Phenotyping and Classifying Asthma Exacerbations

Study Overview
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Brief Summary
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An observational study in patients between 12 and 70 years old with an acute asthma exacerbation, to determine the relation between phenotypical characteristics and the treatment response.

Detailed Description
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Rationale: Asthma is a heterogeneous inflammatory respiratory disease affecting 8 - 9% of the European population. Acute asthma exacerbation (AAE) is characterized as an acute worsening of symptoms and is treated inconsistently with steroids with or without antibiotics. In order to adjust and personalise exacerbation treatment, phenotyping and classifying of asthma exacerbations would be required. Therefore, we want to classify patients with AAEs phenotypically in relation to the treatment response. Objective: The primary objective of the study is to determine the relationship between exacerbation treatment response at day 7 and the phenotypical characteristics of asthma exacerbations. Secondary objectives are 1) developing a prediction model based on biomarkers and/or clinical data to predict the treatment response of AAEs 2) comparing the environmental, inflammatory, microbiological and lipid parameters of patients diagnosed with asthma between exacerbation phase and recovery (baseline). Study design: A prospective cohort study in a tertiary asthma centre. Study population: Patients aged 12 - 70 years, diagnosed with mild to severe asthma according to the Global Initiative for Asthma (GINA) guidelines. Patients will be included at the onset of a severe asthma exacerbation. Main study parameters/endpoints: Primary endpoint is the relation of phenotypical characteristics with treatment response at day 7, defined by 1) the physician - and patient rated global evaluation of treatment effectiveness (GETE) score 2) difference in Asthma Control Questionnaire 5 (ACQ-5) (> 0.5) 3) difference in handheld spirometry values like forced expiratory volume (FEV1 ≥ 10%). Treatment response will be classified as excellent, good, moderate or poor. Secondary endpoints are 1) a prediction model for the treatment response of AAE 2) aetiology of the AAE 3) blood and local respiratory parameters; microbiota composition; lipid metabolomics and volatile compounds composition at baseline and AAE.

Official Title
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Phenotyping and Classifying of Childhood and Adult Asthma Exacerbations: Towards Personalised Treatment. An Observational Study.

Conditions
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Asthma Attack

Intervention / Treatment
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* Behavioral: Questionnaires
* Device: Spirometry
* Device: Fractional Exhaled Nitric Oxide (FeNO)
* Device: Corsano watch
* Device: e-Nose
* Procedure: Nasopharyngeal swabs and nasal lining fluid
* Device: Sputum induction
* Procedure: Blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient diagnosed with asthma according to the GINA guidelines between 12 and 70 years old. If patients are doctor's diagnosed with asthma based on clinical data, the further diagnostics will be performed to confirm the asthma diagnosis after the AAE. Mild to severe asthma, treated according to GINA guidelines with medium - or high dose inhaled corticosteroids (with or without LABA) or treated with a low dose inhaled corticosteroids combined LABA or leukotriene - receptor antagonist. Asthma exacerbation, indicated for systemic corticosteroids. Written personal and/or parental informed consent, prior to any study procedures. Eligibility and willingness to present during an asthma exacerbation at the Franciscus Gasthuis hospital. Ability to use e - health applications. Exclusion Criteria: Recent oral corticosteroid treatment in the last 6 weeks. Immunosuppressive maintenance medication (azithromycin, systemic corticosteroids maintenance therapy and other) or recently (< 6 weeks) discontinued these medications. (Desensitization therapy indicated for allergies can be included in the study) Maintenance medication or recently discontinued (< 6 weeks) biologicals. Other underlying inflammatory or auto-immune diseases, such as rheumatologic disease. Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site) Pregnancy, because of the possible altered immunological status.(31) Participation in an interventional study or randomised controlled trial.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Asthma exacerbation<br>Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines | Behavioral: Questionnaires<br>* Questionnaires about asthma control and quality of life<br>Device: Spirometry<br>* Spirometry monitoring at home<br>Device: Fractional Exhaled Nitric Oxide (FeNO)<br>* Measuring fractional exhaled nitric oxide at home<br>Device: Corsano watch<br>* Monitoring vital parameters at home<br>Device: e-Nose<br>* Breathprint will be performed using e-Nose<br>Procedure: Nasopharyngeal swabs and nasal lining fluid<br>* Nasopharyngeal swabs and nasal lining fluid will be taken<br>Device: Sputum induction<br>* If patients produce sputum, the sputum will be analysed<br>Procedure: Blood sample<br>* Blood sample for standard care and 10 ml extra will be taken<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relation of phenotypical characteristics with treatment response | Relation of phenotyipcal characteristics with treatment response defined by 1) the physician - and patient rated global evaluation of treatment effectiveness (GETE) score 2) difference in Asthma Control Questionnaire 5 (ACQ-5) (> 0.5) 3) difference in handheld spirometry values like forced expiratory volume (FEV1 ≥ 10%). | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prediction model for the treatment response of acute asthma exacerbation | Creating a prediction model for the treatment response of acute asthma exacerbation with phenotypical characteristics | 42 days | 
| Aetiology of the acute asthma exacerbation | Analysing the aetiology of the acute asthma exacerbations | 42 days | 
| Immune system and microbiome | Analysing the blood and local respiratory parameters; the microbiota composition; lipid metabolomics and volatile compounds composition at baseline and acute asthma exacerbation | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Exacerbation, Phenotyping, Classification, Treatment