Early Antiviral Responses to Rhinovirus Infection in Asthma

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 Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Other: Rhinovirus infection

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Research Fellow; Phone Number: 020 7594 3751; Email: imperial.magic@nhs.net

Study Locations

• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, W2 1NY
      • Recruiting
      • Imperial College Respiratory Research Unit, St Mary's Hospital
      • Contact: Research Fellow; Phone Number: 020 7594 3751; Email: imperial.magic@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Potential participants will be identified from hospital outpatient clinics, primary care, spirometry sessions/clinics, other research projects, and advertisements.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls	Other: Rhinovirus infection; Inoculation with rhinovirus-16
Asthma	Other: Rhinovirus infection; Inoculation with rhinovirus-16

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Sebastian Johnston, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 21SM6879

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No