Using Multiomics to Define Mechanisms of RhinoVirus-induced Chronic Obstructive Pulmonary Disease Exacerbations to Develop Novel Therapies and Therapeutic Targets
The goal of this study is to examine exacerbations of chronic obstructive pulmonary disease (COPD) caused by a common cold virus called rhinovirus, to identify new treatments. Exacerbations are flare-ups of respiratory symptoms which are a major cause of ill health in people with COPD, and are most commonly caused by viruses. The main questions the study aims to answer are: * What processes in the body occur in response to rhinovirus infection, and do the differences between people with COPD and healthy volunteers explain why people with COPD develop more severe illness and exacerbations? * Can treatments be identified that target these processes to reduce the severity and frequency of exacerbations in people with COPD? The study will compare eligible participants with COPD to healthy volunteers, and will involve intentionally infecting each participant with rhinovirus in a controlled environment. They will undergo baseline investigations prior to infection including a first bronchoscopy. Post-infection each participant will undergo a range of tests, including a second bronchoscopy, to compare how processes in the body, and especially the lungs, differ between people who do and do not have COPD.
• Male or female sex
• Age ≥40 years and ≤75 years at the time of signing the consent form
• Medical history or clinical diagnosis of COPD
• Significant smoking history, defined as:
‣ Cumulative smoking history of at least 20 pack years
⁃ Permitted to currently use, or have history of use of, e-cigarettes/vapes
• COPD spirometry criteria:
‣ Post bronchodilator FEV1 of \<80% and ≥50% predicted for age and height (equivalent to GOLD criteria stage 2 for 'Moderate' severity COPD9)
⁃ Post-bronchodilator FEV1/FVC ratio \<0.7
⁃ β-agonist reversibility: an improvement of less than 12% predicted FEV1 and less than 200mL after 200 micrograms of salbutamol or equivalent short acting beta-2 agonist bronchodilator.
• History of acute exacerbations of COPD as defined by the participant answering yes to the question: do your COPD symptoms get noticeably worse when you catch a cold?
• Clinically stable with no COPD exacerbations within 8 weeks prior to enrolment
• Permitted to take short and long-acting bronchodilators including beta agonists and muscarinic antagonist inhalers
• Co-morbidity criteria:
‣ Permitted to have a past medical history of asthma, allergic rhinitis and seasonal rhinitis, but not currently active within 8 weeks prior to enrolment
⁃ Absence of current or previous history of significant respiratory disease, other than COPD, asthma and allergic rhinitis
• Permitted to have a positive skin test for atopy
• Male or female sex
• Age ≥ 40 years and ≤ 75 years at the time of signing the consent form
• No history or clinical diagnosis of COPD
• No significant smoking history, defined as:
‣ Less than 5 pack year cumulative smoking history
⁃ Has not smoked or used e-cigarettes/vapes in the last 1 year
• Controls spirometry criteria
‣ FEV1 of ≥80% predicted for age and height
⁃ FEV1/FVC ratio ≥0.7
• Co-morbidity criteria:
‣ Permitted to have a past medical history of asthma, allergic rhinitis and seasonal rhinitis, but not currently active in the 8 weeks prior to enrolment
⁃ Absence of current or previous history of significant respiratory disease, other than asthma and allergic rhinitis
• Permitted to have a positive skin test for atopy.
∙ • Identical to non-smoking controls, with the exception of smoking history:
• Cumulative smoking history of at least 20 pack years.
• Permitted to currently use, or have history of use of, e-cigarettes/vapes