Project

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Defining phenotypes and risk factors of chronic non-specific cough in children

English title Defining phenotypes and risk factors of chronic non-specific cough in children
Applicant Kühni Claudia
Number 137033
Funding scheme ProDoc
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Respiratory Diseases
Start/End 01.10.2012 - 31.12.2016
Approved amount 229'912.00
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All Disciplines (3)

Discipline
Respiratory Diseases
Methods of Epidemiology and Preventive Medicine
Medical Statistics

Keywords (10)

Childhood; Chronic cough; Prediction; Prognosis; Classification; Phenotypes; Longitudinal studies; Clinical epidemiology; Latent class; Risk factors

Lay Summary (English)

Lead
Lay summary

Background: Cough is common in children and contributes significantly to the burden of disease in childhood, including reduced quality of life and healthcare use. There is evidence that children with recurrent cough belong to more than one disease group (or phenotype), some with life-long consequences leading to chronic obstructive pulmonary disease in adulthood. Yet, epidemiological data on cough in children are scarce.

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 cough and if yes, whether the cough is likely to be transient or will persist  throughout childhood.  

Specific objectives are:  1) to summarise the scientific evidence on the natural history of non-specific cough in childhood in a systematic review; 2) to describe frequency, risk factors and characteristics of non-specific cough in children using original data from ongoing cohort studies. For these analyses we will use data from the Leicester respiratory cohorts, 10350 children followed up since their first years of life and the Bern infant lung development (BILD) cohort (N=450); 3) to define different phenotypes of cough using various statistical approaches taking into account the longitudinal nature of the data, and validate findings in independent cohorts.

Significance of the research: This project will add significantly to the scarce evidence on burden of disease, risk factors, time course and prognosis of chronic non-specific cough in childhood. From a clinical perspective, the identification of markers/parameters specific for certain phenotypes will enable a better identification of those children during clinical routine and provide a rationale for phenotype-specific treatment. From a public health point of view, the findings will help to develop strategies to reduce the burden of cough in childhood.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Comparison of two sweat test systems for the diagnosis of cystic fibrosis in newborns
Rueegg Corina S., Kuehni Claudia E., Gallati Sabina, Jurca Maja, Jung Andreas, Casaulta Carmen, Barben Juerg (2019), Comparison of two sweat test systems for the diagnosis of cystic fibrosis in newborns, in Pediatric Pulmonology, 54(3), 264-272.
Age-related changes in childhood wheezing characteristics: A whole population study
Jurca Maja, Pescatore Anina M., Goutaki Myrofora, Spycher Ben D., Beardsmore Caroline S., Kuehni Claudia E. (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 Jingying, Ramette Alban, Jurca Maja, Goutaki Myrofora, Beardsmore Caroline S., Kuehni Claudia E. (2017), Association between breastfeeding and eczema during childhood and adolescence: A cohort study, in PLOS ONE, 12(9), e0185066-e0185066.
Breastfeeding and respiratory tract infections during the first 2 years of life
Wang Jingying, Ramette Alban, Jurca Maja, Goutaki Myrofora, Beardsmore Caroline S, Kuehni Claudia E (2017), Breastfeeding and respiratory tract infections during the first 2 years of life, in ERJ Open Research, 3(2), 00143-2016.
Prevalence of cough throughout childhood: A cohort study
Jurca Maja, Ramette Alban, Dogaru Cristian M., Goutaki Myrofora, Spycher Ben D., Latzin Philipp, Gaillard Erol A., Kuehni Claudia E. (2017), Prevalence of cough throughout childhood: A cohort study, in PLOS ONE, 12(5), e0177485-e0177485.
Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis.
Goutaki Myrofora, Meier Anna Bettina, Halbeisen Florian S, Lucas Jane S, Dell Sharon D, Maurer Elisabeth, Casaulta Carmen, Jurca Maja, Spycher Ben D, Kuehni Claudia E (2016), Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis., in The European respiratory journal, 48(4), 1081-1095.
Newborn screening for cystic fibrosis - The parent perspective.
Rueegg Corina S, Barben Jürg, Hafen Gaudenz M, Moeller Alexander, Jurca Maja, Fingerhut Ralph, Kuehni Claudia E (2016), Newborn screening for cystic fibrosis - The parent perspective., in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 15(4), 443-51.
Measurement of fecal elastase improves performance of newborn screening for cystic fibrosis.
Barben Juerg, Rueegg Corina S, Jurca Maja, Spalinger Johannes, Kuehni Claudia E (2016), Measurement of fecal elastase improves performance of newborn screening for cystic fibrosis., in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 15(3), 313-7.
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 (2014), Environmental and socioeconomic data do not improve the Predicting Asthma Risk in Children (PARC) tool., in The Journal of allergy and clinical immunology, 135(5), 1395-1397.
Can breastfeeding protect children against respiratory tract infections in the first 2 years of life?
Wang Jingying, Ramette Alban, Jurca Maja, Goutaki Myrofora, Beardsmore Caroline S, Kuehni Claudia E, Can breastfeeding protect children against respiratory tract infections in the first 2 years of life?, in ERJ Open Research.

Collaboration

Group / person Country
Types of collaboration
University Children's Hospital Basel (UKBB), Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
University Children's Hospital Bern, Inselspital, Bern, Switzerland Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Department of Infection, Immunity & Inflammation, University of Leicester Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Forschungstag Inselspital 2018 Talk given at a conference Risk factors and prognosis of chronic cough in children 08.11.2018 Bern, Switzerland Jurca Maja; Kühni Claudia; Latzin Philipp;
Annual conference of the Swiss Society of Paediatrics 2017 Talk given at a conference Newborn Screening for Cystic Fibrosis in Switzerland - Evaluation after 6 Years 01.06.2017 St. Gallen, Switzerland Jurca Maja; Kühni Claudia;
European Cystic Fibrosis Congress 2016 Talk given at a conference Newborn screening for cystic fibrosis in Switzerland – evaluation after 5 years 08.06.2016 Basel, Switzerland Kühni Claudia; Jurca Maja;
European Respiratory Society Annual Congress 2015 Talk given at a conference Risk factors for chronic non-specific cough in infants: A cohort study 30.09.2015 Amsterdam, Netherlands Latzin Philipp; Kühni Claudia; Jurca Maja;
European Respiratory Society Annual Congress 2015 Talk given at a conference Does breastfeeding protect against childhood eczema? 28.09.2015 Amsterdam, Netherlands Kühni Claudia; Jurca Maja;
European Cystic Fibrosis Congress 2015 Talk given at a conference Newborn screening for cystic fibrosis in Switzerland – performance after 4 years 10.06.2015 Brussels, Belgium Jurca Maja; Kühni Claudia;
37. Jahrestagung der GPP 2015 Poster Newborn screening for Cystic Fibrosis in Switzerland – Evaluation after four years 05.03.2015 Basel, Switzerland Jurca Maja; Kühni Claudia;
European Respiratory Society Annual Congress 2014 Poster Characteristics of cough reported by adolescents with different ENT disorders 06.09.2014 Munich, Germany Latzin Philipp; Kühni Claudia; Jurca Maja;
Annual conference of the Swiss Society of Paediatrics 2014 Talk given at a conference Prevalence of cough throughout childhood: a cohort study 12.06.2014 Basel, Switzerland Latzin Philipp; Jurca Maja; Kühni Claudia;
European Respiratory Society Annual Congress 2013 Poster Validity of questions used to assess chronic cough in epidemiological surveys 07.09.2013 Barcelona, Spain Latzin Philipp; Kühni Claudia; Jurca Maja;


Associated projects

Number Title Start Funding scheme
123162 Predicting onset and persistence of wheeze in children 01.06.2009 ProDoc
162820 Phenotypes and prognostic modelling in childhood asthma: moving towards clinical applications 01.10.2015 Project funding (Div. I-III)
144068 Breastfeeding and respiratory outcomes from infancy to school-age: pathways and temporal sequence 01.10.2012 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)
69348 Defining phenotypes and modelling prognosis of preschool wheezing disorders. (PROSPER). 01.01.2003 Ambizione

Abstract

Background: Recurrent cough, colds and upper respiratory symptoms are common in early childhood and associated with a large burden to families, the health service and society. Increasing evidence links childhood respiratory morbidity to chronic obstructive pulmonary disease in adults. The underlying causes of chronic cough are diverse: some children have specific diseases such as cystic fibrosis, others cough in the context of childhood asthma, but many children have non-specific chronic cough of unclear aetiology. Yet, their cough can be severe and track over long periods. In the framework of a previous PhD project, we analysed respiratory morbidity in a cohort of children by applying latent class analysis to phenotypic features. We identified three distinct phenotypes of childhood wheeze, but also two phenotypes of cough: children with transient and children with persisting cough. Physiological traits, risk factors and long-term prognosis differed between the groups. Aims: This PhD project will focus on the descriptive and analytic epidemiology of childhood non-specific chronic cough, using original data from three ongoing population-based cohort studies. Specific aims are: i)To summarise the current evidence on prevalence, risk factors and natural history of non-specific chronic cough in childhood in a systematic review;ii)To describe prevalence, risk factors and physiological traits of chronic non-specific cough;iii)To define different phenotypes of cough by using latent class analysis;iv)To characterise identified phenotypes by describing time course, risk factors, prognosis and physiological traits;v)To validate the findings by replicating the analysis in independent cohorts; vi)To describe the public health impact, particularly on avoidable risk factors.Methods: Study population: This PhD will use datasets from three different population-based childhood cohorts: the Leicester 1990 and 1998 cohorts (N=1650 and 8700), and the Bern infant lung development (BILD) cohort (N=400). All include longitudinal data on respiratory symptoms and environmental exposures from birth to school age/early adulthood, and physiological measurements. These include age-appropriate lung function tests e.g. spirometry, multiple-breath washout, exhaled nitric oxide, skin prick tests, bronchial hyperreactivity, nasal swabs for respiratory viruses and overnight cough recording.Work steps: The PhD student will: (i) Systematically search and review the existing epidemiological literature on chronic non-specific cough; (ii) Analyse original data from the three cohort studies to describe incidence, prevalence, associated factors and prognosis of chronic cough at different ages, distinguishing between children with and without asthma/wheeze; define cough phenotypes by applying latent class analysis to these datasets; characterise identified phenotypes by time-course (age of onset, remission and persistence), clinical features and risk factors; (iii) Validate results using data from independent cohorts (subject to agreement, other European Birth Cohort Studies (GA²LEN; ENRIECO)). Research environment: The student will participate in the PhD training offered by the ISPM Bern and the Swiss School of Public Health (SSPH+). This project is embedded in ongoing research of the Leicester and BILD cohort studies, particularly: phenotype definition in childhood asthma; prognostic modelling; environmental exposures and respiratory health; and the role of respiratory viruses. Significance: This project will add significantly to the scarce evidence on burden of disease, risk factors and prognosis of chronic non-specific cough in childhood. From a clinical perspective, the identification of markers/parameters specific for certain phenotypes will enable a better identification of those children during clinical routine and provide a rationale for phenotype-specific treatment. From a public health point of view, the findings will help to develop strategies to reduce the burden of cough in childhood.
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