Sputum Trace Metals Are Biomarkers of Inflammatory and Suppurative Lung Disease

Gray, Robert D.; Duncan, Andrew; Noble, Donald; Imrie, M.; O'Reilly, Dennis St. J.; Innes, J A; Porteous, David J.; Greening, A P; Boyd, A. Christopher

doi:10.1378/chest.09-1047

Cited by 96 publications

(123 citation statements)

References 42 publications

(46 reference statements)

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“…Another study demonstrated that there were elevated levels of Zn and Cu in sputum in suppurative and inflammatory lung disease, whereas the levels of Zn declined after the suppurative and inflammatory lung disease exacerbation was treated. 26 Tanrikulu et al 27 found increased Cu and Zn levels in the COPD exacerbation group, and Cu and Zn levels negatively correlated with FEV 1 and FVC levels. In agreement with this study, we determined in our study that the levels of Cu and Zn were elevated in the COPD exacerbation group, and there was a negative correlation of the Cu and Zn levels with the FEV 1 and FVC levels.…”

Section: Discussionmentioning

confidence: 95%

Serum Telomerase Levels and COPD Exacerbations

Bozkuş¹,

Güler

Sımsek

2016

Respir Care

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BACKGROUND: To our knowledge, there is no study on the level of telomerase in subjects with COPD during an exacerbation period. The objective of this work was to compare lipid peroxidation, telomerase, zinc (Zn), copper (Cu), and malondialdehyde levels in asymptomatic smokers and subjects with COPD exacerbation. METHODS: The study included 45 subjects with COPD exacerbation and 42 healthy subjects with tobacco use as a control group. Samples were taken from blood and after the serum levels of telomerase malondialdehyde, Cu, and Zn were measured, the values were compared between the 2 groups. Tests for respiratory function were performed, and sedimentation and C-reactive protein levels were measured. RESULTS: The COPD exacerbation group had a significantly (P < .001) lower Cu/Zn ratio compared with the control group; however, the COPD exacerbation group had significantly (P < .001) higher levels of telomerase malondialdehyde, Cu, and Zn compared with the control group. Malondialdehyde, Cu, Zn, and FEV 1 were found negatively correlated in the COPD exacerbation and control groups (P < .001). The COPD exacerbation group had lower FEV 1 and FVC compared with the control group. The COPD exacerbation group had significantly (P < .001) higher levels of C-reactive protein and a higher blood cell sedimentation rate compared with the control group. CONCLUSIONS: The reason why the subjects had a reduced Cu/Zn ratio and increased levels of telomerase, Cu, and Zn is likely to be oxidative stress, which can be defined as an increased exposure to oxidants and/or decreased antioxidant capacities It is obvious from this study that lung oxidant-antioxidant balance is abnormal in subjects with COPD exacerbation and also that the increased level of telomerase is associated with this imbalance.

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Section: Discussionmentioning

confidence: 95%

Serum Telomerase Levels and COPD Exacerbations

Bozkuş¹,

Güler

Sımsek

2016

Respir Care

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“…In a recent study of CF pulmonary exacerbation, patients following treatment with intravenous antibiotics had lower hepcidin and IL-6 levels in serum, increased serum iron, and a trend towards lower sputum iron levels -further evidence of the impact of infection and inflammation on iron metabolism (Gifford et al, 2012). Not surprisingly, given the inflammatory environment of the CF lung, elevated levels of iron and ferritin have been detected in CF sputum by a number of studies (Stites et al, 1998(Stites et al, , 1999Reid et al, 2004Reid et al, , 2007Gray et al, 2010). More recently in a comprehensive study of iron in CF, Ghio et al (2013) demonstrated increased levels of iron and iron-related proteins in bronchoalveolar lavage fluids from CF children, in macrophages of explanted CF lungs and in lung tissue from CF patients -clear evidence of altered iron homeostasis and of iron accumulation in the CF airways (Ghio et al, 2013).…”

Section: Iron and Cfmentioning

confidence: 97%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

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Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.

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“…Sputum has also been used to predict lung cancer by detecting its aberrant promoter methylation (19,20) or metal ions (21); however, the screening might be limited by the sample availability or composition variability. Different proteomic technologies have been engaged for this type of biomarker discovery.…”

mentioning

confidence: 99%

Proteomic Analysis of Human Saliva From Lung Cancer Patients Using Two-Dimensional Difference Gel Electrophoresis and Mass Spectrometry

Xiao¹,

Zhang²,

Zhou³

et al. 2012

Molecular & Cellular Proteomics

166

108

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Lung cancer is often asymptomatic or causes only nonspecific symptoms in its early stages. Early detection represents one of the most promising approaches to reduce the growing lung cancer burden. Human saliva is an attractive diagnostic fluid because its collection is less invasive than that of tissue or blood. Profiling of proteins in saliva over the course of disease progression could reveal potential biomarkers indicative of oral or systematic diseases, which may be used extensively in future medical diagnostics. There were 72 subjects enrolled in this study for saliva sample collection according to the approved protocol. Two-dimensional difference gel electrophoresis combined with MS was the platform for salivary proteome separation, quantification, and identification from two pooled samples. Candidate proteomic biomarkers were verified and prevalidated by using immunoassay methods. There were 16 candidate protein biomarkers discovered by two-dimensional difference gel electrophoresis and MS. Three proteins were further verified in the discovery sample set, prevalidation sample set, and lung cancer cell lines. The discriminatory power of these candidate biomarkers in lung cancer patients and healthy control subjects can reach 88.5% sensitivity and 92.3% specificity with AUC ‫؍‬ 0.90. This preliminary data report demonstrates that proteomic biomarkers are present in human saliva when people develop lung cancer. The discriminatory power of these candidate biomarkers indicate that a simple saliva test might be established for lung cancer clinical screening and detection. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.012112, 1-12, 2012.Lung cancer has long been a significant worldwide public health issue. In the United States, lung cancer is the most common cause of cancer-related death in men and women. According to the American Cancer Society, the major type of lung cancer is non-small-cell lung cancer (NSCLC) 1 , which comprises ϳ85% of lung cancers (1, 2). Small cell lung cancer (SCLC) is another type of lung cancer, which represents about 15% of cases (3). Cigarette smoking causes lung cancer, which is by far the major risk factor (4, 5, 6). Lung cancer has a high mortality rate among malignancies, in part because symptoms are frequently absent until disease is already metastatic and is, therefore, incurable (7,8,9). Early detection represents a very promising approach to reduce lung cancer incidence and mortality. However, conventional diagnostic methods for lung cancer are unsuitable for widespread screening because they are either expensive and occasionally miss tumors or invasive cancer (10,11,12,13). Computed tomography has been wildly used for lung cancer early screening, although it often produces a high rate of false positives (7,14,15). Better diagnostic methods are urgently needed to improve the detection of lung cancer.Tissue and blood have been extensively used in attempts to detect lung cancer earlier (1,16,17,18). Sputum has also been used to predict lung cancer by detecting its aberra...

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Sputum Trace Metals Are Biomarkers of Inflammatory and Suppurative Lung Disease

Cited by 96 publications

References 42 publications

Serum Telomerase Levels and COPD Exacerbations

Serum Telomerase Levels and COPD Exacerbations

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Proteomic Analysis of Human Saliva From Lung Cancer Patients Using Two-Dimensional Difference Gel Electrophoresis and Mass Spectrometry

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