Eosinophils and FeNO, not symptom scores, identified who benefits from anti-inflammatory escalation

Design

Individual patient-level meta-analysis of randomised trials and prospective cohorts

Population

7,161 people with asthma across five datasets, including 6,513 from 22 trials

Primary outcome

Severe asthma attacks and treatment response by ACQ-5 and type 2 biomarkers

Effect

ACQ-5 attack rate ratio 1.09 (95% CI 1.06 to 1.12) per 0.5 points; high eosinophils and FeNO with mepolizumab rate ratio 0.38 (0.25 to 0.57)

Asthma symptoms, usually measured with the ACQ-5, drive much day-to-day escalation. This individual-patient meta-analysis, drawing mainly on the ORACLE2 dataset, tested how well they predict future attacks and treatment response across five datasets (7,161 people), anchored on 6,513 control-arm participants from 22 randomised trials.

Symptom scores varied widely and showed no consistent relation with lung function or inflammation. Each 0.5-point rise in ACQ-5 was associated with only a 9% higher attack rate (rate ratio 1.09, 95% CI 1.06 to 1.12), adding little to a prediction model. ACQ-5 did not change how much patients benefited from mepolizumab. By contrast, patients with both high blood eosinophils and high FeNO had the largest benefit: attacks fell from 2.81 to 1.17 a year (rate ratio 0.38, 0.25 to 0.57).

Symptoms still matter to patients, but they are a poor guide to who needs more anti-inflammatory treatment. Blood eosinophils and FeNO, both cheap and widely available, identify patients at risk and likely to respond. Escalating on symptoms alone risks over-treating some patients and missing others.

• Measure blood eosinophils and FeNO before escalating anti-inflammatory treatment in asthma.
• Prioritise patients with both raised eosinophils and raised FeNO for intensified anti-inflammatory therapy or biologics.
• In patients with high symptoms but low type 2 markers, look for other causes such as dysfunctional breathing, reflux or obesity.
• Keep using symptom scores to track how the patient feels, not as the sole basis for escalation.

Why it matters

Much asthma escalation is driven by symptoms that turn out to say little about inflammation or attack risk.

Don't overread it

The treatment-response data come from one biologic trial; the finding about symptoms is the more general one.

The statistics, in plain English

A rate ratio of 1.09 per 0.5 points is a weak association; a ΔR² of 0.02 means symptoms explained almost nothing beyond other predictors. A rate ratio of 0.38 means attacks fell by about 60% with mepolizumab in the high-biomarker group, a large effect.

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