The Two Numbers That Pick the Drug
October 1, 2026
A clinical brief for referring providers — week 2 of a 4-part series on severe and difficult-to-control asthma.
Quick question before you read on: Which biomarker predicts response to dupilumab and tezepelumab, but does not predict response to anti-IL5 therapy?
a) Blood eosinophils b) FeNO c) Total IgE
Once severe asthma is confirmed, the next question is not whether to treat but which pathway is driving it.
Severe asthma is biologically heterogeneous. Type 2 (T2)-high disease is driven by IL-4, IL-5 and IL-13. It represents roughly half of all asthma and likely a higher proportion of severe asthma. It splits into allergic eosinophilic — early onset, atopy, elevated IgE — and non-allergic eosinophilic, which is later onset, often accompanied by nasal polyps, and frequently steroid-dependent.
T2-low disease is less well characterized, with no reliable biomarkers. Subtypes are neutrophilic, paucigranulocytic and mixed granulocytic.
The biomarkers that matter
Blood eosinophils: ≥150–300 cells/µL — biologic eligibility; higher counts predict greater response to most agents
FeNO: ≥25 ppb, high above 50 — predicts ICS, dupilumab and tezepelumab response
Total IgE: 30–1500 IU/mL with sensitization — omalizumab eligibility and dosing
Sputum eosinophils: ≥2–3% — gold standard, rarely available
Three practical points
Oral steroids suppress blood eosinophils, so wherever possible obtain a pre-OCS count. A suppressed value can mislabel a patient as T2-low.
Higher eosinophil counts predict the magnitude of exacerbation reduction across almost all agents, but do not discriminate between agents. FeNO does.
If you are referring, sending a pre-steroid eosinophil count alongside the referral saves weeks.
Want the phenotyping workup walked through with your team?
Dr. Joel Mensing of the Chest & Sleep Team runs a 20-minute clinical briefing covering T2-high versus T2-low phenotyping, which biomarker answers which question, and what to send with a referral so the patient does not wait on repeat labs. Lunch provided. No pitch — just the clinical walkthrough.
Call (847) 860-7250.
The answer
FeNO. It predicts dupilumab and tezepelumab response but does not predict anti-IL5/5Rα outcomes. Eosinophil counts predict the magnitude of benefit across nearly all agents — they do not discriminate between them.