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Explore the latest in COPD science
  • Home
  • Burden of COPD
  • Inflammation in COPD
  • Mucus dysfunction in COPD
  • IL-33 in COPD
  • Resources

Publications

Burden of COPD

For many people with COPD, the burden of moderate and severe exacerbations persists despite inhaled triple therapy

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Congresses

IL-33 Is Not Just IL-33

An ERS 2025 symposium review article by EMJ

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ERS symposium videos

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Materials

IL-33 in COPD

Image outlining the role of IL-33 in COPD pathogenesis

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IL-33: A history video

History of IL-33 in COPD

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Disclaimer

This resource section includes links to peer-reviewed open-access articles. Copyright remains with the authors and/or publishers, as stated in each article. Any reused material is presented in accordance with the applicable license. 

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IL-33 in COPD

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Frequently asked questions

What does ‘dysregulated IL-33’ mean?

IL‑33 is released upon stress or cell damage to initiate a host response—what was adaptive turns maladaptive or ‘dysregulated’ when its levels chronically surpass buffering mechanisms and signalling is persistent1–8

How does smoking affect the IL-33 pathway in patients with COPD?

In COPD, smoking status affects the IL‑33 axis—former smokers show elevated IL-33 compared to current smokers, while current smokers show reduced sST2 and more oxidized IL‑33, indicating aberrant IL‑33–ST2 signalling in both groups9–12

How does the role of IL-33 in COPD differ from other epithelial cytokines?

Damage to the epithelium triggers the release of upstream, alarmin cytokines. IL-33 is pre-formed, rapidly released and initiates a broad inflammatory cascade encompassing Type 1, Type 2 and Type 3 responses1,13,14

What evidence would suggest my patient with COPD has dysregulated IL-33 signalling?

Frequent exacerbations, productive cough and persistent airway/systemic inflammation may suggest heightened IL‑33

pathway activity15–17

What are the potential consequences of dysregulated IL-33 signalling?

IL-33 through its dual forms can drive Type 1 and 3 and Type 2 (eosinophilic, subset) inflammation, and mucus dysfunction, which are key drivers of COPD pathogenesis1–3,12,15

What is mucus dysfunction and what is the impact for patients with COPD?

Mucus dysfunction is the pathological changes in mucus volume, composition and clearance, the airway manifestations of these pathological changes, and the downstream

clinical consequences12,15,18–25

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  1. Cayrol C. Cells. 2021;11(1):107
  2. Calderon AA, et al. Eur Respir Rev. 2023;32(167):220144
  3. Brightling CE, et al. Eur Respir J. 2019;54(6):1900651
  4. England E, et al. Sci Rep. 2023;13(1):9825
  5. Rabe KF, et al. Am J Respir Crit Care Med. 2023;208(4):395–405
  6. Keddache S, et al. Clin Immunol. 2021;229:108798
  7. Scott IC, et al. Biochem Soc Trans. 2018;46(5):1345–1353
  8. Burgoyne RA, et al. Cells. 2021;10(10):2763
  9. Abdo M, et al. Eur Respir J. 2024;64(3):2400347
  10. Faiz A, et al. Am J Respir Crit Care Med. 2023;208(10):1075–1087
  11. Faiz A, et al. Am J Respir Crit Care Med. 2023;208(Suppl.):1075–1087
  12. Strickson S, et al. Eur Respir J. 2023;62(3):2202210
  13. Cayrol C, Girard JP. Cytokine. 2022;156:155891
  14. Varricchi G, et al. Eur Respir J. 2024;63(4):2301619
  15. Diaz AA, et al. JAMA. 2023;329(21):1832–9
  16. Shen Y, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:399–407
  17. Rodrigues SO, et al. Pharmaceuticals (Basel). 2021;14(10):979
  18. Fahy JV, Dickey BF. N Engl J Med. 2010;363(23):2233–2247
  19. Stott-Miller M, et al. Int J Chron Obstruct Pulmon Dis. 2020;15:2467–2476
  20. Hughes R, et al. Respir Med. 2022;200:106921
  21. Choate R, et al. Chronic Obstr Pulm Dis. 2020;7(1):49–59
  22. Cook N, et al. Int J Chron Obstruct Pulmon Dis. 2019;14:1365–1376
  23. Tian PW, Wen FQ. J Transl Int Med. 2015;3(3):89-92
  24. Mettler SK, et al. N Engl J Med. 2025;392(19):1973–1975
  25. Zhou D, et al. Expert Rev Respir Med. 2025:1–7

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