Snapshot

The airway epithelium functions as a physiochemical barrier and immune communicator through the release
of alarmins^1–3

Upstream alarmins drive the release of downstream cytokines, including IL-6,
IL-5, IL-4 and IL-13, which also contribute to COPD pathophysiology³

COPD airway inflammation is heterogeneous, most commonly involving Type 1/3 pathways, with Type 2 inflammation present in a subset of patients¹

Airway epithelial barrier function is central to the progression of COPD¹

View the data

Within the complex and heterogeneous inflammatory environment of COPD, multiple alarmins and cytokines, including IL-33, TSLP, IL-4, IL-5 and IL-13, play a pivotal role in the inflammatory cascade^1–13

View the data

Inflammation drives disease pathogenesis, influences outcomes and may contribute to
comorbidity burden¹

View the data

<h4>Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations<sup>1,2</sup></h4>
<h4>Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations<sup>1,2</sup></h4>
<h4>Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations<sup>1,2</sup></h4>

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 persistent^1–8

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 groups^9–12

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 responses^1,13,14

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 activity^15–17

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 pathogenesis^1–3,12,15

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 consequences^{12,15,18–25}

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

Stay ahead

CD, cluster of differentiation; COPD, chronic obstructive pulmonary disease; ECP, eosinophil cationic protein; EPX, eosinophil peroxidase; IFN, interferon; IL, interleukin; MMP, matrix metalloproteinase; MPO, myeloperoxidase; NETs, neutrophil extracellular traps; Th, T-helper cell; TNF, tumour necrosis factor; TSLP, thymic stromal lymphopoietin

Wechsler ME, Wells JM. ERJ Open Res. 2024;10:00177–02024
Saber Cherif L, et al. Eur J Immunol. 2025;55(1):e202451480
Gabryelska A, et al. Front Immunol. 2019;10:692
Marcuccio G, et al. Front Med Lausanne. 2025;12:1550716
Strickson S, et al. Eur Respir J. 2023;62(3):2202210
Keddache S, et al. Clin Immunol. 2021;229:108798
Brightling CE, et al. Eur Respir J. 2019;54(6):1900651
Calderon AA, et al. Eur Respir Rev. 2023;32(167):220144
Zhou Y, Xu Z, Liu Z. J Transl Med. 2023;21:902
MacNee W. Proc Am Thorac Soc 2005;2:258–26
Rabe KF, et al. Am J Respir Crit Care Med. 2023;208(4):395–405
Paliogiannis P, et al. Eur Respir Rev 2018;27:17011
Cohen ES, et al. Nat Commun 2015;6:8327

Z4-86369 | Date of preparation: August 2026

Inflammation
in COPD

Inflammation
in COPD

Snapshot

The airway epithelium functions as a physiochemical barrier and immune communicator through the release
of alarmins^1–3

Upstream alarmins drive the release of downstream cytokines, including IL-6,
IL-5, IL-4 and IL-13, which also contribute to COPD pathophysiology³

COPD airway inflammation is heterogeneous, most commonly involving Type 1/3 pathways, with Type 2 inflammation present in a subset of patients¹

Airway epithelial barrier function is central to the progression of COPD¹

Airway epithelial barrier function is central to the progression of COPD¹

Within the complex and heterogeneous inflammatory environment of COPD, multiple alarmins and cytokines, including IL-33, TSLP, IL-4, IL-5 and IL-13, play a pivotal role in the inflammatory cascade^1–13

Inflammation drives disease pathogenesis, influences outcomes and may contribute to
comorbidity burden¹

Inflammation drives disease pathogenesis, influences outcomes and may contribute to
comorbidity burden¹

Burden of COPD

Burden of COPD

Mucus dysfunction in COPD

Mucus dysfunction in COPD

Frequently asked questions

What does ‘dysregulated IL-33’ mean?

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

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

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

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

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

Welcome to AZMedical Science

Inflammation in COPD

Inflammation in COPD

Snapshot

The airway epithelium functions as a physiochemical barrier and immune communicator through the release of alarmins1–3

Upstream alarmins drive the release of downstream cytokines, including IL-6, IL-5, IL-4 and IL-13, which also contribute to COPD pathophysiology3

COPD airway inflammation is heterogeneous, most commonly involving Type 1/3 pathways, with Type 2 inflammation present in a subset of patients1

Airway epithelial barrier function is central to the progression of COPD1

Airway epithelial barrier function is central to the progression of COPD1

Within the complex and heterogeneous inflammatory environment of COPD, multiple alarmins and cytokines, including IL-33, TSLP, IL-4, IL-5 and IL-13, play a pivotal role in the inflammatory cascade1–13

Within the complex and heterogeneous inflammatory environment of COPD, multiple alarmins and cytokines, including IL-33, TSLP, IL-4, IL-5 and IL-13, play a pivotal role in the inflammatory cascade1–13

Inflammation drives disease pathogenesis, influences outcomes and may contribute to comorbidity burden1

Inflammation drives disease pathogenesis, influences outcomes and may contribute to comorbidity burden1

Burden of COPD

Burden of COPD

Mucus dysfunction in COPD

Mucus dysfunction in COPD

Frequently asked questions

What does ‘dysregulated IL-33’ mean?

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

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

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

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

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

References (FAQs)

Stay ahead

Stay ahead

Abbreviations

References (Inflammation in COPD)

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Inflammation
in COPD

Inflammation
in COPD

The airway epithelium functions as a physiochemical barrier and immune communicator through the release
of alarmins^1–3

Upstream alarmins drive the release of downstream cytokines, including IL-6,
IL-5, IL-4 and IL-13, which also contribute to COPD pathophysiology³

COPD airway inflammation is heterogeneous, most commonly involving Type 1/3 pathways, with Type 2 inflammation present in a subset of patients¹

Airway epithelial barrier function is central to the progression of COPD¹

Airway epithelial barrier function is central to the progression of COPD¹

Within the complex and heterogeneous inflammatory environment of COPD, multiple alarmins and cytokines, including IL-33, TSLP, IL-4, IL-5 and IL-13, play a pivotal role in the inflammatory cascade^1–13

Within the complex and heterogeneous inflammatory environment of COPD, multiple alarmins and cytokines, including IL-33, TSLP, IL-4, IL-5 and IL-13, play a pivotal role in the inflammatory cascade^1–13

Inflammation drives disease pathogenesis, influences outcomes and may contribute to
comorbidity burden¹

Inflammation drives disease pathogenesis, influences outcomes and may contribute to
comorbidity burden¹