Using Multiomics to Define Mechanisms of Rhinovirus-induced Chronic Obstructive Pulmonary Disease Exacerbations to Develop Novel Therapies and Therapeutic Targets

Inclusion Criteria for COPD subjects * 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 Inclusion Criteria for non-smoking controls * 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. Inclusion Criteria for smoking controls • 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 Exclusion Criteria: * Participants with other causes of chronic airflow limitation, including but not limited to: * Bronchiectasis including cystic fibrosis * Bronchiolitis obliterans * Carcinoma of the bronchus * Fibrosis such as tuberculosis (TB), idiopathic pulmonary fibrosis * Presence of any significant systemic disease, that in the opinion of the investigator would (a) make participation in the study unduly risky, or (b) significantly interfere with important outcomes being measured. * For example, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric conditions. * Pregnant, planning to become pregnant, testing positive for pregnancy at the screening visit test, or nursing females during and within 30 days of treatment. * Treatment with oral, inhaled or nasal corticosteroids within 8 weeks prior to enrolment. * Treatment with antibiotics in the 8 weeks preceding enrolment. * Treatment with nasal medications, anti-leukotrienes, anti-histamine at the time of the study. * Presence (at screening) of serum rhinovirus-A16 neutralising antibodies in a titre \>1:2. * Individuals with close contact to at risk patient group, including: * Infants (less than 6 months); * The extremely elderly or infirm; * Pregnant and/or breastfeeding women; * Patients with immunosuppression (e.g., human immunodeficiency virus (HIV), transplant recipients on anti-rejection medications, those undergoing chemo- or immuno-therapy). * Other factors that in the opinion of the investigator are considered a risk. * Participation in other clinical research studies that, in the opinion of the investigator, would (a) make participation in the study unduly risky, or (b) significantly interfere with important outcomes being measured in this or other studies, or (c) present an unacceptable visit burden to the participant.