Can improved understanding of the airway epithelium provide new insight into asthma?

The epithelium has an incredibly important function in our daily lives, as it forms the first line of defence throughout the body.1,2 It acts as a key sensor of the external environment, forms a protective barrier and helps us respond to insults such as allergy, infection or pollution.1,2 There is increasing evidence that damage to the epithelium, either to its structure or function, is involved in a range of inflammatory conditions, including asthma, atopic dermatitis and chronic rhinosinusitis.2,3

In its healthy state, the epithelium is a highly regulated structure, formed of closely bound cells that provide a solid barrier.2,3 In asthma, the structure and function of the airway epithelium appears to be disrupted, resulting in changes to the immune responses within the airways, and contributing to the features of asthma such as cellular alterations to airway walls.1,3-5 Throughout our airways, the epithelium is the first barrier encountered by inhaled triggers including pathogens (such as viruses), allergens (such as pollen) and irritants (such as cigarette smoke or vehicle exhaust particles).1,4 When inhaled triggers come into contact with the airway epithelium, epithelial cytokines, such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and IL-25, are released.1,6,7  This triggers a cascade of immune responses that have been implicated in inflammation and may contribute to asthma.1,6,7 Evidence suggests that different triggers result in different patterns of inflammation.8,9 However, many questions remain regarding the role of the impaired epithelium and epithelial cytokines in inflammatory diseases such as asthma.1,2



At AstraZeneca, we have a longstanding heritage in respiratory research and are passionate about striving to improve the lives of patients with asthma and other inflammatory airway conditions. As part of this continued commitment, our research is focussing on developing a better understanding and characterisation of the epithelium, as well as the role of epithelial cytokines and their interplay with structural cells associated with inflammatory airway disease. For example, we are building on our understanding of epithelial biology by modelling the airway in vitro. This will allow us to better examine cell abnormalities, along with the effects of cytokines on cellular processes. We are also investigating non-invasive nasal sampling technology to assess detection of epithelial cytokines following exposure to an allergen. There are many benefits to non-invasive sampling, including that it is well tolerated by patients and thus suitable for frequent sampling.

Together, this research, and other research we have ongoing, will help us to better understand the role of the epithelium in asthma (and potentially other inflammatory diseases). This research is crucial in expanding our knowledge and providing new focus to help target the remaining unmet needs in asthma. Our global aim is to improve the lives of patients with asthma, many of whom continue to live with significant and often debilitating disease every day.


References

1. Bartemes KR, Kita H. Clin Immunol 2012;143:222–235

2. Schleimer RP, Berdnikovs S. J Allergy Clin Immunol 2017;139:1752–1761

3. Holgate ST. Immunol Rev 2011;242:205–219

4. Heijink IH, et al. Clin Exp Allergy 2014;44:620–630

5. Caminati M, et al. World Allergy Organ J 2018;11:13

6. Al-Sajee D, et al. Curr Opin Pulm Med 2018;24:32–41

7. Lambrecht BN, et al. Immunity 2019;50:975–991

8. Wark PA, Gibson PG. Thorax 2006;61:909–915

9. Wark PA, et al. Clin Exp Allergy 2002;32:1750–1756

10. Pham TH, et al. J Allergy Clin Immunol 2020;145:AB30

11. Chesne J, Braza F et al. IL-17 in severe asthma. Where do we stand? Am J Respir Crit Care Med. 2014:190(10);1094-1102.

12. Lambrecht BN, Hammad H. Nature Immunol 2015;16(1):45-56.


Veeva ID: Z4-26841
Date of preparation: September 2020