Lungs Under the Microscope

In asthma, the airways in the lungs are constantly inflamed. This can cause symptoms such as shortness of breath and coughing. In about one in ten people with asthma, medication has little or no effect. “We still know too little about exactly what goes wrong in their lungs,” says Rudi Hendriks, professor at Erasmus MC. “That makes effective treatment difficult.” To help these people more effectively, scientists are creating a special “Lung Atlas”. It maps the lungs of people with asthma in great detail. This will help researchers better understand how asthma develops, why lung function declines and why some people respond poorly to medication. The atlas will be made freely available to researchers worldwide. It is an important step towards personalised care. Hendriks says: “The atlas could make a major difference to people whose medication is currently not working well. The knowledge it provides could lead to new treatments and help predict what will work for each individual.”

Unique approach

Asthma does not have one clear cause. Different cells are involved in each patient, which means medicines may work differently from one person to another. Corticosteroids, for example, work well for many people with allergic asthma, but not for everyone. “With our approach, we want to identify exactly which cells are active in each patient and how they work together. This will help us better understand why medicines do or do not work,” Rudi Hendriks explains. “Much of what we know about asthma comes from studies involving mice, lung lavage samples or blood. This research is extremely valuable, but it does not show exactly what happens inside the human lung itself.”

A new perspective

In this study, scientists are combining two important developments. “Over the past few years, lung tissue from people with asthma has been collected around the world. This includes tissue from people with moderate to severe asthma, from patients before and after treatment with a biological therapy, and even from people who died during a severe asthma attack.” At the same time, digital techniques for studying cells have improved significantly. This allows researchers to identify patterns that previously remained hidden. By combining these two developments, they can now:

• Identify every individual cell in the lung
• See which genes and proteins are active in each cell
• Determine which cells interact with one another
• Discover how cells influence one another

“In the past, we could only examine a few types of cells at a time,” Hendriks says. “Now we can see exactly how cells work together and what they do. The Lung Atlas will be available to everyone, allowing scientists worldwide to use it in their research. This will help them investigate new ways to prevent asthma or improve its treatment more quickly.”

Cells working together

“If you place a thin slice of lung tissue under a microscope, you can see around sixty different types of cells,” Hendriks says. “Some cells are always found in the same place, such as the epithelial cells lining the inside of the lung. Others, such as immune cells, move around a great deal. During an asthma attack, many of these cells become particularly active. We want to understand how all these cells influence one another. Their interactions can trigger or intensify inflammation, but they can also help reduce it.” Scientists currently learn a great deal from studies involving laboratory animals. However, things often work slightly differently in human tissue. “With the Lung Atlas, we will be able to see much more clearly what happens inside a human lung,” Hendriks explains. “For example, we will be able to see exactly how cells respond to medicines. This will help us identify more quickly what is important in lung diseases.”

Better care

This is fundamental research. Scientists first want to understand exactly how a lung affected by asthma differs from a healthy lung. It will therefore not immediately result in a new medicine, but it will lay the foundation for better care in the future. “With this knowledge, we will be better able to predict who will develop asthma,” Hendriks says. “We will also gain a clearer understanding of how the disease progresses and how medicines affect it. In the future, the Lung Atlas may also support research into other lung diseases, such as pulmonary fibrosis.”

Text: Judith Langeland

Watch the video about the research below (in Dutch):