Submitted by Yan Pan on Wed, 19/08/2026 - 15:00
A pioneering study led by researchers at the University of Cambridge has reached an important milestone, with the final participant completing the first phase of a study designed to investigate how our immune system responds to viral infections in the lung.
Viral infections are a major cause of asthma exacerbations, yet much remains unknown about the earliest immune responses that occur in our bodies. Steroids have been a mainstay of treatment for asthma and chronic obstructive pulmonary disease (COPD) exacerbations for decades, but they can also cause a range of side effects.
In order to better understand inflammatory lung diseases and help identify more targeted treatments, the MRC-funded Lung Immune Challenge Study, led by Dr Akhilesh Jha at the Victor Phillip Dahdaleh Heart & Lung Research Institute and the Department of Medicine at Cambridge, is exploring why viral infections can cause flare-ups of respiratory conditions, and why our immune responses can be different.
The fundamental question we're trying to get to is: why do some people respond normally to a viral infection, while others respond in an abnormal way?
Dr Akhilesh Jha, MRC Clinician Scientist and Honorary Consultant in Respiratory Medicine, Assistant Research Professor, Department of Medicine, University of Cambridge
While traditional methods like cellular studies and animal models cannot fully capture the complexity of human biology, the Lung Immune Challenge Study takes a different approach.
For the last several years, Dr Jha and his team established a nasal spray model in the Nasal Immune Challenge Study to understand differences in upper airway immune responses between people who have hay fever or asthma versus those who don't.
“But often, when people have an asthma attack, the problem is in the lower airways, in the lungs themselves, rather than necessarily just in the nose,” says Dr Jha. “So the purpose of this first phase of the study was: can we take what we've established in the nose, but do it in the lungs? So that's how we did it. We used an inhaled mist into the airways with the same substance.”
The team recreated the earliest responses to a viral infection in a controlled, safe environment in the lab. Participants inhale a fine mist containing Resiquimod, or R848, a synthetic compound that activates some of the same immune pathways triggered by a viral infection.
“We're not giving people a real virus in the lab, instead we're giving them a synthetic substance which mimics part of a viral infection,” says Jha, “The body then responds in the same way as it would do with a real virus. So in that sense, it is much easier to perform and better tolerated by participants.”
The study has recruited 48 participants for this phase, including people with asthma as well as healthy volunteers.
“People want to do this mainly for altruistic reasons, and that's really important,” he says. “We've had a really good enthusiastic response from people across Cambridge, Cambridgeshire, Bedfordshire, all of Eastern England really, and sometimes even London as well.”
The first phase has now been completed with final participant challenged. The challenge has been well tolerated, with some participants experiencing mild cold- or flu-like symptoms.
To make sure the study generates sufficient immune responses, the team also collected sputum samples, which is phlegm, before and after the challenge to look for changes in immune activity.
“We’ve seen an increase in immune activity like you would with a viral infection, and we've seen that also in a little bit in their blood. So we can see that response both locally and systemically,” says Dr Jha.
For the next stage, the team will use cutting-edge molecular biology techniques, including single-cell RNA sequencing and spatial transcriptomics, to examine the samples at much higher resolution, building on the model established in the first phase.
The aim is to understand which individual cells and biological pathways drive the differences in the immune response between people with asthma and those without airway disease.
The researchers will investigate a range of cells found in the airways, including epithelial cells and different types of immune cells such as monocytes, macrophages and dendritic cells.
Defining the mechanisms behind these differences could eventually help researchers identify potential targets for new treatments.
The model could also have potential as a tool to support drug development. Instead of relying solely on large clinical trials that can take years, a new anti-inflammatory treatment could potentially be tested using the controlled lung immune challenge model to see whether it reduces the immune response to help with decision-making.
“This model can act as a platform for testing whether drugs are worth taking forward,” says Dr Jha. “It could help accelerate drug development by allowing us to test a new idea in a much smaller number of people and over a much shorter timeframe.”
The study is supported by the NIHR Cambridge Biomedical Research Centre and NIHR Cambridge Clinical Research Facility, bringing together clinical and academic expertise from across the Cambridge Biomedical Campus.
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