Phenotyping and Classifying Asthma Exacerbations

Recruiting

• Conditions: Asthma Attack
• Interventions: 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 culture; Procedure: Blood sample

• Registration Number: NCT05304039
• Lead Sponsor: Franciscus Gasthuis

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.

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 multicentre study. 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 Timeline

• Study First Submitted: 2022-03-22
• Study First Submitted QC: 2022-03-22
• Study First Posted: 2022-03-31
• Study Start: 2022-09-28
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-04
• Last Update Posted: 2024-04-05
• Primary Completion: 2025-03
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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

• 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Asthma exacerbation	Corsano watch	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines
Asthma exacerbation	Spirometry	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines
Asthma exacerbation	Questionnaires	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines
Asthma exacerbation	Fractional Exhaled Nitric Oxide (FeNO)	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines
Asthma exacerbation	Nasopharyngeal swabs and nasal lining fluid	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines
Asthma exacerbation	e-Nose	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines
Asthma exacerbation	Sputum culture	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines
Asthma exacerbation	Blood sample	Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Aetiology of the acute asthma exacerbation	42 days	Analysing the aetiology of the acute asthma exacerbations
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
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

Trial Locations

Locations (1)

Franciscus Gasthuis & Vlietland; 🇳🇱 Rotterdam, Netherlands