Pig models to shed light on infant lung disease

Understanding how lungs develop in the final stages of pregnancy is key to improving care for premature babies at risk of serious breathing problems. Babies born too soon may face lifelong challenges if their lungs are not fully ready to adapt to life outside the womb.

Researchers at the Roslin Institute are working to uncover the genetic and developmental processes behind a chronic lung condition, known as bronchopulmonary dysplasia (BPD), which affects premature babies whose lungs are not fully developed, often leaving them reliant on breathing support in the first weeks or months of life.

The aim of this research is to build a deeper understanding of lung development and the processes that make breathing possible at birth using insights from human genomics and large animal models.

Experts hope to improve clinical management of BPD and, in the longer term, develop new ways to protect the health of babies born too soon.

Lung development

Developing lungs are filled with amniotic fluid in the womb. For babies born prematurely, the sudden switch to breathing air can be harsh on immature lung tissues. Most infants born pre-term need ventilation, which can damage delicate tissue and disrupt normal lung development.

BPD is diagnosed when a baby still requires respiratory support at 36 weeks from conception, around the time of a full-term birth, explains Roslin researcher Dr Sara Clohisey Hendry. 

The condition can have lifelong consequences, including an increased risk of breathing difficulties, such as asthma.

Genetic insight

“When a baby takes their first breath, that is a profound moment,” explains Dr Clohisey Hendry. “By understanding the biological processes that lead to this, we hope to improve care for premature babies and support better outcomes for families.”

Through a national study, the research team is collecting DNA from thousands of babies cared for in neonatal intensive care units (NICUs) across the UK. Comparing the genetic material of infants who develop BPD with those who do not may help identify genes that play a role in lung development and disease.

It is not possible to study living tissue showing active gene expression from late-gestation infants. Studies in mice have offered some insight, but their lungs follow a different developmental pathway from those of humans.

Pig models

Lung development in pigs closely resembles that of humans, and newborn piglets are a similar size to preterm babies, Dr Clohisey Hendry explains.

By collecting lung tissue at different stages of pig gestation, researchers aim to map the biological processes behind lung development. This will help them build a detailed picture of how the lungs change over time.

Novel genetic tools make it possible to see which genes are active in various parts of the lung as it grows. In the longer term, scientists may be able to use gene-editing techniques to study how genetic differences and medical treatments, such as ventilation, affect the lungs.

Image credit: Mufid Majnun