Iron build-up in the lung cells and tissues is associated with worse asthma symptoms and lower lung function, according to new research published in the European Respiratory Journal.

The study, which includes data from asthma patient samples and mouse models, is the first to definitively show a relationship between iron build-up in the lung cells and tissues and the severity of asthma, according to the researchers.

In addition, the models show that iron build-up in the lungs triggers immune system responses that are typical in asthma and lead to worsening of the disease. This includes increased mucus secretion and scarring of the lungs, which result in the narrowing of the airways, making breathing more difficult, according to the study.

“Our organs and tissues need iron to support oxygen flow and normal enzyme activity, but infections in the body also need iron to thrive,” study lead author Jay Horvat, associate professor of Immunology and Microbiology at the University of Newcastle and Hunter Medical Research Institute, Australia, said in a press release. “Because of this, our immune system has ways of hiding iron minerals within cells where infections cannot access the iron. This can result in a build-up of iron in the cells and tissues of nearby organs.”

Using a combination of asthma patient samples and experimental models to investigate irregular iron absorption into lung cells, the researchers assessed how lung cell iron levels affect disease severity in 11 severe and 12 mild-to-moderate asthma cases. Asthma severity was compared with the iron levels of 12 healthy people who did not have asthma by how much air a person could breathe out in 1 second and the frequency of experiencing asthma symptoms.

Researchers collected airway cell samples from participants using biopsy and using a bronchoscope “wash,” in which a thin tube is inserted into the mouth and nose to pass a small amount of salty water into a certain part of the lung. After the liquid is sucked back out through the tube, it is tested.

The data was accompanied by high-quality lung cell samples collected via bronchial brushing, in which a small, stiff-bristle brush is passed through the bronchoscope tube into the lungs, brushing along the inside of the airways to collect cells. Samples were collected from 39 severe and 29 mild-to-moderate asthmatics, as well as 29 healthy people as part of the wider data collection for the Europe-wide U-BIOPRED project.

The researchers found that iron levels outside of the lung cells were lower in patients with asthma compared with healthy people. Iron levels were also significantly lower in severe asthmatics compared with mild-to-moderate asthmatics.

Meanwhile, iron levels within the lung cells were markedly higher in the bronchoscope “wash” samples of mild-to-moderate and severe asthmatics compared with healthy people. Although the difference in lung cell iron levels between severe asthmatics compared with mild-to-moderate asthmatics was not significant, the analyses showed that having high levels of iron in the lung cells and less iron outside of cells was associated with more severe airflow obstruction. Together, the results show that lower iron levels outside of cells and higher iron levels within cells were both associated with lower lung function and worse asthma, according to the study authors.

The research team also carried out lab tests using 2 different mouse models to investigate the effects of increased lung cell iron levels on asthma severity. Over 8 weeks, 1 group of mice was exposed to iron overload through diet and another group were fed a normal low-iron diet. Liver and lung tissues were collected from the mice at the end of the study period for further analysis and airway inflammation was measured.

The study showed that increasing lung cell iron levels caused inflammatory cell responses, such as increased mucus secretion and scarring in the airways, which leads to the worsening of asthma, according to the researchers.

Although the findings suggest the potential for the development of asthma treatments that target irregular iron absorption in the lung cells and tissues, more research is needed to determine why there is increased absorption in the lungs of asthmatics, according to the study authors.

“We still know so little about how iron intake and the way the body regulates iron can affect iron levels in lung cells and tissues, but we hope this data will encourage more funding for research that investigates the role and therapeutic use of iron in asthma, as targeted treatments, dietary iron or supplement use could improve patient outcomes,” Horvat said in a press release.

The research team is currently investigating ways to modify the iron storage process in lung cells and whether it is possible to alter the number of the cells that are responsible for iron absorption into the lung cells. These approaches could lead to therapies for rare lung diseases, such as idiopathic pulmonary fibrosis, on top of asthma, according to the study authors.

REFERENCE

High levels of iron in the lung linked to increased asthma severity. ScienceDaily. https://www.sciencedaily.com/releases/2020/03/200317215628.htm. Published March 17, 2020. Accessed March 23, 2020.