Crossed wires: what goes wrong in emphysema?

Emphysema is a severe form of COPD in which the alveoli are permanently damaged. “The damage occurs deep in the lungs, where oxygen is absorbed into the bloodstream,” explains researcher Padmini Khedoe of Leiden University Medical Center. “People with emphysema become short of breath more easily and are more prone to lung infections.”

Detecting damage earlier

Two findings may be particularly relevant to detecting emphysema earlier and stopping its progression.

• First, damaged alveoli contain more immune cells. “These cells also seem to be more active and release harmful substances. We want to understand better why this happens.”
• In addition, tiny blood vessels surround the alveoli. They are lined with cells known as endothelial cells. These cells help with oxygen uptake and may also play a role in lung repair. “In emphysema, these blood vessels sometimes disappear before there is any clear visible damage to the alveoli. That is interesting, because it may allow us to detect the disease earlier and prevent further damage.”

This new study brings these two findings together: on the one hand, an increased number of immune cells, and on the other, a loss of blood vessels.

An atlas of the lung

The researchers are creating an “atlas of the lung”: a detailed map of the cells found in healthy and damaged lung tissue. Their aim is to understand how immune cells interact with the cells lining the blood vessels. To do this, they compare sections of healthy lung tissue with sections of lung tissue from people with emphysema. They examine which cells are present and which substances those cells produce. In this way, they hope to gain a better understanding of how the cells influence one another.

Emphysema in a laboratory dish

In the second part of the study, the researchers recreate this process in the laboratory. “We bring together immune cells and blood vessel cells from people with and without emphysema in a laboratory dish,” Khedoe explains. “We also investigate which substances and signals identified in the first part of the study cause damage to the blood vessels.” The researchers are also exploring whether certain responses can be inhibited using medication. “The techniques have improved considerably in recent years. This means we can now study these processes very precisely using human cells. The great advantage is that we no longer need laboratory animals for this.”

Searching for new treatments

Finally, Padmini Khedoe compares the results with patients’ medical data, such as lung function tests and CT scans. She hopes to discover whether certain substances can indicate how severe the disease is or how quickly it is progressing. “With this approach, we hope to identify important leads. Ultimately, this may help us detect emphysema earlier and perhaps even stop further damage.”

Research without laboratory animals

Animal models are still used in around a quarter of the research projects supported by the Lung Foundation Netherlands. We are working to reduce their use as much as possible, while considerable effort is being devoted to developing alternatives that do not require laboratory animals. That is why we also invest in lung research that does not use laboratory animals, such as the work of Dr Padmini Khedoe. She received a grant of €250,000 for her research into the earlier detection and treatment of COPD.

Text: Judith Langeland