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Up to


of COPD patients may have
type 2 inflammation1-8,a

aBased on findings from 5 studies in COPD patients without asthma. Eosinophil levels used to define type 2 inflammation ranged from ≥300 cells/μL to ≥340 cells/μL (blood), ≥2% in induced sputum or 3% peripheral blood. Percentages of patients with type 2 inflammation ranged from 12.3% to ~40%.1-8

COPD exacerbations
may have a devastating
impact on lung function

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COPD exacerbations may continue to occur in patients even if treatment is optimized with triple inhaler therapy.9
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In a retrospective study of
COPD patients,


of patients died 3.6 years (median; range 1 day to 17 years) after their first hospitalization for a severe COPD exacerbation10,b

bBased on data from a large, population-based cohort of 73,106 Canadian patients (mean age, 75 years) who were hospitalized for the first time because of a severe exacerbation of COPD (1990-2005, followed until death or March 31, 2007).10
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  • Based on data from a large, population-based cohort of 73,106 Canadian patients (mean age, 75 years) who were hospitalized for the first time because of a severe exacerbation of COPD (1990-2005, followed until death or March 31, 2007)10
  • cAdjusted for age, sex, calendar time, and the modified Chronic Disease Score.10
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Loss of lung function nearly doubled11

Irreversible lung function decline may occur after only one COPD exacerbation11


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After 1 moderate/severe exacerbation

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Mean annual
decline in
postbronchodilator FEV1 (P=0.003)d

dFEV1 decline after a single moderate-to-severe exacerbation. Based on a retrospective analysis of data from 586 patients with moderate-to-severe COPD.11

Pathogenesis in COPD
may reveal that type 2
inflammation plays a role

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COPD is characterized by mucus production, airway obstruction, and coughing14,15


Signs of Systemic Inflammation

Elevated blood eosinophils are associated with:


greater risk
for a severe COPD


More impaired
lung function13,f

Histologic Signs of Localized

eA severe exacerbation was defined as a hospitalization due to COPD. Exacerbations had to be a minimum of 4 weeks apart to be considered separate exacerbations.12
fIn a cohort of patients with EOS >200 cells/µL.13
gAlcian blue PAS staining of mucus in airway epithelial cells.16
Reproduced with permission of the American Thoracic Society. Fritzsching B et al. Am J Respir Crit Care Med. 2015;191(8):902-913.16

Chronic airway inflammation in
COPD can involve multiple
pathways, cytokines, and
inflammatory cells3,17-33

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IL-4, IL-13, and IL-5 are
type 2 cytokines involved
in COPD17-23,34-36



IL-4 and IL-13 drive inflammatory cell activity

IL-4 and IL-13 promote the activation and trafficking of type 2 inflammatory cells, including eosinophils, to the lungs, which may contribute to airway remodeling and parenchymal destruction in COPD19,20,36-43


The critical role of IL-13 in airflow limitation

IL-13 plays a role in emphysema, fibrosis, and goblet cell hyperplasia and increases expression of MUC5AC, a major constituent of airway mucus20,34,38,44-47

  • Levels of IL-13 are significantly increased in lungs from patients with severe COPD compared with healthy donor tissue34
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Identifying type 2 inflammation may help you discover at-risk patientsh

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Patients with blood eosinophil levels ≥200 cells/μL had an 83% increased risk of COPD-related rehospitalization within 1 year.49,i

hResults from an observational study of 1553 patients with GOLD spirometry grade 2-4 COPD (postbronchodilator FEV1/FVC ratio <0.7, with FEV1 >80% predicted).48
iResults from a 1-year observational study of 479 patients with COPD, 173 of whom had blood eosinophil levels ≥200 cells/μL and/or ≥2% of the total white blood cell count.49
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Understanding type 2 inflammation in COPD may help shed light on why some patients continue to experience exacerbations.

To learn more about type 2 inflammation
in other disease states, visit
aHR, adjusted hazard ratio; COPD, chronic obstructive pulmonary disease; EOS, eosinophils; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IFN, interferon; ILC2, type 2 innate lymphoid cell; ILC3, type 3 innate lymphoid cell; MUC5AC, mucin 5AC; PAS, periodic acid–Schiff; TGF-β, transforming growth factor beta; TNF, tumor necrosis factor; TSLP, thymic stromal lymphopoietin.
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Stability of blood eosinophils in patients with chronic obstructive pulmonary disease and in control subjects, and the impact of sex, age, smoking, and baseline counts. Am J Respir Crit Care Med. 2017;195(10):1402-1404. 6. Górska K, Paplińska-Goryca M, Nejman-Gryz P, Goryca K, Krenke R. Eosinophilic and neutrophilic airway inflammation in the phenotyping of mild-to-moderate asthma and chronic obstructive pulmonary disease. COPD. 2017;14(2):181-189. 7. Singh D, Bafadhel M, Brightling CE, et al; on behalf of the COPD Foundation Eosinophil Working Group. Blood eosinophil counts in clinical trials for chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020;202(5):660-671. 8. Wang HH, Cheng SL. From biomarkers to novel therapeutic approaches in chronic obstructive pulmonary disease. Biomedicines. 2021;9(11):1638. doi:10.3390/biomedicines9111638 9. Halpin DMG, Dransfield MT, Han MK, et al. The effect of exacerbation history on outcomes in the IMPACT trial. 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Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles. J Allergy Clin Immunol. 2018;141(6):2027-2036.e12. 26. Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2006;173(10):1114-1121. 27. Smithgall MD, Comeau MR, Yoon BRP, Kaufman D, Armitage R, Smith DE. IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol. 2008;20(8):1019-1030. 28. Allakhverdi Z, Smith DE, Comeau MR, Delespesse G. Cutting edge: the ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol. 2007;179(4):2051-2054. 29. Chan BCL, Lam CWK, Tam LS, Wong CK. IL33: roles in allergic inflammation and therapeutic perspectives. Front Immunol. 2019;10:364. doi:10.3389/fimmu.2019.00364 30. Griesenauer B, Paczesny S. The ST2/IL-33 axis in immune cells during inflammatory diseases. Front Immunol. 2017;8:475. doi:10.3389/fimmu.2017.00475 31. McCarthy PC, Phair IR, Greger C, et al. IL-33 regulates cytokine production and neutrophil recruitment via the p38 MAPK-activated kinases MK2/3. Immunol Cell Biol. 2019;97(1):54-71. 32. Blom L, Poulsen BC, Jensen BM, Hansen A, Poulsen LK. IL-33 induces IL-9 production in human CD4+ T cells and basophils. PLoS One. 2011;6(7):e21695. doi:10.1371/journal.pone.0021695 33. Calderon AA, Dimond C, Choy DF, et al. Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD. Eur Respir Rev. 2023;32(167):220144. doi:10.1183/16000617.0144-2022 34. Alevy YG, Patel AC, Romero AG, et al. IL-13–induced airway mucus production is attenuated by MAPK13 inhibition. J Clin Invest. 2012;122(12):4555-4568. 35. Cooper PR, Poll CT, Barnes PJ, Sturton RG. Involvement of IL-13 in tobacco smoke-induced changes in the structure and function of rate intrapulmonary airways. Am J Respir Cell Mol Biol. 2010;43(2):220-226. 36. Saatian B, Rezaee F, Desando S, et al. Interleukin-4 and interleukin-13 cause barrier dysfunction in human epithelial cells. Tissue Barriers. 2013;1(2):e24333. doi:10.4161/tisb.24333 37. Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138(1):16-27. 38. Zheng T, Zhu Z, Wang Z, et al. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase–and cathepsin-dependent emphysema. J Clin Invest. 2000;106(9):1081-1093. 39. Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007;119(6):1303-1310. 40. Defrance T, Carayon P, Billian G, et al. Interleukin 13 is a B cell stimulating factor. J Exp Med. 1994;179(1):135-143. 41. Yanagihara Y, Ikizawa K, Kajiwara K, Koshio T, Basaki Y, Akiyama K. Functional significance of IL-4 receptor on B cells in IL-4–induced human IgE production. J Allergy Clin Immunol. 1995;96(6 pt 2):1145-1151. 42. Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017;13(5):425-437. 43. Kaur D, Hollins F, Woodman L, et al. Mast cells express IL-13Rα1: IL-13 promotes human lung mast cell proliferation and FcεRI expression. Allergy. 2006;61(9):1047-1053. 44. Brightling CE, Saha S, Hollins F. Interleukin-13: prospects for new treatment. Clin Exp Allergy. 2010;40(1):42-49. 45. Garudadri S, Woodruff PG. Targeting chronic obstructive pulmonary disease phenotypes, endotypes, and biomarkers. Ann Am Thorac Soc. 2018;15(suppl 4):S234-S238. 46. Singanayagam A, Footitt J, Marczynski M, et al. Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease. J Clin Invest. 2022;132(8):e12901. doi:10.1172/JCI120901 47. Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103(6):779-788. 48. Yun JH, Lamb A, Chase R, et al; for the COPDGene and ECLIPSE Investigators. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141(6):2037-2047.e10. 49. Bélanger M, Couillard S, Courteau J, et al. Eosinophil counts in first COPD hospitalizations: a comparison of health service utilization. Int J Chron Obstruct Pulmon Dis. 2018;13:3045-3054.