Iron level in the airways may be closely related to the pathogenesis and severity of asthma, according to study results published in the European Respiratory Journal.
According to clinical and experimental evidence, altered levels of lung iron and/or iron regulatory molecules are associated with lung inflammation in asthma. However, there are sparse data on the effects of altered iron levels in the lungs on asthma, and whether altered iron levels play a role in the pathogenesis of asthma or occur as a result of asthma. The objective of this study was to assess iron levels and iron-related gene expression in the airways of patients with asthma and healthy study participants.
Researchers assessed iron regulatory factors in airway biopsy tissues and levels of iron in bronchoalveolar lavage (BAL) cells in 11 patients with severe asthma, 12 patients with mild to moderate asthma, and 13 healthy control individuals.
To model iron overload, researchers fed a high-iron diet to hemochromatosis protein gene-deficient mice and mice with wild-type genes for 8 weeks. House dust mite-induced experimental asthma was induced in these mice and in mice that were fed normal or low iron diets. Researchers then assessed multiple characteristics including iron quantification, airway inflammation, lung function, and iron-related gene expression in primary bronchial airway epithelial cells.
Researchers revealed that nonhaem iron levels in BAL supernatant were lower in patients with asthma compared with healthy controls, and were further reduced in patients with severe asthma when patients were separated into mild to moderate and severe asthma groups. The number of iron-loaded cells was higher in the BAL of patients with mild to moderate and severe asthma (0.129±0.021 and 0.853±0.327) compared with that in healthy controls (0.170±0.026; P <.05). Higher levels of extracellular iron were associated with better lung function whereas higher levels of iron positive cells were associated with worsened lung function.
Limitations to this study were the inability to measure iron levels in airway tissue biopsies and iron regulatory gene expression in BAL cells because of the lack of available tissue. Additionally, researchers used bronchoscopy samples from 2 different cohorts.
The study researchers concluded that in patients with asthma, altered levels of iron and iron-related gene expression in the airways are associated with lung function and that high accumulation of iron in the lungs may drive the pathogenesis and severity of asthma.
Ali MK, Kim RY, Brown AC, et al. Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma [published online March 17, 2020]. Eur Respir J. doi:10.1183/13993003.01340-2019