SYMPTOMS

PATIENTS with COPD CARRY A HEAVY DISEASE BURDEN1-3

The most common COPD symptoms have a serious impact on patients’
daily living1,2

COMMON SYMPTOMS1,2

  • Dyspnea
  • Cough
  • Wheezing
  • Fatigue
  • Excess MUCUS

THE MORE SEVERE THEIR DYSPNEA, THE HIGHER THEIR EXACERBATION RISK3

~1 in 2 patients

with MRC grade 3 or higher had at least 1 exacerbation within a year*3

>40% of patients

report moderate-to-severe dyspnea1

In addition to dyspnea, serious risks in COPD are driven by mucus4-7

IL-33 IS ASSOCIATED WITH MUCUS DYSFUNCTION—HYPERSECRETION, IMPAIRED CLEARANCE, AND MUCUS PLUGS—INCREASING AIRFLOW OBSTRUCTION AND EXACERBATION RISK4-10

Icon Representing Hospitalizations Associated with Chronic Mucus Hypersecretion In COPD Icon Representing Hospitalizations Associated with Chronic Mucus Hypersecretion In COPD

Chronic mucus hypersecretion is associated with excessive lung function decline and increased COPD hospitalizations1,7

  • Mucus hypersecretion should be suspected in all patients with COPD, even without chronic productive cough
Mucus Plugs Icon Representing Dyspnea as Symptoms of Impaired Mucus Clearance In COPD Mucus Plugs Icon Representing Dyspnea as Symptoms of Impaired Mucus Clearance In COPD

Cough and dyspnea are key symptoms of impaired mucus clearance1,11,12

  • While productive cough can clear the large airways, mucus can build up in the small airways, leading to airway obstruction, infection, and inflammation
Icon Representing Mucus Plugs Linked to Worsening COPD Disease and Reduced Lung Function Icon Representing Mucus Plugs Linked to Worsening COPD Disease and Reduced Lung Function

Mucus plugs are associated with worsening disease, such as lower FEV1 and greater dyspnea scores6,13-15

  • Newly formed or persistent mucus plugs accelerated lung function decline by an additional 48% to 62% per year
  • Patients with higher mucus plug scores reported needing to walk slower than usual or stop for breath when they walk at their own pace (MRC score 1 or 2)

Mucus plugs can lead to poor outcomes as they are associated with increased risk of exacerbation and mortality5,16

Icon Representing Increased Mucus Plugs Associated with Higher COPD Exacerbation Risk Icon Representing Increased Mucus Plugs Associated with Higher COPD Exacerbation Risk

INCREASED MUCUS PLUGS ARE ASSOCIATED
WITH HIGHER EXACERBATION RISK5

1.5

MODERATE-TO-SEVERE EXACERBATIONS

(95% CI: 1.12-2.02)

2.1

SEVERE EXACERBATIONS

(95% CI: 1.43-3.10)

Icon Representing Mucus Plugs as an Independent Risk Factor For COPD Mortality Icon Representing Mucus Plugs as an Independent Risk Factor For COPD Mortality

MUCUS PLUGS ARE AN INDEPENDENT RISK FACTOR FOR MORTALITY16

up to24%

INCREASED RISK OF DEATH

COMPARED WITH NO MUCUS PLUGS

Even when controlling for smoking, lung function, and other comorbidities

Mucus dysfunction is under-recognized in COPD AND IS ASSOCIATED WITH SERIOUS RISKS, INCLUDING
EXACERBATIONS AND DEATH16,17

Want more information? Download the Mucus Dysfunction Infographic

COULD IL-33 REVEAL NEW WAYS OF THINKING ABOUT COPD?

Learn more about the dual pathways of IL-33 and their roles in COPD.

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CI=confidence interval; COPD=chronic obstructive pulmonary disease; FEV1=forced expiratory volume in one second; IL=interleukin; MRC=Medical Research Council; MSL=medical science liaison.

*Retrospective observational cohort study that evaluated risk factors associated with exacerbation frequency in 58,589 patients with COPD identified from primary care in the UK Clinical Practice Research Datalink.3

  1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD: 2026 Report. Accessed July 6, 2026. https://goldcopd.org/2026-gold-report-and-pocket-guide/
  2. World Health Organization. Chronic obstructive pulmonary disease (COPD). Accessed July 6, 2026. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)
  3. Müllerová H, Shukla A, Hawkins A, Quint J. Risk factors for acute exacerbations of COPD in a primary care population: a retrospective observational cohort study. BMJ Open. 2014;4(12):e006171. doi:10.1136/bmjopen-2014-006171
  4. Strickson S, Houslay KF, Negri VA, et al. Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex. Eur Respir J. 2023;62(3):2202210. doi:10.1183/13993003.02210-2022
  5. Jin KN, Lee HJ, Park H, et al. Mucus plugs as precursors to exacerbation and lung function decline in COPD patients. Arch Bronconeumol. 2025;61(3):138-146. doi:10.1016/j.arbres.2024.07.017
  6. Mettler SK, Nardelli P, Campo MI, et al. Longitudinal changes in airway mucus plugs and FEV1 in COPD. N Engl J Med. 2025;392(19):1973-1975. doi:10.1056/NEJMc2502456
  7. Mettler SK, Nath HP, Grumley S, et al. Silent airway mucus plugs in COPD and clinical implications. Chest. 2024;166(5):1010-1019. doi:10.1016/j.chest.2023.11.033
  8. Borger JG, Lau M, Hibbs ML. The influence of innate lymphoid cells and unconventional T cells in chronic inflammatory lung disease. Front Immunol. 2019;10:1597. doi: 10.3389/fimmu.2019.01597
  9. Shah BK, Singh B, Wang Y, Xie S, Wang C. Mucus hypersecretion in chronic obstructive pulmonary disease and its treatment. Mediators Inflamm. 2023;2023:8840594. doi: 10.1155/2023/8840594
  10. Washko G, Bhatt SP, Gispert JD, et al. Tozorakimab reduces quantitative mucus plugging metrics in patients with moderate-to-severe COPD. Poster presented at: American Thoracic Society (ATS) International Conference 2026; May 15–20, 2026; Orlando, FL, USA. Poster D96-08.
  11. Button B, Goodell, HP, Atieh E, et al. Roles of mucus adhesion and cohesion in cough clearance. Proc Natl Acad Sci U S A. 2018;115(49):12501-12506. doi:10.1073/pnas.1811787115
  12. van der Veer T, Andrinopoulou ER, Braunstahl GJ, et al. Association between automatic AI-based quantification of airway-occlusive mucus plugs and all-cause mortality in patients with COPD. Thorax. 2025;80(2):105-108. doi:10.1136/thorax-2024-221928
  13. Yang C, Zeng HH, Du YJ, Huang J, Zhang QY, Lin K. Correlation of luminal mucus score in large airways with lung function and quality of life in severe acute exacerbation of COPD: a cross-sectional study. Int J Chron Obstruct Pulmon Dis. 2021;16:1449-1459. doi:10.2147/COPD.S311659
  14. Li X, Feng S, Yang Y, et al. Association between airway mucus plugs and risk of moderate-to-severe exacerbations in patients with COPD: results from a Chinese prospective cohort study. Chest. 2025;168(3):627-638. doi:10.1016/j.chest.2025.03.026
  15. UpToDate. Modified medical research council (mMRC) dyspnea scale. Accessed July 6, 2026. https://www.uptodate.com/contents/image?imageKey=PULM%2F86426
  16. Diaz AA, Orejas JL, Grumley S, et al. Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease. JAMA. 2023;329(21):1832-1839. doi:10.1001/jama.2023.2065
  17. Mettler SK, Diaz AA. Mucus plugs and COPD exacerbations: an emerging therapeutic target. Chest. 2025;168(3):561-563. doi:10.1016/j.chest.2025.05.012