None listed
Conditions
Brief summary
Inflammation in the lungs and circulation can cause asthma symptoms and can be treated with anti-inflammatory medications. For people with severe asthma, the inflammation and associated asthma symptoms are still problematic despite treatment with high dose puffer medications. Eosinophils are a type of cell in the blood and airways that promote inflammation. Mepolizumab (Nucala) and benralizumab (Fasenra) are treatments that can be prescribed for people with a type of severe asthma who have high eosinophil counts in their blood. Mepolizumab and benralizumab lower the number of blood and airway eosinophils and have been shown to reduce asthma flare-ups by about half. Recent research has described some new biological functions of eosinophils in inflammation. This study will aim to determine if these eosinophil functions and other important inflammation processes are a) changed in severe asthma in people with or without high blood eosinophil counts and b) whether any inflammation remains in people treated with mepolizumab or benralizumab. This new knowledge could help researchers to develop new asthma medications and better use existing medications in the future.
Interventions
A cross-sectional observational study will be conducted in participants with stable severe asthma.
Participants will be categorized into three groups:
1. Stable severe asthma not treated with biologics without elevated blood eosinophils (non-eosinophilic)
2. Stable severe asthma not treated with biologics with elevated blood eosinophils (eosinophilic)
3. Stable severe asthma currently receiving mepolizumab treatment
All participants in groups 1,2 and 3 will attend a cross-sectional study visi
A cross-sectional observational study will be conducted in participants with stable severe asthma. Participants will be categorized into three groups: 1. Stable severe asthma not treated with biologics without elevated blood eosinophils (non-eosinophilic) 2. Stable severe asthma not treated with biologics with elevated blood eosinophils (eosinophilic) 3. Stable severe asthma currently receiving mepolizumab treatment All participants in groups 1,2 and 3 will attend a cross-sectional study visit. Participants in group 2 who commence mepolizumab (Nucala) or benralizumab (Fasenra) treatment as part of their routine clinical care subsequent to the initial cross-sectional study visit will also attend longitudinal follow up study visits at >4 weeks post treatment commencement and >6 months post treatment commencement. Each study visit (cross-sectional and longitudinal) will involve collection of blood and induced sputum samples, spirometry (lung function) tests, measurement of height and weight. The participant will also complete some questionnaires to gain information about general health or quality of life, medical history and medications and asthma symptoms. Study visits are anticipated to be 1-2 hours in duration. All participants will consent to: A. Completing the tests involved in the study B. Completing questionnaires to obtain research data C. Allowing research personnel to access their medical record Participants may optionally consent to: D. Storage of biospecimens for use in future research studies relating to asthma and respiratory disease.
Sponsors
University of Newcastle
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to provide informed written consent 2. Adults (18 years or older) with doctor diagnosed severe asthma based on Global Initiative For Asthma (GINA) 2019 guidelines and PBS eligibility criteria for initiation of treatment of severe asthma with mepolizumab as follows: a. Evidence or documented evidence of asthma defined by: i. Forced expiratory volume (FEV1) reversibility greater than or equal to 12%, and greater than or equal to 200 mL at baseline within 30 minutes after administration of salbutamol (200 to 400 micrograms), OR ii. Airway hyper-responsiveness defined as a greater than 20% decline in FEV1 during a direct bronchial provocation test or greater than 15% decline during an indirect bronchial provocation test, OR iii. Peak expiratory flow (PEF) variability of greater than 15% between the two highest and two lowest peak expiratory flow rates during 14 days, OR iv. Diagnosis of asthma from at least two physicians experienced in the management of patients with severe asthma b. Asthma is uncontrolled* or not well-controlled^ despite adherence with optimized moderate to high dose inhaled corticosteroid-long-acting beta-2 agonist (ICS-LABA)# therapy and treatment of contributory factors, or that worsens when high dose treatment is decreased. c. *Uncontrolled asthma includes one or both of the following: i. Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma) ii. Exacerbations (1 or more in prior year) requiring oral corticosteroids (OCS), or serious exacerbations (1 or more in prior year) requiring hospitalization ^Not well-controlled asthma is defined by ACQ5 greater than or equal to 1.0 during study screening or at baseline visit (see O’Byrne PM, Reddel HK, Eriksson G et al. Measuring asthma control: a comparison of three classification systems. Eur Resp J. 2010;36:269-276 and Juniper EF, Bousquet J et al. Identifying ‘well-controlled’ and ‘not well-controlled’ asthma using the Asthma Control Questionnaire. Resp Med. 2006;100(4):616-621.) d. # For GINA definition of moderate to high dose ICS see (https://ginasthma.org/wp-content/uploads/2019/04/GINA-2019-main-Pocket-Guide-wms.pdf) 3. Stable disease, defined by lack of respiratory infection, exacerbation of asthma or alteration of maintenance asthma medication dose in prior 4 weeks to visit.
Exclusion criteria
- Pregnancy/breastfeeding - Participants currently receiving or having received in past 6 months treatment with benralizumab or omalizumab. - No exacerbation of asthma in prior 4 weeks at screening.
Outcome results
None listed