Accelerated lung ageing in early-life: molecular mechanisms driving abnormal lung function

How do early-life factors such as infections and allergies in children result in poor lung health in adulthood?
Background:
Long term lung diseases are the third most common cause of deaths in adults worldwide. Long-term follow-up has shown that frequent preschool asthma attacks and lung infections reduce the way the lungs work (lung function) which persists to adulthood. About one-third of these children develop school-age and adult asthma, however, some children may stop having symptoms by school-age and may appear to have “grown out” of their asthma, even though they may still have a loss in lung function. We now know low lung function in childhood is associated with long-term health consequences such as higher rates and earlier onset of heart disease and diabetes, and high risk of the lung condition chronic obstructive pulmonary disease (COPD) in adulthood. We therefore need to understand which factors are important in causing early-life asthma attacks and lung infections, how we can prevent them, and how we can stop children with preschool attacks from developing low lung function.
We have shown that preschool children can be split into two groups, those with allergies with or without infection in their lungs, and secondly those without allergies, but lots of bacterial and viral infections in their lungs. The children that have abnormal smooth muscle in their lungs are the ones that go on to have poor outcomes as adolescents. But we have not followed them to adulthood.
Aim:
To work out how environmental factors that all preschool children are exposed to (infections, allergies) result in adult low lung function, and how we can intervene to prevent the development of low lung function.

Using a test called a bronchoscopy, which is a fibreoptic camera used to sample the lungs of patients, we will look at the cells and infections in the lungs of adults who we had previously tested as children and we will relate lung smooth muscle to their lung function. We will also take blood samples and see if we can find a “surrogate” marker in the blood that shows which children will go on to have continued low lung function in adulthood.
We want to confirm this blood marker in separate children who have been followed since birth. We will include 2 such groups. The first is a group from London who are now aged 8-10 years and the second from the Born in Bradford cohort who are at the age where they reach their best “maximal” lung function.