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 researchers say that 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.
Jay Horvat, Associate Professor of Immunology and Microbiology at the University of Newcastle and Hunter Medical Research Institute, Australia, is the lead author of the study. He explained: “We know that both high and low iron levels are reported in asthma, but it is not clear whether iron build-up in the lungs contributes to disease development. We sought to build on this by investigating the link between iron and asthma, to better understand whether increased or decreased iron levels in the lung cells makes the disease worse.”
First, researchers at the University of Newcastle, Australia, assessed airway cell iron levels in 11 severe and 12 mild-to-moderate asthma patients and compared their iron levels with 12 healthy people who did not have asthma. Lung cell samples were collected using biopsy and bronchoscope wash. Asthma severity was determined by spirometry test and based on the frequency of experiencing asthma symptoms.
This data was supplemented by high-quality lung cell samples collected via bronchial brushing, including samples from 39 severe and 29 mild-to-moderate asthmatics and 29 healthy people taken from the Europe-wide U-BIOPRED cohort.
Multiple analyses showed that iron levels outside of the lung cells were lower in asthma patients compared with healthy people; iron levels were also significantly lower in severe asthmatics compared with mild-to-moderate asthmatics.
In contrast, 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. The difference in lung cell iron levels between severe asthmatics compared with mild-to-moderate asthmatics was not significant, but 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.
Professor Horvat explained the results: “We showed that lung function was lowest among patients with the highest levels of iron build-up in their airway cells and tissues. As lower iron levels outside of cells and higher iron levels within cells were both associated with worse lung function, we think that the immune system’s role in ‘hiding’ iron minerals within the lung cells may be contributing to asthma severity. However, data from the patient samples is not able to confirm this relationship, and the symptoms of increased iron in lung cells were not clear.”
Next, the researchers carried out lab tests using two different mouse models to investigate the effects of increasing lung cell iron levels on asthma severity. In one of the experimental models, mice were exposed to iron overload through diet and in another the researchers triggered iron overloading in the lung cells of mice that were fed a normal iron diet.
The analyses showed that increasing the lung cell iron levels caused inflammatory cell responses such as increased mucus secretion and scarring in the airways, which the researchers say leads to worsening of asthma.
Professor Horvat explained: “In humans, mucous secretion and lung scarring narrows the airways, causing airflow obstruction and breathing difficulties. These symptoms are common in asthma and other chronic lung diseases, and our data shows that increasing iron in the lung cells and tissues led to an increase in these effects. Our tests were well controlled to ensure that mice were not exposed to pathogens or other factors that might influence asthma, so we are confident that the data clearly demonstrates the link between increasing lung cell and tissue iron levels and these immune system responses.”
Professor Horvat added: “This study should not be interpreted as high lung iron levels being related to iron intake from diet or use of supplements. 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.”
The research team are now 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.
Christopher Brightling, Chair of the European Respiratory Society’s Science Council and Clinical Professor in Respiratory Medicine at the University of Leicester, UK, was not involved in the research. He said: “This research offers interesting data to suggest that more iron is absorbed into lung tissue in people with asthma, and that this is associated with disease severity. Further research needs to confirm this finding and investigate this process, which could possibly lead to new therapies.
“It is important to note that the research does not suggest high iron levels in the lungs is because of diet. People who are living with asthma should not avoid iron-rich foods based on this research.”