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, Jurgen Schwarze, Michael Shields, Andrew Bush

Research output: Contribution to journalArticlepeer-review

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
Pages (from-to)60
JournalWellcome Open Research
Volume3
DOIs
Publication statusPublished - 17 May 2018

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