RHiNO: Respiratory Health In Preterm Neonatal Outcomes

Preterm-births account for 10% of all world-wide births. Increasing numbers of prematurely born children are surviving into childhood and beyond but there is limited understanding of the long term outcomes of being born early. It is clear that those who are born extremely prematurely (32 weeks gestation or less) have decreases in their lung function in childhood and beyond. Perhaps this is not surprising as many of these babies receive mechanical ventilation and added oxygen therapy which both cause lung injury. However, we have recently shown that babies who are born only late prematurely at 33 - 34 weeks gestation also have marked lung function deficits even though they are usually not ventilated or receive oxygen after birth. We have received >7,000 responses to our questionnaire survey investigating respiratory symptoms and drug usage in preterm children born in Wales. The initial analyses show that children born prematurely have increased respiratory symptoms which increase with increasing immaturity when compared to children born on time. Prematurely-born children also have increased GP visits and increased hospital admissions during childhood but are often not receiving treatment which may be beneficial. Some are often labelled as asthmatics despite no evidence of traditional symptoms associated with asthma. Since 56,000 babies in the UK and 480,000 in the US each year are born prematurely, there is an urgent need to understand the reasons or mechanisms why premature babies have long term lung function abnormalities. The decreased lung function may be a consequence of being born early at an early stage of lung development, or there may be persistent lung inflammation, or they may have increased allergic reaction as in children with asthma, or they may have structural abnormalities of the airways. The list of potential causes is unending. Our overall aims are to understand the underlying mechanisms that cause the airway obstruction in preterm-born children. Our specific aims are: 1. to identify and accurately define the breathing disorder (including symptoms, lung function and growth) of 7 - 12 years old children who were born prematurely (<= 34 weeks gestation) and who had wheeze any time during their life ("wheeze-ever"); and to identify children with marked airway obstruction for detailed study of the mechanisms of why they may have airway obstruction. We shall also test if any airway obstruction responds to a single dose of inhaled drug typically used for asthma and related disorders. 2. to study the possible mechanisms of airway obstruction in children who had previous symptoms and have marked airway obstruction (defined as FEV1<=85%); this will include comprehensive lung function testing including exercise testing; role of allergy; airway inflammation, etc. 3. to determine if inhaled drug treatment (which is routinely used in asthma) can specifically affect the underlying mechanisms. The aim is to determine if drug therapy is effective in these children who had previous respiratory symptoms and if they affect any specific mechanism that cause the airway obstruction. 4. to use state-of-the-art MRI scanning technology to study the lung structure and function in prematurely-born children with marked airway obstruction especially those who do and do not respond to treatment comparing the results with children born prematurely or at term and who have normal lung function. The aim is to determine the structural consequences of being born prematurely using state-of-the-art MRI technology which is only available in 2-3 centres in the UK. It is clear that this is a neglected but large population that needs further attention. By better understanding the mechanisms of why children born prematurely develop airway obstruction, we should be able to develop targeted drug therapies and avoid labelling them as suffering from asthma to ensure they receive the correct treatment.