Epithelial Science
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Our commitment to the respiratory community and expanding scientific knowledge around the multiple drivers and biological mechanisms underlying epithelial-driven diseases.
Following the science to improve patient outcomes
The epithelium plays a central role in immune function, acting as the first line of defence against environmental triggers, cellular damage and pathogens in both the upper and lower airways.1,2
In diseases like severe asthma and nasal polyps, inflammation is often driven by dysregulation of the epithelial barrier, which has been shown to activate Type-2 and beyond Type-2 inflammatory pathways.2 These inflammatory cascades contribute to persistent symptoms and suboptimal disease control for patients, despite advances in treatment.2-4
Pioneering research continues to improve our understanding of epithelial-driven inflammation in upper and lower airway diseases.5 By understanding the role key epithelial cytokines play at the top of the inflammatory cascade, we can begin to further understand the complex nature of severe asthma, a challenging disease.6
Severe asthma deep dive: advancing epithelial science
Severe asthma is a debilitating disease that affects up to 26 million people worldwide, resulting in frequent exacerbations and significant limitations on lung function and quality of life.7,8 We know that people with asthma are underserved today and that asthma remains a significant public, and personal, health challenge.9,10
Managing severe asthma is challenging because airway inflammation is complex, heterogeneous and dynamic. Patients often present with more than one type of inflammation, complicating their treatment.11,12
Despite treatment advancements and increased scientific understanding over the last two decades, there remains vast potential to improve treatment particularly for patients with unknown, unclear, or multiple drivers of inflammation. That’s why our scientists are working to further expand scientific knowledge around the drivers and biological mechanisms of asthma to tackle the disease pathophysiology in new and powerful ways.10,13,14
At AstraZeneca, we’re building on our 50-year heritage in respiratory care by pursuing scientific breakthroughs that will revolutionise our understanding of the pathophysiology of asthma and inform the development of much-needed innovation that could improve patient care and outcomes.
Pioneers in Asthma: Where is the science leading us?
"We remain committed to advancing the science so that people living with severe asthma who are underserved today will have a better future tomorrow. That’s why we are focused on following the science to understand the underlying causes and biological mechanisms of this debilitating disease.
Other epithelial-driven inflammatory diseases
We are currently exploring potential candidates across a broad range of respiratory diseases that may be caused by epithelial disfunction and inflammation, and where unmet medical need remains.
Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
CRSwNP is a complex inflammatory disorder, characterised by persistent inflammation of the nasal mucosa accompanied by benign growths, called nasal polyps.2,15,16 Nasal polyps and the accompanying inflammation can block nasal passages, and lead to breathing problems, difficulty in sense of smell, nasal discharge, facial pain and other adverse effects on quality of life.2
Epithelial dysfunction and inflammation are important characteristics of chronic rhinosinusitis and impede the ability of the epithelium to act as a physical and immunological barrier against the external environment.2
Chronic Obstructive Pulmonary Disease (COPD)
COPD refers to a group of lung diseases, including chronic bronchitis and emphysema, that cause airflow blockage and breathing-related problems.17 COPD is a major public health threat and a leading cause of death.17 It is a highly complex disease with multiple pathways and disease drivers, including epithelium-driven inflammation.17
A single, moderate COPD exacerbation has been shown to increase the risk of hospitalisation and is associated with an increased risk of death.17,18
References
1. Jakwerth CA, et al. Cells. 2022; 11:1387
2. Shah SA, Kobayashi M. Pathogenesis of chronic rhinosinusitis with nasal polyp and a prominent T2 endotype. Heliyon. 2023 Aug 23;9(9): e19249.
3. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2024. Available from: http://ginasthma.org/2024-report/ (Last accessed: March 2025)
4. Wang E, et al. Chest. 2020;157:790–804
5. Fokkens W, et al. Clin N Am. 2023;56:1–10
6. Agache I, et al. Allergy. 2012;67:835–846.
7. Global Asthma Network. The Global Asthma Report 2022.
8. Chung, KF., et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73.
9. WHO Asthma. Available at: http://www.who.int/news-room/fact-sheets/detail/asthma. (Last accessed: March 2025)
10. Fernandes AG, Souza-Machado C, Coelho RC, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372.
11. Godar M, Blanchetot C, de Haard H, et al. Personalized medicine with biologics for severe type 2 asthma: current status and future prospects. MAbs. 2018; 10 (1): 34‐45.
12. Amaral R, et al. Having concomitant asthma phenotypes is common and independently relates to poor lung function in NHANES 2007-2012. Clin Trans Allergy. 2018 May 4;8:13.
13. Peters SP, Ferguson G, Deniz Y et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. 2006: 100: 1139-51.
14. Chen S, et al. Systemic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment. Curr Med Res Opin. 2018; 34: 2075-2088.
15. Chen S et al. Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis. Curr Med Res Opin. 2020;36(11):1897-1911.
16. Del Toro E, Portela J. Nasal Polyps. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: http://www.ncbi.nlm.nih.gov/books/NBK560746/ (Last accessed: March 2025).
17. GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024. [Online]. Available at: http://goldcopd.org/2024-gold-report/. (Last accessed: March 2025).
18. Whittaker H, Rubino A, Mullerova H, et al. Frequency and Severity of Exacerbations of COPD Associated with Future Risk of Exacerbations and Mortality: A UK Routine Health Care Data Study. Int J Chron Obstruct Pulmon Dis. 2022;17:427-437.
Veeva ID: Z4-71933
Date of preparation: March 2025