Biomarker Commons

Hyperoxidized peroxiredoxins in peripheral blood mononuclear cells of asthma patients is associated with asthma severity.

Life Sci. 2012 Apr 9;90(13-14):502-8

Authors: Kwon HS, Bae YJ, Moon KA, Lee YS, Lee T, Lee KY, Kim TB, Park CS, Moon HB, Cho YS

Abstract
AIMS: Oxidative stress is involved in the pathogenesis of asthma, and peroxiredoxins (PRDX) may be critical in controlling intracellular oxidative stress. The aim of this study was to evaluate expressions of PRDX and their hyperoxidized forms in asthmatic individuals.
MAIN METHODS: The levels of expression of PRDX1, PRDX2, PRDX3, and PRDX6 and their hyperoxidized forms (PRDX-SO(3)) were measured in PBMCs from asthma patients and control subjects. In addition, cells from these subjects were treated with hydrogen peroxide (H(2)O(2)) and their intracellular concentrations of reactive oxygen species (ROS) were measured.
KEY FINDINGS: The ratios of hyperoxidized to total PRDX (PRDX-SO(3/)PRDX) in PBMCs were significantly higher in asthma patients than in normal subjects and were correlated with disease severity, with the highest ratio seen in patients with severe asthma. Furthermore, H(2)O(2) treatment of PBMCs, particularly lymphocytes, increased intracellular ROS concentrations with greater and more persistent increases observed in cells from asthmatic than from control subjects.
SIGNIFICANCE: Hyperoxidation of PRDX may serve as a biomarker of asthma severity and may predict enhanced susceptibility to oxidative stress load in PBMCs of asthmatics.

PMID: 22285837 [PubMed - indexed for MEDLINE]

Daily exhaled nitric oxide measurements and asthma exacerbations in children.

Allergy. 2012 Feb;67(2):265-71

Authors: van der Valk RJ, Baraldi E, Stern G, Frey U, de Jongste JC

Abstract
BACKGROUND: Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short-term increase in FeNO may indicate a higher risk of future asthma exacerbations.
OBJECTIVE: To assess changes in FeNO before and after asthma exacerbations compared to a stable control period.
METHODS: A post hoc analysis was performed on daily FeNO measurements over 30 weeks in children with asthma (n = 77). Moderate exacerbations were defined by an increase in symptom scores and severe exacerbations by prescription of prednisone. Individual mean and maximum FeNO, the variability of FeNO assessed by the coefficient of variation (CV), and slopes of FeNO in time were all quantified in 3-week blocks. Cross-correlation of FeNO with symptoms and autocorrelation of FeNO were assessed in relation to exacerbations and examined as predictors for exacerbations compared to reference periods using logistic regression.
RESULTS: Fractional exhaled nitric oxide could be assessed in relation to 25 moderate and 12 severe exacerbations. The CV, slope, cross-correlation, and autocorrelation of daily FeNO increased before moderate exacerbations. Increases in slope were also randomly seen in 19% of 2-week blocks of children without exacerbations. At least 3-5 FeNO measurements in the 3 weeks before an exacerbation were needed to calculate a slope that could predict moderate exacerbations. No specific pattern of FeNO was seen before severe exacerbations.
CONCLUSION: Fractional exhaled nitric oxide monitoring revealed changes in FeNO prior to moderate exacerbations. Whether this can be used to prevent loss of asthma control should be further explored.

PMID: 21999328 [PubMed - indexed for MEDLINE]

Self-assembled micellar formulation of chafuroside A with improved anti-inflammatory effects in experimental asthma/COPD-model rats.

Eur J Pharm Sci. 2012 Jan 23;45(1-2):184-9

Authors: Onoue S, Matsui T, Aoki Y, Ishida H, Nukaya H, Kou K, Yamada S

Abstract
Chafuroside A (CFA), a poorly water-soluble flavone C-glycoside, was firstly isolated from oolong tea, and it acts as a potent anti-inflammatory agent. The present study was undertaken to develop a water-soluble formulation of CFA using a self-assembled micellar (SAM) system, with the aim of improved dissolution behavior and potent anti-inflammatory effects. The SAM formulation of CFA (CFA/SAM) was characterized in terms of its morphology, particle size distribution, crystallinity, and dissolution behavior. In dissolution testing, the CFA/SAM exhibited marked improvement in dissolution behavior when compared with crystalline CFA, and then, nano-micellar particles were constituted with a mean diameter of 84 nm. The therapeutic potential of the crystalline CFA and CFA/SAM was assessed using an experimental asthma/chronic obstructive pulmonary disease (COPD)-like model. Orally-administered CFA at 0.5mg/kg or higher could attenuate inflammatory symptoms in a dose-dependent manner, as evidenced by decreases of infiltrated granulocytes, including macrophages and neutrophils, and myeloperoxidase, a specific biomarker for neutrophilia. Biomarker profiling demonstrated that the CFA/SAM at 0.1mg CFA/kg was equipotent to CFA at 1.0mg/kg in ameliorating antigen-induced airway inflammation, suggesting the better pharmacological effect of CFA/SAM due to improved dissolution behavior. From these observations, the SAM formulation might be an efficacious approach for enhancing the therapeutic potential of CFA for treatment of inflammatory diseases.

PMID: 22108345 [PubMed - indexed for MEDLINE]

Plasma biomarkers distinguish non-small cell lung cancer from asthma and differ in men and women.

Cancer Genomics Proteomics. 2012 Jan;9(1):27-35

Authors: Izbicka E, Streeper RT, Michalek JE, Louden CL, Diaz A, Campos DR

Abstract
BACKGROUND: Lung cancer (LC) is the leading cause of deaths caused by cancer worldwide. A diagnostic test for LC is needed for monitoring high-risk populations.
PATIENTS AND METHODS: Fifty-seven markers were measured using multiplex immunoassays of plasma of patients with non-small cell lung cancer (NSCLC); (245 men, 114 women, 1 unknown), asthma (67 men, 111 women, 2 unknown) and of healthy controls (165 men, 122 women, 1 unknown). Mass spectrometry was used for biomarker discovery. A support vector machine (SVM) was used for data analysis.
RESULTS: When all biomarkers and both genders were co-analyzed, SVM classified NSCLC and asthma with an accuracy of 0.94. Restricting to NSCLC versus healthy using best subsets of variables (males: epidermal growth factor (EGF), interleukin-8 (IL-8), soluble Fas (sFas), matrix metalloproteinase-9 (MMP-9), plasminogen activator inhibitor-1 (PAI-1); females: EGF, soluble cluster of differentiation 40 (sCD40) ligand, IL-8) yielded sensitivity and specificity of 1. Expression of eleven mass spectrometric biomarkers differed between pathologies.
CONCLUSION: Significant inter-pathology and gender differences between biomarkers may improve diagnosis of LC.

PMID: 22210046 [PubMed - indexed for MEDLINE]

Proteomics in asthma and COPD phenotypes and endotypes for biomarker discovery and improved understanding of disease entities.

J Proteomics. 2011 Dec 10;75(1):192-201

Authors: O'Neil SE, Lundbäck B, Lötvall J

Abstract
The application of proteomics to respiratory diseases, such as asthma and COPD, has been limited compared to other fields, like cancer. Both asthma and COPD are recognised to be multi-factorial and complex diseases, both consisting of clusters of multiple disease phenotypes. The complexity of these diseases combined with the inaccessibility and invasiveness of disease relevant samples have provided a hurdle to the progress of respiratory proteomics. Advances in proteomic instrumentation and methodology have led to the possibility to identify proteomes in much smaller quantities of biological material. This review focuses on the efforts in respiratory proteomics in relation to asthma and COPD, and the importance of identifying subgroups of disease entities to establish appropriate biomarkers, and to enhance the understanding of underlying mechanisms in each subgroup. Careful phenotype characterisation of patient subpopulations is required to make improvement in the field of heterogeneous diseases such as asthma and COPD, and the clusters of phenotypes are likely to encompass subgroups of disease with distinct molecular mechanisms; endotypes. The utilisation of modern advanced proteomics in endotypes of asthma and COPD will likely contribute to the increased understanding of disease mechanisms, establishment of biomarkers for these endotypes and improved patient care.

PMID: 22037230 [PubMed - indexed for MEDLINE]

Air exposure assessment of TDI and biological monitoring of TDA in urine in workers in polyurethane foam industry.

Occup Environ Med. 2012 Feb;69(2):93-8

Authors: Geens T, Dugardin S, Schockaert A, De Cooman G, van Sprundel M

Abstract
OBJECTIVES: Toluene diisocyanate (TDI) is used in the manufacturing process of polyurethane (PU) foams and is a potent inducer of occupational asthma. The objective of this study was to evaluate the correlation between the exposure to total TDI (2,4- and 2,6-TDI) in air and the corresponding biomarker concentration of total TDA (2,4- and 2,6-TDA) in hydrolysed urine. The aim was also to propose an appropriate biological exposure limit for total TDA in urine.
METHODS: 9 workers from two production lines in a PU foam producing plant were studied. Personal exposure to TDI during four representative production shifts was monitored by an active air sampling method (filter impregnated with 1-(2-methoxyphenyl)piperazine) and quantified by high-performance liquid chromatography and diode array detection (NIOSH n° 2535, 5521). In parallel, pre-shift and post-shift urinary samples were collected from the exposed workers, and TDA concentrations were determined by gas chromatography-mass spectrometry after alkaline hydrolysis. All samples were collected on four measuring days: two Fridays (end of workweek) and two Mondays (start of workweek) separated by a weekend without exposure.
RESULTS: Strong correlations between the personal air concentrations of total TDI and the corresponding biomarker levels of total TDA in urine (r=0.816) were observed. An increase of 18.12 μg TDA/l (post-shift minus pre-shift concentration) corresponds to an exposure of 5 ppb (37 μg/m(3), the current American Conference of Governmental Industrial Hygienists threshold limit value) during the shift.
CONCLUSIONS: The increase in TDA during the shift is a suitable biomarker for exposure to TDI during the same shift. Further research is needed to evaluate the use of start of week or end of week post-shift TDA in urine as biomarker since TDA was found to accumulate during the working week and thus the moment of sampling will clearly influence the result.

PMID: 21725071 [PubMed - indexed for MEDLINE]

Inflammatory biomarkers in severe asthma.

Curr Opin Pulm Med. 2012 Jan;18(1):35-41

Authors: Chung KF

Abstract
PURPOSE OF REVIEW: Severe asthma remains a condition in search of deeper understanding and of newer effective therapies. Risk factors for developing severe asthma, phenotyping of disease, characterizing the inflammatory response and understanding of poor therapeutic responses to corticosteroids are important areas of research. The development of biomarkers for phenotypic diagnosis and prognostic reasons is important.
RECENT FINDINGS: Severe asthma has been defined as asthma that does not respond adequately to asthma medications, particularly corticosteroids, with continuing loss of control of asthma and future risk of exacerbations and side effects from corticosteroid therapy. This is a heterogeneous condition and cluster analyses have yielded phenotypes on the basis of age of onset of disease, sex, lung function, atopy and questionnaire data. Use of sputum eosinophil counts has further defined a group with persistent eosinophilic inflammation despite corticosteroid therapy, and a noneosinophilic group with uncontrolled asthma.
SUMMARY: Use of a single biomarker provides value in phenotyping and in predicting response to treatment but many more biomarkers such as those derived from -omic approaches remain to be used in the analysis. A systems biology approach to finding novel biomarkers is the way forward to stratify severe asthma so that appropriate and distinct therapies can be selected for each subtype.

PMID: 22045348 [PubMed - indexed for MEDLINE]

Association between biomarker-quantified antioxidant status during pregnancy and infancy and allergic disease during early childhood: a systematic review.

Nutr Rev. 2011 Nov;69(11):627-41

Authors: Patelarou E, Giourgouli G, Lykeridou A, Vrioni E, Fotos N, Siamaga E, Vivilaki V, Brokalaki H

Abstract
Recent findings suggest a significant association between the antioxidant status of pregnant women and of their children during the first years of life and the development of allergic disease during childhood. The aim of this review was to identify all studies that estimated the effect of intake of antioxidants in pregnant women and their children on the development of allergic disease during early childhood. A systematic review was conducted of epidemiological studies featuring original peer-reviewed data on the association between dietary antioxidant status and allergic disease during childhood. A systematic search was performed following the Meta-analysis of Observational Studies in Epidemiology Guidelines. A comprehensive search of the literature yielded 225 studies, 18 of which were selected for the extraction of results and were related to antioxidant status and allergic disease. The systematic review included five prospective cohort studies, four cross-sectional studies, and nine case-control studies. Eight studies reported an important association between antioxidant status and asthma onset during childhood. Similarly, wheezing and eczema were studied as an outcome in six and in five studies, respectively. Recent observational studies suggest that a higher intake of antioxidant vitamins, zinc, and selenium during pregnancy and childhood reduces the likelihood of childhood asthma, wheezing, and eczema.

PMID: 22029830 [PubMed - indexed for MEDLINE]

The biochemistry of asthma.

Biochim Biophys Acta. 2011 Nov;1810(11):1017-24

Authors: Gaston B

Abstract
BACKGROUND: Asthma is not one disease. Different patients have biochemically distinct phenotypes.
SCOPE OF REVIEW: Biomarker analysis was developed to identify inflammation in the asthmatic airway. It has led to a renewed interest in biochemical abnormalities in the asthmatic airway. The biochemical determinants of asthma heterogeneity are many. Examples include decreased activity of superoxide dismutases; increased activity of eosinophil peroxidase, S-nitrosoglutathione reductase, and arginases; decreased airway pH; and increased levels of asymmetric dimethyl arginine.
MAJOR CONCLUSIONS: New discoveries suggest that biomarkers such as exhaled nitric oxide reflect complex airway biochemistry. This biochemistry can be informative and therapeutically relevant.
GENERAL SIGNIFICANCE: Improved understanding of airway biochemistry will lead to new tests to identify biochemically unique subpopulations of patients with asthma. It will also likely lead to new, targeted treatments for these specific asthma subpopulations. This article is part of a Special Issue entitled Biochemistry of Asthma.

PMID: 21718756 [PubMed - indexed for MEDLINE]