Fetal Origins of Obstructive Airway Disease – Preterm Birth Complications
Obstructive airway disease is a major global health problem, associated with significant morbidity and mortality. There is now increasing evidence to suggest the origin of many adult respiratory diseases, including asthma and chronic obstructive airway disease, may arise due to early life insults. Adverse events occurring during critical periods of development (in the womb, or soon after birth) produce permanent structural, physiological and epigenetic changes in the airways with lifelong consequences. Preterm delivery is the most common cause of abnormal lung development particularly when the infant also requires mechanical ventilation. The consequences of mechanical ventilation include direct mechanical and structural changes to lung and airway tissue and initiation of an inflammatory response that prolongs the need for mechanical support and increases the risk of systemic infection and inflammation. Postnatal glucocorticoids are commonly used to accelerate weaning from mechanical ventilation. The extent to which the above medical interventions interfere with the normal maturation of the airway is unclear.
The studies undertaken for my thesis will determine the effects of preterm birth, mechanical ventilation and postnatal steroids on airway structure and function from birth in a relevant pre-clinical model (preterm lamb). Studies will also assess how these outcomes are influenced by exposure of the fetus to inflammation whilst in the womb. Our overarching hypothesis is that abnormalities in airway structure and function from birth increase susceptibility to future obstructive airway disease.
Why my research is important
The improved survival rate of preterm infants (due to neonatal medical advances) is associated with prominence of chronic respiratory disorders characterised by abnormal lung development and reduced airway function. The proposed research will lead to a considerable advancement in knowledge of how preterm birth and associated clinical interventions can impact structural and functional properties of the airway wall in early life, increasing the susceptibility to airway disease in later life. Understanding the nature of the changes to the airway wall that occur in the preterm individual, beginning from the day of birth, will ultimately lead to new treatments mitigating airway abnormalities and thereby improving respiratory health throughout life.