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Phenotypes and prognostic modelling in childhood asthma: moving towards clinical applications

English title Phenotypes and prognostic modelling in childhood asthma: moving towards clinical applications
Applicant Kühni Claudia
Number 162820
Funding scheme Project funding (Div. I-III)
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Respiratory Diseases
Start/End 01.10.2015 - 30.09.2018
Approved amount 556'733.00
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All Disciplines (2)

Discipline
Respiratory Diseases
Paediatrics

Keywords (7)

wheeze; childhood; prediction tool; cough; prognostic modelling; asthma; phenotype

Lay Summary (German)

Lead
Asthma ist das häufigste chronische Krankheit bei Kindern. Sein Verlauf ist variabel, mit milden Formen, aber auch schweren Verläufen. Diese Studie entwickelt prognostische Modelle, die helfen, einen chronischen Verlauf vorauszusagen. Voraussagemodelle aus Geburtskohorten werden im klinischen Alltag getestet und weiterentwickelt.
Lay summary

Hintergrund: Asthma bei Kindern hat einen variablen zeitlichen Verlauf, mit milden selbstlimitierenden Formen, und chronischen Verläufen. Auch das klinische Bild variiert. Verschiedene statistische Methoden ermöglichen, Kinder mit unterschiedlichen Verläufen frühzeitig zu unterscheiden. Die bestehenden Modelle haben jedoch eine beschränkte Aussagekraft. Ausserdem lässt sich Forschung aus Geburtskohorten– bestehend aus gesunden Kindern –nur bedingt auf den klinischen Alltag übertragen. Bisher fehlt in der Schweiz einen repräsentative klinische Asthma-Kohortenstudie für Kinder.

Ziele dieser Studie:

1.Entwicklung statistischer Modelle, zur Unterscheidung verschiedener Asthma- Phänotypen.

2.Entwicklung prognostischer Modelle, zur Voraussage der Langzeit- Prognose.

3. Anwendung und Weiterentwicklung dieser Modelle für den klinischen Alltag. 

Methodik: Dieses Projekt benutzt vorhandene Daten aus Geburtskohorten: den Leicester Kohortenstudien (10‘350 Kinder), der ALSPAC –Kohorte aus Bristol (3’000) und der Schweizer BILD Kohorte (>800). Zusätzlich wird eine neue klinische Kohortenstudie aufgebaut aus Kindern, welche zur Abklärung von Asthma Symptomen oder chronischem Husten an Polikliniken von Schweizer Kinderspitälern kommen: die Schweizerische Pädiatrische Asthmakohorte (Swiss Paediatric Asthma Cohort, SPAC). Resultate klinischer Routineuntersuchungen werden in einer Datenbank erfasst und der Langzeitverlauf durch jährliche Fragebogen an die Eltern.

Analyse: Wir werden in bestehende statistische Modelle weiterentwickeln. Insbesondere soll die Voraussagekraft der Modelle verbessert, die Anwendung auf Kinder unterschiedlicher Altersgruppen erweitert und für den klinischen Gebrauch angepasst werden.

Bedeutung: Voraussage des klinischen Verlaufs einer Asthmaerkrankung erlaubt den Ärzten, die Behandlung an den Schwergrad und das künftige Risiko anzupassen. Eltern können unnötige Ängste erspart sowie frühzeitig präventive Massnahmen und vorbeugende Therapie angeboten werden.
Direct link to Lay Summary Last update: 16.10.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Longitudinal Associations between Respiratory Infections and Asthma in Young Children
Ramette Alban, Spycher Ben D, Wang Jingying, Goutaki Myrofora, Beardsmore Caroline S, Kuehni Claudia E (2018), Longitudinal Associations between Respiratory Infections and Asthma in Young Children, in American Journal of Epidemiology, 187(8), kwy053.
Temporal stability of multitrigger and episodic viral wheeze in early childhood
Spycher Ben D., Cochrane C, Granell R, Sterne JAC, Silverman M, Pedersen E, Gaillard EA, Henderson J, Kuehni CE (2017), Temporal stability of multitrigger and episodic viral wheeze in early childhood, in European Respiratory Journal, 50(5), 1700014.
Age-related changes in childhood wheezing characteristics: A whole population study.
Jurca M, Pescatore AM, Goutaki M, Spycher BD, Beardsmore CS, Kuehni CE (2017), Age-related changes in childhood wheezing characteristics: A whole population study., in Pediatric Pulmonology, 52(10), 1250-1259.
Association between breastfeeding and eczema during childhood and adolescence: A cohort study.
Wang J, Ramette A, Jurca M, Goutaki M, Beardsmore CS, Kuehni CE (2017), Association between breastfeeding and eczema during childhood and adolescence: A cohort study., in Plos ONE, 12(9), 0185066.
Breastfeeding and respiratory tract infections during the first 2 years of life.
Wang J, Ramette A, Jurca M, Goutaki M, Beardsmore CS, Kuehni CE (2017), Breastfeeding and respiratory tract infections during the first 2 years of life., in ERJ Open Res, 3(2), 00143-2016.
Prevalence of cough throughout childhood: A cohort study.
Jurca M, Ramette A, Dogaru CM, Goutaki M, Spycher BD, Latzin P, Gaillard EA, Kuehni CE (2017), Prevalence of cough throughout childhood: A cohort study., in Plos ONE, 12(5), 0177485.
Asthma phenotypes in childhood: conceptual thoughts on stability and transition.
Spycher BD, Kuehni CE (2016), Asthma phenotypes in childhood: conceptual thoughts on stability and transition., in Eur Respir J., 47(2), 362-365.

Collaboration

Group / person Country
Types of collaboration
University Children's Hospital, Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Avon Longitudinal Study of Parents and Children (ALSPAC) - University of Bristol Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Basel-Bern Infant Lung Development (BILD) study/University Children’s Hospital, Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Department of Infection, Immunity and Inflammation (Child Health), University of Leicester Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Children's Hospital of Eastern Switzerland, St.Gallen Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University Children's Clinic, Inselspital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University Children's Hospital, Basel (UKBB) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
European Respiratory Symposium Poster The simple 10-item PARC tool to predict childhood asthma- an external validation 18.09.2018 Paris, France Pedersen Eva Sophie Lunde; Halbeisen Florian; Kühni Claudia; Ramette Alban; Goutaki Myrofora; de Jong Carmen;
European Respiratory Symposium Poster Do clinical investigations predict long-term outcome? A follow-up of paediatric respiratory outpatients 16.09.2018 Paris, France Pedersen Eva Sophie Lunde; Goutaki Myrofora; Kühni Claudia; de Jong Carmen;
European Respiratory Symposium Poster Snoring in schoolchildren: prevalence and risk factors 16.09.2018 Paris, France Ardura Garcia Cristina; Kühni Claudia; Latzin Philipp; Goutaki Myrofora; Mozun Rebeca;
Jahreskongress der Schweizerischen Gesellschaft für Pädiatrie Talk given at a conference Snoring in Swiss schoolchildren: prevalence and risk factors 24.05.2018 Lausanne, Switzerland Latzin Philipp; Kühni Claudia; Mozun Rebeca; Ardura Garcia Cristina; Goutaki Myrofora;
Jahreskongress der Schweizerischen Gesellschaft für Pädiatrie Talk given at a conference Do clinical investigations predict long-term outcome? A follow-up of paediatric respiratory outpatients 24.05.2018 Lausanne, Switzerland Kühni Claudia; Pedersen Eva Sophie Lunde; de Jong Carmen; Goutaki Myrofora;
Jahreskongress der Schweizerischen Gesellschaft für Pädiatrie Talk given at a conference The simple 10-item PARC tool to predict childhood asthma- an external validation 24.05.2018 Lausanne, Switzerland Halbeisen Florian; de Jong Carmen; Pedersen Eva Sophie Lunde; Kühni Claudia; Ramette Alban; Goutaki Myrofora;
European Respiratory Symposium Poster The Swiss Paediatric Airway Cohort – embedding research in clinical routine. 09.09.2017 Milano, Italy Latzin Philipp; Kühni Claudia; de Jong Carmen; Goutaki Myrofora; Pedersen Eva Sophie Lunde;
Jahreskongress der Schweizerischen Gesellschaft für Pädiatrie Talk given at a conference The Swiss Paediatric Airway Cohort – embedding research in clinical routine. 02.06.2017 St. Gallen, Switzerland Pedersen Eva Sophie Lunde; Goutaki Myrofora; de Jong Carmen; Kühni Claudia; Latzin Philipp;
Allergology and Immunology Update Individual talk Predicting Childhood Asthma using a Swiss clinical cohort 21.01.2017 Grindelwald, Switzerland Pedersen Eva Sophie Lunde;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Science Flash Talk, Geneva Health Forum Talk 10.04.2018 Geneva, Switzerland de Jong Carmen;


Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) spac-study.ch German-speaking Switzerland International 2018
Talks/events/exhibitions 8x8 Junge Forschende erzählen, Mittelbauvereinigung der Universität Bern German-speaking Switzerland 2017

Awards

Title Year
Prize for best presentation 2018 on the SwissPedNet Translational & Clinical Research Session 2018
Swiss PedNet Travel Award 2017
Best Abstract 2016 TOPIC 8 Pneumology and Thoracic Surgery of the Swiss Society of Pneumology. 2016

Associated projects

Number Title Start Funding scheme
69349 Defining phenotypes and modelling prognosis of preschool wheezing disorders. (zu PROSPER). 01.01.2003 Project funding (Div. I-III)
182628 Phenotypes and prognostic modelling in childhood asthma: moving towards clinical applications (Phase II) 01.10.2018 Project funding (Div. I-III)
122341 Breastfeeding and the risk of childhood asthma: a population-based study 01.05.2009 Project funding (Div. I-III)
182719 Multiple Breath Washout in Children with Cystic Fibrosis: Transition from a Specialised Tool to Clinical Implementation 01.01.2019 Project funding (Div. I-III)
137033 Defining phenotypes and risk factors of chronic non-specific cough in children 01.10.2012 ProDoc
144068 Breastfeeding and respiratory outcomes from infancy to school-age: pathways and temporal sequence 01.10.2012 Project funding (Div. I-III)
69348 Defining phenotypes and modelling prognosis of preschool wheezing disorders. (PROSPER). 01.01.2003 Ambizione
144068 Breastfeeding and respiratory outcomes from infancy to school-age: pathways and temporal sequence 01.10.2012 Project funding (Div. I-III)
46481 Long-term outcome of girls and boys with different respiratory symptom patterns. 01.09.1996 Fellowships for advanced researchers
173044 Natural history, phenotypes and disease classification in primary ciliary dyskinesia 01.05.2017 Project funding (Div. I-III)
123162 Predicting onset and persistence of wheeze in children 01.06.2009 ProDoc

Abstract

This proposal builds on previous work by the research team on phenotypes and prognostic modelling in childhood asthma. As a novel element, it shifts the previous focus on the general population to the real-world patient population in need of such tools. Background: Wheezing disorders and chronic cough are the most common chronic health problem in childhood. Defining clinical phenotypes and identifying children with high risk of persisting disease remain two of the major challenges in paediatric respiratory medicine. Efforts to identify phenotypes by applying clustering techniques to data from cohort studies are beginning to show a clearer picture of phenotypic variation, but many uncertainties remain. In particular, it is unclear to what extent changes in clinical presentation over time represent the natural course of certain phenotypes or rather phenotype switching. Several asthma prediction tools for childhood asthma have been proposed. Most have focused on a narrow age-range, have not been developed for the clinical population and show moderate predictive performance. We recently developed a simple and non-invasive 10-item tool to Predict Asthma Risk in pre-school Children with wheeze or chronic cough (PARC) for application in 1-3 year old children in primary care. Objectives: The aims of the planned project are to: 1.Progress in phenotype definition of childhood wheeze and cough with a special focus on defining age specific phenotypes (1-3, 4-6, 7-14 years) and the transition between them as children grow older, 2.Develop prediction tools for childhood asthma in clinical care for the age range 1-14 years and begin evaluating their clinical utility 3.Validate findings in external cohortsMethods: We will analyse existing data from population-based cohorts (the Leicester Respiratory Cohorts (LRC; in 1990, N=1,650 and in 1998, N=8,700); the Bern-Basel Infant Lung Development (BILD) cohort (N=837) and the Avon Longitudinal Study on Parents and Children [ALSPAC], N=7,000). In addition, we will set up a new clinical cohort of children seen for wheeze or chronic cough in tertiary care settings in Switzerland (Swiss Paediatric Asthma Cohort, SPAC). Phenotypes and transition patterns between phenotypes will be identified using latent class analysis (SPAC) and latent transition analyses (LRC) and symptoms and physiological measurements at different ages. Using penalized logistic regression we will extend the PARC tool to older age groups, and include repeated symptom assessments and physiological measurements should these be selected as predictors (LRC). For preliminary assessment its clinical utility, risk scores developed prediction tool will be compared to physicians assessments.Output and significance: Ability to predict children at risk for chronic asthma would be of great benefit: for physicians, to adapt management to the most likely clinical course; for parents, to alleviate unfounded concerns and motivate lifestyle changes when indicated; for researchers to recruit high-risk children for intervention studies and gain new insights about mechanisms for disease progression. Using appropriate populations and state-of-the-art methodology, this project will significantly add to the understanding of phenotypic variability in asthma and chronic cough, and to the development and implementation of clinical prediction tools.
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