FeNO Testing in General Practice

Fractional, Exhaled, Nitric Oxide.

The diagnosis of asthma in general practice has long relied on a combination of clinical history, spirometry, and reversibility testing. However, recent updates to NICE guidelines have highlighted the importance of incorporating biomarkers, such as blood eosinophil count and exhaled nitric oxide (FeNO) levels, into the diagnostic process. This shift reflects a growing emphasis on precision medicine, ensuring patients receive the most accurate diagnosis and tailored treatment for their respiratory condition.

BTS/SIGN/NICE Asthma Guidelines published 2024 state:

'Measure the blood eosinophil count or FeNO level in adults with a history suggestive of asthma. Diagnose asthma if the eosinophil count is above the laboratory reference range or the FeNO level is 50 ppb or more'

What is Nitric Oxide?

Nitric oxide (NO) is a naturally occurring gas continuously produced within the airways of healthy individuals. It plays an important role in various physiological processes, including maintaining normal airway function. However, in conditions such as allergic asthma, the production of nitric oxide is significantly elevated. This increase reflects the heightened inflammatory activity characteristic of asthma.

The link between exhaled nitric oxide and airway inflammation lies in the role of eosinophils, a type of white blood cell associated with allergic responses and asthma.

When eosinophil levels rise in the airways, they stimulate the airway epithelium to produce more nitric oxide. As a result, the levels of nitric oxide detectable in exhaled breath increase, serving as an indirect marker of eosinophilic inflammation.

This correlation between elevated eosinophils and increased exhaled nitric oxide highlights the value of FeNO testing as a diagnostic tool.

By measuring the amount of nitric oxide in a patient’s exhaled breath, clinicians can infer the presence and degree of eosinophilic airway inflammation, which is often seen in asthma but less prominent in other respiratory conditions.

This non-invasive, simple test provides a practical way to assess airway inflammation and supports the diagnosis and management of asthma in primary care settings.

This table which categorizes the levels of exhaled nitric oxide (FeNO) measured in parts per billion (ppb) and their implications for airway inflammation in adults and children under 12 years old.

The table provides clinicians with a quick reference for interpreting FeNO test results and their correlation with the likelihood and severity of eosinophilic airway inflammation. The thresholds guide diagnostic and management decisions in conditions such as asthma.

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Theory to Practice

A 35 year old male presents with symptoms suggestive of asthma. His spirometry test result is as follows:

• The patient has an FEV/FVC ratio LLN of 0.71

• His actual FEV/FVC ratio of 0.65 (65%) is less than his LLN suggesting the presence of airflow obstruction

• His FVC of 4.60 is greater than his LLN of 3.88, which would exclude the presence of a co-existing restrictive defect

• His FEV1 is 3.00 which is 72% of his predicted FEV1 of 4.11 and indicates that this falls within the moderate airflow obstruction category

Exhaled nitric oxide testing is carried out and his FeNO levels comes back at 128 ppb.

This is in excess of the BTS/SIGN/NICE recommended cut off point of 50ppb, confirming a diagnosis of asthma and the need for inhaled corticosteroid therapy.

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A Note of Caution

FeNO test results can be influenced in those who are being treated with inhaled corticosteroids. This is particularly relevant when interpreting FeNO levels, as ICS therapy directly targets eosinophilic inflammation, which is the primary contributor to elevated nitric oxide levels in the airways.

How ICS Affects FeNO Levels

Inhaled corticosteroids work by suppressing inflammation in the airways, specifically targeting eosinophils, which are key inflammatory cells in asthma. Eosinophils release inflammatory mediators that stimulate the production of nitric oxide in the airway epithelium. When ICS therapy effectively reduces the number of eosinophils in the airways, it also reduces the amount of nitric oxide produced. As a result, FeNO levels in patients undergoing ICS treatment may appear lower than they would have been in the absence of treatment.

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