Early Antiviral Responses to Rhinovirus Infection in Asthma

Overview

The bulk of the morbidity and mortality related to asthma is during periods of acutely increased symptomatology called 'exacerbations'. Roughly half of asthma sufferers experience such an exacerbation each year. Most of these events are triggered by viral infections, usually the common cold virus (rhinovirus). A key part of the body's defence against viral infections is to produce antiviral proteins called 'interferons', which have a myriad of effects to stop viruses. Previous work on cells taken from volunteers with asthma and healthy controls and infected with rhinovirus in the lab suggests interferon production is impaired in asthma. However when human volunteers with asthma are infected with rhinovirus, high levels of interferon are found a few days later - along with high numbers of virus. Whether the high virus numbers are the result of an initially weak interferon response, with subsequently unchecked viral replication leading to exaggerated interferon levels, is unknown as no one has measured interferons early in infection. By infecting volunteers with asthma and healthy controls with rhinovirus at a known time, only done in a handful of centres worldwide, we will be able to measure interferons within hours of infection and well before symptoms develop.

Study Type

• Study Type: Observational
• Study Design
  • Time Perspective: Prospective
• Study Primary Completion Date: November 1, 2022

Interventions

• Other: Rhinovirus infection
  • Inoculation with rhinovirus-16

Arms, Groups and Cohorts

• Asthma
• Healthy controls

Clinical Trial Outcome Measures

Primary Measures

• Nasal IFN-λ at 6 hours post rhinovirus infection
  • Time Frame: 6 hours
  • Difference in IFN-λ in nasal lining fluid 6 hours following rhinovirus infection in subjects with asthma compared to healthy controls

Secondary Measures

• Nasal IFN-α at 6 hours post rhinovirus infection
  • Time Frame: 6 hours
  • Difference in IFN-α in nasal lining fluid 6 hours following rhinovirus infection in subjects with asthma compared to healthy controls
• Nasal IFN-λ at 3 hours post rhinovirus infection
  • Time Frame: 3 hours
  • Difference in IFN-λ in nasal lining fluid 3 hours following rhinovirus infection in subjects with asthma compared to healthy controls
• Nasal IFN-λ at 24 hours post rhinovirus
  • Time Frame: 24 hours
  • Difference in IFN-λ in nasal lining fluid 24 hours following rhinovirus infection in subjects with asthma compared to healthy controls
• Nasal IFN-α at 3 hours post rhinovirus infection
  • Time Frame: 3 hours
  • Difference in IFN-α in nasal lining fluid 3 hours following rhinovirus infection in subjects with asthma compared to healthy controls
• Nasal IFN-α at 24 hours post rhinovirus infection
  • Time Frame: 24 hours
  • Difference in IFN-α in nasal lining fluid 24 hours following rhinovirus infection in subjects with asthma compared to healthy controls

Participating in This Clinical Trial

For Asthma group: Inclusion Criteria:

• Age 18-55 years – Doctor diagnosis of asthma – Previous asthma exacerbation Exclusion Criteria:

• Smoking history over past 12 months – Sinonasal disease, including current symptoms of allergic rhinitis – Asthma exacerbation or an upper respiratory viral infection within the previous six weeks – Current or concomitant use of oral steroids, monoclonal antibodies or nasal sprays – Neutralising antibodies to rhinovirus (RV)-16 – Clinically significant diseases other than asthma which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, influence the results of the study, an/or the patient's ability to take part in it – Inability to understand written or verbal information in English For healthy control group: Inclusion Criteria:

• Age 18-55 years Exclusion Criteria:

As for Asthma group and in addition: • History of asthma

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • Imperial College London
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Sebastian Johnston, Principal Investigator, Imperial College London
• Overall Contact(s)
  • Research Fellow, 020 7594 3751, imperial.magic@nhs.net