Smoking-induced iron dysregulation in the lung

Abstract

Iron is one of the most abundant transition elements and is indispensable for almost all organisms. While the ability of iron to participate in redox chemistry is an essential requirement for participation in a range of vital enzymatic reactions, this same feature of iron also makes it dangerous in the generation of hydroxyl radicals and superoxide anions. Given the high local oxygen tensions in the lung, the regulation of iron acquisition, utilization, and storage therefore becomes vitally important, perhaps more so than in any other biological system. Iron plays a critical role in the biology of essentially every cell type in the lung, and in particular, changes in iron levels have important ramifications on immune function and the local lung microenvironment. There is substantial evidence that cigarette smoke causes iron dysregulation, with the implication that iron may be the link between smoking and smoking-related lung diseases. A better understanding of the connection between cigarette smoke, iron, and respiratory diseases will help to elucidate pathogenic mechanisms and aid in the identification of novel therapeutic targets.

Iron status and risk factors for iron depletion in a racially/ethnically diverse blood donor population

“…Although confounding by alcohol use, which is positively correlated with both smoking and ferritin values, might explain in part our findings, the Pfeiffer study, which controlled for alcohol, showed that smoking and alcohol had independent effects on ferritin of comparable magnitude . While the mechanism of how smoking impacts iron homeostasis is under active investigation, ferritin's being an acute‐phase reactant responsive to inflammation, infection, and other stimuli is relevant. A large study of the Danish cohort confirms low‐grade inflammation, as measured by C‐reactive protein, in donors who smoked, were obese, and used oral contraceptives .…”

Decreased lung function is associated with elevated ferritin but not iron or transferrin saturation in 42,927 healthy Korean men: A cross-sectional study

“…Ferritin is a specialized iron storage protein that regulates body iron homeostasis and reflects iron stores in the body. Ferritin also can become elevated in the presence of oxidative stress and inflammation irrespective of iron status and can contribute to various clinical diseases, especially pulmonary and cardio-metabolic diseases [2,3]. Moreover, decreased lung function is associated with oxidative stress and systemic inflammation [4] and increased risk of insulin resistance, diabetes, and cardiovascular disease [5].…”

“…However, these previous studies were not conducted only in healthy subjects. Recent studies have continuously shown that pulmonary [2] and cardio-metabolic diseases [13][14][15][16][17][18] are a recognized complication of excess iron accumulation, and such patients are prone to poor lung function [2,5]. This suggests that inclusion of patients with clinical disease could distort the magnitude of association between lung function and ferritin.…”

Increased airway iron parameters and risk for exacerbation in COPD: an analysis from SPIROMICS

“…The regulation of iron acquisition, utilization, and storage is fundamental to the correct function of lung epithelial, endothelial, and immune cells 37 . Iron is also crucial for the metabolism and growth of native and pathogenic microbes, including those associated with recurrent infections in COPD such as Haemophilus influenzae and Pseudomonas aeruginosa 38,39 .…”