Six genes predict the outcome of lung fibrosis

Prof. Dr. Antje Prasse, scientist at BREATH, the Hannoverian site of the German Center for Lung Research, is the lead author of a study that can help predict the course of idiopathic pulmonary fibrosis. With only six genes, a stable risk assessment is possible. The study contributes to a better understanding of this fatal lung disease.

The lung is made up of many different cell types. In addition to the air-bearing parts, a scaffold of connective tissue cells ensures the structure of the lungs. Fibrosis leads to a pathological increase of this pulmonary connective tissue. The resulting increased scarring stiffens and shrinks the lungs. As a result, there is a lack of oxygen. If no specific trigger for the fibrotic changes can be identified, it is referred to as idiopathic pulmonary fibrosis - IPF for short.

The course of an IPF varies greatly from patient to patient and is not easily predictable. The disease is generally considered to be aggressive and usually is fatal within a few years. A study from Germany, Italy and Belgium now investigated if the gene expression of cells obtained by means of a lung lavage, the bronchoalveolar lavage (BAL), is able to predict the disease course. The study was conducted by Prof. Dr. Antje Prasse, a scientist from BREATH, the Hanoverian location of the German Center for Lung Research, and her research group at the Department of Pneumology of the Hannover Medical School and the Fraunhofer Institute for Toxicology and Experimental Medicine in collaboration with international cooperation partners.

The prediction of IPF disease progression based on clinical values is only hardly possible. There has been no information on the molecular changes in the actually changing cells of the lungs. The study at hand now closes this gap. For the diagnosis of IPF, only less than 30 percent of all patients undergo invasive lung biopsies. This approach, therefore, is of limited use for the routine extraction of lung cells for further research. Instead, this study used cells harvested during bronchoalveolar lavage (BAL). Here, rinsing of deep-set structures of the lungs, the alveoli, flushes out cells of the outer layers of the alveoli.

In the pulmonary cells obtained by BAL, the expressed genes were analysed. By comparison with gene expression from healthy control patients, well over 1,500 genes were identified that are associated with the risk of death in IPF patients. Statistical predictive models were then used to identify six genes that could be used to establish stable risk ratings in the three European patient cohorts studied. These six genes alone allowed for a better prediction of the risk of death than the commonly used GAP index for predicting the course of the disease in IPF, which only takes clinical parameters into account. Prof. Prasse explains: "By analyzing the GAP index and the results of the risk assessment of the gene panel together, we can predict the course of the disease with a much higher accuracy. For the patients with an IPF, the gene panel has a considerable added value. "

In addition, for the first time, the study provides evidence that bronchial basal cells, a progenitor cell of the respiratory epithelium, play a key role in the development of IPF. In the long term, this finding could lead to a better treatment of this still poorly understood disease.

Bild: MHH / Figiel


Prof. Dr. Antje Prasse, Lead scientist at the Department of Pulmonology at Hannover Medical School and scientist at Fraunhofer-ITEM