A Pilot Study of the Use of 129Xe and 1H MRI to Measure the Modulation of Eosinophil-Related Inflammation by Mepolizumab In COPD

The investigators aim to recruit 32 people with COPD who have frequent exacerbations and high eosinophil counts which indicates "asthmatic type" inflammation and treat them for a year with mepolizumab. This is a licenced medication for asthma. Mepolizumab is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels and is effective at reducing exacerbations in asthmatics. To determine whether mepolizumab may be an effective treatment in people with COPD and "asthmatic type" inflammation participants will have MRI scans before the treatment, after 12 weeks and after a year to see how the drug affects inflammation. The investigators will also compare our measurements with the number of exacerbations people get (measured by diaries), with measures of their quality of life (using a questionnaire), and with ordinary laboratory breathing tests. The investigators are especially interested to know if the reduction in inflammation early on after 12 weeks is associated with fewer exacerbations and better quality of life over the year.


Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of COPD as determined by a post bronchodilator FEV1/FVC \<70% and an FEV1 of between 20 and 80% at screening visit
* Treatment with inhaled triple therapy (licensed combination of long acting beta 2 agonist, long acting anti-muscarinic and corticosteroid) at constant dose for at least 12 weeks before screening visit. Treatment with roflumilast, theophyillines and macrolides will be permitted so long as they were introduced at stable dose \> 12 weeks prior to screening visit. (If maintenance drug dosing has not been with stable dosages for 12 weeks the screening visit may be rescheduled until this is achieved: see sections 7.3 and 7.10)
* At least 2 acute exacerbations of COPD (AECOPD) requiring treatment with oral steroids and/or antibiotics in the last 12 months, or 1 acute AECOPD requiring hospital admission in the last 12 months.
* At least one eosinophil count of \>0.3 cells·μL-1 in the 12 months prior to screening
* Age over 18 years

Exclusion Criteria:

* Contraindication to MRI scanning, including Gadovist (ie hypersensitivity or poor renal function; see below); this includes claustrophobia and musculoskeletal difficulties, this information is collected on the UoS MRI unit screening form.
* Inability to give informed consent or comply with study procedures
* Hypersensitivity to mepolizumab or its excipients
* Untreated helminthic infection
* Exacerbation of COPD requiring treatment with oral steroids and/or antibiotics within 4 weeks of screening. A repeat screening visit may be scheduled in order to achieve this criterion. The participant will be required to successfully complete all screening procedures at the rescheduled visit, including that for exacerbation-free stability.
* SpO2 \<90% on room air at screening
* Clear history of childhood and/or current asthma
* Past history of lung surgery
* Other significant lung disease
* Long term oral steroid treatment
* eGFR \< 30 ml/min/1.73 m2 at screening
* NYHA class 3 or 4, where the functional limitation from heart disease is greater than that from COPD, or uncompensated heart failure
* Chronic liver disease (Any elevation of ALT above twice the upper limit of normal at screening. Lower levels of abnormality are permitted after investigator review if felt not to compromise safety)
* Malignancy unless treated and disease free for 5 years
* Conditions causing significant immunosuppression
* Active infection with blood borne viruses (including hepatitis A and B and HIV)
* Other significant medical condition compromising participant safety or fidelity of study.
* Pregnant or breast feeding
* Of childbearing potential and not willing to use highly effective methods of contraception during the course of the study and for 100 days post last dose of mepolizumab.
* Participants who have received an investigational drug within 30 days of first dose, or within 5 drug half-lives of the investigational drug, whichever is longer