Snapshot

Many patients with COPD continue to experience exacerbations despite triple inhaled therapy, leading to substantial systemic steroid exposure^1,2

Oral corticosteroid exposure and exacerbations contribute to adverse outcomes, including increased cardiopulmonary risk and
premature mortality^1,3

Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations^1,2

View the data

Patients with COPD exacerbating on triple therapy were exposed to systemic steroids for
1 in every 5 days of the year^1,2

View the data

Oral corticosteroid exposure is associated with increased risk of adverse outcomes in patients with COPD^3*

View the data

Exacerbations are a key component of cardiopulmonary risk in COPD and can be associated with
premature death^4,5

View the data

Experiencing even one exacerbation* can profoundly increase the risk of
premature mortality^6,7†

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>
<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

ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; SABA, short-acting β2-agonist; SAMA, short-acting muscarinic antagonist

Nordon C, et al. Int J Chron Obstruct Pulmon Dis. 2025;20:1851–1864
Nordon C, et al. Eur Respir J. 2024;64(Suppl. 68):PA1287 (Abstract)
Tse G, et al. Int J Chron Obstruct Pulmon Dis. 2023;18:2565–2580
Daniels K, et al. Int J Chron Obstruct. Pulmon Dis. 2024;19:225–241
Singh D, et al. Adv Ther. 2024;41:2151–2167
Whittaker H, et al. Int J Chron Obstruct Pulmon Dis. 2022;17:427–437
Whittaker H, et al. Int J Chron Obstruct Pulmon Dis. 2022;17:427-437 (Supplement)

Z4-86369 | Date of preparation: August 2026

Burden of COPD

Burden of COPD

Snapshot

Many patients with COPD continue to experience exacerbations despite triple inhaled therapy, leading to substantial systemic steroid exposure^1,2

Oral corticosteroid exposure and exacerbations contribute to adverse outcomes, including increased cardiopulmonary risk and
premature mortality^1,3

Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations^1,2

Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations^1,2

Patients with COPD exacerbating on triple therapy were exposed to systemic steroids for
1 in every 5 days of the year^1,2

Patients with COPD exacerbating on triple therapy were exposed to systemic steroids for
1 in every 5 days of the year^1,2

Oral corticosteroid exposure is associated with increased risk of adverse outcomes in patients with COPD^3*

Oral corticosteroid exposure is associated with increased risk of adverse outcomes in patients with COPD^3*

Exacerbations are a key component of cardiopulmonary risk in COPD and can be associated with
premature death^4,5

Exacerbations are a key component of cardiopulmonary risk in COPD and can be associated with
premature death^4,5

Experiencing even one exacerbation* can profoundly increase the risk of
premature mortality^6,7†

Experiencing even one exacerbation* can profoundly increase the risk of
premature mortality^6,7†

Home

Home

Inflammation in COPD

Inflammation 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

Burden of COPD

Snapshot

Many patients with COPD continue to experience exacerbations despite triple inhaled therapy, leading to substantial systemic steroid exposure1,2

Oral corticosteroid exposure and exacerbations contribute to adverse outcomes, including increased cardiopulmonary risk and premature mortality1,3

Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations1,2

Patients with COPD exacerbating on triple therapy were exposed to systemic steroids for 1 in every 5 days of the year1,2

Oral corticosteroid exposure is associated with increased risk of adverse outcomes in patients with COPD3*

Exacerbations are a key component of cardiopulmonary risk in COPD and can be associated with premature death4,5

Experiencing even one exacerbation* can profoundly increase the risk of premature mortality6,7†

Home

Inflammation 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

Abbreviations

References (Burden of COPD)

SIRIUS

A US retrospective cohort study of patients with COPD with 1 year of continuous triple therapy and a history of frequent exacerbations* (N=4920)1,2

SIRIUS

A US retrospective cohort study of patients with COPD with 1 year of continuous triple therapy and a history of frequent exacerbations* (N=4920)1,2

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Many patients with COPD continue to experience exacerbations despite triple inhaled therapy, leading to substantial systemic steroid exposure^1,2

Oral corticosteroid exposure and exacerbations contribute to adverse outcomes, including increased cardiopulmonary risk and
premature mortality^1,3

Over half of patients with COPD receiving triple inhaled therapy have been shown to continue to experience exacerbations^1,2

Patients with COPD exacerbating on triple therapy were exposed to systemic steroids for
1 in every 5 days of the year^1,2

Oral corticosteroid exposure is associated with increased risk of adverse outcomes in patients with COPD^3*

Exacerbations are a key component of cardiopulmonary risk in COPD and can be associated with
premature death^4,5

Experiencing even one exacerbation* can profoundly increase the risk of
premature mortality^6,7†

A US retrospective cohort study of patients with COPD with
1 year of continuous triple therapy and a history of frequent exacerbations* (N=4920)^1,2

A US retrospective cohort study of patients with COPD with
1 year of continuous triple therapy and a history of frequent exacerbations* (N=4920)^1,2