Severe Eosinophilic Asthma

How can eosinophil production affect your severe asthma patients?

Learn why it could be time to refine your approach

Understanding severe asthma is just
the beginning

Properly identifying severe asthma could help your patients down the line

Severe asthma is a distinct type of asthma that affects

of all patients with asthma.¹

The American Thoracic Society (ATS) and the European Respiratory Society (ERS) define severe asthma as a specific type of asthma that requires treatment with high-dose inhaled corticosteroids (ICS), plus a second controller therapy and/or systemic corticosteroid to control symptoms. If your patients meet these criteria—or have uncontrolled symptoms despite this therapy—severe asthma may be a more appropriate diagnosis.¹

Patients with severe asthma often experience frequent or persistent symptoms, plus^1,2:

Exacerbations

Reduced lung
function

Poor quality
of life

Comorbidities

These negative effects make it critical that you properly identify your patients with severe asthma and provide a personalized treatment.³

Factor in phenotyping

Based on emerging data, it’s increasingly accepted that severe asthma is a complex disease with greater heterogeneity than traditionally diagnosed in asthma. There is also increasing recognition of the presence of multiple phenotypes in severe asthma, defined by both clinical and pathophysiological characteristics. However, this remains an evolving field and consensus on the defining features of each asthma phenotype has not been reached.⁴ Severe eosinophilic asthma is a distinct phenotype that can include airway inflammation and increased eosinophil levels, leading to poor asthma control and increased exacerbations.¹ Recognizing there are multiple phenotypes within severe asthma, including an eosinophilic phenotype, helps you give a more accurate diagnosis—and a more personalized treatment.^5,6

If your patients with severe asthma still have uncontrolled symptoms, consider whether eosinophilic inflammation could be the cause.

How do eosinophils affect your patients?

Eosinophils are multifunctional leukocytes that can be both helpful and harmful, making their role difficult to determine.⁷ While the role of eosinophils in inflammatory disease is well-established, understanding their role in immunity continues to evolve. At appropriate levels, eosinophils could contribute to overall health and immunoregulation.⁸

In fact, many blood- and tissue-resident eosinophils deliver protective effects in response to infection and disease, including polarizing and activating adaptive immune responses.^7,9 Tissue-resident eosinophils are also involved in tissue maintenance, metabolism, and immune homeostasis.⁷

Eosinophils have many different roles

Eosinophils also play a critical role in some types of severe asthma. Through degranulation, eosinophils release cytokines and chemokines to target foreign antigens, promote inflammation, and damage surrounding structures.¹⁰

During immune responses mediated by T helper 2 (T_H2) cells and group 2 innate lymphoid cells (ILC2), eosinophils become activated and multiply.⁷ This inflammation can lead to bronchial wall thickening and reduced airflow, which may be harmful to your patients with severe asthma and could increase the risk of exacerbations.^1,10

Due to the multifunctional nature of eosinophils, it’s important to understand whether eosinophilic inflammation plays a role in your patients with severe asthma.

The harmful effects of overproduction

Approximately 50% of patients with severe asthma have persistent airway tissue eosinophils—despite continued high-dose systemic and inhaled steroids.¹¹

Elevated eosinophil levels are associated with chronic airway inflammation and obstruction in severe asthma, resulting in increased symptoms and exacerbations in your patients.^1,11

Understanding pathophysiology

The chronic inflammation caused by eosinophils may result in harmful structural changes to the airway walls, known as remodeling. This inflammation could also cause damage resulting in airway smooth muscle contraction, loss of lung function, and airway hyperresponsiveness.¹² Remodeling can both increase the frequency and worsen the severity of exacerbations.¹

Identifying the presence of eosinophilic inflammation in severe asthma is an important step in the clinical evaluation process.¹²

Targeting eosinophil production

Multiple cell types, including eosinophils, are involved in airway inflammation.¹³ Regulating eosinophil levels and inflammation could therefore be critical to managing severe asthma.¹²

However, given the evolving science around the role of eosinophils, the amount needed to balance their harmful inflammatory qualities and their protective immunoregulatory role is unknown.^8,12

Biologic treatment options that target the IL-5 pathway can reduce the production and survival of eosinophils at the source.³

Learn More

IL-5

Multiple cytokines, such as interleukin 5 (IL-5), IL-3, and granulocyte-macrophage colony stimulating factor (GM-CSF), activate eosinophils that cause airway inflammation.^13,14

EOSINOPHILS

ACTIVATED

INFLAMMATION

IL-5 is the major cytokine responsible for the growth, proliferation, and survival of eosinophils¹⁴

Should you reassess your patients?

To determine if your patients have severe eosinophilic asthma, look for these potential indicators^1,15,16:

Multiple controller medications, including high-dose ICS

Frequent exacerbations requiring OCS use, ER visits, or hospitalizations

Late-onset disease

Sinus disease

Elevated blood eosinophil levels

Note: Consensus on the defining features of an individual phenotype has not been established.

A simple blood test can help identify your patients with an eosinophilic phenotype

Your patients’ blood eosinophil levels can be measured through a complete blood count (CBC) with differential. Blood eosinophil levels can be used as a guide to initiate individualized treatment of severe asthma.¹⁷

Use this unit conversion tool to easily convert blood eosinophil lab results to cells/μL.

Try It Now

When is it time to regulate eosinophil production?

For patients with severe asthma, elevated blood eosinophil counts have a strong correlation with increased exacerbations.¹³ In fact, patients with eosinophil levels ≥300 cells/μl were shown to have exacerbations at rates nearly four times higher than patients with persistent asthma.¹⁸ But what levels should you consider when initiating treatment?

Although there is not yet an exact consensus for initiating treatment of patients with severe eosinophilic asthma, different baseline blood eosinophil levels have been evaluated for different biologic therapies (eg, ≥150 cells/μL, ≥300 cells/μL, and ≥400 cells/μL) that may help identify patients who could benefit from treatment.^19,20

Blood eosinophils can be used as a biomarker to guide diagnosis and treatment.^19,20

OCS USE AND POTENTIAL IMPACT

Oral corticosteroids (OCS) can play an important role in the management of severe asthma. In fact, almost 1/3 of patients with severe asthma require OCS to control their symptoms.²¹

However, continued OCS use could put your patients at risk of developing adverse effects.^21,22 Patients with asthma intermittently exposed to multiple prescriptions of systemic steroids had a higher risk of experiencing the following adverse effects²¹:

Osteoporosis

Hypertension

Obesity

Type 2 diabetes

Gastrointestinal ulcers/bleeds

Fractures

Cataracts

Learn about a targeted treatment option for severe eosinophilic asthma.

Don’t miss out on news about severe eosinophilic asthma

Stay up-to-date on the role of eosinophils in severe asthma and learn more about what you could do to help your patients.

References

View all references

1003418R0 August 2018

References

Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-373.
Chipps BE, Zeiger RS, Borish L, et al. Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. J Allergy Clin Immunol. 2012;130(2):332-343.e10.
Eng SS, DeFelice ML. The role and immunobiology of eosinophils in the respiratory system: a comprehensive review. Clinic Rev Allerg Immunol. 2016;50:140-158.
Wenzel S. Severe asthma: from characteristics to phenotypes to endotypes. Clinical & Experimental Allergy. 2012;42:650-658.
Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178:218-224.
Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med. 2010;181:315-323.
Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17:746-760.
Marichal T, Mesnil C, Bureau F. 2017. Homeostatic eosinophils: characteristics and functions. Front Med. 2017;4(101):1-6.
Rothenberg ME. A hidden residential cell in the lung. J Clin Invest. 2016;126(9):3185-3187.
Travers J, Rothenberg ME. Eosinophils in mucosal immune responses. Mucosal Immunol. 2015;8(3):464-475.
Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172(2):149-160..
Trivedi SG, Lloyd CM. Eosinophils in the pathogenesis of allergic airways disease. Cell Mol Life Sci. 2007;64(10):1269-1289.
Malinovschi A, Fonseca J, Jacinto T, et al. Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects. J Allergy Clin Immunol. 2013;132(4):821-827.e5.
Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13(1):9-22.
de Groot JC, ten Brinke A, Bel EHD. Management of the patient with eosinophilic asthma: a new era begins. ERJ Open Res. 2015;1:1-11.
Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716-725.
Wagener AH, de Nijs SB, Lutter R, et al. External validation of blood eosinophils, FE_NO and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70(2):115-120.
Data on file, GSK.
Patel SS, Casale TB, Cardet JC. Biological therapies for eosinophilic asthma. Expert Opin Biol Ther. 2018;18(7):747-754.
Fricker M, Heaney LG, Upham JW. Can biomarkers help us hit targets in difficult-to-treat asthma? Respirology. 2017;22(3):430-442.
Sullivan PW, Ghushchyan VH, Globe G, Schatz M. Oral corticosteroid exposure and adverse effects in asthmatic patients. J Allergy Clin Immunol. 2017;141(1):110-116.e8.
Fardet L, Petersen I, Nazareth I. Monitoring of patients on long-term glucocorticoid therapy: a population-based cohort study. Medicine. 2015;94(15):1-10.

Leaving GSK Source

Leaving GSKSource

Understanding severe asthma is just the beginning

Properly identifying severe asthma could help your patients down the line

Patients with severe asthma often experience frequent or persistent symptoms, plus1,2:

Exacerbations

Reduced lungfunction

Poor qualityof life

Comorbidities

Factor in phenotyping

If your patients with severe asthma still have uncontrolled symptoms, consider whether eosinophilic inflammation could be the cause.

How do eosinophils affect your patients?

Eosinophils have many different roles

Due to the multifunctional nature of eosinophils, it’s important to understand whether eosinophilic inflammation plays a role in your patients with severe asthma.

The harmful effects of overproduction

Understanding pathophysiology

Targeting eosinophil production

Should you reassess your patients?

To determine if your patients have severe eosinophilic asthma, look for these potential indicators1,15,16:

Multiple controller medications, including high-dose ICS

Frequent exacerbations requiring OCS use, ER visits, or hospitalizations

Late-onset disease

Sinus disease

Elevated blood eosinophil levels

A simple blood test can help identify your patients with an eosinophilic phenotype

When is it time to regulate eosinophil production?

OCS USE AND POTENTIAL IMPACT

Oral corticosteroids (OCS) can play an important role in the management of severe asthma. In fact, almost 1/3 of patients with severe asthma require OCS to control their symptoms.21

However, continued OCS use could put your patients at risk of developing adverse effects.21,22 Patients with asthma intermittently exposed to multiple prescriptions of systemic steroids had a higher risk of experiencing the following adverse effects21:

Osteoporosis

Hypertension

Obesity

Type 2 diabetes

Gastrointestinal ulcers/bleeds

Fractures

Cataracts

Don’t miss out on news about severe eosinophilic asthma

Understanding severe asthma is just
the beginning

Patients with severe asthma often experience frequent or persistent symptoms, plus^1,2:

Reduced lung
function

Poor quality
of life

To determine if your patients have severe eosinophilic asthma, look for these potential indicators^1,15,16:

Oral corticosteroids (OCS) can play an important role in the management of severe asthma. In fact, almost 1/3 of patients with severe asthma require OCS to control their symptoms.²¹

However, continued OCS use could put your patients at risk of developing adverse effects.^21,22 Patients with asthma intermittently exposed to multiple prescriptions of systemic steroids had a higher risk of experiencing the following adverse effects²¹: