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UNDERSTANDING
TYPE 2 INFLAMMATION right arrow
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Up to

40%

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
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IMPACT OF COPD

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,

50%

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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COPD EXACERBATION RISK HAS BEEN SHOWN TO ACCELERATE AFTER EACH EXACERBATION10
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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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COPD EXACERBATIONS MAY LEAD TO ACCELERATED LUNG FUNCTION DECLINE11

Loss of lung function nearly doubled11

Irreversible lung function decline may occur after only one COPD exacerbation11

Pre-exacerbation

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39.1

mL

After 1 moderate/severe exacerbation

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76.5

mL

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
TYPE 2 INFLAMMATION

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

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TYPE 2 INFLAMMATION MAY INCREASE THE RISK OF EXACERBATIONS AND LUNG FUNCTION IMPAIRMENT IN COPD12,13

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

lung-function

Signs of Systemic Inflammation

Elevated blood eosinophils are associated with:

1.76x

greater risk
for a severe COPD
exacerbation12,e

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More impaired
lung function13,f

Histologic Signs of Localized
Inflammation

Control16
fritzsching-histo-control
COPD16
fritzsching-histo-copd
Mucusg
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
INFLAMMATION IN COPD

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

IL-13

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

IL-13

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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LOOK FOR ELEVATED BLOOD EOSINOPHILS (≥300 CELLS/µL)—A BIOMARKER OF TYPE 2 INFLAMMATION IN COPD48
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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
UNDERSTANDING
TYPE 2 INFLAMMATION right arrow
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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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. 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