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Eosinophils could be holding the missing link between symptoms, diagnosis and treatment

Around the world, a vast number of people, with very different symptoms, are unknowingly linked to each other due to elevated levels of eosinophils (type of white blood cell). From severe asthma to nasal polyps, these people all have an eosinophil-driven disease (EDD).

A missing link can be the connection between people around the world with seemingly unrelated conditions.

For more than 25 years we have been fascinated by the complex roles eosinophils play in health and disease, exploring the possibilities eosinophil science can offer to patients. We are eager to find new ways to unlock the potential of these often-overlooked white blood cells.1,2

Not only can eosinophils be a key driver of disease, but importantly for a range of conditions that are frequently mis-diagnosed,1,2 they can also be used as a blood biomarker (a biological signpost). Elevated levels indicate the presence of a condition, aiding accurate diagnosis and providing direction to a potential treatment. Our research is both helping to diagnose EDDs earlier and reduce the burden on people.

What's a biomarker?

Biomarkers, short for biological markers, are a characteristic that can be measured as an indicator of health or disease.3 They may indicate if a biological process is working normally or if something has gone wrong.3 A biomarker may also indicate if someone has been exposed to certain molecules e.g. something that triggers an allergy, or how someone is responding to medical treatment.3,4

Biomarkers may be molecules, proteins, fats or entire cells3. They are used as part of a clinical assessment to inform health assessment and to help direct to an appropriate treatment. A wide range of biomarkers are used today and are often relatively easy to measure in clinical practice. Familiar ones are cholesterol, heart rate, and fasting glucose levels3.

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The many and varied roles of eosinophils

Professor Peter Howarth has been working in eosinophil research for nearly 40 years. His interest grew from his work in the clinic, treating patients with asthma and allergies. He started to investigate whether eosinophils could play a role in these conditions and in partnership with others, he has helped unpick the many different roles that eosinophils play in human health and disease.

Too many eosinophils in the wrong place can be a very serious problem indeed. However, like many things in life, there is a balance. Emerging science suggests that eosinophils have multi-functional roles that can be both helpful and harmful, and this is what we want to better understand.

Professor Peter Howarth

Global Clinical Scientific Lead for Biologics, GSK

We now know that eosinophils are involved in many processes essential to our health.1,2 As a type of white blood cell, eosinophils contribute to our immune defence against infections.1,2 But eosinophils are even more hard working than we thought, with a role in homeostasis (maintaining balance in the body), cancer immunology, and also the body’s metabolism.1,2 Since they are central to so many functions, it’s no surprise that if eosinophil levels rise, they can turn from friend to foe and cause disease5.

Emerging science also suggests there are many subtypes of eosinophils that play distinct roles – some contribute to disease, some fight disease and some maintain a normal, healthy immune system.1 This discovery is very exciting for our ongoing work in improving the future for people with EDD.

Where eosinophils go, disease can follow

As the scientific community learn more about the immune system, we’re discovering that increased levels of eosinophils in the blood or tissue can cause a range of symptoms across a variety of conditions. When eosinophils infiltrate certain tissues, they can cause inflammation and organ damage which, over time, can affect patients’ day-to-day life.

There are many EDDs that have a range of symptoms, some severe and all characterised by an imbalance in the number and activity of eosinophils1,2 Interestingly, it’s been shown that there are links and overlaps between EDDs and many people can live with more than one of these conditions at the same time11, for example Chronic rhinosinusitis with nasal polyps (CRSwNP) is closely linked with asthma6 and people with severe asthma often also have EGPA.7

EDDs explained

Severe eosinophilic asthma (SEA) - A type of severe asthma. Symptoms of SEA include wheezing, coughing and chest tightness8

Hypereosinophilic syndrome (HES) - A rare disorder. Symptoms of HES include coughing, fever, fatigue, shortness of breath and wheezing9

Chronic rhinosinusitis with nasal polyps (CRwNP) - Symptoms of CRwNP include stuffy/runny nose, facial pain, and mucus running down the back of your throat10

Eosinophilic granulomatosis with polyangiitis (EGPA) - Symptoms of EGPA include fever, tiredness and numb or tingling hands and feet11

Chronic eosinophilic pneumonia (CEP) - A rare lung disease. Symptoms include shortness of breath, cough and less commonly chest pain12

Eosinophilic esophagitis (EOE) - A chronic disorder of the digestive system. Symptoms include difficulty swallowing, food getting stuck in the throat, nausea and malnutrition13

Inflammatory Bowel Disease (IBD) and Gastroenteritis – Symptoms include pain, recurring diarrhoea, weight loss and fatigue14

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I was diagnosed in 2010 with severe asthma. I have had asthma all my life. When it changed to severe asthma, it was very difficult for me. I had no quality of life. I have missed out on some things from my family, on my daughter’s college graduation, my other daughter’s high school graduation.

Brenda

Patient, USA

Targeting eosinophils

The role of eosinophils in contributing to the inflammation that causes these diseases is well-established, particularly in respiratory diseases like severe asthma.1,2,15 Importantly, recognising a life impacted by EDD is a chance to potentially help change it and long-term complications.1,2  

Spotting raised eosinophil levels could bring clarity to patients who may have been fighting for a definitive diagnosis for years.1 Elevated blood eosinophils can be measured by a straightforward blood test.1

Some EDDs currently have limited or no approved treatment options, so further research is needed to find effective treatments to improve the lives of people living with these conditions.  

Ambitious treatment goals

Through our research, we are committed to modifying the course of EDD. We want to go further for patients and strive for remission. Remission is not a cure, but it is a step closer.

We have amassed a huge amount of knowledge from three decades of researching EDD, but there’s more to be done. We were first to identify the eosinophil as a biomarker, changing disease diagnosis for people around the world and for many decades to come.

We want to continue that momentum.

Harnessing the power of the immune system can do incredible things – help to treat cancer, help prevent the body self-harming, and help protect against dangerous disease through vaccines.16 – 20 What might we achieve next?

References

  1. Wechsler ME et al. Eosinophils in health and disease: a state-of-the-art review. Mayo Clin Proc. 2021;96(10):2694–2707.
  2. Klion AD, Ackerman SJ, Bochner BS. Contributions of eosinophils to human health and disease. Annu Rev Pathol. 2020;15:179–209.
  3. Strimbu K, Tavel JA. What are biomarkers?. Curr Opin HIV AIDS. 2010;5(6):463-466. doi:10.1097/COH.0b013e32833ed177
  4. Ogulur I, Pat Y, Ardicli O, et al. Advances and highlights in biomarkers of allergic diseases. Allergy. 2021;76(12):3659-3686. doi:10.1111/all.15089
  5. Ramirez GA, Yacoub MR, Ripa M, et al. Eosinophils from Physiology to Disease: A Comprehensive Review. Biomed Res Int. 2018;2018:9095275. Published 2018 Jan 28. doi:10.1155/2018/9095275
  6. Ryu, G., Min, C., Park, B. et al.Bidirectional association between asthma and chronic rhinosinusitis: Two longitudinal follow-up studies using a national sample cohort. Sci Rep 10, 9589 (2020). https://doi.org/10.1038/s41598-020-66479-8
  7. Porsbjerg C, Menzies-Gow A. Co-morbidities in severe asthma: Clinical impact and management. Respirology. 2017;22(4):651-661. doi:10.1111/resp.13026
  8. What is asthma. Severe asthma. https://gaapp.org/what-is-asthma/severe-asthma/ (Accessed August 2022)
  9. What are Hypereosinophilic Syndromes? www.apfed.org/about-ead/hypereosinophilic-syndrome/ (Accessed August 2022)
  10. Stevens WW, Schleimer RP, Kern RC. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016 Jul-Aug;4(4):565-72. doi: 10.1016/j.jaip.2016.04.012.
  11. Maxime Samson, Xavier Puéchal, Hervé Devilliers, Camillo Ribi, Pascal Cohen, Marc Stern, Christian Pagnoux, Luc Mouthon, Loïc Guillevin, Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome) enrolled in two prospective trials, Journal of Autoimmunity, Volume 43, 2013, Pages 60-69, ISSN 0896-8411, https://doi.org/10.1016/j.jaut.2013.03.003.)
  12. Crowe M, Robinson D, Sagar M, Chen L, Ghamande S. Chronic eosinophilic pneumonia: clinical perspectives. Ther Clin Risk Manag. 2019;15:397-403. Published 2019 Mar 13. doi:10.2147/TCRM.S157882
  13. Rare Disease Database. Eosinophilic Esophagitis. https://rarediseases.org/rare-diseases/eosinophilic-esophagitis/ (Accessed August 2022)
  14. Conditions. Inflammatory bowel disease. https://www.nhs.uk/conditions/inflammatory-bowel-disease/ (Accessed August 2022)
  15. Bakakos A, Loukides S, Bakakos P. Severe eosinophilic asthma. J Clin Med. 2019;8(9):1375.
  16. Mebrahtu TF, Morgan AW, West RM, Steward PM, Pujades-Rodriguez. Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study. CMAJ. 2020;192:E295–301. doi: 10.1503/cmaj.191012.
  17. Waljee AK, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017;357:j1415. doi: 10.1136/bmj.j1415.
  18. Buckley L, Humphrey MB. Glucocorticoid-Induced Osteoporosis. N Engl J Med. 2018;379:2547–2556.
  19. Lizee G, Overwijk WW, Radvanyi L, Gao J, Sharma P, Hwu P. Harnessing the power of the immune system to target cancer. Annu Rev Med. 2013;64:71–90.
  20. Santana-Davila R, Bhatia S, Chow LQ. Harnessing the Immune System as a Therapeutic Tool in Virus-Associated Cancers. JAMA Oncol. 2017;3(1):106-112. doi:10.1001/jamaoncol.2016.4574
     
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