Abstract
Under normal physiological conditions, the lung remains an oxygen rich environment. However, prominent regions of hypoxia are a common feature of infected and inflamed tissues and many chronic inflammatory respiratory diseases are associated with mucosal and systemic hypoxia. The airway epithelium represents a key interface with the external environment and is the first line of defense against potentially harmful agents including respiratory pathogens. The protective arsenal of the airway epithelium is provided in the form of physical barriers, and the production of an array of antimicrobial host defense molecules, proinflammatory cytokines and chemokines, in response to activation by receptors. Dysregulation of the airway epithelial innate immune response is associated with a compromised immunity and chronic inflammation of the lung. An increasing body of evidence indicates a distinct role for hypoxia in the dysfunction of the airway epithelium and in the responses of both innate immunity and of respiratory pathogens. Here we review the current evidence around the role of tissue hypoxia in modulating the host-pathogen interaction at the airway epithelium. Furthermore, we highlight the work needed to delineate the role of tissue hypoxia in the pathophysiology of chronic inflammatory lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease in addition to novel respiratory diseases such as COVID-19. Elucidating the molecular mechanisms underlying the epithelial-pathogen interactions in the setting of hypoxia will enable better understanding of persistent infections and complex disease processes in chronic inflammatory lung diseases and may aid the identification of novel therapeutic targets and strategies.
Highlights
The airway epithelium is located at the interface between the internal and external environment and is strategically positioned to interact with the environment in a dynamic fashion
The importance of the lung epithelium is exemplified in chronic inflammatory lung diseases, where epithelial cell dysfunction is associated with compromised immunity and chronic inflammation in the lung [5,6,7,8,9]
The airways of respiratory disease patients are characterized by chronic inflammation, structural changes and fibrosis, and airways obstruction through excessive mucus accumulation [19,20,21,22], which can lead to regions of local tissue hypoxia
Summary
The airway epithelium is located at the interface between the internal and external environment and is strategically positioned to interact with the environment in a dynamic fashion. Increased expression of hypoxia-inducible factor (HIF)-1a is detected in the bronchial epithelium in COPD in areas of airway remodeling and goblet cell hyperplasia [28,29,30] Asthma, is another obstructive airway disease that involves chronic airway inflammation of the respiratory tract and excessive mucus production which is triggered by a variety of airborne insults including allergens, dust, smoking and respiratory pathogens. Pulmonary diseases associated with infection, excessive airway inflammation, airway obstruction, airway remodeling and emphysema can lead to decreased blood and tissue oxygenation and a fall in the partial pressure of oxygen in the arterial blood [10, 32, 33] This is evident in COVID-19 where hypoxia is a major risk factor for pneumonia and respiratory distress following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [34, 35]. We highlight the essential work needed to outline the role of tissue hypoxia in the pathophysiology of inflammatory lung diseases and emerging lung diseases such as COVID-19 and post-COVID-19 chronic lung disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
