of their software for NO analysis at multiple exhaled flow rates. BM has no competing interests.
Provenance and peer review Not commissioned; not externally peer reviewed.
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