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

Wellcome Open Research

article

Jurgen Schwarze¹  Michael Shields²  Andrew Bush³  Steve Turner⁴  Adnan Custovic³  Peter Ghazal⁵  Jonathan Grigg⁶  Mindy Gore³  John Henderson⁷  Clare M. Lloyd⁸  Ben Marsland⁹  Ultan F. Power²  Graham Roberts^1,10  Sejal Saglani³ 

[1] Child Life and Health and MRC-Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh;Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast;Department of Paediatrics, Imperial College and Royal Brompton Hospital;Child Health, University of Aberdeen;Division of Infection and Pathway Medicine, Deanery of Biomedical Sciences, University of Edinburgh Medical School;Centre for Child Health, Blizard Institute, Queen Mary University of London;Population Health Sciences, Bristol Medical School, University of Bristol;Faculty of Medicine, National Heart & Lung Institute, Imperial College London;Department of Immunology and Pathology, Monash University;Clinical and Experimental Sciences and Human Development and Health, Faculty of Medicine, University of Southampton;NIHR Southampton Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust;The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital

关键词: Asthma;    Child;    Epithelial cell;    Genetics;    Infant;    Longitudinal studies;    Lymphocyte;    Microbiome;    Ribonucleic acid;   

DOI  :  10.12688/wellcomeopenres.14489.1

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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.

【 授权许可】

CC BY