Fractional Excretion of Nitric Oxide in Assessment of Inflammatory Asthma

The National Institute of Clinical Excellence (NICE) in the United Kingdom recently recommended measurement of fractional excretion of Nitric Oxide (FeNO) in exhaled air as a surrogate for inflammatory, i.e. eosinophil driven asthma, which, by definition, would be corticosteroid responsive.(1)

Nitric Oxide is produced in response to Th2 lymphocyte driven inflammation. While a Cochrane review in 2009 could not find sufficient evidence to recommend this approach, subsequent studies have shown that the fraction of NO in exhaled air predicts response to anti-inflammatory therapy such as inhaled corticosteroids even in subjects with FEV1 >80% of predicted. Conversely, low FeNO levels indicate well controlled asthma, allowing reduction or discontinuation of oral/inhaled steroids.

Levels of NO in exhaled air of less than 25 parts per billion is characterised as "low", levels of 25-50 ppb as "intermediate" and >50 ppb as "high".

FeNo should be used in addition to standard PFTs such as FEV1, FEV1/FVC ratio and PEF. However, experience shows that these tests are imperfect predictors of response to inhaled steroid treatment. Observational studies show that 60% of subjects with putative asthma referred to secondary care and 30% of subjects diagnosed with asthma in primary care, have no evidence of airway dysfunction, and that in a majority of such subjects, inhaled steroid therapy can be stepped down without adverse consequences. (2)

Measurement of FeNO is therefore a welcome addition to the current diagnostic/monitoring modalities for inflammatory asthma. Following widespread adoption in the UK, I expect that this will now find acceptance elsewhere.

References:

1. Povard ID, Bush A, Holgate S. Asthma diagnosis: addressing the challenges. Lancet Respir Med 2015; 3: 184

2. Hawkins G, McMahon AD, Twaddle S, Wood SF, Ford I, Thomson NC.
Stepping down inhaled corticosteroids in asthma: randomised controlled
trial. BMJ 2003; 326: 1115.