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Predicting onset and persistence of wheeze in children

English title Predicting onset and persistence of wheeze in children
Applicant Kühni Claudia
Number 123162
Funding scheme ProDoc
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Paediatrics
Start/End 01.06.2009 - 31.08.2013
Approved amount 200'360.00
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All Disciplines (4)

Discipline
Paediatrics
Medical Statistics
Methods of Epidemiology and Preventive Medicine
Respiratory Diseases

Keywords (15)

infant; childhood; preschool; asthma; wheeze; preschool wheezing disorders; prognosis; classification; phenotypes; longitudinal studies; epidemiology; asthma; children; prediction; epidemiology

Lay Summary (English)

Lead
This project looked at factors that determine, which children develop asthma-like symptoms during early childhhood, and which develop persistent symptoms and continue to suffer from asthma at school-age. The main output was the development of a novel prognostic tool (CARAT Childhood ASsthma Risk Assessement Tool, http://www.leicestercohorts.org/index.php?id=3351), which allows to predict later asthma for preschool children with wheeze or cough.
Lay summary

Background: Wheezing disorders are the most common chronic health problem in childhood and place a large burden on children, their families and society. Wheezing disorders in adults, including asthma and chronic obstructive pulmonary disease (COPD), appear to have their origins in early childhood. In order to prevent these diseases it is important to understand what causes young children to begin wheezing and what causes wheezing to become a problem persisting throughout childhood and into adulthood.

Many previous studies have tried to determine the factors in early life that cause children to wheeze. However, these studies differ in the groups of children studied (children from hospitals and clinics or from the general population), and in the particular early life events and influences considered. Also, few studies have examined whether different types of wheezing have different causes. The Leicester childhood cohorts represent a rich data resource for studying the effects of early life influences on later respiratory health.

Objectives of the planned research: This PhD project from the Swiss School of Public Health (SSPH+), aims to develop models to predict whether or not a child will develop wheeze, and if yes, whether the child will continue to suffer from the disease in later life. Specific objectives are:

  1. To perform a systematic review of the published literature on factors affecting the development and persistence of wheeze and asthma in children.
  2. To find out, using a variety of statistical techniques on original datasets, which factors predict the development and persistence of wheeze in children. A multitude of information from early childhood, including environmental exposures, hereditary factors, and childhood illnesses will be considered as potential predictors. For these analyses we will use data from the Leicester respiratory cohorts, 8700 children followed up since their first years of life. To validate the results, we will compare them with data from other cohort studies.
  3. To translate the findings into simple decision rules, which help doctors predict how a particular child might be affected by wheezing disorders.

Significance of the research: By increasing our understanding of the causes of wheezing disorders this project should help designing ways to prevent and treat these diseases. The project will also provide simple tools for prediction that should be useful for informed counselling of parents and clinical management.

Direct link to Lay Summary Last update: 18.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
"Attacks" or "Whistling": Impact of Questionnaire Wording on Wheeze Prevalence Estimates.
Pescatore Anina M, Spycher Ben D, Beardsmore Caroline S, Kuehni Claudia E (2015), "Attacks" or "Whistling": Impact of Questionnaire Wording on Wheeze Prevalence Estimates., in PloS one, 10(6), 0131618-0131618.
Airway eosinophils in older teenagers with outgrown preschool wheeze: a pilot study.
Marshall Lucy, Beardsmore Caroline S, Pescatore Anina M, Kuehni Claudia E, Gaillard Erol A (2015), Airway eosinophils in older teenagers with outgrown preschool wheeze: a pilot study., in The European respiratory journal, 46(5), 1486-9.
Breastfeeding, lung volumes and alveolar size at school-age.
Dogaru Cristian M, Narayanan Manjith, Spycher Ben D, Pescatore Anina M, Owers-Bradley John, Beardsmore Caroline S, Silverman Michael, Kuehni Claudia E (2015), Breastfeeding, lung volumes and alveolar size at school-age., in BMJ open respiratory research, 2(1), 000081-000081.
Environmental and socioeconomic data do not improve the Predicting Asthma Risk in Children (PARC) tool
Pescatore Anina M., Spycher Ben D., Jurca Maja, Gaillard Erol A., Kuehni Claudia E. (2015), Environmental and socioeconomic data do not improve the Predicting Asthma Risk in Children (PARC) tool, in Journal of Allergy and Clinical Immunology, 135(5), 1395-1397.
A simple asthma prediction tool for preschool children with wheeze or cough
Pescatore Anina, Dogaru Cristian, Duembgen Lutz, Silverman Michael, Gaillard Erol, Spycher Ben, Kuehni Claudia (2014), A simple asthma prediction tool for preschool children with wheeze or cough, in Journal of Allergy and Clinical Immunology, 133(1), 111-118.
Breastfeeding and childhood asthma: systematic review and meta-analysis.
Dogaru Cristian M, Nyffenegger Denise, Pescatore Aniña M, Spycher Ben D, Kuehni Claudia E (2014), Breastfeeding and childhood asthma: systematic review and meta-analysis., in American journal of epidemiology, 179(10), 1153-67.
Dogaru et al. respond to "Does breastfeeding protect against 'asthma'?"
Dogaru Cristian M, Nyffenegger Denise, Pescatore Aniña M, Spycher Ben D, Kuehni Claudia E (2014), Dogaru et al. respond to "Does breastfeeding protect against 'asthma'?", Oxford University Press, -.
Increased prevalence of pre-school wheeze is not explained by time trends in body mass index
Goutaki Myrofora, Pescatore Anina M., Singh Parvinder, Beardsmore Caroline S., Kuehni Claudia E. (2014), Increased prevalence of pre-school wheeze is not explained by time trends in body mass index, in European Respiratory Journal, 44(4), 1078-1082.
Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts
Spycher Ben, Silverman Michael, Pescatore Anina, Beardsmore Caroline, Kuehni Claudia (2013), Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts, in Journal of Allergy and Clinical Immunology, 132(5), 1058-1067.
Viral wheezing is virus-specific – not only host-specific (author’s reply)
Strippoli MPF, Spycher BD, Pescatore AM, Beardsmore CS, Silverman M, Kuehni CE (2012), Viral wheezing is virus-specific – not only host-specific (author’s reply), European Respiratory Society, Sheffield S10 2PX United Kingdom.
Exclusive viral wheeze and allergic wheeze: evidence for discrete phenotypes.
Strippoli M-P F, Spycher B D, Pescatore A M, Beardsmore C S, Silverman M, Kuehni C E (2011), Exclusive viral wheeze and allergic wheeze: evidence for discrete phenotypes., in The European respiratory journal : official journal of the European Society for Clinical Respiratory, 38(2), 472-4.
Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules.
Leonardi Nora A, Spycher Ben D, Strippoli Marie-Pierre F, Frey Urs, Silverman Michael, Kuehni Claudia E (2011), Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules., in The Journal of allergy and clinical immunology, 127(6), 1466-1466.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
European Respiratory Society Annual Congress Poster Predicting later asthma in toddlers: Do environmental exposure data improve a clinical tool? 07.09.2013 Barcelona, Spain Kühni Claudia; Pescatore Anina;
European Respiratory Society Annual Congress Poster How do patterns of wheeze change over the first 14 years of life? 01.09.2012 Vienna, Austria Kühni Claudia; Pescatore Anina;
Kongress der Schweizerischen Gesellschaft für Pädiatrie Talk given at a conference How do patterns of wheeze change over the first 17 years of life? 31.05.2012 Luzern, Switzerland Pescatore Anina; Kühni Claudia;
Swiss Pediatric Respiratory Research Group meeting Talk given at a conference Prediction of School-Age Asthma in Symptomatic Preschoolers 24.11.2011 Basel, Switzerland Kühni Claudia; Pescatore Anina;
European Respiratory Society Annual Congress Poster Robust prediction of later asthma in symptomatic toddlers: a novel approach 24.09.2011 Amsterdam, Netherlands Pescatore Anina; Kühni Claudia;
Gemeinsamer Kongress der Schweizerischen Gesellschaften für Pädiatrie, Kinderchirurgie, Kinder-und Jugend-Psychiatrie und –Psychotherapie Poster Robust prediction of school-age asthma: a novel approach 01.09.2011 Montreux, Switzerland Pescatore Anina; Kühni Claudia;
Swiss Public Health Conference Poster Robust prediction of school-age asthma: a novel approach 25.08.2011 Basel, Switzerland Pescatore Anina; Kühni Claudia;
Swiss Pediatric Respiratory Research Group meeting Talk given at a conference Predicting asthma at school age in symptomatic preschool children 17.11.2010 Burgdorf, Switzerland Pescatore Anina; Kühni Claudia;
European Respiratory Society Annual Congress Talk given at a conference Validating of the Tucson asthma predictive index in an independent cohort 18.09.2010 Barcelona, Spain Kühni Claudia; Leonardi Nora;
Jahresversammlung der Schweizerischen Gesellschaft für Pädiatrie Talk given at a conference Validating of the Tucson asthma predictive index in an independent cohort 17.06.2010 Crans-Montana, Switzerland Kühni Claudia; Leonardi Nora;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Asthma-Risiko für Kinder kann in einem Modell dargestellt werden ShortNews International 2013
Media relations: print media, online media Husten – Neue Methode ermittelt Asthmarisiko SRF German-speaking Switzerland 2013
Media relations: print media, online media Mit einfacher Methode das Risiko für Kinder-Asthma abschätzen Online Medienmitteilungen der Universität Bern German-speaking Switzerland 2013
Media relations: print media, online media Predicting Asthma Risk in Children (PARC) www.leicestercohorts.org International 2013
Media relations: print media, online media Risiko für chronisches Asthma abschätzen der Standard International 2013

Awards

Title Year
Paediatric Respiratory Epidemiology Abstract Grant 2010

Associated projects

Number Title Start Funding scheme
137033 Defining phenotypes and risk factors of chronic non-specific cough in children 01.10.2012 ProDoc
162820 Phenotypes and prognostic modelling in childhood asthma: moving towards clinical applications 01.10.2015 Project funding (Div. I-III)

Abstract

Background: Wheezing disorders are the most common chronic health problem in childhood and place a large burden on children, their families and society. There is evidence that wheezing disorders in adults, including asthma and COPD, have their origins in early childhood. Once established, persistent wheeze in children shows strong tracking throughout adolescence and adulthood, a disease process which is accompanied by a decline in lung function and airway remodelling from the first years of life. Knowledge of the main factors leading to the onset of wheezing disorders and to their persistence is a prerequisite for designing interventions to prevent development of the disease, or modify its course early in life. In spite of numerous original papers and systematic reviews on the predictors of wheeze and asthma, these factors are still poorly understood. Previous studies vary greatly in their populations, predictor and outcome definitions, prediction intervals and methodology. What is lacking is a study that systematically assesses the role of a common set of predictors, at different ages, and for different prediction intervals, in a single cohort. Furthermore previous studies have often not discriminated between predictors of onset and predictors of persistence, have paid little attention to phenotypic heterogeneity, and have rarely used alternative statistical methods such as classification and regression trees (CART) and artificial neural networks (ANNs). The Leicester cohorts with their diversity in age spread and recruitment years provide an excellent dataset for such systematic prediction analyses.Aims: This PhD project will focus on the prediction of onset and persistence of childhood wheezing disorders. Specifically the aims are to i) summarise the current evidence of onset and persistence of wheeze and asthma in a systematic review, ii) to identify the important predictors of onset and persistence of childhood wheezing disorders, and iii) to develop simple prognostic tools for use in clinical practice. Methods: In a first step the PhD candidate will systematically search and review the existing literature on predictors of onset and persistence of wheeze and asthma. She or he will then apply methods of prediction to various datasets differing systematically in children’s age at the time of baseline measurements and at assessment of outcomes. All available information at baseline, including pre- and postnatal environmental exposures, hereditary factors, and symptom history will be considered as potential predictors. For these analyses data will be taken from the two Leicester respiratory cohorts. For validation purposes, data from the infant cohorts from Bern and (subject to agreement by individual primary investigators) from cohort studies united in the European Birth Cohort Studies on Allergies and Asthma (GA²LEN) will be used. The PhD candidate will explore and choose from a variety of statistical techniques (regression modelling, classification and regression trees, and artificial neural networks) based on best predictive performance. Based on the results from these prognostic models, the student will then develop simple prognostic tools (scores or decision trees) for use in clinical practice. Again collaboration with the GA2LEN network will be sought for validation of these tools. The PhD project is embedded in ongoing research activities linked to the Leicester cohort studies, particularly studies related to the phenotypic variability of childhood wheezing disorders. The PhD candidate will work closely together with the rest of the team and integrate findings on phenotypic variability into her or his work on prognostic modelling. Significance: By identifying main determinants of onset and persistence of wheeze this project will ultimately contribute to designing interventions for prevention of wheezing disorders in childhood, and for modification of the clinical course once the disease is established. The project will also provide prognostic tools to be used in clinical practice for informed counselling of parents and clinical management.
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