Size Matters: Why Small Lungs Are More Likely to Get Sick

For more than ten years, lung researchers and epidemiologists at the Helmholtz Zentrum München have been investigating genetic factors associated with lung function and lung diseases within the framework of international consortia. Now they collaborated in a study that was recently published in ‘Nature Genetics’ and were able to show why people with smaller lungs have a higher risk of developing lung diseases. The genetic information revealed by this study can be translated into clinical practice to improve the prediction for the risk of chronic obstructive pulmonary disease (COPD) and to develop new approaches for treatment.

chronic obstructive pulmonary disease
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Lung diseases are a major health challenge for our society, and COPD alone is the third most common cause of death in the world. In order to develop efficient treatments, scientists are working to understand the underlying mechanisms in the lung. The focus is increasingly on the interaction between genes and the environment.

Researchers in the SpiroMeta consortium have been working for years to determine numerous areas in the genetic material that play a role in lung function. The group headed by Prof. Dr. Holger Schulz, acting Director of the Institute of Epidemiology I (EPI I) at the Helmholtz Zentrum München, has been involved since the beginning. “Since the project started in 2007, we have been able to expand our knowledge regarding lung-relevant genes substantially,” Schulz says in retrospect. “We are highly interested in the association between certain genes and lung function, since it is known that people with healthy but smaller lungs have a higher risk of developing lung diseases.”

World’s biggest study regarding genetics of lung health and disease

The consortium’s current work, in which the Helmholtz scientists are again involved, produced genetic evidence of why this might be. Dr. Christian Gieger, head of the Molecular Epidemiology Research Unit (AME) at the Helmholtz Zentrum München, explains: “We were able to identify genetic variants that are associated with lower lung function and increase the risk of developing COPD. This new and world’s biggest study regarding genetics of lung health and disease has also supplied the first pathophysiological explanations for the association between pulmonary function and certain genes.” These genes are furthermore candidates for innovative approaches to treatment. This translational aspect is especially important to the researchers.

Dr. Stefan Karrasch, scientist at the EPI I and likewise involved in the study, describes the methodological procedure. “First we examined the genome data from almost 49,000 persons with widely varying pulmonary function levels. The genetic variants found here were then followed up in a second stage that was based on the data of a further 95,000 subjects.”* This allowed the scientists to increase the number of variants from 54 to 97. The scientists hope that in the future, it will be possible to intervene at these points in the lung biology in order to battle diseases. Active substances are already being developed for some areas, according to the authors of the work, which was conducted under the aegis of the University of Leicester (please find the respective press release here). The scientists furthermore developed a risk score** in order to predict the probability of COPD development. Patients with the highest scores had an almost four times greater risk of developing COPD than those with the lowest scores.