ExCluSie-F: Phenotyping and Classifying Asthma Exacerbations

Sponsor

Franciscus Gasthuis (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05304039

Collaborator

Erasmus Medical Center (Other), TNO (Other)

200

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma Attack	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

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Asthma exacerbation

Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines

Behavioral: Questionnaires

Questionnaires about asthma control and quality of life

Device: Spirometry

Spirometry monitoring at home

Device: Fractional Exhaled Nitric Oxide (FeNO)

Measuring fractional exhaled nitric oxide at home

Device: Corsano watch

Monitoring vital parameters at home

Device: e-Nose

Breathprint will be performed using e-Nose

Procedure: Nasopharyngeal swabs and nasal lining fluid

Nasopharyngeal swabs and nasal lining fluid will be taken

Device: Sputum induction

If patients produce sputum, the sputum will be analysed

Procedure: Blood sample

Blood sample for standard care and 10 ml extra will be taken

Outcome Measures

Primary Outcome Measures

Relation of phenotypical characteristics with treatment response [7 days]
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%).

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.