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New Hope for Lung Diseases

Lung research at Helmholtz Munich has made some spectacular breakthroughs. They could pave the way for the therapy of serious diseases such as COPD and pulmonary fibrosis.

Lung research at Helmholtz Munich has made some spectacular breakthroughs. They could pave the way for the therapy of serious diseases such as COPD and pulmonary fibrosis.

Lung Model Simulates Pulmonary Fibrosis

The high-tech device that Dr. Otmar Schmid and and his Postdoc Dr. Ali Doryab built is located behind closed doors in a medical laboratory of the Lung Health and Immunity Institute (LHI). Tubes are mounted to it, along with two larger vessels and a membrane that raises and lowers. "This is our bioreactor," Schmid says, "a kind of artificial lung." A device that can be used, for example, to study how effective newly developed drugs are when patients inhale them. This opens up completely new possibilities for lung research.

 

The highly complex device simulates pulmonary fibrosis - a disease in which the tissue hardens and becomes less elastic. As a result, the lungs lose volume for breathing. This is exactly what the model imitates - with a stretchable membrane on which lung cells grow, whose stretchability can be changed.

 

Video: BETA-Membrane of the mini-lung-fibrosis model (© Ali Doryab | Helmholtz Munich)
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Until now, studying lung fibrosis has been a problem for researchers because artificial models using lung cells were oversimplified. Comparisons with animals are also often out of the question because there are too many differences from humans in this case. The bioreactor of the Munich researchers fills this gap, even if Otmar Schmid qualifies: "A human lung consists of about 60 different cell types. We simulate three in our model - so it's much less complex."

The three cell types, however, are precisely those that occur at the air barrier and the blood barrier; the place in the lung where oxygen enters the bloodstream. For the study of pulmonary fibrosis, this is the crucial spot. "For our specific questions, the model offers exactly the right possibilities," says Otmar Schmid. In pneumology, the field of lung medicine, the lung model caused a sensation with its innovative approach - along with other spectacular developments from Helmholtz Munich.

 

 

Deciphering Diseases With the Latest Technology

Modern high-tech methods are promising when it comes to finding drugs for lung diseases. One example is the so-called single-cell analyses, which can be used to seamlessly track developments in individual cells. "In the past, we could look at the lungs when a human or animal had died. That's when we saw the endpoint of a disease. But we were unable to observe how it developed over time," says Otmar Schmid. "With the new methods, we can now determine interaction pathways and find out in real time what exactly a certain treatment does, for example."

Schmid has high hopes for drugs that are inhaled - drugs for lung diseases, but also for completely different diseases. "So far, the problem is that patient behavior has a big impact on how much of the active ingredient actually gets there," Schmid says. Correct inhalation requires some practice, while a pill, for example, automatically delivers the same amount of an active ingredient to the target each time.

Schmid is therefore working with his team on what he calls "precision inhalation therapy": "You can imagine it as being as simple and correct for sufferers to inhale as if they were taking a pill. They hold a device in front of their mouth and continue breathing normally - and at some point they get the message that they've absorbed enough of the active ingredient." In this field, Otmar Schmid believes, great strides in development are ahead.

 

On the Trail of COPD

Behind all these developments is the research team of Prof. Önder Yildirim, head of the Institute for Lung Health and Immunity (LHI) at Helmholtz Munich. "The lungs have always fascinated me," Yildirim says: "Without nutrition, a person can last three weeks, without water, three days - but without air, three minutes at most." Despite this, research into lung diseases led a somewhat shadowy existence worldwide for many decades. This is despite the fact that the lungs are behind one of the world's leading causes of death - chronic obstructive pulmonary disease (COPD), in which lung tissue is gradually destroyed.

Prof. Önder Yildirim on COPD and the approach to better understand the disease

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New Therapeutic Approaches

In two spectacular studies, Yildirim and his team have made important advances in the fight against COPD: they have been able to stop the progression of the disease in experiments on mice and organoids, and even ensure that a damaged lung regenerates."At the molecular level, the way the disease works is that B cells accumulate and destroy the alveoli," Önder Yildirim explains. "So we wondered if we could stop COPD by preventing the accumulation of B cells."

B cells clump together to form what is known as lymphoid follicles. So the goal is to destroy those follicles. To do this, Yildirim and his team used clotrimazole - an active ingredient commonly used to treat fungal infections. They found that it was indeed possible to halt the progression of the disease in mouse experiments.

 

How the Lungs Can Repair Themselves

The core: Certain molecules cause cell death in the lung - and at the same time prevent the lung from regenerating itself. These so-called ligands are formed in T and B cells of the lung. They then dock onto receptors of epithelial cells; it is from this site that they do the damage. "Our idea was therefore to block these ligands," explains Önder Yildirim. With his team, he first tried out this idea on mice whose lungs had been damaged by exposure to smoke.
"And one day, a coworker came to my office and said, "I think we have something special!" recalls Yildirim. He immediately ran off to the lab to see for himself: the sick animals, he noticed, looked healthy again. He immediately had the amazing experiment repeated - and was successful again. "The fact that this was possible and that the disease that had already developed could be reversed, is unique in the world." In the meantime, the researchers have been able to achieve this success not only in mice, but also in so-called organoids - artificial organs that resemble those of humans.

Lifelong Risk Factors for the Lungs

COPD - just a “smoker's disease” that will soon be on the decline? On the contrary. New figures from the World Health Organization (WHO) are alarming: The numbers of COPD patients in Europe are projected to increase by 23 percent by 2050. Nearly 80 percent of all deaths resulting from chronic lung diseases are caused by COPD. And there is growing evidence that many more risk factors across the life course must be taken into account: air pollution, wildfires, stress, food, obesity – and our genes. New findings in epigenetics show that even the behavior of our relatives is a risk factor. Simply put: How our parents or grandparents lived, what they did to their lungs, can change how our genes work. This is known as epigenetic changes and can be passed down to future generations, increasing the likelihood of asthma or COPD. As there are new findings on the risk factors for and the development of chronic lung diseases, there is - on the other hand - a great lack of awareness about how important it is to keep our lungs healthy as a fundamental part of future health.

Current Clinical Studies

Here is some more information on this topic:

Latest update: June 2025.