The natural history of asthma and wheezing illnesses from birth to adolescence: Determinants of the remission of asthma
Lead Research Organisation:
University of Bristol
Department Name: Cellular and Molecular Medicine
Abstract
We aim to discover factors associated with the resolution of asthma during adolescence. This may lead to the development of interventions that will resolve or minimise asthma symptoms.
Most asthma begins in childhood but, despite intensive research efforts, the causes of asthma remain elusive. A substantial proportion of children with asthma appear to outgrow their symptoms during teenage years. By concentrating on events during this period of childhood, we hope to identify important differences between children who outgrow their asthma and those in whom it persists.
We will study an established cohort of children (the ALSPAC study) in whom we have extensive information about early life environment and symptoms. We will study the progression of asthma as the participants go through puberty and link this to aspects of their lifestyle (such as diet, smoking, and exercise). An evolving database of variations in genes associated with asthma will also allow us to find out if environmental factors interact with particular genes to cause persistence or resolution of asthma.
No interventions have been discovered that prevent the development of asthma. Exposures that appear to favour asthma resolution in this study will be developed into intervention studies to test whether these show promise in helping to resolve asthma symptoms once they have become established.
Most asthma begins in childhood but, despite intensive research efforts, the causes of asthma remain elusive. A substantial proportion of children with asthma appear to outgrow their symptoms during teenage years. By concentrating on events during this period of childhood, we hope to identify important differences between children who outgrow their asthma and those in whom it persists.
We will study an established cohort of children (the ALSPAC study) in whom we have extensive information about early life environment and symptoms. We will study the progression of asthma as the participants go through puberty and link this to aspects of their lifestyle (such as diet, smoking, and exercise). An evolving database of variations in genes associated with asthma will also allow us to find out if environmental factors interact with particular genes to cause persistence or resolution of asthma.
No interventions have been discovered that prevent the development of asthma. Exposures that appear to favour asthma resolution in this study will be developed into intervention studies to test whether these show promise in helping to resolve asthma symptoms once they have become established.
Technical Summary
Background: The proposed project is based on the accompanying core programme for the Avon Longitudinal Study of Parents & Children (ALSPAC), a longitudinal birth cohort of 13,971 infants followed from before birth. This proposal builds on well-characterised asthma phenotypes, including objective measures of allergy and lung function, to age 8? years in this cohort, detailed assessments of early childhood environmental exposures, and collection of information on exposures during adolescence and asthma outcomes in late puberty as part of the accompanying core proposal.
Aims & Objectives: The aims are to describe the natural history of asthma from birth to adolescence and to examine the factors that influence asthma remission. The principal hypothesis to be tested is that exposures during the critical period of pubertal development will interact with asthma phenotype to determine remission, persistence or incidence of asthma symptoms from 8? to 15+ years. Within this overall aim, specific hypotheses will be tested relating to individual exposures during adolescence, including nutrition, changes in body size, including objective measures of fat mass and body composition (DXA), activity measurements using an accelerometer, and smoking uptake validated by measurement of urinary cotinine concentrations.
Methods: The data for this project will be available from existing information collected by ALSPAC and from new data collection included in the core proposal. No specific fieldwork is planned apart from measurement of urinary cotinine. The project will utilise these data to analyse wheezing trajectories from birth to adolescence using novel statistical approaches, including multilevel modelling and structural equations, to determine the contribution of environmental exposures to defined outcomes, including remission of asthma symptoms. The outcomes at 15+ years will include remission or persistence or asthma symptoms linked to objective lung function measurements, including reversibility to bronchodilator. Existing data on asthma phenotype in earlier childhood will be used to examine interactions between these detailed phenotypes and subsequent exposures in the remission or persistence of asthma symptoms.
Outcomes: The project will produce novel information on exposures associated with the natural history of asthma through adolescence in a contemporary cohort of children. Knowledge of factors associated with remission of asthma may give rise to new therapeutic approaches in future studies. In addition, these data will provide a platform for studies of gene-environment interaction studies to determine the effects of exposures on candidate genotypes in determining the natural history of asthma throughout childhood.
Aims & Objectives: The aims are to describe the natural history of asthma from birth to adolescence and to examine the factors that influence asthma remission. The principal hypothesis to be tested is that exposures during the critical period of pubertal development will interact with asthma phenotype to determine remission, persistence or incidence of asthma symptoms from 8? to 15+ years. Within this overall aim, specific hypotheses will be tested relating to individual exposures during adolescence, including nutrition, changes in body size, including objective measures of fat mass and body composition (DXA), activity measurements using an accelerometer, and smoking uptake validated by measurement of urinary cotinine concentrations.
Methods: The data for this project will be available from existing information collected by ALSPAC and from new data collection included in the core proposal. No specific fieldwork is planned apart from measurement of urinary cotinine. The project will utilise these data to analyse wheezing trajectories from birth to adolescence using novel statistical approaches, including multilevel modelling and structural equations, to determine the contribution of environmental exposures to defined outcomes, including remission of asthma symptoms. The outcomes at 15+ years will include remission or persistence or asthma symptoms linked to objective lung function measurements, including reversibility to bronchodilator. Existing data on asthma phenotype in earlier childhood will be used to examine interactions between these detailed phenotypes and subsequent exposures in the remission or persistence of asthma symptoms.
Outcomes: The project will produce novel information on exposures associated with the natural history of asthma through adolescence in a contemporary cohort of children. Knowledge of factors associated with remission of asthma may give rise to new therapeutic approaches in future studies. In addition, these data will provide a platform for studies of gene-environment interaction studies to determine the effects of exposures on candidate genotypes in determining the natural history of asthma throughout childhood.