The proposed project is based on the follow up of a well-characterised population of children in the

Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate factors associated with the onset and

remission of asthma symptoms during adolescence. ALSPAC is a longitudinal birth cohort of 13,971 infants

followed from birth. Detailed analyses of asthma phenotypes have been made on data from early childhood to age

8 1/2 years, including objective measurements of lung function and allergic status. The proposed study will extend

these observations through the critical period of adolescence to study exposures associated with onset or remission

of asthma symptoms and their relationships with further objective outcome measures proposed in this project.

Aims & Objectives: The aims are to describe the natural history of asthma from birth to adolescence and to examine

the factors that influence the remission of asthma symptoms. The primary hypotheses to be tested in this project are

that changes in body fat composition, diet, habitual activity and the uptake of active smoking are independently

associated with the remission, persistence or onset of asthma symptoms during adolescence (from 8 1/2 to 15+ years)

and that effects differ between males and females in this population. We will investigate the possible mechanisms

of these effects by measuring objective outcomes, including lung function, bronchodilator reversibility and a marker

of airway inflammation, exhaled nitric oxide. Finally, we will investigate whether exposures during adolescence

interact with prior exposures and asthma history in determining the resolution of asthma symptoms in adolescence.

Methods: Exposure data will be collected as part of the ALSPAC Core Programme. Data on body composition will

be available from whole body DXA scans repeated at 11, 13+, and 15+ years, reports of physical activity are

available from annual questionnaires and objective measurements of activity have been made using accelerometers.

Dietary intake is calculated from food frequency questionnaires and tobacco smoke exposure will be estimated from

parental and child questionnaires. We will also measure urinary cotinine at 15+ years to validate these reports as

part of this project. Outcomes will include extending the analysis of asthma symptoms from 8 1/2 years to 15+ years

using data from annual self-report questionnaires. From these we will establish asthma trajectories for each child

from birth to adolescence. We will measure lung function by spirometry at 15+ years and measure bronchodilator

reversibility. We will also assess airway inflammation by measuring exhaled nitric oxide (FeNO) at 15+ years.

These measurements will be used to characterise subjects with asthma remission depending on the presence or

absence of airflow obstruction and airway inflammation.

Outcomes: the project will provide novel information on factors associated with asthma remission during the

critical period of adolescence in a large contemporary cohort of children. Knowledge of these factors and their

associations with persistent abnormalities of pulmonary function and/or airway inflammation may help to identify

targets for interventions aimed at encouraging asthma remission. In addition, the data generated by this project will

provide important new data for the study of genetic susceptibilities and gene-environment interactions in the natural

history of asthma during childhood.