Exhaled nitric oxide in asthma: progress since the introduction of standardized methodology

Abstract

The measurement of nitric oxide (NO) in exhaled breath has given us the ability to learn about and monitor the inflammatory status of the airway through a non-invasive method that is easy to perform and repeat. This has been most useful in the diagnosis and management of asthma and has promised a seemingly unlimited potential for evaluating the airways and how clinical decisions are made (Grob N M and Dweik R A 2008 Chest133 837-9). The exhaled NO field was initially limited, however, due to the absence of standardized methodology. The ATS and ERS jointly released recommendations for standardized methods of measuring and reporting exhaled NO in 1999 that were revised in 2005 (1999 Am. J. Respir. Crit. Care. Med. 160 2104-17; 2005 Am. J. Respir. Crit. Care. Med. 171 912-30). In this paper, we summarize the literature that followed this standardization. We searched the literature for all papers that included the term 'exhaled nitric oxide' and selected those that followed ATS guidelines for online measurement for further review. We also reviewed cut-off values suggested by groups studying exhaled nitric oxide. We found a wide range of NO values reported for normal and asthma populations. The geometric mean for FE(NO) ranged from 10 ppb to 33 ppb in healthy adult control populations. For asthma, the FE(NO) geometric mean ranged from 6 ppb to 98 ppb. This considerable variation likely reflects the different clinical settings and purposes of measurement. Exhaled NO has been used for a multitude of reasons that range from screening, to diagnosis, to monitoring the effect of therapy. The field of exhaled NO has made undeniable progress since the standardization of the measurement methods. Our challenge now is to have guidelines to interpret exhaled NO levels in the appropriate context. As the utility of exhaled NO continues to evolve, it can serve as a good example of the crucial role of the standardization of collection and measurement methods to propel any new test in the right direction as it makes its way from a research tool to a clinically useful test.

Figure 1

The number of novel publications on exhaled nitric oxide, by year. Data were collected from an internet search for ‘exhaled nitric oxide’ and ‘year.’ The circled dates are the years of ATS guidelines.