CHRONIC-OBSTRUCTIVE-PULMONARY-DISEASE-(COPD)

RESPIRATORY

A deeper look at the inflammation behind exacerbations in COPD

Role of type 2 inflammation in type 2 COPD

<h2>Each Copd Exacerbation May Increase the Risk of Another, Putting Patients’ Lives at Greater Risk</h2>
<h3>Exacerbation risk accelerates after each exacerbation1</h3>

Based on data from a large population-based cohort of 73,106 Canadian patients who were hospitalized for the first time because of a severe exacerbation of COPD (1990-2005, followed until death or March 31, 2007) with a median follow-up of 3.6 years (range 1 day to 17 years). The mean age of patients in this retrospective study was 75 years old.1
aAdjusted for age, sex, calendar time, and the modified Chronic Disease Score.1
<h3>Exacerbations have been shown to accelerate lung function decline2</h3>
Significant lung function decline may occur even after a single COPD exacerbation2
<ul>
 <li>The annual decline in postbronchodilator FEV1&nbsp;nearly doubled after 1 moderate-to-severe exacerbation (pre-exacerbation 39.1 mL/year vs 76.5 mL/year postexacerbation [P=0.003])2,b</li>
</ul>
bBased on data from a retrospective analysis of 586 patients with moderate-to-severe (postbronchodilator FEV1&nbsp;70% of the predicted normal and FEV1&nbsp;70% of FVC) COPD participating in the 4-year, randomized, double-blind, placebo-controlled, parallel-group UPLIFT trial.
<h2>Exacerbations may increase morbidity risk3-6</h2>
Patients with exacerbations leading to hospitalization are at an increased risk for hospital readmissions
<ul>
 <li>Up to 35% of patients were readmitted within 90 days following an exacerbation3-5,c</li>
</ul>
COPD exacerbations are associated with a worsening of symptoms that can seriously impact quality of life
Patients typically experience:

Limited activity levels and exercise capacity6

Sleep-related disturbances8,9

Anxiety and depression8

cBased on data from an investigation that examined outcomes (in-hospital and 90-day postdischarge mortality and 90-day readmission) in patients with a severe COPD exacerbation (n=15,191) seen within the European COPD Audit.3
<h3>Exacerbations may increase mortality risk1</h3>

<h3>~2x&nbsp;</h3>
higher riske

After second exacerbationd

black

<h3>~3x&nbsp;</h3>
higher riske

After fifth exacerbationd

<h4>Noteworthy</h4>
<h3>All-cause mortality data showf:&nbsp;&nbsp;50%&nbsp;&nbsp;of patients died less than 4 years after their first COPD-related hospitalization1,d</h3>
dBased on data from a large population-based cohort of 73,106 Canadian patients who were hospitalized for the first time because of a severe exacerbation of COPD (1990-2005, followed until death or March 31, 2007) with a median follow-up of 3.6 years (range 1 day to 17 years). The mean age of patients in this retrospective study was 75 years old. eRelative risk of mortality compared to the first exacerbation (adjusted hazard ratio). fThe median survival was 3.6 years.

<h2>Chronic Underlying Inflammation Drives the Downward Spiral of Copd Progression10-18</h2>
Different types of chronic inflammation have an important role in COPD pathophysiology
Many cell types and cytokines are involved in these processes, including:

<h4>Noteworthy</h4>
<h3>Up to&nbsp;&nbsp;37%&nbsp;&nbsp;of COPD patients without an asthma comorbidity had evidence of type 2 inflammation25-29,g</h3>
gBased 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% (blood and sputum), or &gt;3% nonsquamous cells (sputum). Percentages of patients with type 2 inflammation ranged from 12.3% to 37%.25-29
<h2>Type 2 inflammation may drive poor outcomes in COPD9,30,31</h2>
Type 2 inflammation encompasses both type 2 effector cells (eg, Th2, ILC2, eosinophils, and mast cells) and key cytokines (eg, IL-4, IL-13, and IL-5)16,19,20,32-41

Persistent symptoms (dyspnea, chronic cough, sputum)9

Progressive lung function decline9

Exacerbations9

Select cytokines play important roles in type 2 inflammation

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 COPD32,34,42-48

IL-4 and IL-13 drive inflammatory cell activity

IL-13 plays a role in emphysema, fibrosis, and goblet cell hyperplasia and increases expression of MUC5AC, a major constituent of airway mucus17,33,34,48-51

The critical role of IL-13 in airflow limitation

IL-33 initiates and amplifies the broad inflammatory cascades in COPD, inclusive of type 2 inflammation and beyond22,23

The role of IL-33

IL-5 is required for the growth and differentiation, recruitment, activation, and survival of eosinophils, which may be biomarkers of a broader type 2 inflammatory response32

The role of IL-5

<h2>Look for Elevated Blood Eosinophils (≥300 Cells/μl)—a Biomarker of Type 2 Inflammation in Copd9,31</h2>
<h3>Identifying COPD patients with type 2 inflammation may help determine those at increased risk of exacerbations</h3>

Blood eosinophils
<h3>≥300</h3>
cells/μL

<h3>32%</h3>
increased risk of 
 COPD exacerbations30,h,i

hResults from an observational analysis of 1553 patients with GOLD spirometry grade 2-4 COPD evaluating the relationship between blood eosinophil counts and COPD exacerbation risk.30
iStratified analysis confirmed that increased exacerbation risk was driven by subjects with a history of frequent exacerbations, defined as ≥2 exacerbations per year.
<h3>Elevated eosinophils and a history of frequent exacerbations help identify patients and guide treatment options9,52</h3>
According to GOLD 2023 recommendations, patients with frequent exacerbations (GOLD Group E) and blood eosinophils ≥300 cells/μL may receive an ICS in combination with LABA + LAMA9
<h4>Noteworthy</h4>
Even when treatment is optimized with inhaled triple therapy, many patients with COPD may continue to experience exacerbations52

Understanding type 2 inflammation in COPD may help shed light on why some patients continue to experience exacerbations

Abbreviations

References

A deeper look at the inflammation behind exacerbations can IGNITE NEW THINKING IN COPD

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Chronic obstructive pulmonary disease (copd)

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A deeper look at the inflammation behind exacerbations in COPD

A deeper look at the inflammation behind exacerbations can IGNITE NEW THINKING IN COPD