FeNO rules asthma in at 65 ppb and largely out below 20 ppb when spirometry is normal

Design

Systematic review and meta-analysis of 30 diagnostic studies, with prospective validation cohort

Population

7,141 adults and 989 children with suspected asthma and normal spirometry; 123 primary care referrals

Primary outcome

Accuracy (AUC) against bronchial provocation testing

Effect

Adult FeNO AUC 0.80 (95% CI 0.73–0.85); ≥65 ppb PPV 80%; <20 ppb NPV 93%

This meta-analysis, published on 15 September in Lancet Respiratory Medicine, pooled 30 studies (7,141 adults and 989 children) of patients with suspected asthma and normal spirometry, comparing FeNO and blood eosinophils against bronchial provocation testing. The findings were then checked prospectively in 123 primary care referrals in Quebec.

FeNO had good accuracy in adults (AUC 0.80) and fair accuracy in children (0.75). At the 20% prevalence typical of primary care, an adult FeNO of 65 ppb or more gave a positive predictive value of about 80%, and below 20 ppb a negative predictive value of 93% — though that still missed 18% of cases. In children, 30 ppb or more gave a positive predictive value of 80% at higher study prevalence. Blood eosinophils were weak alone (AUC 0.65) and added nothing to FeNO. Accuracy fell within two weeks of starting inhaled steroids.

Asthma is both over- and under-diagnosed because reversibility testing often misses it and provocation tests are hard to access, including across most of India. A FeNO-based algorithm offers a practical middle path.

The thresholds rest on accuracy, not outcomes, and one in five true cases can sit below 20 ppb. FeNO devices are not widely available in Indian primary care. The study was partly funded by a FeNO device maker.

• Consider FeNO in adults with suspected asthma and normal spirometry before starting inhaled steroids.
• Treat a FeNO of 65 ppb or more as strong support for asthma in adults.
• Treat a FeNO below 20 ppb as making asthma less likely, but not excluded; consider provocation testing if suspicion stays high.
• Test before starting inhaled steroids, since accuracy drops within two weeks of treatment.
• Do not rely on blood eosinophil count to diagnose asthma.

Why it matters

It turns a test many clinics already have into usable rule-in and rule-out thresholds.

Don't overread it

Diagnostic accuracy only; it does not show that FeNO-guided diagnosis improves patient outcomes.

The statistics, in plain English

AUC measures how well a test separates people with and without a condition; 0.80 is good. Positive predictive value depends on how common the condition is, so the 80% figure applies to a population where about one in five tested has asthma. A negative predictive value of 93% still left 18% of true cases with a low reading.

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