Early antiviral responses to rhinovirus infection in asthma

We are looking for healthy volunteers and patients with asthma aged 18-55 years old to take part in a human infection study with rhinovirus (the common cold).

The study involves:

• A screening visit with blood tests
• Short (~15 minute) visits daily for five days from Monday to Friday, with three visits on the Monday and one morning visit each day thereafter (seven in total), for nasal sampling only
• Remote monitoring of symptoms (questionnaire once daily) and a quick (~2 minute) breathing test (peak flow, morning and night) for two weeks

To get in touch with the study team, please email: imperial.icrru@nhs.net

Study summary

Many people with asthma have increased asthma symptoms when they have a cold. The reasons for this are not well understood, but it has been proposed that the immune response to cold viruses is different in people with asthma. In particular, the production of antiviral proteins called interferons is thought to be reduced compared to healthy individuals. Studies to confirm this have so far been inconclusive, but none have looked at the earliest, pre-symptomatic stages of infection in human volunteers. This study will recruit volunteers with and without asthma to compare their immune responses to cold viruses. We will do so by infecting participants with a cold virus.

What does taking part involve?

If you are interested in participating we will ask you to attend a dedicated clinical research facility, Imperial Clinical Respiratory Research Unit (ICRRU), at St Mary’s Hospital for a screening visit lasting 30-60 minutes. This will involve taking details of your medical history and a blood test to find out if you are suitable to take part. If you are eligible and decide to continue, you will have the tests and procedures described below over seven visits, each lasting ~15 minutes:

• Monday morning first thing followed by two more visit at three hour intervals e.g. 9am, 12pm, 3pm
• Tuesday to Friday mornings first thing, one visit daily                                          

We perform three procedures as part of nasal sampling:

• Nasosorption: This test involves placing a piece of blotting paper inside each nostril to collect a sample of the fluid lining your nose. We will use this to measure the antiviral interferon proteins.
• Nasal washings: One nostril will be gently washed with 5mL (1 teaspoon) of salt water. This will be done to look for the virus, to check if you get infected.
• Nasal brushings: A little brush will be inserted into each nostril in turn and gently rotated to collect a few of the cells that line your nasal passages. These samples will be used to look for evidence of a protein that can suppress antiviral interferon production, by genetic analysis.

On the first visit we will also spray the virus that causes the common cold (rhinovirus 16) into your nose. You may get a cold and have typical cold symptoms such as a sore throat and runny nose, which usually last 3-4 days. If you have asthma, you may also notice a mild worsening of your usual asthma symptoms.

In addition, we will ask you to record your symptoms daily using an app and give you a ‘smart’ peak flow meter and ‘smart’ inhaler that will link with the app to record your peak flow readings daily and inhaler use. We will ask you to do this for 14 days in total.

Are there any side effects or risks involved?

You may get a cold and, if you have asthma, a worsening of your usual asthma symptoms. These asthma symptoms are normally mild and usually settle within 1-2 weeks. Some symptoms such as a slight increase in mucus production may persist for up to 5 weeks, but this would be unusual. Participants are free to self-medicate as they usually would for a cold and/or asthma symptoms. From our previous experience with similar studies, no volunteers with asthma have required additional treatment with steroid tablets, nebulisers, emergency department attendances or hospital admission. The virus we use was prepared especially for research and has been stored carefully in our laboratory. We have used it in many previous studies over 20 years, where it has been shown to be safe.

Are there any potential benefits?

Taking part will not improve anyone’s health, although they might develop some immunity to the study virus and benefit from a general health check at screening. Participants will be compensated for their time and the inconvenience of being infected with a cold virus (£200).

Who is conducting this study?

This study is being conducted by a research team in the National Heart and Lung Institute at Imperial College London and is funded by a grant from the British Medical Association Foundation.