Severe Asthma Exacerbations and Mepolizumab Treatment
- Conditions
- Severe Asthma
- Interventions
- Registration Number
- NCT04914078
- Lead Sponsor
- Università degli Studi di Ferrara
- Brief Summary
This is a hypothesis-generating project to investigate a) infective etiology and b) inflammatory profile of the exacerbations of asthma in severe asthmatic patients treated with the humanized monoclonal antibody against interleukin-5 Mepolizumab. Under these treatment conditions the study will inform on the relationship between these two axes: infection \& innate immunity Vs inflammatory profile changes occurring during exacerbation events.
In addition, the study will also explore the effect of Mepolizumab treatment on airway microbial composition and on airway/systemic immune response both at stable state and at the exacerbation.
- Detailed Description
Longitudinal, observational study to evaluate the infective etiology and the inflammatory profile of asthma exacerbations in severe asthmatic patients treated (as part of routine medical care) with the humanized monoclonal antibody against interleukin-5 Mepolizumab.
The participants receive Mepolizumab as part of routine medical care (see inclusion criteria). The study will assess the effect of the intervention (Mepolizumab) on airway microbial compositions and on airway/systemic inflammation at exacerbation and at stable state.
The patients will be evaluated at baseline (the day of Mepolizumab initiation, before Mepolizumab administration - V0), at 1 month after Mepolizumab initiation (treatment visit - V1), at exacerbation (exacerbation visit - V2) and at 3 months after the exacerbation event (convalescence visit - V3) up to 12-month study period (Table 1). To perform the convalescence visit, a 3-month extension of the study period will be applied if the exacerbation occurs from month 9 to month 12 from the initiation of Mepolizumab. Recurrent exacerbation events will be evaluated separately when a paired-3-month convalescence visit can be performed within the study period.
The patients will contact the center/researchers in case of worsening of the respiratory symptoms to schedule the exacerbation visit. The visit will be performed within 7 days from the beginning of the deterioration of the symptoms.
At each visit, the following procedures will be performed in all the patients: 1) Clinical/pharmacological assessment (including assessment of asthma control; and measurements of central and peripheral fractional exhaled nitric oxide); 2) lung function tests (including lung volumes evaluation and small airway functional assessment by impulse oscillometry - IOS); 3) blood and sputum differential inflammatory cell counts; 4) sputum samples for microbiological assays (conventional sputum cultures and Multiplex Real Time PCR for virus and bacterial detection); 5) blood and sputum samples for cytokine profiling.
In a representative subgroup of patients (n=30) breath condensate, blood and sputum samples will be performed for: 1) airway microbiome (16S ribosomal RNA Sequencing) evaluation; 2) blood innate immune responses; 3) transcriptomics and proteomics of sputum inflammatory cells; 4) breathomics.
The study has been submitted for approval to the ethics committee, and informed written consent will be obtained from each enrolled subject.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 70
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Mepolizumab treated patients Mepolizumab 100 MG Severe eosinophil severe asthmatic patients treated with anti IL-5 monoclonal antibody Mepolizumab
- Primary Outcome Measures
Name Time Method Inflammation 1 year Co-primary measurements will be: i) changes in blood and sputum eosinophil counts at exacerbation compared to stable state
Infections 1 year Co-primary measurements will be: ii) changes in the frequency of microbial agent detection in sputum samples at exacerbation compared to stable state.
- Secondary Outcome Measures
Name Time Method Lung function FEV1 l 1 year FEV1 litre
Lung function FEV1 % 1 year FEV1% predicted
Lung function FVC l 1 year FVC litre
Lung function FVC % 1 year FVC % predicted
Lung function VC l 1 year vital capacity (VC) litre
Fractional exhaled nitric oxide (FeNO) 1 year parts per billions (ppb) in the exhaled breath
Lung function VC % 1 year vital capacity (VC) % predicted
Lung function - Impulsed Oscillometry kPa 1 year R5-R20 (kPa/L/s)
Lung function - Impulsed Oscillometry % 1 year R5-R20 % predicted
Asthma control questionnaire (ACT) 1 year Score ranging from 5 to 25
Sputum Quantitative bacteriology 1 year Serial dilutions (up to 10-12) of sputum samples will be made and cultured on the appropriate media. Colony- forming units (CFU)/mL will be calculated.
Sputum virus profiling 1 year The commercially available multiplex PCR assay RespiFinder RG® (Qiagen) was used according to manufacture instructions for the simultaneous detection and differentiation of 21 respiratory pathogens, including both viruses and atypical bacteria
Cytokines 1 year cytokines profiling (Th1/Th2/Th17 - pg/ml) in blood serum and sputum supernatants will be assessed by by multiplex immunoassay-based (EMD Millipore Burlington, MA, USA)
Trial Locations
- Locations (1)
Azienda Ospedaliero Universitaria Ferrara
🇮🇹Ferrara, Italy