Systems Pharmacology Approach to Uncontrolled Pediatric Asthma

Study Overview
=================
Brief Summary
-----------------
Background: Asthma is a heterogeneous respiratory disease and the most common chronic disease in children. A small subset of children has continuous poor asthma control despite appropriate adherence to asthma medication. There is a clinical need to identify these children as early as possible to optimize treatment and/or to find therapeutic alternatives. Therefore, the Systems Pharmacology approach to uncontrolled Pediatric Asthma (SysPharmPediA) study was set up. Objective: To establish a cohort of pediatric moderate-to-severe uncontrolled and controlled patients with asthma in order to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. Methods: In this multicenter observational case-control study, moderate-to-severe asthmatic children (n=145, age 6-17 years), were included in specialized hospitals in four European countries (Netherlands, Germany, Spain and Slovenia). Recruited subjects were selected based on good asthma control (controlled asthmatics, n=54) or poor asthma control / recurrent exacerbations (uncontrolled asthmatics, n=91). Comprehensive details concerning demographics, current and past patient/family history and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics and metabolomics will be evaluated from multiple collected, relatively non-invasive, samples of from the recruited individuals, such as: blood, feces, saliva, nasal swabs and exhaled breath. Follow-up visits were performed 6 and 12 months after inclusion.

Official Title
-----------------
Systems Pharmacology Approach to Uncontrolled Pediatric Asthma (SysPharmPediA)

Conditions
-----------------
Pediatric Asthma, Uncontrolled Asthma

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: General: Between 6-17 years of age Doctor diagnosis of asthma In addition to the general criteria, a case with uncontrolled asthma (case group A) should meet: Asthma treatment Global INitiative of Asthma (GINA) step 3 or higher ≥ 1of the following criteria (based on the guideline 'Childhood Asthma' of the section paediatric pulmonology of the Dutch Society of Paediatricians, 2007): Frequent exacerbations requiring OCS use (≥1 in the past year) and/or Severe exacerbations requiring hospitalization or ER visits in the past year and/or ACQ/ACT scores indicating uncontrolled asthma In addition to the general criteria, a case with an acute exacerbation (case group B) should meet: Asthma treatment Global INitiative of Asthma (GINA) step 2 or higher Current severe asthma exacerbation requiring hospitalization In addition to the general inclusion criteria, a control (controlled asthma) should meet the following criteria: Asthma treatment Global INitiative of Asthma (GINA) step 3 or higher Lack of severe exacerbations requiring OCS use or hospitalizations or ER visits in the past year ACQ/ACT scores indicating well controlled asthma or few reported asthma symptoms during asthma checks in the past year. Exclusion Criteria: Recent use of a course of antibiotics (< 1 month). This will affect the microbiome analyses. A patient can be re-screened 1 month after the use of the antibiotic treatment has finished.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| controlled asthmatics<br>moderate-to-severe asthmatic children with good asthma control | |
| uncontrolled asthmatics<br>moderate-to-severe asthmatic children with poor asthma control / recurrent exacerbations | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Saliva and stool microbiome | Differences in 16S rRNA microbial α- and ß- diversities between cases and controls | Baseline | 
| Exhaled breath metabolome | Differences in presence and levels of volatile organic compounds between cases and controls | Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Systems Pharmacology, Omics