FeNO gives primary care usable rule-in and rule-out thresholds for asthma when spirometry is normal

Design

Diagnostic meta-analysis with prospective validation cohort

Population

30 studies (8,130 patients) with suspected asthma and normal spirometry; 123-patient primary care cohort

Primary outcome

AUC for airway hyper-responsiveness on bronchial provocation testing

Effect

FeNO AUC 0.80 adults, 0.75 children; ≥65 ppb PPV 80%, <20 ppb NPV 93%

A meta-analysis of 30 diagnostic studies (22 adult, 7,141 patients; 9 paediatric, 989 patients) assessed FeNO and blood eosinophils against bronchial provocation testing in people with suspected asthma and normal spirometry. A prospective cohort of 123 adults referred from primary care (DIVE) then tested the thresholds.

FeNO had good accuracy in adults (AUC 0.80) and fair accuracy in children (0.75). In adults at a primary care prevalence of 20%, FeNO of 65 ppb or more gave a positive predictive value of 80%, and below 20 ppb a negative predictive value of 93%, though 18% of true asthma fell below that cut-off. In children, 30 ppb or more gave a positive predictive value of 80%. Blood eosinophils were weak (AUC 0.65) and added nothing. DIVE replicated the adult results. Accuracy fell within 2 weeks of starting inhaled corticosteroids.

Most patients with suspected asthma cannot get a methacholine test, and a normal spirometry often ends the work-up, or leads to an inhaler trial without a diagnosis. FeNO offers a way to confirm or make asthma unlikely at the first visit. The key practical rule is to measure it before inhaled steroids are started. Access to FeNO devices in Indian primary care remains limited.

• Measure FeNO before starting inhaled corticosteroids
• Adults: FeNO ≥65 ppb supports asthma; <20 ppb makes it less likely
• Children: FeNO ≥30 ppb supports asthma
• Refer intermediate results (20–65 ppb in adults) for further testing
• Do not use blood eosinophils to diagnose asthma

Why it matters

It gives the many patients who cannot access challenge testing a route to a real diagnosis rather than a trial inhaler.

Don't overread it

A low FeNO still missed about 1 in 5 adults with asthma, and the rule-out threshold was derived post hoc.

The statistics, in plain English

A positive likelihood ratio of 10 means a high FeNO makes asthma about ten times more likely than before the test, a strong shift. Predictive values depend on how common asthma is in the tested group: the 80% figure assumes 20% prevalence and will be lower where asthma is rarer. The DIVE cohort's wide interval for positive predictive value (39% to 94%) reflects only 22 positive patients.

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