Pediatric Asthma, Uncontrolled Asthma
Conditions
Keywords
Systems Pharmacology, Omics
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.
Interventions
None listed
Sponsors
University of Maribor, Maribor, Slovenia.
University Children's Hospital, University of Regensburg, Regensburg, Germany
Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
University of the Basque Country (UPV/EHU)
Hospital Universitario Donostia, San Sebastián, Spain.
Instituto de Salud Carlos III
Utrecht University, Utrecht, the Netherlands.
Karolinska Institutet
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled breath metabolome | Baseline | Differences in presence and levels of volatile organic compounds between cases and controls |
| Saliva and stool microbiome | Baseline | Differences in 16S rRNA microbial α- and ß- diversities between cases and controls |
Other
| Measure | Time frame | Description |
|---|---|---|
| BMI | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | kg/m2 |
| Uncontrolled asthma | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | according to the Asthma Control Test (ACT) questionnaire (\<19 score) and frequent exacerbation within the past 12 months (\>n of exacerbation in the past 12 months |
| Exacerbations | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | Exacerbation requiring OCS use, hospitalization or ER visit |
| Spirometry | Baseline | FEV1 (L, percent predicted value) |
| Age | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | Age in years |
| Atopy | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | Questionnaire on history of allergic diseases |
| Current asthma medication intake | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | ICS: inhaled corticosteroids, LTRA: leukotriene antagonist, SABA: short-acting beta agonist, LABA: long-acting beta agonist, OCS: oral corticosteroids, Omalizumab, Mepolizumab |
| Asthma severity | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | Asthma Control Test (ACT) |
| Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | Questionnaire including 23 questions in 3 domains (symptoms, activity limitation, emotional function) and a 7-point scale (7 = not bothered at all; 1 = extremely bothered) |
| Sex | Baseline (+ follow-up at 6 and 12 months after baseline inclusion) | Female/Male |
Countries
Germany, Netherlands, Slovenia, Spain, Sweden
Outcome results
None listed