Diagnosing T2I

Diagnosing type 2 inflammation (T2I) requires a comprehensive, multidisciplinary approach involving primary care specialists, allergists, pulmonologists, otolaryngologists, gastroenterologists, and dermatologists.1

An accurate and timely diagnosis is critical given the advent of monoclonal antibodies that target specific inflammatory cytokines involved in the disease process. If the disease is not driven by T2I, then these drugs may not be beneficial; conversely, if the disease is driven by T2I, then certain therapies, including inhaled corticosteroids, may be even more effective.2,3

Diagnosis relies on established criteria for the type 2 inflammatory diseases, which can be found in the guidelines listed below.

Diagnostic Testing

Skin Prick Testing

Skin prick testing is the most frequently used method for detecting IgE antibodies due to its rapidity, simplicity, and low cost. It is particularly useful for identifying specific allergens that may be triggering the inflammatory response.7

Serum Specific IgE Testing

Serum specific IgE assays are commonly used in-vitro diagnostic tests for type 2 inflammatory diseases. These tests measure the levels of IgE antibodies specific to particular allergens in the blood.7

Blood Eosinophil Count

Blood eosinophil levels ≥150 cells/μL suggest type 2 inflammation in asthma and other airway diseases.8 For instance, the Global Initiative for Asthma (GINA) defines type 2 airway inflammation when blood eosinophils are ≥150 cells/μL, among other criteria, while GOLD guidelines note that higher thresholds, such as ≥300 cells/μL, can help identify patients with COPD at greater risk for exacerbations.3 Eosinophil levels are often considered alongside other biomarkers, such as fractional exhaled nitric oxide (FeNO) ≥20 ppb, to assess type 2 inflammation.9

Fractional Exhaled Nitric Oxide (FeNO)

FeNO is a non-invasive test that measures the level of nitric oxide in exhaled breath, which is elevated in type 2 airway inflammation. It can help clinicians choose the most appropriate targeted biologic treatment. For instance, omalizumab is most effect in reducing asthma exacerbations in patients with a FeNO value greater than 19.5 ppb, while dupilumab reduces the risk of exacerbations in patients with FeNO values above 25 ppb compared to placebo, and response to tezepelumab treatment is greater in patients with high baseline FeNO values.10

Total IgE

While less specific than other tests, total IgE levels can provide general information about allergic status. Elevated levels may indicate an allergic condition, but normal levels do not rule out type 2 inflammation.7

References

  1. Palomares O, Cisneros C, Ortiz de Frutos FJ, Villacampa JM, Dávila I. Multidisciplinary management of type 2 inflammation diseases using a screening tool. Front Allergy. 2024;5:1427279.
  2. Global Initiative for Asthma. 2024 GINA Main Report: Global Strategy for Asthma Management and Prevention. 2024. https://ginasthma.org/2024-report/
  3. Hirano I, Chan ES, Rank MA, et al. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Gastroenterology. 2020;158:1776-1786.
  4. AAAAI/ACAAI JTF Atopic Dermatitis Guideline Panel, Chu DK, Schneider L, et al. Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters. Ann Allergy Asthma Immunol. 2024;132:274-312.
  5. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for prevention, diagnosis and management of COPD: 2025 report. 2025. https://goldcopd.org/2025-gold-report/
  6. Fokkens WJ, Lund VJ, Hopkins C, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;58(suppl S29):1-464.
  7. Ansotegui IJ, Melioli G, Canonica GW, et al. IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper. World Allergy Organ J. 2020;13:100080.
  8. Hirano T, Matsunaga K. Measurement of blood eosinophils in asthma and chronic obstructive pulmonary disease. Intern Med. 2023;62:21-25.
  9. Pavord ID, Afzalnia S, Menzies‐Gow A, Heaney LG. The current and future role of biomarkers in type 2 cytokine‐mediated asthma management. Clin Exp Allergy. 2017;47:148-160.
  10. Maniscalco M, Fuschillo S, Mormile I, et al. Exhaled nitric oxide as biomarker of type 2 diseases. Cells. 2023;12:2518.

All URLs accessed January 23, 2025

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