Type 2 inflammation – understanding the connection between allergic diseases

Type 2 inflammation – understanding the connection between allergic diseases

Johannesburg, 11 November 2020 – Allergic diseases are increasingly becoming a worldwide epidemic. As medical research progresses, there is evidence that many allergic diseases such as asthma, atopic dermatitis (AD), and allergic rhinitis may be the result of an overstimulated type 2 immune reaction known as type 2 inflammation.

What is type 2 inflammation?  

The type 2 immune response is the part of the immune system that protects the body against parasites and functions as a wound repair mechanism.^1aa,16 In some people, this type 2 immune function may become overactive for several reasons: genetic factors, environmental triggers (allergens), or specific types of infections. The result of these triggers is an upregulation of the type 2 response and an “abnormal” type 2 inflammatory response. This can explain why some allergic conditions run in families, and why some people suffer from more than one allergic disease.

How common are type 2 inflammatory diseases and what is their impact on health and well-being?  

Asthma:

Asthma, an inflammatory disease of the lower airways, is triggered by allergens, pollutants, and exercise. It is one of the most common chronic conditions in the world, affecting as many as one in 13 people. People with asthma may suffer periodic symptoms of chest tightness, coughing, wheezing, shortness of breath, and phlegm production.^,5c Many cases of childhood asthma have been associated with allergy, and this association remains into adulthood. ^6e Uncontrolled asthma has a negative impact on productivity and quality of life, with 30–50% of asthma patients experiencing anxiety and depression. Patients with more severe and uncontrolled asthma are more likely to be depressed.

Eosinophilic oesophagitis

EoE is an allergic condition of the oesophagus, the organ which connects the throat to the stomach. It is also known as “asthma of the oesophagus” because it shares many symptoms of asthma.^8a The most common symptom of EoE is difficulty in swallowing food. People with other allergic conditions such as allergic rhinitis, asthma, and AD have a higher risk of developing EoE, but genetic and environmental risk factors also play a role.

Chronic Rhinosinusitis:

CRS is a common inflammatory disease of the nasal sinus cavities, with symptoms that include a blocked nose, a runny nose, facial pain, and a loss of sense of smell.^2a,6a The longer the duration of CRS nasal symptoms, the higher the incidence of nasal polyps with a characteristic complete loss of sense of smell.^9x

Atopic Dermatitis:

AD, also known as atopic eczema, is an inflammatory skin disorder with symptoms of a visible skin rash, intense itching, and inflammation. Besides the itch, people with uncontrolled AD suffer from bleeding skin, loss of sleep, lack of concentration, and impaired school-work productivity. AD affects 15-20% of children and 1-5% of adults in developed countries. There is a considerable impact of AD on quality of life, especially in severe cases. AD also has a greater negative effect on the mental health of patients compared with other chronic conditions such as diabetes and hypertension, and these effects can extend to a patient’s family.

What is the impact of excessive type 2 inflammation on developing multiple allergic diseases? 

A person who already suffers from one allergic disease may well suffer from other allergic diseases because of the underlying type 2 inflammation pathophysiology that connects these conditions. As an example, people with CRS are more likely to have asthma and as many as half of people with asthma have CRS. Also, the more severe and long-standing CRS, the more likely it is that the person will develop asthma.

People with severe asthma are more likely to suffer from CRSwNP, and AERD as a result of aspirin sensitivity is more likely to develop in these individuals. Severe asthmatics have double the risk of developing AERD, while patients with AERD are more likely to suffer from allergies in general.

AD has also been associated with many allergic diseases that seem to influence one another, with AD patients showing a higher likelihood of having asthma, hay fever, food allergy, anxiety and depression, and autoimmune disease.^14a These associations are significant in mild and moderate disease, with even stronger effects in severe AD.

What to do if you are struggling with symptom control for allergic diseases?

It is recommended that you visit your local clinic or book an appointment with a doctor if you think you may be suffering from any of the allergic diseases that have been described above. It is also recommended that you consult with a specialist doctor if you are struggling to manage the symptoms of a diagnosed allergic disease.

References

1. Gandhi NA, Bennett BL, Graham NMH, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016 Jan;15(1):35-50. doi: 10.1038/nrd4624.
2. Philpott CM, Erskine S, Hopkins C, et al. Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: data from the UK National Chronic Rhinosinusitis Epidemiology Study. Respir Res. 2018 Jun 27;19(1):129. doi: 10.1186/s12931-018-0823-y.
3. Sanofi information leaflet. Available at https://www.sanofi.com/-/media/Project/One-Sanofi-Web/Websites/Global/Sanofi-COM/Home/common/docs/about-us/5-TYNTK-TYPE-2-INFLAMMATION-EN.pdf
4. Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014 Jun 12;24:14009. doi: 10.1038/npjpcrm.2014.9.
5. Shaw DE, Sousa AR, Fowler SJ, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015 Nov;46(5):1308-21. doi: 10.1183/13993003.00779-2015.
6. Staniorski CJ, Price CPE, Weibman AR, et al. Asthma onset pattern and patient outcomes in a chronic rhinosinusitis population. Int Forum Allergy Rhinol. 2018 Apr;8(4):495-503. doi: 10.1002/alr.22064.
7. Rand CS, Wright RJ, Cabana MD, et al. Mediators of asthma outcomes. J Allergy Clin Immunol. 2012 Mar;129(3 Suppl):S136-41. doi: 10.1016/j.jaci.2011.12.987.
8. Carr S, Chan ES, Watson W. Eosinophilic esophagitis. Allergy Asthma Clin Immunol. 2018 Sep 12;14(Suppl 2):58. doi: 10.1186/s13223-018-0287-0.
9. Staikuniene J, Vaitkus S, Japertiene LM, et al. Association of chronic rhinosinusitis with nasal polyps and asthma: clinical and radiological features, allergy and inflammation markers. Medicina (Kaunas). 2008;44(4):257-65.
10. Zuberbier T, Orlow SJ, Paller AS, et al. Patient perspectives on the management of atopic dermatitis. J Allergy Clin Immunol. 2006 Jul;118(1):226-32. doi: 10.1016/j.jaci.2006.02.031.
11. Schram M, Roekevisch E, Leeflang M. A randomized trial of methotrexate versus azathioprine for severe atopic eczema. J Allergy Clin Immunol. 2011 Aug;128(2):353-9. doi: 10.1016/j.jaci.2011.03.024.
12. Ashcroft DM, Dimmock P, Garside R, et al. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. BMJ. 2005 Mar 5;330(7490):516. doi: 10.1136/bmj.38376.439653.D3.
13. Steinke JW, Wilson JM. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances. J Asthma Allergy. 2016 Mar 10;9:37-43. doi: 10.2147/JAA.S88739.
14. Silverberg JI, Gelfand JM, Margolis DJ, et al. Association of atopic dermatitis with allergic, autoimmune, and cardiovascular comorbidities in US adults. Ann Allergy Asthma Immunol. 2018 Nov;121(5):604-612.e3. doi: 10.1016/j.anai.2018.07.042.
15. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2018. Available at: http://ginasthma.org/download/832/
16. Helminth protection by innate Type 2 immunity. Available at: https://www.immunopaedia.org.za/breaking-news/2017-articles/helminth-protection-by-innate-type-2-immunity/  [Accessed 28/10/20]
17. Asthma and Allergy Foundation of America. https://www.aafa.org/asthma-facts/#:~:text=According%20to%20the%20Centers%20for,in%2013%20people%20have%20asthma.&text=More%20than%2025%20million%20Americans,age%2C%20sex%20and%20racial%20groups.   [Accessed 28/10/20].

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Kerry Simpson
Mantis Communications