New research from the University of Newcastle and Hunter Medical Research Institute, Australia, has suggested that people with asthma have a greater build-up of iron in their lung tissue than people without asthma and that this increased iron accumulation is associated with disease severity.
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The research, which was recently published in the European Respiratory Journal, demonstrated that iron accumulation in asthmatics is associated with decreased lung function and worse disease symptoms.
Lead author Jay Horvat and colleagues say the study is the first to clearly demonstrate an association between iron accumulation in lung tissue and the severity of asthma symptoms.
Iron in health and in asthma
Iron is an essential dietary mineral required by red blood cells to transport oxygen around the body. However, excess iron absorption can lead to unhealthy levels of it accumulating in cells.
Our organs and tissues need iron to support oxygen flow and normal enzyme activity, but infections in the body also need iron to thrive. 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."
Jay Horvat, lead author
Horvat also says that research has suggested that abnormal iron levels are associated with lung disease: “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.”
The researchers, therefore, set out to further investigate the association, aiming to find out whether it is more or less iron in the lung tissue that worsens disease symptoms.
What did the study involve?
Using biopsies to collect airway cell samples, the team tested iron levels in the airways of 11 patients with severe asthma and 12 patients with mild-to-moderate disease and compared the findings with airway tests of 12 healthy individuals who did not have the condition.
The team also used lung samples collected using a process called bronchial washing, which uses a bronchoscope to guide a tiny brush that collects cells from inside the airways. These samples had been taken from 39 patients with severe disease and 29 with mild-to-moderate disease as part of the U-BIOPRED (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes) project.
After conducting a number of iron level tests, the team found that asthma patients had lower levels of iron in the extracellular environment than healthy individuals did and that people with severe asthma had significantly lower extracellular iron than people with mild-to-moderate disease.
The researchers also found that intracellular iron concentrations were significantly higher among people with mild-to-moderate and severe disease than among people without asthma.
The difference in iron concentration between those with severe disease and mild-to-moderate disease was not significant, but the higher the intracellular iron and the lower the extracellular iron, the more obstructed airflow was.
What are the implications of the study?
The findings suggest that decreased extracellular iron and increased intracellular iron are linked to decreased lung function and more severe asthma symptoms.
"We showed that lung function was lowest among patients with the highest levels of iron build-up in their airway cells and tissues,” says Horvat. “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."
The team says the results could potentially pave the way for new asthma treatments that are designed to target unhealthy iron absorption in lung tissue, although further investigations are required to find out the reason for excess iron absorption among asthma patients in the first place.
People should not misinterpret the findings
Horvat warns that people should not interpret the findings as meaning iron absorbed from food or supplements can cause increased iron in the lungs, as too little is understood about iron regulation in the body and the effects this has on lung tissue. However, “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," he adds.
The researchers are now exploring how the process of storing iron in the lungs can be changed, as well as whether the number of cells involved in iron absorption can be changed. The team hopes that such approaches may lead the way for new treatments for asthma, as well as other lung conditions.
Chair of the European Respiratory Society's Science Council, Christopher Brightling, says that further research is needed to confirm the interesting findings and to explore the underlying process in the hope of discovering new therapies. However, Brightling also warns against assuming that dietary iron intake causes the iron accumulation in the lungs and that asthmatics should not stop eating foods that are a good source of iron-based on these results:
“To manage their condition most effectively, people with asthma should continue to eat a balanced diet that includes their recommended daily level of iron, and they should use the medications prescribed by their doctors and try to lead an active lifestyle."
High levels of iron in the lung linked to increased asthma severity. EurekAlert! 2020. Available at: https://doi.org/10.1183/13993003.01340-2019