Eosinophils in COPD&nbsp;
In patients with COPD, raised eosinophil levels in the blood are associated with higher eosinophil levels in the lungs, which is a biomarker of type 2 inflammatory activity in the airway.1 It has been found that up to 37% of COPD patients show indication of type 2 inflammation.2-5&nbsp;
<ul>
 <li><a href="https://pro.campus.sanofi/copd/articles/role-of-type-2-inflammation">Link to Role of Type 2 Inflammation in COPD</a>&nbsp;</li>
</ul>
Raised blood eosinophil levels are detectable by ordering a complete blood count with differential. A large population-based study (N=39,824) evaluated the stability of blood eosinophilia over time. The stability of the blood eosinophil count was observed to be higher in patients with COPD with baseline counts &lt;340 cells/µL vs ≥340 cells/µL. The findings from this study extend the understanding of blood eosinophil as a potential biomarker.5 &nbsp;
Raised blood eosinophil count in COPD is associated with poor clinical outcomes and increased healthcare cost&nbsp;
Raised blood eosinophil count in COPD increased the risk of exacerbation,6 1-year COPD-related readmission,7 and severe exacerbations8 as shown in the illustration below:&nbsp;

COPD exacerbation risk increases with higher eosinophil counts. In the COPDGene study, COPD patients with blood eosinophil count ≥300 cells/μL demonstrated an increased risk of exacerbations. This was prospectively validated in the ECLIPSE study.6
&nbsp;
Type 2 inflammation in COPD (Eosinophilic COPD) and its risks&nbsp;
Raised blood eosinophils are associated with higher emergency department visits, outpatient visits, numbers of prescriptions* and increased rate of lung function decline.9,10 Raised eosinophils in COPD may also lead to increased risk of 1-year COPD-related readmission, decreased time to first COPD-related readmission and increased number of 1-year COPD-related Emergency Department (ED) visits7 as shown in the illustration and table below: &nbsp;
Risks associated with raised blood eosinophil levels&nbsp;

To learn more about the impact of raised eosinophiles in COPD read this article&nbsp;
An Overview of the impact of Type 2 Inflammation in COPD: Insights from Dr. Surya Bhatt&nbsp;
&nbsp;
<h2>Impact of blood eosinophil count in COPD on management decisions&nbsp;</h2>

Initial pharmacological management (Group E†)1:&nbsp;
GOLD references suggest that ICS should be added to long-acting bronchodilators therapy in patients with high blood eosinophils counts (≥300 cells/µL). Consider triple therapy (LABA+LAMA+ICS) if eosinophil count is ≥300 cells/μL and this is based on the effect of ICS on exacerbation prevention correlated to blood eosinophil count. There is no direct data on initiation with triple therapy in newly diagnosed patients. However, available studies in treated patients provide a rationale to initiate treatment with triple therapy in patients with high eosinophils counts (≥300 cells/µL).1&nbsp;
&nbsp;
Blood eosinophil count impact on initial management decisions, according to GOLD references1&nbsp;

Follow-up pharmacological management:&nbsp;
Exacerbations:1 &nbsp;
GOLD references recommend escalation to LABA + LAMA for patients with persistent exacerbations on bronchodilator therapy.&nbsp;
ICS is suggested to be added to LABA + LAMA in patients who develop further exacerbations. Beneficial response of ICS may be observed at blood eosinophil counts of ≥100 cells/μL.&nbsp;
For patients treated with LABA + LAMA + ICS or those with eosinophil counts of &lt;100 cells/μL who still have exacerbations — <a href="https://goldcopd.org/">Please refer to GOLD guidelines for more information</a>&nbsp;
&nbsp;
Blood eosinophil count impact on follow-up pharmalogical management decisions, according to GOLD1&nbsp;

*Regardless of inhaled therapy&nbsp;
†Group “E” are patients with frequent exacerbations (defined as ≥2 in the past 12 months or 1 exacerbation requiring hospitalization).&nbsp;
&nbsp;
COPD, chronic obstructive pulmonary disease; ED, emergency department; FEV1, forced expiratory volume in first second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HR, hazard ratio; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; OR, odds ratio; IRR, incidence rate ratio; ULN, upper limit of normal.&nbsp;

This article discusses the role of blood eosinophils as a biomarker in patients with Chronic Obstructive Pulmonary Disease (COPD). It highlights that measuring blood eosinophil levels can help predict exacerbations, guide corticosteroid therapy, and tailor treatment strategies for COPD patients. The article emphasizes the importance of personalized treatment approaches based on eosinophil counts to improve patient outcomes and manage COPD more effectively.

CHRONIC-OBSTRUCTIVE-PULMONARY-DISEASE-(COPD)

Blood Eosinophils as a Biomarker in Patients with COPD

<h2>Learn more on how to assess these goals below&nbsp;</h2>
How to evaluate success in achieving treatment goals?
Success in managing chronic obstructive pulmonary disease (COPD) is multifaceted and can be measured by reduction in symptom severity and disease progression, clinically meaningful reductions in exacerbations, significant improvement in lung function, improved exercise tolerance and an increase in a patient’s quality of life (QoL). Treatment success requires a continuous cycle of assessment, treatment adjustment, and a review of response.1 Evidence-based metrics can be used to gauge outcomes in COPD patients and provide a structured way to assess the effectiveness of treatments and guide clinical decisions towards improving the lives of patients with COPD as discussed in the following sections.
What is the impact of exacerbations on patients’ disease trajectory?
Frequent exacerbations are associated with poor health status, morbidity, and mortality. They can result in a decline in lung function and frequent hospitalizations.1,2 Minimizing the negative impact of ongoing exacerbations and reducing the number and severity of exacerbations is critical to COPD management.2&nbsp;Successful treatment is often reflected in fewer hospitalizations due to exacerbations and a better control of symptoms.2,3 
To learn more about the impact of exacerbations, read this article <a href="https://pro.campus.sanofi/copd/articles/the-impact-of-exacerbations-in-copd" style="color:#69a020; text-decoration:underline">The Impact of exacerbations in COPD | Campus Sanofi</a>.
&nbsp;
How is lung function assessed in patients with COPD?
Rapidly declining lung function in patients with COPD results in impaired health status and increases risk of mortality.<a name="_Hlk169000230">4</a> Assessment of lung function by spirometry, particularly the Forced Expiratory Volume in 1 second (FEV1), plays an important role in determining the severity of COPD and guiding treatment.4 A slower decline in FEV1 over time is indicative of successful disease management.4
&nbsp;
How can symptoms and their impact be assessed?
Symptoms impact the daily lives of patients by significantly influencing physical activity, health status and QoL.2 COPD treatment guidelines recommend using standardized multidimensional measures, COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scale and, St. George’s Respiratory Questionnaire (SGRQ), for assessing health status and QoL.1,5
&nbsp;
Which symptoms can be scored on CAT?
CAT is simple and easy to administer and scores 8 functional parameters — cough, phlegm, chest tightness, breathlessness while climbing up a hill or flight of stairs, activity limitation at home, confidence leaving home, sleep, and energy. These 8 parameters are scored on a scale of 1 to 5, with a total score of 40.1,5 The CAT score provides a measure of the impact of disease on patient’s daily life. A CAT score of 5 is the upper limit of normal in healthy non-smoking individuals.6 A worsening CAT score in COPD patients may suggest unreported exacerbations by patients, discontinuation of medications, ineffective intake of treatment, rapid disease progression, or the need for specialist intervention.<a name="_Hlk169000349">6</a>
CAT™ Assessment1,7

What is the use of mMRC questionnaire in symptom assessment?
Dyspnea shows poor association with objective evaluation of lung function, exercise capacity, and other outcomes as it is a subjective metric.4 The mMRC questionnaire is used to assess the severity of dyspnea by grading its impact on daily activities on a scale of 0 to 4.2,8 A decrease in mMRC scores indicates successful alleviation of the symptoms.8
How does St. George’s Respiratory Questionnaire (SGRQ) help physicians assess COPD patients?
Health Status and QoL are vital outcome parameters that should be assessed in patients with COPD. Perceptions about the impact of symptoms on patient’s QoL may considerably vary between HCPs and their patients.2,9 Tools like the SGRQ, encompassing domains of symptoms, activity, and psychosocial impact, evaluate the effects of COPD on respiratory health and daily life.4,10,11 With a maximum total score of 100 points, COPD treatment guidelines recommend regular symptomatic treatment in case of SGRQ score ≥25.1,4 A lower score on SGRQ reflects improved health status. A minimum change in SGRQ score of 4 units is considered as clinically relevant.10

What other parameters should be monitored to evaluate treatment success? 
According to COPD treatment guidelines, walking tests can be used to evaluate disability and risk of mortality.1 Reduced exercise capacity is associated with disease progression, increasing predisposition to poor QoL, hospitalization and mortality.1 A six-minute walk test (6MWT) can be performed to assess exercise tolerance.12 An increase in the distance covered during the 6MWT signifies enhanced physical fitness, a key goal to reduce symptoms.

This article provides pulmonologists with essential insights into evaluating COPD management. It delves into the multifaceted approach required to measure success, including reducing symptom severity, preventing exacerbations, improving lung function, enhancing exercise tolerance, and boosting the quality of life. By employing standardized assessment tools such as the COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and St. George’s Respiratory Questionnaire (SGRQ), clinicians can accurately gauge treatment effectiveness. Additionally, the article highlights the importance of continuous assessment and adjustment in managing COPD, ensuring better patient outcomes.

Key tools to measure the success of COPD management

<h1>Chronic Obstructive Pulmonary Disease (COPD) is a major health concern globally, with a significant impact on the quality of life and life expectancy of affected individuals. Surya Bhatt, a distinguished professor of medicine at the University of Alabama at Birmingham and a COPD researcher, provides valuable insights into the progression and management of this disease. This article will delve into key aspects of COPD exacerbations, drawing on the expertise of Dr. Bhatt to enhance our understanding.</h1>

The burden and Risk of Exacerbations in COPD according to Dr. Surya Bhatt

My name is Surya Bhatt. I'm a professor of medicine at the University of Alabama at Birmingham, and I'm a COPD researcher. This talk is sponsored by Sanofi and Regeneron, and you won't get any CME credit. One of the other things that's very important in COPD is acute exacerbations. And these are not just an inconvenience but are associated with significant disease progression. Now there's plenty of data to suggest that these exacerbations are associated with lung function decline. They're commonly caused by infections such as viruses and bacterial infections sometimes due to environmental pollution and occupational exposures. Regardless of the cause, the severity is determined by where they're treated, which is not ideal. But if they manage to adjust steroids and antibiotics at home, that classifies as a moderate exacerbation. But if it's severe enough to end up in the hospital, and then that causes a severe exacerbation and people will suffer from exacerbations, have a faster rate of lung function decline than those who do not have exacerbations at all. And here on the right is data from the COPD gene study where they looked at the FEV one decline by exacerbation or the frequency of exacerbations.
&nbsp;
And especially for severe exacerbations and especially for those with milder disease who have more lung function to lose the effect can be quite dramatic. The FEV even decline can be up to 87mm for a severe exacerbation in world stage one, for example. And as you can imagine, if you get 4 or 5 exacerbations, you can lose up to a half a meter of fev1 over the next 4 to 5 years. The severe exacerbations appear to be sentinel events in the course of the COPD patients. When somebody gets a first exacerbation it seems like it begets more exacerbations. In a retrospective study by Sammy Sosa of about 75,000 patients in Canada. He modeled the severe exacerbation frequency and found that the usual median interval between a first and a second exacerbation is about five and a half years, and then the exacerbations happen at progressively shorter intervals to the point that by about the 10th exacerbation the median interval is about four months. So you can imagine a patient within a few years settling into a pattern of 3 to 4 exacerbations needing hospitalization in a single year.
&nbsp;
And this is not without consequence. These kind of exacerbations can have an effect on mortality. The hazards of mortality is about twice. If you get two severe exacerbations as opposed to one severe exacerbation. And the hazards of mortality is five fold. If you get ten exacerbations as opposed to one severe exacerbation. So there's almost a monotonic increase in the hazards with increasing severe exacerbation frequency. And the curve on the right shows your risk of dying after a single severe exacerbation requiring hospitalization. So the mortality within one year is about 25%, and the mortality within four years after discharge after the first severe exacerbation is 50%.

Read podcast transcript

<h2>What is COPD?</h2>
COPD is a chronic inflammatory lung disease that causes obstructed airflow from the lungs. Symptoms include breathing difficulty, cough, mucus (sputum) production, and wheezing. It is typically caused by long-term exposure to irritating gases or particulate matter, most often from cigarette smoke. Individuals with COPD are at increased risk of developing heart disease, lung cancer, and a variety of other conditions.

<h2>The Critical Role of Exacerbations in COPD Progression</h2>
Dr. Bhatt emphasizes that acute exacerbations of COPD are not merely inconveniences but are pivotal events that significantly influence the course of the disease. "One of the other things that's very important in COPD is acute exacerbations. And these are not just an inconvenience but are associated with significant disease progression," he states. Exacerbations are typically triggered by infections such as viruses and bacterial infections or by environmental pollution and occupational exposures.
<h3>Impact on Lung Function</h3>
Exacerbations have a profound impact on lung function, with data suggesting a link between exacerbations and accelerated lung function decline. Dr. Bhatt notes, "There's plenty of data to suggest that these exacerbations are associated with lung function decline." This decline is more severe in the case of frequent exacerbations. For instance, he cites the COPD Gene study, which shows how the frequency of exacerbations correlates with the rate of FEV1 decline—a measure of lung function.

<h3>Severity and Treatment</h3>
The severity of exacerbations can vary, significantly affecting treatment approaches and outcomes. "But if they manage to adjust steroids and antibiotics at home, that classifies as a moderate exacerbation. But if it's severe enough to end up in the hospital, then that causes a severe exacerbation," explains Dr. Bhatt. The distinction between moderate and severe exacerbations is crucial as it determines the immediate treatment protocol and the long-term management strategy.

<h2>The Cascading Effects of Severe Exacerbations</h2>
Severe exacerbations are particularly concerning due to their cascading effects on health. Dr. Bhatt discusses a study by Sammy Sosa, which modeled severe exacerbation frequency among approximately 75,000 patients in Canada. The study found that the interval between exacerbations tends to decrease over time, indicating a worsening pattern of the disease. "When somebody gets a first exacerbation, it seems like it begets more exacerbations," he explains.
<h3>Mortality Risks</h3>
The mortality risks associated with severe exacerbations are stark. Dr. Bhatt highlights, "The hazards of mortality is about twice if you get two severe exacerbations as opposed to one severe exacerbation. And the hazards of mortality is fivefold if you get ten exacerbations as opposed to one severe exacerbation." Furthermore, the risk of dying within one year of a severe exacerbation requiring hospitalization is about 25%, which increases to 50% within four years after discharge.

<h2>In Summary</h2>
The insights provided by Dr. Surya Bhatt illuminate the severe implications of COPD exacerbations. Understanding the triggers, frequency, and severity of these exacerbations is crucial for managing COPD effectively. As research continues to evolve, it is essential for healthcare providers to stay informed about the best practices for treating and managing exacerbations to improve the quality of life for COPD patients. Additionally, preventative strategies, including smoking cessation and reducing exposure to pollutants, remain key components of COPD management. Through a comprehensive approach that includes both prevention and effective exacerbation management, the impact of COPD can be significantly mitigated.

Chronic Obstructive Pulmonary Disease (COPD) is a major health concern globally, with a significant impact on the quality of life and life expectancy of affected individuals. Surya Bhatt, a distinguished professor of medicine at the University of Alabama at Birmingham and a COPD researcher, provides valuable insights into the progression and management of this disease. This article will delve into key aspects of COPD exacerbations, drawing on the expertise of Dr. Bhatt to enhance our understanding.

Chronic Obstructive Pulmonary Disease (COPD) remains a significant health challenge worldwide, characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities. Traditionally, COPD has been associated with neutrophil-driven inflammation, but recent insights suggest a more complex picture, involving Type 2 inflammation in a subset of patients. Dr. Surya Bhatt, a renowned COPD researcher and professor of medicine at the University of Alabama at Birmingham, provides valuable insights into this emerging area of COPD research.

An Overview of the impact of Type 2 Inflammation in COPD: Insights from Dr. Surya Bhatt

My name is Surya Bhatt. I'm a professor of Medicine at the University of Alabama at Birmingham and I'm a COPD researcher.
&nbsp;
This talk is sponsored by Sanofi and Regeneron and you won't get any (CME) credit. In response to any kind of insult. For example, cigarette smoke, viral infections, bacterial infections, pollution, there is some element of epithelial injury and epithelial damage. And the first response to this usually is once there is enough epithelial damage, there is release of damage associated molecular patterns or (DAMPs) which are now perhaps more popularly called alarmins and these are IL-33, IL-25 and TSLP or thymic stromal lymphopoietin. So all these can be released and they all have specific roles in terms of furthering inflammation. And IL-33 is perhaps best understood and some people consider it the master inflammation switch where once it's activated, it stays activated for a long time. It promotes both type 1 and type 3 inflammation as well as type 2 inflammation.
The traditional thinking has been that the prime driver of type two inflammation is IL-5, which causes eosinophilic inflammation. But now we understand that both IL-4 and IL-13 are important in driving type 2 inflammation. And here's a list of all the things that they can do. lL-4 and IL-13:
Can both cause epithelial barrier disruption.
They can cause B cell class switching and enhance an increased production of IgE
They can cause mast cell degranulation
They can cause basophil degranulation
And also eosinophilic inflammation just like IL-5.
They can also result in goblet cell hyperplasia and mucus production especially IL-13.
And as a consequence of these, they can cause significant airway remodeling as well as alveolar destruction.
IL-4 and IL-13 levels are also elevated during an acute exacerbation as opposed to in the stable state or patients without COPD. So this is also important to note that these pathways are activated in patients with acute exacerbation of COPD and they present and important in COPD.
And then, you know, we all know that there's been a lot of understanding of mucin and mucus production in COPD. And one of the prime drivers of that is MUC5A and IL-4 can induce increased expression of MUC5AC in human epithelial cells. And there's also a dose dependent response almost of IL-13 on MUC5A as well as increased mucus production. So, especially IL-13 has been found to be an important driver of mucus production in patients with COPD.

Understanding COPD and Inflammation Pathways
COPD has historically been viewed through the lens of neutrophilic inflammation, driven primarily by the DH1 and DH17 pathways. However, Dr. Bhatt highlights a shift in understanding, noting that "there's increasing recognition that Type 2 inflammation may actually play a role in COPD." This inflammation is not as straightforward to detect, with varying degrees of presence in the patient population. "It's between 20 to 40 percent of patients seem to have some evidence of Type 2 inflammation," Dr. Bhatt explains.

Diagnostic Markers of Type 2 Inflammation
One of the key markers for detecting Type 2 inflammation is the eosinophil count in the blood. Dr. Bhatt points out the diagnostic value of this marker: "It correlates relatively well with eosinophilic inflammation in the lungs and it's more likely to be specific than sensitive." This means that a high eosinophil count can be a reliable indicator of Type 2 inflammatory activity within the lungs. However, he also cautions that fluctuating eosinophil levels can complicate the diagnosis, stating, "if you don't find it, that doesn't mean they don't have Type 2 inflammation."

Clinical Implications of Type 2 Inflammation in COPD
Dr. Bhatt refers to data from significant studies such as COPD Gene and Eclipse, which show a clear correlation between eosinophil counts and exacerbation frequency in COPD patients. "There's almost a monotonic increase in the frequency of exacerbations with increasing eosinophil count," he notes, highlighting the clinical relevance of these findings. Notably, around 300 cells per microliter marks a significant increase in exacerbation frequency, which continues to rise with higher counts.
Additionally, other diagnostic tools like fractional exhaled nitric oxide (FeNO) can offer insights into Type 2 inflammation. Dr. Bhatt discusses a study involving 220 patients, which found that varying levels of FeNO were associated with different exacerbation frequencies. Those with persistently elevated FeNO levels showed a continuous increase in exacerbations, suggesting ongoing Type 2 inflammation.

Prognostic Value of Type 2 Inflammation
Type 2 inflammation not only correlates with exacerbation frequency but also has implications for hospital readmissions. Dr. Bhatt cites a retrospective study of almost 2,500 patients from an administrative database, revealing that "high eosinophils, defined as greater than 300 cells per microliter, was associated with a higher COPD-related readmission at 30 days as well as at 52 weeks." This finding underscores the importance of monitoring eosinophil levels for predicting both moderate and severe exacerbations, and potentially tailoring treatment strategies to reduce hospital readmissions.

In Summary
Dr. Surya Bhatt's insights into Type 2 inflammation in COPD highlight a significant shift in understanding and managing this complex disease. Recognizing the role of Type 2 inflammation could lead to more personalized treatment approaches, potentially improving outcomes for a substantial subset of COPD patients. As research continues to evolve, pulmonologists and other healthcare providers must stay informed about these developments to optimize care for their patients with COPD.
In summarizing the impact of these findings, Dr. Bhatt emphasizes the need for continued research and awareness, "I think we need to keep looking," he asserts, pointing towards a future where COPD treatment may become more targeted and effective based on individual inflammatory profiles. This approach could revolutionize the management of COPD, making it not just a matter of managing symptoms but potentially altering the disease course for many patients.

Chronic Obstructive Pulmonary Disease (COPD) remains a significant health challenge worldwide, characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities. Traditionally, COPD has been associated with neutrophil-driven inflammation, but recent insights suggest a more complex picture, involving Type 2 inflammation in a subset of patients. Dr. Surya Bhatt, a renowned COPD researcher and professor of medicine at the University of Alabama at Birmingham, provides valuable insights into this emerging area of COPD research.

What is the role of type 2 inflammation in COPD?&nbsp;
A deeper look into the underlying pathophysiology and drivers of chronic inflammation, particularly type 2 inflammation, can help us better understand COPD. The key cytokines involved in type 2 inflammation are elevated during acute exacerbations of COPD, and can play a role in mucus hypersecretion in lungs.&nbsp;
Watch the video below to get an understanding on type 2 inflammation and its role in COPD.&nbsp;

Understanding type 2 inflammation is the key to managing symptoms and exacerbations of COPD.&nbsp;&nbsp;

Decoding Type 2 Inflammation in COPD: An Expert’s Perspective 

My name is Surya Bhatt. I'm a professor of Medicine at the University of Alabama at Birmingham and I'm a COPD researcher.
This talk is sponsored by Sanofi and Regeneron and you won't get any (CME) credit. In response to any kind of insult. For example, cigarette smoke, viral infections, bacterial infections, pollution, there is some element of epithelial injury and epithelial damage. And the first response to this usually is once there is enough epithelial damage, there is release of damage associated molecular patterns or (DAMPs) which are now perhaps more popularly called alarmins and these are IL-33, IL-25 and TSLP or thymic stromal lymphopoietin. So all these can be released and they all have specific roles in terms of furthering inflammation. And IL-33 is perhaps best understood and some people consider it the master inflammation switch where once it's activated, it stays activated for a long time. It promotes both type 1 and type 3 inflammation as well as type 2 inflammation.
The traditional thinking has been that the prime driver of type two inflammation is IL-5, which causes eosinophilic inflammation. But now we understand that both IL-4 and IL-13 are important in driving type 2 inflammation. And here's a list of all the things that they can do. lL-4 and IL-13:
<ul type="disc">
 <li>Can both cause epithelial barrier disruption.</li>
 <li>They can cause B cell class switching and enhance an increased production of IgE</li>
 <li>They can cause mast cell degranulation</li>
 <li>They can cause basophil degranulation</li>
 <li>And also eosinophilic inflammation just like IL-5.</li>
 <li>They can also result in goblet cell hyperplasia and mucus production especially IL-13.</li>
 <li>And as a consequence of these, they can cause significant airway remodeling as well as alveolar destruction.</li>
</ul>
IL-4 and IL-13 levels are also elevated during an acute exacerbation as opposed to in the stable state or patients without COPD. So this is also important to note that these pathways are activated in patients with acute exacerbation of COPD and they present and important in COPD.
And then, you know, we all know that there's been a lot of understanding of mucin and mucus production in COPD. And one of the prime drivers of that is MUC5A and IL-4 can induce increased expression of MUC5AC in human epithelial cells. And there's also a dose dependent response almost of IL-13 on MUC5A as well as increased mucus production. So, especially IL-13 has been found to be an important driver of mucus production in patients with COPD.

<h2>The Genesis of Inflammation in COPD</h2>
COPD is traditionally associated with exposure to harmful stimuli such as cigarette smoke, air pollution, and respiratory infections. Dr. Bhatt explains that these insults lead to epithelial damage in the respiratory tract, which is the first step in a cascade of inflammatory responses. "In response to any kind of insult, there is some element of epithelial injury and damage," Dr. Bhatt notes, outlining the release of damage-associated molecular patterns (DAMPs), also known as alarmins. These include IL-33, IL-25, and TSLP (thymic stromal lymphopoietin), each playing a crucial role in the amplification of inflammation.
<h2>Type 2 Inflammation: Beyond Eosinophils</h2>
While eosinophilic inflammation (driven by IL-5) has been the traditional focus in Type 2 inflammation, Dr. Bhatt emphasizes the significant roles of IL-4 and IL-13. These interleukins contribute to various pathological processes in COPD:
<ol>
 <li>
 Epithelial Barrier Disruption: IL-4 and IL-13 can compromise the integrity of the epithelial barrier, making it more susceptible to environmental insults.</li>
 <li>
 B Cell Class Switching and IgE Production: These cytokines facilitate B cell transformation and increase IgE levels, which are critical in allergic responses and may exacerbate respiratory symptoms.</li>
 <li>
 Mast Cell and Basophil Degranulation: This leads to further release of inflammatory mediators, worsening inflammation and symptom severity.</li>
 <li>
 Goblet Cell Hyperplasia and Mucus Overproduction: Particularly driven by IL-13, this results in excessive mucus production, a hallmark of COPD that contributes to airway obstruction and difficulty clearing infections.</li>
 <li>
 Airway and Alveolar Remodeling: Chronic inflammation driven by these cytokines can lead to structural changes in the lung, reducing its functionality over time.</li>
</ol>

<h4>Acute Exacerbations and Mucus Production in COPD</h4>
Dr. Bhatt notes that IL-4 and IL-13 levels are elevated during acute exacerbations of COPD compared to stable states, underscoring the activation of these pathways during flare-ups. He also addresses the role of mucins in COPD, particularly MUC5AC, which is induced by IL-4 in human epithelial cells. IL-13 also shows a dose-dependent effect on MUC5A and enhances mucus production, marking it as a significant factor in COPD exacerbations.

<h2>The MUC5AC Connection</h2>
A significant aspect of Dr. Bhatt’s discussion revolves around mucin production, specifically driven by MUC5AC and its regulation by IL-4 and IL-13. "IL-4 can induce increased expression of MUC5AC in human epithelial cells," he explains, highlighting a dose-dependent increase in mucus production driven by IL-13. This pathway is particularly important as it contributes to the characteristic mucus hypersecretion observed in COPD patients.

<h2>In Summary</h2>
Dr. Surya Bhatt’s insights into the role of Type 2 inflammation in COPD underscore the complexity of this disease and the multifaceted nature of its inflammatory processes. Understanding these mechanisms not only sheds light on the pathophysiology of COPD but also opens new avenues for targeted treatments that could potentially modulate these inflammatory pathways, offering hope for better management of this debilitating disease.
As the field of COPD research continues to evolve, it is clear that integrating insights from experts like Dr. Bhatt will be crucial in developing more effective therapeutic strategies that address the underlying inflammation and its diverse manifestations in COPD patients.

Understanding type 2 inflammation is the key to managing symptoms and exacerbations of COPD.  

<h2>COPD Exacerbation risk has been shown to accelerate after each exacerbation.2,a&nbsp;</h2>
<h3>Exacerbation risk accelerates after each exacerbation1</h3>

*Severe exacerbations were defined as those which resulted in hospitalization with a primary discharge diagnosis of COPD2
<h3>Despite triple inhaled therapyc, the current standard of care, many patients remain symptomatic as defined by persistent symptoms and exacerbations.</h3>

<h2>Listen to Prof&nbsp;Nicola Hanania: “Prevention of exacerbations is the key goal”</h2>

2:07 minutes 
 Nicola Hanania is Professor of Medicine, Section Chief of Pulmonary Critical Care and Sleep Medicine at the Ben Taub Hospital in Houston, Texas, and Director of the Airways Clinical Research Center, ACRC, at the Bear College of Medicine.

The Impact of Exacerbations in COPD

Listen to the whole episode of the podcast on the <a href="https://www.emjreviews.com/respiratory/podcasts/the-negative-impact-of-chronic-inflammation-on-quality-of-life-in-patients-with-copd/">EMJ website</a> 
 Sponsored by Sanofi and Regeneron, in partnership with EMJ.

COPD unfortunately is a chronic disease as the name implies. So, it’s a progressive disease. While we cannot cure it, we can manage it, we can treat it. Unfortunately, there are several events in the course of the disease that makes it worse, not only for the patient but for the healthcare system: it increases risk of hospitalization, mortality… And one of them is exacerbations. I call it “lung attacks”. Pretty much what happens with exacerbations is these patients who have daily symptoms become having more symptoms, they may have more cough, increasing sputum production, sometimes these exacerbations are driven by infections – most of the time actually – and they end up needing more and more treatments including antibiotics, steroids. And sometimes unfortunately may end up pushing the patient to go to emergency department or getting hospitalized. Unfortunately, exacerbations is not just the fact that they occur and we can treat them, it’s every time the patient gets an exacerbation it puts his or her lung function down. In fact, there has been good data now to show that repeated exacerbations can contribute to increase risk of worsening exacerbations subsequently, but worsening lung function over long time, and they don’t recuperate lung function, so, meaning every time they get an exacerbation it puts them down both the lung function and the quality of life. There is definitely good data to show that repeated exacerbations have been linked to increased mortality and so on. So that’s why one of the major goals in managing this disease is try to prevent these lung attacks from occurring. Prevention of exacerbations is the key goal in managing this disease. Naturally exacerbations tend to be more frequent in those patients with more severe disease. But they can occur even in moderate COPD as well, in some situations.

<h2>COPD Exacerbations may lead to accelerated lung function decline3,e</h2>

<ul>
 <li>
 Loss of lung function nearly doubled3</li>
 <li>
 Irreversible lung function decline may occur after only one COPD exacerbation3</li>
</ul>
&nbsp;&nbsp;

&nbsp;
aBased 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).2 bAdjusted for age, sex, calendar time, and the modified Chronic Disease Score.2 cOr double inhaled therapy if ICS is contraindicated.15 d52-week, randomized, double-blind, phase 3 trial that assessed the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol triple therapy versus fluticasone furoate/vilanterol or umeclidinium/vilanterol in patients aged ≥40 years with symptomatic COPD and a history of exacerbations.2 eFEV1 decline after a single moderate-to-severe exacerbation. Based on a retrospective analysis of data from 586 patients with moderate-to-severe COPD.5&nbsp; 
 aHR, adjusted hazard ratio; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; QoL, quality of life&nbsp;

<h2>Type 2 Inflammation may increase the risk of exacerbations and lung function impairment in COPD23,24</h2>
<h3>COPD is characterized by mucus production, airway obstruction, and coughing13</h3>

<h3>Inflammation manifests systemically and locally</h3>

<ul>
 <li>Chronic inflammation causes structural changes, including narrowing of the airways and decreased lung elasticity13</li>
 <li>Studies have identified a relationship between inflammation and mucus hypersecretion in respiratory conditions such as COPD25</li>
</ul>
&nbsp;&nbsp;

<h2>Listen to Prof Nicola Hanania : “We no longer look at it as a one-size-fits-all disease”</h2>

1:36 minutes
Nicola Hanania is Professor of Medicine, Section Chief of Pulmonary Critical Care and Sleep Medicine at the Ben Taub Hospital in Houston, Texas, and Director of the Airways Clinical Research Center, ACRC, at the Bear College of Medicine.

Role of type 2 Inflammation 

I think our approach to this all disease has changed, knowing that it has multiple what we call phenotypes, but also not only that, but we have identified multiple mechanism of the disease, so we no longer look at it as a one-size-fits-all disease. And so therefore it's very important for clinician to do some really digging deep into history to identify these phenotypes, whether it's a frequent exacerbative phenotype, whether it's a chronic bronchitic phenotype, whether it's an emphysema mainly phenotype, but now we use biomarkers like blood eosinophils and maybe more to come, including radiology biomarkers in the future, may help us subdivide this group of patients so that we can do a more personalized approach. And I think it's very exciting time for COPD, so we have moved from this blue-bloater pink puffer type approach to now having multiple, as I mentioned, subtypes or phenotypes, and including the identifying more mechanism so that we have more targeted approach to this disease. And hopefully that will help improve outcomes in the future, obviously. That's the main goal is to move that increased risk of mortality that we have seen in COPD, while we have seen so much achievement with other diseases in COPD. Unfortunately, we haven't moved that envelope a lot, so I think we're hoping with new approaches we may improve outcomes.

<h2>Look for elevated blood eosinophils (&gt;300 Cells/Lμ) - A Biomarker of Type 2 Inflammation in COPD13</h2>

<h4>&nbsp;</h4>
<h3>Elevated eosinophils in COPD are a treatable trait and marker of type 2 inflammation13</h3>
The 2024 GOLD Report recognizes elevated blood EOS as a clinically used biomarker in identifying COPD with type 2 inflammation
<h2>Type 2 inflammation in COPD can involve multiple pathways, cytokines, and inflammatory cells28-33</h2>

<h2>IL-4, IL-13, an IL-5 are type 2 cytokines involved in COPD</h2>

&nbsp;&nbsp;
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% in peripheral blood. Percentages of patients with type 2 inflammation ranged from 12.3% to ~40%23,24 bA 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.27 cIn a cohort of patients with EOS &gt;200 cells/μL.26 dReproduced with permission of the American Thoracic Society. Fritzsching B et al. Am J Respir Crit Care Med. 2015;191(8):902-91325 eAlcian blue PAS staining of mucus in airway epithelial cells.25 fResults from an observational study of 1553 patients with GOLD spirometry grade 2-4 COPD (postbronchodilator FEV1/FVC ratio &lt;0.7, with FEV, &gt;80% predicted)23 gResults 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.24 
 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-y, interferon-gamma; ILC2, innate lymphoid type-2 cells; MUC5AC, mucin 5AC; PAS, periodic acid-Schiff; TNF-a, tumor necrosis factor alpha; TSLP, thymic stromal lymphopoietin.

<h2>The SGRQ measures the qualitative impact of COPD14,a</h2>
Some domains evaluated by the SGRQ include16:

Cough

Sputum production

Breathlessness

Wheezing

Exacerbations

Work activities

Daily activities*

Medication use

*Such as walking upstairs or getting dressed.
<h3>E-RS-COPD assess COPD symptomsb</h3>
Some domains evaluated by the E-RS-COPD include16:

Cough

Breathlessness

Chest congestion

This is not an exhaustive list of items evaluated by the SGRQ and E-RS-COPD.
&nbsp;
<h2>Listen to Prof Claus Vogelmeier : "We are now starting to characterize patients more carefully"</h2>

0:37 minutes
Claus Vogelmeier is Professor of Medicine and Head of the Department of Pneumology at the University Hospital Marburg, Germany

Quality of life and symptom measurement in COPD Patients

Listen to the whole episode of the podcast on the <a href="https://www.emjreviews.com/respiratory/podcasts/the-negative-impact-of-chronic-inflammation-on-quality-of-life-in-patients-with-copd/" target="_blank">EMJ website</a> 
 Sponsored by Sanofi and Regeneron, in partnership with EMJ.

We are now starting to characterize patients more carefully. We have to get to a better understanding what patients will profit (meaning = benefit) from what kind of treatment. This is just at the starting point from my perspective, and what we already know is that patients at (meaning = who) exacerbate need different treatment compared to patients that do not exacerbate. But there is still a lot to learn, and only if we can characterize patients more carefully, and we also have to identify the so-called treatable traits. So we have to look for features that may have therapeutic consequences.

&nbsp;
a The SGRQ is a 50-item questionnaire designed to measure the qualitative impact of COPD on overall health , daily life, and perceived well-being. Higher scores mean greater disease severity. 14 b E-RS-COPD is an 11-item patient-reported derivative tool that measures the effect of treatment on respiratory symptom severity in patients with stable COPD . Higher scores mean greater disease severity. 17
 
  COPD, chronic obstructive pulmonary disease; E-RS-COPD, Evaluating Respiratory Symptoms in COPD; QoL, quality of life; SGRQ, St George’s Respiratory Questionnaire

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.

Read video transcript

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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