Exhaled nitric oxide thresholds can help rule asthma in or out in primary care

Design

Systematic review and meta-analysis of 30 diagnostic studies with prospective single-centre replication (DIVE)

Population

7,141 adults and 989 children with suspected asthma; 123 adults in the replication cohort

Primary outcome

Diagnostic accuracy (AUC) of FeNO and blood eosinophils against bronchial provocation testing

Effect

FeNO AUC 0.80 (95% CI 0.73 to 0.85) in adults; 65 ppb or more PPV 80%; under 20 ppb NPV 93%; blood eosinophils AUC 0.65

Asthma is hard to confirm when spirometry is normal and bronchodilator reversibility is negative, and bronchial provocation tests are not widely available. This meta-analysis of 30 studies (22 adult studies with 7,141 patients, nine paediatric with 989) assessed fractional exhaled nitric oxide (FeNO) and blood eosinophil count against bronchial provocation testing. It was then replicated in DIVE, a single-centre cohort of 123 primary-care-referred adults.

FeNO accuracy was good in adults (AUC 0.80, 95% CI 0.73 to 0.85) and fair in children (0.75, 0.65 to 0.82). At a 20% prevalence, a FeNO of 65 ppb or more gave a positive predictive value of 80% (95% CI 72 to 86), and below 20 ppb a negative predictive value of 93% (91 to 94), with 18% of diagnoses missed. In children, 30 ppb or more gave a positive predictive value of 80% at 56% prevalence. Blood eosinophils were poor alone (AUC 0.65) and added nothing to FeNO. In DIVE, thresholds held up (FeNO above 65 ppb: PPV 73%, interval 39 to 94; below 20 ppb: NPV 92%). Accuracy fell within two weeks of inhaled corticosteroid use.

The rule-out thresholds were derived post hoc, DIVE was small and single-centre, and the study was partly industry-funded, including by a FeNO device maker. FeNO devices are not widely available in Indian primary care, so this applies mainly where they exist.

• Where FeNO is available, consider using it in adults with suspected asthma and normal spirometry.
• A very high result (65 ppb or more) supports asthma; a very low one (under 20 ppb) makes it less likely but misses some cases.
• Test before starting inhaled corticosteroids, since recent use lowers FeNO accuracy.
• Do not use blood eosinophils alone to diagnose asthma.
• If the result does not fit the story, go on to bronchial provocation testing or specialist review.

Why it matters

It offers a bedside route to a diagnosis that is often made by guesswork or by treating and seeing.

Don't overread it

The rule-out thresholds were derived post hoc, the adult primary care replication was small, and the work was partly funded by a device manufacturer.

The statistics, in plain English

An AUC of 0.80 means FeNO ranks a person with asthma above one without about 80% of the time. A negative predictive value of 93% means that 7 in 100 people with a low result still have asthma, and 18% of those with asthma have a low result and could be missed. Predictive values depend on how common asthma is in the group tested.

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