Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study

Steve Turner, Adnan Custovic, Peter Ghazal, Jonathan Grigg, Mindy Gore, John Henderson, Clare M. Lloyd, Ben Marsland, Ultan F. Power, Graham Roberts, Sejal Saglani, Jürgen Schwarze, Michael Shields, Andrew Bush

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Abstract

Background. Childhood asthma is a common complex condition whose aetiology is thought to involve gene-environment interactions in early life occurring at the airway epithelium, associated with immune dysmaturation. It is not clear if abnormal airway epithelium cell (AEC) and cellular immune system functions associated with asthma are primary or secondary. To explore this, we will (i) recruit a birth cohort and observe the evolution of respiratory symptoms; (ii) recruit children with and without asthma symptoms; and (iii) use existing data from children in established STELAR birth cohorts. Novel pathways identified in the birth cohort will be sought in the children with established disease. Our over-arching hypothesis is that epithelium function is abnormal at birth in babies who subsequently develop asthma and progression is driven by abnormal interactions between the epithelium, genetic factors, the developing immune system, and the microbiome in the first years of life.

Methods. One thousand babies will be recruited and nasal AEC collected at 5-10 days after birth for culture. Transcriptomes in AEC and blood leukocytes and the upper airway microbiome will be determined in babies and again at one and three years of age. In a subset of 100 individuals, AEC transcriptomes and microbiomes will also be assessed at three and six months. Individuals will be assigned a wheeze category at age three years. In a cross sectional study, 300 asthmatic and healthy children aged 1 to 16 years will have nasal and bronchial AEC collected for culture and transcriptome analysis, leukocyte transcriptome analysis, and upper and lower airway microbiomes ascertained. Genetic variants associated with asthma symptoms will be confirmed in the STELAR cohorts.

Conclusions. This study is the first to comprehensively study the temporal relationship between aberrant AEC and immune cell function and asthma symptoms in the context of early gene-microbiome interactions.
Original languageEnglish
Article number60
JournalWellcome open research
Volume3
DOIs
Publication statusPublished - 17 May 2018

Fingerprint

Respiration
Asthma
Epithelium
Parturition
Microbiota
Lung
Gene Expression Profiling
Immune system
Transcriptome
Immune System
Leukocytes
Genes
Gene-Environment Interaction
Nasal Mucosa
Nose
Blood Cells
Cell Culture Techniques
Cross-Sectional Studies
Blood

Keywords

  • asthma
  • child
  • epithelial cell
  • genetics
  • infant
  • longitudinal studies
  • lymphocyte
  • microbiome
  • ribonucleic acid

Cite this

Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study. / Turner, Steve; Custovic, Adnan; Ghazal, Peter; Grigg, Jonathan; Gore, Mindy; Henderson, John; Lloyd, Clare M.; Marsland, Ben; Power, Ultan F.; Roberts, Graham; Saglani, Sejal; Schwarze, Jürgen; Shields, Michael; Bush, Andrew.

In: Wellcome open research, Vol. 3, 60, 17.05.2018.

Research output: Contribution to journalArticle

Turner, Steve ; Custovic, Adnan ; Ghazal, Peter ; Grigg, Jonathan ; Gore, Mindy ; Henderson, John ; Lloyd, Clare M. ; Marsland, Ben ; Power, Ultan F. ; Roberts, Graham ; Saglani, Sejal ; Schwarze, Jürgen ; Shields, Michael ; Bush, Andrew. / Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma? A description of the protocol for the Breathing Together study. In: Wellcome open research. 2018 ; Vol. 3.
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title = "Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma?: A description of the protocol for the Breathing Together study",
abstract = "Background. Childhood asthma is a common complex condition whose aetiology is thought to involve gene-environment interactions in early life occurring at the airway epithelium, associated with immune dysmaturation. It is not clear if abnormal airway epithelium cell (AEC) and cellular immune system functions associated with asthma are primary or secondary. To explore this, we will (i) recruit a birth cohort and observe the evolution of respiratory symptoms; (ii) recruit children with and without asthma symptoms; and (iii) use existing data from children in established STELAR birth cohorts. Novel pathways identified in the birth cohort will be sought in the children with established disease. Our over-arching hypothesis is that epithelium function is abnormal at birth in babies who subsequently develop asthma and progression is driven by abnormal interactions between the epithelium, genetic factors, the developing immune system, and the microbiome in the first years of life.Methods. One thousand babies will be recruited and nasal AEC collected at 5-10 days after birth for culture. Transcriptomes in AEC and blood leukocytes and the upper airway microbiome will be determined in babies and again at one and three years of age. In a subset of 100 individuals, AEC transcriptomes and microbiomes will also be assessed at three and six months. Individuals will be assigned a wheeze category at age three years. In a cross sectional study, 300 asthmatic and healthy children aged 1 to 16 years will have nasal and bronchial AEC collected for culture and transcriptome analysis, leukocyte transcriptome analysis, and upper and lower airway microbiomes ascertained. Genetic variants associated with asthma symptoms will be confirmed in the STELAR cohorts.Conclusions. This study is the first to comprehensively study the temporal relationship between aberrant AEC and immune cell function and asthma symptoms in the context of early gene-microbiome interactions.",
keywords = "asthma, child, epithelial cell, genetics, infant, longitudinal studies, lymphocyte, microbiome, ribonucleic acid",
author = "Steve Turner and Adnan Custovic and Peter Ghazal and Jonathan Grigg and Mindy Gore and John Henderson and Lloyd, {Clare M.} and Ben Marsland and Power, {Ultan F.} and Graham Roberts and Sejal Saglani and J{\"u}rgen Schwarze and Michael Shields and Andrew Bush",
note = "Acknowledgements The authors are indebted to the participants and parents who have already been recruited. We also acknowledge the enthusiasm and endeavour of the research nurse team which includes: Stephen Main, Margaret Connon, Catherine Beveridge, Julie Baggott, Kay Riding, Ellie McCamie, Maria Larsson, Lynda Melvin, Mumtaz Idris, Tara Murray, Nicky Tongue, Nicolene Plaatjies, Sheila Mortimer, Sally Spedding, Susy Grevatt, Victoria Welch, Morag Zelisko, Jillian Doherty, Jane Martin, Emma Macleod and Cilla Snape. We are also delighted to be working alongside the following colleagues in laboratories: Marie Craigon, Marie McWilliam, Maria Zarconi, Judit Barabas, Lindsay Broadbent, Ceyda Oksel and Sheerien Manzoor. Grant information The study is supported by the Wellcome Trust [108818]; and the PHA HSC R&D Division, Northern Ireland.",
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TY - JOUR

T1 - Pulmonary epithelial barrier and immunological functions at birth and in early life - key determinants of the development of asthma?

T2 - A description of the protocol for the Breathing Together study

AU - Turner, Steve

AU - Custovic, Adnan

AU - Ghazal, Peter

AU - Grigg, Jonathan

AU - Gore, Mindy

AU - Henderson, John

AU - Lloyd, Clare M.

AU - Marsland, Ben

AU - Power, Ultan F.

AU - Roberts, Graham

AU - Saglani, Sejal

AU - Schwarze, Jürgen

AU - Shields, Michael

AU - Bush, Andrew

N1 - Acknowledgements The authors are indebted to the participants and parents who have already been recruited. We also acknowledge the enthusiasm and endeavour of the research nurse team which includes: Stephen Main, Margaret Connon, Catherine Beveridge, Julie Baggott, Kay Riding, Ellie McCamie, Maria Larsson, Lynda Melvin, Mumtaz Idris, Tara Murray, Nicky Tongue, Nicolene Plaatjies, Sheila Mortimer, Sally Spedding, Susy Grevatt, Victoria Welch, Morag Zelisko, Jillian Doherty, Jane Martin, Emma Macleod and Cilla Snape. We are also delighted to be working alongside the following colleagues in laboratories: Marie Craigon, Marie McWilliam, Maria Zarconi, Judit Barabas, Lindsay Broadbent, Ceyda Oksel and Sheerien Manzoor. Grant information The study is supported by the Wellcome Trust [108818]; and the PHA HSC R&D Division, Northern Ireland.

PY - 2018/5/17

Y1 - 2018/5/17

N2 - Background. Childhood asthma is a common complex condition whose aetiology is thought to involve gene-environment interactions in early life occurring at the airway epithelium, associated with immune dysmaturation. It is not clear if abnormal airway epithelium cell (AEC) and cellular immune system functions associated with asthma are primary or secondary. To explore this, we will (i) recruit a birth cohort and observe the evolution of respiratory symptoms; (ii) recruit children with and without asthma symptoms; and (iii) use existing data from children in established STELAR birth cohorts. Novel pathways identified in the birth cohort will be sought in the children with established disease. Our over-arching hypothesis is that epithelium function is abnormal at birth in babies who subsequently develop asthma and progression is driven by abnormal interactions between the epithelium, genetic factors, the developing immune system, and the microbiome in the first years of life.Methods. One thousand babies will be recruited and nasal AEC collected at 5-10 days after birth for culture. Transcriptomes in AEC and blood leukocytes and the upper airway microbiome will be determined in babies and again at one and three years of age. In a subset of 100 individuals, AEC transcriptomes and microbiomes will also be assessed at three and six months. Individuals will be assigned a wheeze category at age three years. In a cross sectional study, 300 asthmatic and healthy children aged 1 to 16 years will have nasal and bronchial AEC collected for culture and transcriptome analysis, leukocyte transcriptome analysis, and upper and lower airway microbiomes ascertained. Genetic variants associated with asthma symptoms will be confirmed in the STELAR cohorts.Conclusions. This study is the first to comprehensively study the temporal relationship between aberrant AEC and immune cell function and asthma symptoms in the context of early gene-microbiome interactions.

AB - Background. Childhood asthma is a common complex condition whose aetiology is thought to involve gene-environment interactions in early life occurring at the airway epithelium, associated with immune dysmaturation. It is not clear if abnormal airway epithelium cell (AEC) and cellular immune system functions associated with asthma are primary or secondary. To explore this, we will (i) recruit a birth cohort and observe the evolution of respiratory symptoms; (ii) recruit children with and without asthma symptoms; and (iii) use existing data from children in established STELAR birth cohorts. Novel pathways identified in the birth cohort will be sought in the children with established disease. Our over-arching hypothesis is that epithelium function is abnormal at birth in babies who subsequently develop asthma and progression is driven by abnormal interactions between the epithelium, genetic factors, the developing immune system, and the microbiome in the first years of life.Methods. One thousand babies will be recruited and nasal AEC collected at 5-10 days after birth for culture. Transcriptomes in AEC and blood leukocytes and the upper airway microbiome will be determined in babies and again at one and three years of age. In a subset of 100 individuals, AEC transcriptomes and microbiomes will also be assessed at three and six months. Individuals will be assigned a wheeze category at age three years. In a cross sectional study, 300 asthmatic and healthy children aged 1 to 16 years will have nasal and bronchial AEC collected for culture and transcriptome analysis, leukocyte transcriptome analysis, and upper and lower airway microbiomes ascertained. Genetic variants associated with asthma symptoms will be confirmed in the STELAR cohorts.Conclusions. This study is the first to comprehensively study the temporal relationship between aberrant AEC and immune cell function and asthma symptoms in the context of early gene-microbiome interactions.

KW - asthma

KW - child

KW - epithelial cell

KW - genetics

KW - infant

KW - longitudinal studies

KW - lymphocyte

KW - microbiome

KW - ribonucleic acid

U2 - 10.12688/wellcomeopenres.14489.1

DO - 10.12688/wellcomeopenres.14489.1

M3 - Article

VL - 3

JO - Wellcome open research

JF - Wellcome open research

SN - 2398-502X

M1 - 60

ER -