Asthma
Conditions
Brief summary
The goal of this exploratory and observational prospective study is to study the composition and phenotypes of blood leukocytes collected from asthmatic patients before and after instantiated treatment with the interleukin-5 neutralizing antibody mepolizumab. Comparisons will be made to leukocyte profiles in patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.
Detailed description
Asthma is a chronic inflammatory and obstructive condition affecting the airways. The disease is commonly associated with elevated blood eosinophils and tissue eosinophilia. Many aspects of the pathophysiological mechanisms and clinical symptoms are controlled by conventional therapies such as inhaled corticosteroids (ICS) and long acting β2 agonists. However, some patients remain clinically uncontrolled and need additional treatment such as direct targeting of eosinophil granulocytes by neutralizing the eosinophil-promoting cytokine interleukin 5 (IL5). Mepolizumab is a humanized monoclonal IL-5 neutralizing antibody that is used to treat patients with moderate-severe eosinophilic asthma. While a marked reduction of eosinophils is a key effect of mepolizumab, the exact mechanism of action is unknown. Apart from basophils, that also express the receptor for IL-5, other leukocytes are likely to be indirectly affected by the suppressed eosinophilia. In addition, it is largely unknown to what extent the few eosinophils remaining after anti-IL5 treatment differ from pre-treatment eosinophils. The present study is a prospective observational asthma study that aims to use microscopic analysis to investigate the composition and subtypes of blood leukocytes collected before and after instantiated mepolizumab treatment. Comparisons are made to patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.
Interventions
BIOLOGICALMepolizumab
Mepolizumab is administered by subcutaneous injection with guideline recommended patient selection and dosing for treatment of eosinophilic asthma. Accordingly, the Mepolizumab treatment is given as add-on therapy to standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
DRUGStandard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Sponsors
Lund University
Region Skane
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Clinical diagnosis of asthma (the asthma patient arms) * Eligible for Mepolizumab treatment as per the country-specific prescribing information (the arms with Mepolizumab)
Exclusion criteria
* Any diagnosed infection (all arms) * Previous history of lung disease, chronic inflammatory condition, atopy, or cardiovascular disease. Diagnosed or perceived infection within 3 weeks prior to blood sampling (Healthy non-asthma control subjects)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Leukocyte Composition | Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment | Immunohistochemical determination of the relative proportion (percent) of the leukocyte populations in blood leukocyte pellets |
| Change in Blood Eosinophil Marker Expression | Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment | Quantitative immunohistochemical analysis of eosinophil marker expression in blood leukocyte pellets |
| Change in Blood Basophil Marker Expression | Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment | Quantitative immunohistochemical analysis of basophil marker expression in blood leukocyte pellets |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood B Lymphocyte Marker Expression | Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment | Quantitative immunohistochemical analysis of T lymphocyte marker expression in paraffin-embedded blood leukocyte pellets |
| Change in Blood T Lymphocyte Marker Expression | Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment | Quantitative immunohistochemical analysis of T lymphocyte marker expression in paraffin-embedded blood leukocyte pellets |
| Leukocyte Total Cell Counts | Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment | Routine hemacytometer total leukocyte cell counts |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Forced Expiratory Volume in 1 second (FEV1) | Change from baseline at 4 weeks, and 4 months after initiated biological treatment. | Spirometry: Forced Expiratory Volume, 1s; (FEV1). |
| Change in Exhaled FeNo | Before and 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment. | Fractional exhaled NO will be measured at multiple flows |
| Change in Forced Vital Capacity (FVC) | Change from baseline at 4 weeks, and 4 months after initiated biological treatment. | Spirometry: Forced Vital Capacity (FVC) |
Countries
Sweden
Contacts
Primary ContactDavid Aronsson
Backup ContactLeif Bjermer
Outcome results
None listed