Do blood eosinophils have a role in COPD?
In COPD, raised blood eosinophils (EOS) levels are associated with type 2 inflammation1 and have been linked to a higher risk of exacerbations.2 Understanding the role of EOS levels and their evolution through time can be important for clinicians to phenotype their patients and evaluate potential risk of exacerbation.3 However, a look-back period is warranted while assessing EOS levels in patients because EOS levels may fluctuate as a result of treatment.4
Discover more about the <a href="https://pro.campus.sanofi/copd/articles/role-of-type-2-inflammation" style="color:#0563c1; text-decoration:underline">Role of type 2 Inflammation in COPD</a>
Eosinophilic inflammation endotype 
Eosinophilic inflammation is a stable endotype. The <a href="https://bmjopen.bmj.com/content/4/3/e004546.long" style="color:#0563c1; text-decoration:underline">AERIS</a> study investigated the stability of this phenotype over time. The study results demonstrated that eosinophilic inflammation (blood EOS count ≥2%) is common at the time of exacerbation in patients with predominantly raised EOS during stable state.5 The likelihood of an exacerbation being eosinophilic was nine folds higher in patients with blood EOS ≥2% than in those with blood EOS &lt;2% at enrolment (OR = 9.16; 95% CI: 4.10–20.47­­­­­; P &lt;0.001).5
What is known about EOS level stability?
Temporal stability of EOS Levels 
The concept of temporal stability refers to the consistency of a biomarker over time.6 In a study by Landis et al., the blood EOS counts taken during stable COPD were reasonably reproducible.7 
A study by Long et al., provides robust data on the temporal stability of EOS levels in COPD patients. In their analysis of 225 patients from the COPDMAP cohort, Long and colleagues investigated EOS stability over 1 year using 2019 GOLD COPD thresholds (&lt;100, 100–&lt;300 and ≥300 EOS/μL).8 They found that 69.3% of patients had good stability of EOS levels from baseline to 1 year (measurements taken during stable state) within the same 2019 GOLD COPD thresholds.8 This temporal stability indicates that EOS levels measured during the stable phase of COPD are not random fluctuations but reflect an underlying and consistent inflammatory phenotype. Moreover, the study demonstrated that patients (no exacerbation, 66.7% patients; ≥1 exacerbation, 72.7% patients; ≥2 exacerbations, 74.3% patients) had stable blood EOS levels over 1 year when stratified into subgroups by number of exacerbations within a year.8 
Association between EOS levels and future exacerbation risk9,10

Yun et al., prospectively validated the association of increased EOS levels with exacerbations in COPD in the <a href="https://erj.ersjournals.com/content/31/4/869.long" style="color:#0563c1; text-decoration:underline">ECLIPSE</a> study.9 In this study, the researchers measured EOS levels during the stable phase and tracked the occurrence of exacerbations over a 3-year period.9 They found that raised EOS level (≥300 cells/μL) at baseline during the stable phase was a consistent predictor of risk of exacerbations in the following year (IRR = 1.20; 95% CI: 1.05–1.36 at 1 year).9 Specifically, the exacerbation risk was higher in patients with persistently raised (vs low) EOS levels, indicating that such patients had the greatest risk. Furthermore, the study revealed that the predictive capability of EOS levels extended beyond just a year (IRR = 1.22; 95% CI: 1.06–1.42 for overall study period).9 Patients with high EOS levels were consistently more likely to exacerbate over 3 years. This extended predictive capability underscores the utility of EOS level as a long-term predictor of exacerbation risk, allowing for early and proactive management strategies.9

Impact of oral corticosteroids use on blood EOS levels in patients with COPD
An inverse linear relationship between blood EOS levels and oral corticosteroids (OCS) dose was observed by Prazma et al., in patients with severe asthma, with an increase in blood EOS levels by 41% for every 5 mg/day decrease in OCS dose.11 To our knowledge, the impact of OCS use on blood EOS levels has not been studied in patients with COPD. However, OCS use is known to suppress EOS levels in patients with COPD.12 A study reported significant reduction in sputum EOS counts of six folds, following daily OCS use for 2 weeks.13 Measurement of EOS levels in patients whose levels are suppressed due to OCS administration could give an inaccurate assessment of EOS levels.12
Learn more about <a href="https://pro.campus.sanofi/copd/articles/blood-eosinophils-as-a-biomarker-in-patients-with-copd" style="color:#0563c1; text-decoration:underline">Blood Eosinophils as a Biomarker in Patients with COPD</a>
What are the clinical implications of EOS stability and predictive capability? 
The evidence supporting the EOS stability8 and long-term predictive capability9 of EOS levels in COPD has significant clinical implications. By identifying patients with consistently raised EOS levels, healthcare providers can stratify patients based on their risk of future exacerbations. This stratification can guide treatment decisions, particularly the use of OCS,14 inhaled (ICS)15 or biologics16 that target type 2 inflammation. For instance, a COPD patient with consistently high EOS levels (&gt;300 cells/μL) during the stable phase may be an ideal candidate for early intervention with ICS,15 which has been shown to reduce the frequency and severity of exacerbations in eosinophilic COPD.17,18 On the contrary, absence of raised blood EOS levels of &gt;2% may help identify a subgroup with an adverse impact of OCS on their recovery.14 The stability of EOS levels over time allows clinicians to monitor these levels as part of routine care, making it easier to identify changes in the patient’s inflammatory profile and adjust treatment accordingly. 
For further guidance on how to manage COPD patients please refer to the <a href="https://pro.campus.sanofi/copd/articles/gold-recommendations-for-treatment-and-management-of-copd" style="color:#0563c1; text-decoration:underline">GOLD Recommendations for Treatment and Management of COPD</a>

The long-term predictive capability of blood EOS levels9 is particularly useful, as it enables healthcare providers to anticipate and mitigate the risk of exacerbations, which are a major driver of morbidity and healthcare costs in COPD.14,19,20
How can EOS measurements be incorporated into clinical practice?
Incorporating EOS measurements into routine COPD management requires careful consideration of the data thresholds and the specific clinical context. The threshold of ≥300 cells/μL is commonly used to define raised EOS levels,9 based on evidence from multiple studies, including that by Yun et al.,9 However, some variability exists in the optimal threshold depending on the patient population and the specific outcomes being predicted.21
In practice, measuring EOS levels during the stable phase of COPD can be easily integrated into routine blood tests.22 Given the evidence of temporal stability, a single measurement can provide a reliable assessment of the patient’s eosinophilic phenotype.7 Patients with raised EOS levels should be closely monitored for signs of exacerbation,23 and consideration should be given to the early initiation of ICS1. Currently various clinical trials are in progress to evaluate the role of therapies targeting type 2 inflammation in COPD with raised EOS levels.24
Moreover, the predictive capability of EOS levels means that these measurements can inform long-term management strategies. For instance, patients with high baseline EOS levels may require more intensive follow-up and a lower threshold for escalating treatment in the event of early signs of exacerbation. This proactive approach can help reduce the frequency and severity of exacerbations, ultimately improving patient outcomes and reducing the burden on healthcare systems.22
Challenges and future directions
While the evidence supporting the use of EOS levels as a biomarker in COPD is compelling, several challenges remain. One challenge is the variability in EOS levels due to external factors such as infections,25 medications,21 and environmental exposures.26 These factors can influence EOS levels and potentially confound their predictive value. Therefore, it is essential for clinicians to interpret EOS measurements in the context of the patient’s overall clinical picture and consider repeat measurements if necessary.
Another challenge is the need for further research to refine the thresholds for EOS levels in different clinical scenarios. While the ≥300 cells/μL threshold is widely used, there is a need for more data to establish the optimal cut-off points for different patient populations and to validate these thresholds in diverse clinical settings.23
Future research should also explore the potential for combining EOS levels with other biomarkers and clinical features to enhance predictive accuracy. For example, integrating EOS measurements with markers of airway inflammation, such as fractional exhaled nitric oxide (FeNO),27,28 or with clinical features such as exacerbation history29, could provide a more comprehensive risk assessment tool for COPD patients.

This article highlights the stability and predictive value of blood eosinophil levels in COPD, showing their strong link to exacerbation risk. Consistently elevated eosinophil levels can guide personalized treatment, including early use of inhaled corticosteroids (ICS). Integrating eosinophil measurements into routine practice can improve long-term disease management and patient outcomes.

CHRONIC-OBSTRUCTIVE-PULMONARY-DISEASE-(COPD)

RESPIRATORY

A review of the clinical implications of eosinophil stability and predictive capability in COPD

<h2 style="margin-bottom: 8px;">Recognizing Moderate Exacerbations: The Need for Vigilance</h2>
Moderate exacerbations are those that require treatment with short acting bronchodilators, systemic corticosteroids and/or antibiotics.2 Early recognition and prompt management of moderate exacerbations are critical to mitigating their impact on COPD progression and patient outcomes. 
Criteria for moderate exacerbation2,4

According to GOLD Group ABE assessment tool, patients with a history of 0 or 1 moderate exacerbation, not leading to hospitalization, but with significant symptom burden [CAT (COPD assessment test) ≥10 or a mMRC (modified Medical Research Council dyspnea questionnaire) ≥2] are categorized as GOLD Group B.2,5 Patients with ≥2 moderate exacerbations (or ≥1 exacerbation requiring hospitalization) are categorized as GOLD Group E, irrespective of symptom burden.2
For more information, please read <a href="https://pro.campus.sanofi/copd/articles/gold-recommendations-for-treatment-and-management-of-copd" style="color:blue; text-decoration:underline">GOLD recommendations for treatment and management of COPD</a>.
Clinicians must be vigilant for key indicators that may signal a need for hospitalization:
Potential indicators for hospitalization assessment*2

Recognizing these clinical signs and intervening promptly can help prevent moderate exacerbations from escalating to more severe levels; thereby, reducing the overall burden of COPD. Remote home monitoring of patients, including the use of patient-reported outcomes and spirometry,6 is essential to detecting exacerbations early and improving overall management.
Please click on the link to know <a href="https://pro.campus.sanofi/copd/articles/What-tests-can-help-diagnose-and-monitor-your-patients-with-COPD-" style="color:blue; text-decoration:underline">what tests can help diagnose and monitor your patients with COPD?</a>
<h2 style="margin-bottom: 8px;">Moderate Exacerbation: The Unseen Drivers of COPD Progression</h2>
Moderate and/or severe exacerbations are not merely transient events; they are pivotal in shaping the trajectory of COPD.5 Acute moderate exacerbations are linked with worsening of airflow obstruction and lung hyperinflation.7 Furthermore, patients with frequent moderate to severe exacerbations exhibit a more rapid decline in lung function — forced expiratory volume in 1 second of 40 mL/year and peak expiratory flow of 2.9 L/min/year — compared with those with infrequent exacerbations.8 
Dr Surya Bhatt, a distinguished professor of medicine at the University of Alabama at Birmingham and a COPD researcher talks about <a href="https://pro.campus.sanofi/copd/articles/the-burden-and-risk-of-exacerbations-in-copd-according-to-dr-surya-bhatt" style="color:blue; text-decoration:underline">the burden and risk of exacerbations in COPD</a>.

The likelihood of subsequent moderate and severe exacerbations, and death are increased by 1.58 times, 2.08 times and 1.85 times, respectively, for 3 years following one moderate exacerbation with high symptom burden compared with no exacerbation.5 The risk of future exacerbations increases with even one episode of moderate exacerbation; thus, each episode is critical.5
Risk of future exacerbations with increasing frequency of moderate exacerbations9

For healthcare providers (HCP), the ability to recognize and treat frequent exacerbations early is crucial. This requires a proactive approach to COPD management, including increased HCP awareness on treatment recommendations, patient education, the development of integrated care action plans, and the provision of timely access to appropriate therapies.10 Such strategies are essential to maintaining disease control, preventing exacerbations from escalating, and reducing the overall burden of COPD on both patients and the healthcare system.
Learn more about <a href="https://pro.campus.sanofi/copd/articles/understanding-and-managing-copd-exacerbations" style="color:blue; text-decoration:underline">understanding and managing COPD exacerbations</a>.
<h2 style="margin-bottom: 8px;">The Ripple Effect: Impact of Moderate Exacerbations on Quality of Life (QoL)</h2>
Frequent exacerbations significantly impact the QoL for patients with COPD.11,12 The psychological impact of exacerbations is also considerable. Studies have shown that patients with frequent exacerbations are more likely to suffer from anxiety, post-traumatic stress and depression,13 with reportedly high prevalence (depression: 19.4%–50.0%; anxiety 9.3%–58.0%) soon after recovery.14 This psychological burden not only affects QoL, but also complicates disease management by impairing treatment adherence and increasing the risk of future exacerbations.15
Read this article to learn more about <a href="https://pro.campus.sanofi/copd/articles/the-impact-of-exacerbations-in-copd" style="color:blue; text-decoration:underline">the impact of exacerbations in COPD</a>.
Economically, moderate exacerbations contribute to substantial healthcare costs. Data indicate that the direct costs associated with moderate exacerbation can range from $248 to $1,011 per episode, depending on the setting of care.16 Indirect costs, including lost productivity and the need for informal caregiving, further amplify the economic impact.17 Overall, exacerbations account for approximately 50%–75% of the total annual COPD-related healthcare costs, highlighting their significant economic burden.16
In conclusion, moderate exacerbations play a critical role in the clinical course of COPD, with significant implications for both patient outcomes and healthcare resources. By prioritizing the early recognition and management of these exacerbations, healthcare providers can help mitigate their impact on disease progression and improve the overall QoL for patients with COPD.18 This approach, supported by appropriate maintenance treatment and patient-centered care such as pulmonary rehabilitation, is essential to achieving optimal outcomes in COPD management.10

Exacerbations are key events in COPD1 that play a crucial role in disease progression. Although often managed in outpatient settings, exacerbations contribute significantly to the overall burden of COPD.2 These events are characterized by an acute worsening of respiratory symptoms, including increased dyspnea associated with cough and production of purulent sputum, increased wheezing and chest discomfort.1,3 These characteristics reflect an underlying inflammatory response2 that exacerbates the disease process.

Navigating the Hidden Burden: The Critical Role of Moderate Exacerbations in COPD

COPD diagnosis is suspected in a patient with symptoms of dyspnea, chronic cough, or sputum production. Key clinical indicators that increase the probability of a COPD diagnosis are progressive persistent dyspnea, worsening with exercise, recurrent wheezing, chronic cough, recurrent lower respiratory infections and a history of risk factors. However, spirometry is required to establish COPD diagnosis.1 
COPD needs to be accurately diagnosed for optimal management. Therefore, differential diagnoses, such as asthma, congestive heart failure, bronchiectasis, tuberculosis, obliterative bronchiolitis, and diffuse panbronchiolitis, should be considered to make a clear distinction from COPD.1 Asthma is difficult to distinguish from COPD by current imaging modalities or physiological tests in some patients.1 
View this article to know how to <a href="https://pro.campus.sanofi/copd/articles/copd-vs-asthma-learn-the-difference" style="color:#0563c1; text-decoration:underline">differentiate between COPD and asthma</a>.
After establishment of COPD diagnosis, further assessment is required to guide treatment. The goals of initial assessment of COPD are to determine the severity of airflow obstruction, impact of disease on patient’s health status, and risk of future events. 1
There are various tools for COPD monitoring. Read this article to find out more about the <a href="https://pro.campus.sanofi/copd/articles/key-tools-to-measure-the-success-of-copd-management" style="color:#0563c1; text-decoration:underline">key tools to measure the success of COPD management</a>. 
Spirometry
Spirometry is one of the useful tools for pulmonary function test for COPD.2 It is readily available, non-invasive, reproducible and objective.1 During early stages of COPD when respiratory symptoms may be absent, spirometry can help identify COPD.1
Key variables associated with spirometry

Assessment of lung function by spirometry, particularly the post-bronchodilator FEV1, plays an important role in determining COPD severity and guiding treatment.5 Possible dosage protocols for measuring post-bronchodilator FEV1 are 10-15 minutes after a short-acting beta2-agonist (dose: 400 mcg) or 30-45 minutes a short-acting anticholinergic (dose: 160 mcg) or a combination of both drug classes.1 A decline in FEV1 over time is indicative of disease progression.5
GOLD grades and severity of air flow obstruction in COPD (based on post-bronchodilator FEV1)1

A refined GOLD ABE assessment tool, combining severity of exacerbations and symptoms, was proposed to guide pharmacological treatment. The level of symptoms is assessed based on the modified Medical Research Council (mMRC) dyspnea scale or COPD assessment test (CAT™)
Different grades of disease severity based on GOLD ABE assessment tool1

Additional clinical assessments1
Other clinical assessments may be required in specific patients to characterize severity and guide management, make a differential diagnosis, identify comorbidities or underlying other abnormalities.1

Symptom assessment using validated questionnaires
COPD impacts patient lives beyond dyspnea.1 The severity of airflow obstruction correlates weakly with symptom severity and impairment in health status.1 Therefore, changes in FEV1 are unable to capture the impact of COPD on patient’s health in its entirety.7,8 Short patient-centered questionnaires are the most efficient and accurate tools to assess severity of symptoms, limitation in activities of daily living and health-related quality of life (HRQoL).6 
Understand which <a href="https://pro.campus.sanofi/copd/articles/quality-of-life-and-symptom-measurement-in-copd-patients" style="color:#0563c1; text-decoration:underline">validated tools can be used to measure quality of life and symptoms</a> in patients with COPD.
The implementation of quick and easy-to-use questionnaires in routine clinical practice can enable physicians fully comprehend the HRQoL of their patients, improve transparency, and prescription of appropriate treatment and effective COPD monitoring.7,8
The modified Medical Research Council (mMRC) dyspnea scale 
Dyspnea is a subjective measure; therefore, it shows poor association with objective evaluation of lung function, exercise capacity, and other outcomes.5 The mMRC dyspnea scale is a simple to administer questionnaire, which assess the severity of dyspnea by grading its impact on daily activities on a scale of 0 to 4.6 Patients are required to select on a self-applied scale one of five statements that most closely describe their everyday activities or situation levels provoking breathlessness and level of impairment.5,8
COPD assessment test (CAT™)
For routine use in clinical practice, the CAT is a reliable, validated, practical, simple short patient-centered questionnaire, which can quantify COPD impact on patient health.6,7 The CAT items are broad and encompass several effects of COPD on patient’s health.7 The CAT scores 8 items on a scale of 1 to 5 with a maximum total score of 40. 
Read the <a href="https://www.catestonline.org/hcp-homepage/clinical-practice.html" style="color:#0563c1; text-decoration:underline">CAT HCP user guide and FAQ</a> to learn more about COPD assessment test
Functional parameters assessed using CAT™1,8

Blood eosinophil count
In the ECLIPSE study, 37.4% of patients with COPD had persistently raised blood eosinophil count (≥2%) over 3 years.9 When not confounded by use of inhaled corticosteroids (ICS), blood eosinophil count has a potential role as a prognostic biomarker for declining lung function.1

Blood eosinophil count can serve as a surrogate marker for sputum eosinophils to guide oral corticosteroid treatment of COPD exacerbations.9 It can help identify patients who are suitable for addition of ICS to regular bronchodilator therapy, allowing corticosteroid use in a more tailored way.1 
Do you know <a href="https://pro.campus.sanofi/copd/articles/blood-eosinophils-as-a-biomarker-in-patients-with-copd" style="color:#0563c1; text-decoration:underline">how blood eosinophil count can help guide treatment</a>?
Physiological test 
In case of a substantial gap between perceived symptoms and severity of airflow obstruction, a better understanding of the lung physiology is required, which may require additional assessments.1 Thus, in patients with persistent symptoms after initial treatment, additional clinical assessment, including measurement of lung volumes, diffusion capacity, exercise testing and/or lung imaging may be considered. 1

Chronic Obstructive Pulmonary Disease (COPD) is typically suspected in patients with symptoms like dyspnea, chronic cough, or sputum production. Accurate diagnosis is crucial for effective management, with spirometry being essential for confirmation. Distinguishing COPD from similar conditions, such as asthma, is challenging yet vital. This article provides clear guidance on differentiating COPD from asthma and highlights key tools like spirometry and validated questionnaires for monitoring disease progression and guiding treatment. Understanding and applying these tools can significantly enhance patient outcomes in COPD management.

What tests can help diagnose and monitor your patients with COPD?

What if you could identify higher-risk patients?&nbsp;&nbsp;
A deeper look at the inflammation behind exacerbations could ignite new thinking in COPD. Look for blood eosinophils, a biomarker of COPD with Type 2 Inflammation, which may help you identify those patients at increased risk of exacerbations.
Watch the video below to better understand exacerbations in COPD and better identify patients at risk.&nbsp;&nbsp;&nbsp;

Understanding type 2 inflammation may help shed light on why some patients continue to exacerbate. Watch this video to learn how.

One minute to ignite new thinking in COPD

Ignite new thinking in COPD -&nbsp;COPD, chronic obstructive pulmonary disease
In patients with COPD, exacerbations may :&nbsp;
<ul>
 <li>Increase the risk of another&nbsp;1</li>
 <li>Accelerate lung function decline&nbsp;2</li>
 <li>Increase morbidity and mortality risk&nbsp;1,3-6</li>
</ul>
Different types of chronic inflammation have an important role in COPD&nbsp;7-15 
 Type 2 inflammation and beyond type 2 inflammation 
 Identifying COPD patients with type 2 inflammation may help determine those at increased risk of exacerbations 16 
 Look for blood eosinophils, a biomarker of COPD with type 2 inflammation 17,18, a, b 
 EOS ≥ 300 cells/ μL à 32% increased risk of COPD exacerbations 16a,b 
 Understanding type 2 inflammation in COPD may shed light on why some patients continue to experience exacerbations
a Results from an observational analysis of 1553 patients with GOLD spirometry grade 2-4 COPD evaluating the relationship between blood eosinophil count and COPD exacerbation risk. b Stratified analysis confirmed that increased exacerbation risk was driven by subjects with a history of frequent exacerbations, defined as ≥2 exacerbations per year.

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Understanding type 2 inflammation may help shed light on why some patients continue to exacerbate. Watch this video to learn how.

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One minute to ignite new thinking in COPD

Latest COPD articles

A review of the clinical implications of eosinophil stability and predictive capability in COPD

Navigating the Hidden Burden: The Critical Role of Moderate Exacerbations in COPD

What tests can help diagnose and monitor your patients with COPD?