Asthma Respiratory
Conditions
Interventions
This is a prospective observational study, which will use routinely collected data, enhanced with brain magnetic resonance imaging (MRI) and additional measures of cognition and well-being to address
Sponsors
North Bristol NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cases: 1. Aged 18+ years 2. Physician-diagnosed severe eosinophilic asthma eligible for mepolizumab therapy as per National Institute for Health and Care Excellence guidance 2017, satisfying one of the following criteria: 2.1. Peripheral blood eosinophils =300 cells per microlitre, with =4 exacerbations requiring oral corticosteroids in the previous 12 months or continuous oral corticosteroids of at least the equivalent of prednisolone 5 milligrams per day over the previous 6 months 2.2. Peripheral blood eosinophils =400 cells per microlitre, with =3 exacerbations requiring oral corticosteroids in the previous 12 months or continuous oral corticosteroids of at least the equivalent of prednisolone 5 milligrams per day over the previous 6 months 3. A regional asthma MDT decision was made to start mepolizumab 4. The patient agrees to start mepolizumab and is able to provide written informed consent and participate in the study Controls: 1. Aged 18+ 2. Physician-diagnosed mild or moderate asthma for >3 months, GINA step 2-4 3. Well-controlled asthma defined by an Asthma Control Questionnaire–5 (ACQ-5) =/< 1.5 4. Participant is willing and able to give informed consent to take part in the study
Exclusion criteria
Exclusion criteria: Cases 1. Current smoking, or a greater than 10 pack-year history of smoking in ex-smokers. 2. A diagnosis of an alternative lung disease, including, but not limited to, allergic bronchopulmonary aspergillosis, eosinophilic granulomatous polyangiitis, bronchiectasis or chronic obstructive pulmonary disease. 3. Previous anti-asthma biological therapies including mepolizumab, benralizumab, omalizumab, reslizumab and dupilimab. 4. Pregnancy/childbearing age not using contraception. 5. Alcohol and drug addiction. 6. CNS diseases the investigators consider would have a significant effect on outcomes – including stroke, MS, epilepsy, tumour or significant cognitive impairment (including dementia, or severe learning disabilities). 7. Participants with contraindications to MRI will not be able to take part in the MRI study, but can be recruited to complete the questionnaires. 8. Contraindications to completing pulmonary function tests. Controls 1. Oral corticosteroid use in the last 3 months, or =3 oral corticosteroid courses in the last 12 months. 2. Current smoking, or a greater than 10 pack-year history of smoking in ex-smokers. 3. A diagnosis of an alternative lung disease, including, but not limited to, allergic bronchopulmonary aspergillosis, eosinophilic granulomatous polyangiitis, bronchiectasis, chronic obstructive pulmonary disease or interstitial lung disease. 4. Previous anti-asthma biological therapies including mepolizumab, benralizumab, omalizumab, reslizumab, dupilumab or tezepelumab. 5. Pregnancy/childbearing age not using contraception. 6. Alcohol and drug addiction. 7. CNS diseases the investigators consider would have a significant effect on outcomes – including stroke, MS, epilepsy, tumour or significant cognitive impairment (including dementia, or severe learning disabilities). 8. Participants with contraindications to MRI will not be able to take part in the MRI study, but can be recruited to complete the questionnaires. 9. Contraindications to completing pulmonary function tests.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Brain microstructural imaging (quasi-diffusion) measured with a magnetic resonance imaging brain scan at baseline (case and control) and after 6 months of mepolizumab treatment (case only) | — |
Secondary
| Measure | Time frame |
|---|---|
| The following secondary outcome measures will be assessed at baseline (case and control) and after 6 months of mepolizumab treatment (case only): 1. Resting-state functional MRI network measured using an MRI brain scan 2. Routine clinical measures: 2.1. Asthma exacerbation frequency/hospitalisation/intensive care unit admission measured using data extracted from medical records as an annualised frequency 2.2. Oral corticosteroid use, current and past measured using data extracted from medical records as annualised exacerbation frequency and total steroid burden 2.3. Asthma medication use measured using data extracted from medical records as changes to asthma medication over the 6-month period for Cases 2.4. FEV1 and FVC measured using spirometry 2.5. Airway inflammation measured using fractional exhaled nitric oxide 2.6. Blood eosinophil count measured using a blood test and standard laboratory methods 2.7. Side effects of mepolizumab and glucocorticoids measured using data extracted from medical records as the frequency of incidents reported by the patient 3. Cognitive, wellbeing and symptom perception scores: 3.1. Asthma control measured using the Asthma Control Questionnaire (ACQ-7) 3.2. Asthma-related quality of life measured using the Mini Asthma Quality of Life Questionnaire (Mini AQLQ) 3.3. Wellbeing measured using the Warwick-Edinburgh mental wellbeing scale 3.4. Depression measured using the Patient Health Questionnaire (PHQ-9) 3.5. Anxiety measured using the Generalised Anxiety Disorder Assessment (GAD-7) 3.6. Dyspnoa experience measured using the Multidimensional Dyspnea Profile (MDP) 3.7. Impact of the well-being of obstructive lung disease measured using the St George's Respiratory Questionnaire (SGRQ) 3.8. Cognition measured using the Montreal Cognitive Assessment (MoCA) 3.9. Illness perception measured using the Brief Illness Perception Questionnaire (Brief IPQ) 3.10. Sleep quality measured using the Athens Insomnia Scale (AIS) | — |
Countries
England, United Kingdom
Contacts
Public ContactGeorge Nava
Outcome results
None listed