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The prospective Basel-Bern infant lung development birth cohort (BILD): early impact of genetic and environmental factors on lung growth and respiratory morbidity

English title The prospective Basel-Bern infant lung development birth cohort (BILD): early impact of genetic and environmental factors on lung growth and respiratory morbidity
Applicant Frey Urs
Number 144280
Funding scheme Project funding (special)
Research institution Abteilung für Pneumologie Medizinische Universitäts-Kinderklinik Inselspital
Institution of higher education University of Basel - BS
Main discipline Paediatrics
Start/End 01.10.2012 - 30.09.2015
Approved amount 615'397.00
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All Disciplines (2)

Discipline
Paediatrics
Environmental Research

Keywords (8)

infants; asthma; environmental air pollution; genetic; lung function; lung development; large nested project; SAPALIDA Cohort on Healthy Aging

Lay Summary (German)

Lead
Lay summary

Die Häufigkeit von Lungenerkrankungen bei Kindern nimmt weiterhin zu. Im Projekt mit dem Titel „Bern and Basel Infant Lung Development“ („BILD Studie“) untersuchen wir die Auswirkungen verschiedener Einflussfaktoren auf die Lungenentwicklung vor und nach der Geburt und den weiteren Verlauf bis zum Schuleintritt.

Die Zunahme von Lungenerkrankungen bei Kindern stellt ein Problem dar. Viele Säuglinge leiden während des 1. Lebensjahres an Husten, pfeifenden Atemgeräuschen oder Atemnot. Diese Zeichen einer Atemwegserkrankung treten meist bei Infekten auf und verschwinden nach dem 3. Lebensjahr, andere Kinder entwickeln ein Asthma. Aus noch ungeklärten Ursachen kommt es bei einem Teil der Kinder zu einer beeinträchtigten Lungenreifung und einer eingeschränkten Lungenfunktion. Es zeigte sich, dass diese über das gesamte weitere Leben bestehen bleiben kann.

Andere Kinder kommen zu früh auf die Welt, durch die Unreife der Lunge kann es zu dauerhaften Lungenproblemen kommen. Der Verlauf ist bei jedem Kind anders: Einige Frühgeborene haben über viele Jahre schwere Atemprobleme, bei anderen heilt die Erkrankung während der ersten Lebensjahre ab. Es ist sehr wenig über die Ursachen dieser gestörten Lungenentwicklung von reif- und frühgeborenen Kindern bekannt. Man nimmt an, dass es bei erblicher Veranlagung und gewissen Umwelteinflüssen während bzw. nach der Schwangerschaft zu einer gestörten Lungenreifung kommen kann.

Über die Auswirkung von Luftverschmutzung auf die Lungenreifung ist bisher wenig bekannt. In unserem Projekt konnten wir u.a. zeigen, dass eine hohe Luftverschmutzung Auswirkungen auf die Lungenfunktion im Säuglingsalter hat. Es ist wahrscheinlich, dass Luftverschmutzung allgemein für die Lungengesundheit der Kinder und Erwachsenen eine grosse Rolle spielt. Das wirkt sich auch auf die zukünftige finanzielle Belastung der Gesundheitssysteme aus.

Die BILD Studie hat zum Ziel, die Ursachen für eine beeinträchtigte Lungenreifung und der Entwicklung von Lungenerkrankungen und Allergien bei Reif- und Frühgeborenen zu erforschen. Hierzu untersuchen wir u.a. den Effekt von Luftverschmutzung und Tabakrauch sowie Variationen der Erbinformation auf die Lungenfunktion direkt nach Geburt sowie auf Atemwegserkrankungen mit Husten und pfeifender Atmung im 1. Lebensjahr. Des weiteren untersuchen wir den Verlauf von Lungenfunktion und Atemwegssymptomen bis zum Schuleintritt.

Wenn man die zugrundeliegenden Mechanismen besser versteht, kann man möglicherweise die Kinder früher erkennen, welche aufgrund der beeinträchtigten Lungenentwicklung gefährdet sind, eine Lungenerkrankung zu entwickeln. Aufgrund der Ergebnisse dieses Projektes hoffen wir, vorbeugende Maßnahmen und neue Therapieansätze entwickeln zu können.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Accuracy of Tidal Breathing Measurement of Floright Compared to an Ultrasonic Flowmeter in Infants
Petrus Nicole C. M., Thamrin Cindy, Fuchs Oliver, Frey Urs (2015), Accuracy of Tidal Breathing Measurement of Floright Compared to an Ultrasonic Flowmeter in Infants, in PEDIATRIC PULMONOLOGY, 50(4), 380-388.
Dynamics of the nasal microbiota in infancy: A prospective cohort study
Mika Moana, Mack Ines, Korten Insa, Qi Weihong, Aebi Suzanne, Frey Urs, Latzin Philipp, Hilty Markus (2015), Dynamics of the nasal microbiota in infancy: A prospective cohort study, in JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 135(4), 905-905.
HUMAN RHINOVIRUS TYPES AND ASSOCIATION WITH RESPIRATORY SYMPTOMS DURING THE FIRST YEAR OF LIFE
Mueller Loretta, Mack Ines, Tapparel Caroline, Kaiser Laurent, Alves Marco P., Kieninger Elisabeth, Frey Urs, Regamey Nicolas, Latzin Philipp (2015), HUMAN RHINOVIRUS TYPES AND ASSOCIATION WITH RESPIRATORY SYMPTOMS DURING THE FIRST YEAR OF LIFE, in PEDIATRIC INFECTIOUS DISEASE JOURNAL, 34(8), 907-909.
Validation of multiple-breath washout equipment for infants and young children
Schmidt Anne, Yammine Sophie, Proietti Elena, Frey Urs, Latzin Philipp, Riedel Thomas, Singer Florian (2015), Validation of multiple-breath washout equipment for infants and young children, in PEDIATRIC PULMONOLOGY, 50(6), 607-614.
Abnormal Small Airways Function in Children With Mild Asthma
Singer Florian, Abbas Chiara, Yammine Sophie, Casaulta Carmen, Frey Urs, Latzin Philipp (2014), Abnormal Small Airways Function in Children With Mild Asthma, in CHEST, 145(3), 492-499.
Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?
Proietti Elena, Riedel Thomas, Fuchs Oliver, Pramana Isabelle, Singer Florian, Schmidt Anne, Kuehni Claudia, Latzin Philipp, Frey Urs (2014), Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?, in EUROPEAN RESPIRATORY JOURNAL, 43(6), 1642-1651.
Lung clearance index: should we really go back to nitrogen washout?
Schulzke Sven M., Frey Urs (2014), Lung clearance index: should we really go back to nitrogen washout?, in EUROPEAN RESPIRATORY JOURNAL, 43(2), 656-657.
Ventilatory Response to Nitrogen Multiple-Breath Washout in Infants
Singer Florian, Yammine Sophie, Schmidt Anne, Proietti Elena, Kieninger Elisabeth, Barben Juerg, Casaulta Carmen, Regamey Nicolas, Gustafsson Per, Frey Urs, Latzin Philipp (2014), Ventilatory Response to Nitrogen Multiple-Breath Washout in Infants, in PEDIATRIC PULMONOLOGY, 49(4), 342-347.
Volumetric Capnography in Infants with Bronchopulmonary Dysplasia
Fouzas Sotirios, Haecki Christoph, Latzin Philipp, Proietti Elena, Schulzke Sven, Frey Urs, Delgado-Eckert Edgar (2014), Volumetric Capnography in Infants with Bronchopulmonary Dysplasia, in JOURNAL OF PEDIATRICS, 164(2), 283-283.
A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease
Singer Florian, Stern Georgette, Thamrin Cindy, Thamrin Cindy, Abbas Chiara, Casaulta Carmen, Frey Urs, Frey Urs, Latzin Philipp (2013), A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease, in European Respiratory Journal, 41(2), 339-345.
A Prospective Study of the Impact of Air Pollution on Respiratory Symptoms and Infections in Infants
Stern Georgette, Latzin Philipp, Roeoesli Martin, Fuchs Oliver, Proietti Elena, Kuehni Claudia, Frey Urs (2013), A Prospective Study of the Impact of Air Pollution on Respiratory Symptoms and Infections in Infants, in AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 187(12), 1341-1348.
A prospective study of the impact of air pollution on respiratory symptoms and infections in infants
Stern Georgette, Stern Georgette, Latzin Philipp, Röösli Martin, Fuchs Oliver, Fuchs Oliver, Proietti Elena, Proietti Elena, Kuehni Claudia, Frey Urs (2013), A prospective study of the impact of air pollution on respiratory symptoms and infections in infants, in American Journal of Respiratory and Critical Care Medicine, 187(12), 1341-1348.
Air pollution during pregnancy and neonatal outcome: A review
Proietti Elena, Proietti Elena, Röösli Martin, Röösli Martin, Frey Urs, Latzin Philipp (2013), Air pollution during pregnancy and neonatal outcome: A review, in Journal of Aerosol Medicine and Pulmonary Drug Delivery, 26(1), 9-23.
Consensus statement on inert gas washout measurement: at the threshold of clinical use
Schulzke Sven M., Frey Urs (2013), Consensus statement on inert gas washout measurement: at the threshold of clinical use, in European Respiratory Journal, 41(3), 500-502.
Normal lung function in infants with cystic fibrosis shortly after birth
Kieninger Elisabeth, Yammine Sophie, Proietti Elena, Casaulta Carmen, Regamey Nicolas, Frey Urs, Latzin Philipp (2013), Normal lung function in infants with cystic fibrosis shortly after birth, in EUROPEAN RESPIRATORY JOURNAL, 42(2), 2-3.
Pregnancy and birth cohort resources in Europe: A large opportunity for aetiological child health research
Larsen Pernille Stemann, Kamper-Jørgensen Mads, Adamson Ashley, Barros Henrique, Bonde Jens Peter, Brescianini Sonia, Brophy Sinead, Casas Maribel, Casas Maribel, Casas Maribel, Devereux Graham, Eggesbø Merete, Fantini Maria Pia, Frey Urs, Frey Urs, Gehring Ulrike, Grazuleviciene Regina, Henriksen Tine Brink, Hertz-Picciotto Irva, Heude Barbara, Hryhorczuk Daniel O., Inskip Hazel, Jaddoe Vincent W V, Lawlor Debbie A., Ludvigsson Johnny (2013), Pregnancy and birth cohort resources in Europe: A large opportunity for aetiological child health research, in Paediatric and Perinatal Epidemiology, 27(4), 393-414.
Rhinovirus infections in infancy and early childhood
Kieninger Elisabeth, Fuchs Oliver, Fuchs Oliver, Latzin Philipp, Frey Urs, Regamey Nicolas (2013), Rhinovirus infections in infancy and early childhood, in European Respiratory Journal, 41(2), 443-452.
Cohort profile: The Bern Infant Lung Development cohort
Fuchs Oliver, Fuchs Oliver, Latzin Philipp, Latzin Philipp, Kuehni Claudia E., Frey Urs, Frey Urs (2012), Cohort profile: The Bern Infant Lung Development cohort, in International Journal of Epidemiology, 41(2), 366-376.
Comparison of online single-breath vs. online multiple-breath exhaled nitric oxide in school-age children
Fuchs Oliver, Latzin Philipp, Singer Florian, Petrus Nicole, Proietti Elena, Kieninger Elisabeth, Casaulta Carmen, Frey Urs (2012), Comparison of online single-breath vs. online multiple-breath exhaled nitric oxide in school-age children, in Pediatric Research, 71(5), 605-611.
Practicability of nitrogen multiple-breath washout measurements in a pediatric cystic fibrosis outpatient setting
Singer Florian, Kieninger Elisabeth, Abbas Chiara, Yammine Sophie, Fuchs Oliver, Fuchs Oliver, Proietti Elena, Proietti Elena, Regamey Nicolas, Casaulta Carmen, Frey Urs, Latzin Philipp (2012), Practicability of nitrogen multiple-breath washout measurements in a pediatric cystic fibrosis outpatient setting, in Pediatric Pulmonology, 48(8), 739-746.

Collaboration

Group / person Country
Types of collaboration
Dept. of Immunology, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dept. of Infectiology, University of Geneva Switzerland (Europe)
- Research Infrastructure
Dept. of Paediatrics, University Hospital of Munich Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
ENRIECO Environmental Health Risks in European Birth Cohort Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dept. of Social and Preventative Medicine, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dept. of Molecular Genetics, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dept. of Social and Preventative Medicine, University of Bern Switzerland (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
European Respiratory Society conference Talk given at a conference Longitudinal lung volume data in preterm children from infancy to early childhood. 30.09.2015 Amsterdam, Netherlands Schmidt Anne;
European Respiratory Society conference Poster YKL-40 levels in cord blood – Associations with respiratory symptoms and asthma in children? 29.09.2015 Amsterdam, Netherlands Usemann Jakob;
European Respiratory Society conference Talk given at a conference Symptomatic rhinovirus infections are associated with a lower diversity of the nasopharyngeal microbiota in infants. 28.09.2015 Amsterdam, Netherlands Korten Insa;
European Respiratory Society Conference Talk given at a conference Press Conference 27.09.2015 Amsterdam, Netherlands Korten Insa;
European Respiratory Society Talk given at a conference Paediatric severe asthma: not little adults 10.09.2014 Barcelona, Spain Frey Urs;
European Respiratory Society Conference Poster Validation of multiple-breath washout equipment for infants and preschool children 10.09.2014 Barcelona, Spain Schmidt Anne;
European Respiratory Society Conference Talk given at a conference Physiological lung growth between infancy and early childhood – Impact of gender, body growth, and tobacco smoke exposure 07.09.2014 Münich, Germany Schmidt Anne;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Symptomatic rhinovirus infections are associated with a lower diversity of nasopharyngeal microbiot European Respiratory Society press release International 2015

Awards

Title Year
Paediatric Research Award Awarded to Florian Singer, whose work with BILD data enabled his research. This award was used to further his research. 2015
“Lung growth in healthy children from infancy to early childhood – longitudinal data from a Swiss birth cohort study (BILD Study)” Im Rahmen der Jahrestagung der Schweizerischen Gesellschaft für Pneumoloie (SGP) wird alljährlich ein Award für den besten Abstract in der Pädiatrie verliehen. 2014

Associated projects

Number Title Start Funding scheme
68025 Early Environmental and Maternal Determinants of Airway Inflammation in Wheezing Disorders in Infants 01.01.2003 Project funding (Div. I-III)
174655 NEWS - Newborn Early Warning Signs 01.06.2017 International short research visits
153158 Swiss Pediatric Sepsis Study - a national prospective cohort study to assess epidemiology, novel immunodeficiencies and the impact of genetic variation on susceptibility to sepsis in children 01.07.2014 Project funding (special)
148470 SAPALDIA Cohort on Healthy Aging 01.04.2014 Cohort Studies Large
124654 Impact of early environmental and genetic determinants on lung development from infancy to preschool age 01.09.2009 Project funding (special)
124654 Impact of early environmental and genetic determinants on lung development from infancy to preschool age 01.09.2009 Project funding (special)
51974 Alterations in Airway Wall Properties as a Possible Mechanism forWheezing Disorders in Infants. (SCORE B) 01.04.1998 Ambizione
146679 Pathophysiology and clinical implications of respiratory virus infections in early cystic fibrosis lung disease 01.05.2013 Project funding (special)
112099 The impact of early environmental and maternal factors on airway development in and wheezing disorders up to preschool age 01.06.2006 Project funding (Div. I-III)
163311 Integrating the impact of genetic and environmental factors on trajectories of respiratory disease from birth to school age 01.10.2015 Project funding (Div. I-III)

Abstract

Background: This is a direct continuation of the ongoing prospective birth cohort BILD (SNF 124564), which investigated the impact of environmental factors on lung growth and development and subsequent consequences for later respiratory morbidity in early childhood. Since the cohort itself is extremely data-rich, the general aims have not been changed for the current project phase, but are instead more focused. The recruitment areas have also been extended from a single study centre (Bern) to a two-centre cohort (Bern and Basel), with identical equipment and standard operating procedures. The motivation for the study is the fact that the high prevalence of wheezing disorders and asthma in infants and preschool children has become a major health issue. Wheezing disorders can occur as a result of simple viral infections and are mostly episodic and transient in nature. However, they may occur recurrently and be an expression of disturbed fetal growth or lung development, or the consequence of early allergic bronchial asthma. While genetic risk factors such as parental atopy (allergy) play an important role, environmental factors such as tobacco exposure, Western lifestyle or air pollution are also known risk factors for wheezing disorders in children. The hypothesis - that different mechanisms may be responsible for the impairment of lung growth to those for the impairment of the immune, allergic or inflammatory system - has been recently reinforced by several longitudinal studies. These show that this loss of lung function tracks throughout life, and impaired lung function at a young age is related to chronic respiratory morbidity in old age. Evidence that air pollution impairs lung growth has recently been demonstrated in school children, but until now there has been no evidence regarding how air pollution affects lung function in infants and preschoolers. In project phase 124654, we improved our pre- and postnatal exposure modelling to air pollution of all infants using a spatial land use regression model combined with the assessment of temporal variations of pollutant exposure during pregnancy and early infancy. We have shown for the first time that prenatal exposure to particulate matter air pollution affects lung function after birth in a particularly significant manner, suggesting a specific vulnerability of fetuses and infants to pollutants. Furthermore, we found elevated levels of pro-inflammatory cytokines in cord blood of exposed infants and environmental effects on components of innate immunity. Aims: Now we are continuing to investigate whether air pollution during pregnancy and early infancy is correlated with functional lung growth and subsequent asthma in preschool age. We are especially interested in whether there is a genetic susceptibility of certain infants and whether particularly vulnerable phases during lung development can be identified based on the current exposure model. Methods: In this prospective birth cohort of unselected healthy term infants and preterm infants we: estimate indoor and outdoor air pollution exposure during pregnancy and in early infancy; assess family, obstetric and birth history; measure immunological factors and known target genes in cord blood (known polymorphism in target genes of lung growth and asthma); assess weekly respiratory symptoms by telephone interview; and determine viral samples in the first lower respiratory tract infection in the first year of life. We then follow these children to school age where we again determine lung functional measures (primary outcomes) as well as standardised respiratory outcomes and immunological factors related to asthma and allergy (secondary outcomes). Significance: The consequence of today’s air pollution on fetal lung development has an unknown, but potentially very relevant, impact on global respiratory health in the future, with unpredictable costs. If genetic and physiological mechanisms that lead to impaired lung growth at this early vulnerable phase of lung development are better understood, we will be better able to identify infants at risk and to develop environmental, preventative, and therapeutic strategies for infants and children.
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