Lung Immune Challenge Study: Controlled Exposure to Inhaled Resiquimod (R848)

Respiratory viral infections can be a cause of significant illness, particularly in vulnerable individuals as seen in the COVID-19 pandemic. An underactive or overactive immune response can lead to ineffective resolution of inflammation after an infection, especially in people with airway diseases such as asthma. A better understanding of immune responses to infection that does not rely on cell or animal models is crucial to help develop better treatments for lung inflammation. An established method of studying inflammation in humans is through careful and controlled exposure (or "challenge") with a mimic of a virus to simulate an infection in a similar manner to that of a virus, but with the advantage of not causing an infection. The investigators have already developed a well-tolerated mimic of human viral infection using a sterile substance called Resiquimod (or R848). Since it does not contain living organisms there is no possibility of being infected. This has been used previously as a nasal spray to cause a mild short-lived inflammation that mimics a mild cold. This has been used safely in a range of people of different ages including those who have asthma. There are differences however in how the nose and lungs respond to viral infections. This is particularly true in those with airway diseases such as asthma, who have cells in the airways of their lungs that respond in a different way to inflammatory triggers (such as viruses). The current study aims to build on previous research by developing a new approach of studying inflammation in the lungs using a small volume of Resiquimod. This will be done by gently inhaling a fine mist through a mouthpiece into the lungs. Blood and phlegm samples would then be collected to assess inflammation and how well people tolerate the procedure.