Evaluation Of New Biomarkers Research Articles

Comparison of the Level of Vitamins A, D and E of Plasma Seminal of Azoospermia and Normozoospermia.

<b>Background and Objective:</b> Biological exploration of male infertility is important for its treatment. Seminal plasma, by its composition, presents numerous molecules that can be exploited in the investigation of new sperm biomarkers. The evaluation of new biomarkers of azoosperm seminal plasma aims to identify vitamins A, D and E which can serve as discriminating biochemical markers in the exploration of azoospermia. <b>Materials and Methods:</b> Thirty normozoospermic and 30 azoospermic sperm samples were collected by masturbation after three days of sexual abstinence from consulting patients at the Pasteur Institute of Côte d'Ivoire. After centrifugation of the sperm, the seminal plasma was collected and were analyzed for vitamin A, D and E. After extracting the vitamins from the seminal plasma, they were quantified using high-performance liquid chromatography. <b>Results:</b> The concentration of vitamin A in seminal plasma from normal samples was 1.66±1.81 and 0.28±0.52 mg/L in pathological samples. The average vitamin D concentration in seminal plasma of normospermia was 0.27±0.40 and 0.08±0.12 mg/L in seminal plasma of azoospermia. For vitamin E, the results obtained show an average concentration of 2.56±3.58 mg/L in normal ejaculate and 0.33±0.51 mg/L in pathological ejaculate. Only vitamins A and E showed a significant difference in the two categories of sperms. <b>Conclusion:</b> The determination of the concentration of vitamins A, D and E in seminal plasma showed that only vitamins A and E can serve as a biomarker for the differentiation of normozoospermic and azoospermic sperm.

Evaluation Of New Biomarkers As A Predictor For Thrombosis In Patients with Thyroid Dysfunction

Evaluation Of New Biomarkers As A Predictor For Thrombosis In Patients with Thyroid Dysfunction

Evaluation of New Biomarkers in Early Diagnosis of Neonatal Bacterial Infections

Evaluation of New Biomarkers in Early Diagnosis of Neonatal Bacterial Infections

Evaluation of new biomarkers in stage III and IV endometriosis

Objective To investigate the efficacy of new endometriosis biomarkers in diagnosis and treatment. Methods Thirty women with Stage III-IV endometriosis who were given an indication for surgery and 49 control patients were compared. Preoperative and postoperative serum levels of Annexin A5 (ANXA5), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble vascular cell adhesion molecule-1 (sVCAM-1), vascular endothelial growth factors (VEGF) and Ca-125 measurements were compared. Results AUCs of ANXA5, sICAM-1, IL-6, TNF-α, VCAM-1, VEGF biomarkers were not found to be significant in diagnosing endometriosis when evaluated alone (p > 0.05). Only the AUC of the Ca-125 biomarker values were found to be significant with 73% sensitivity and 98% specificity (p < 0.001). However, when Ca-125 and ANXA5 were evaluated together, it was concluded that the diagnosis of endometriosis could be made with 73% sensitivity and 100% specificity. Conclusion When Ca-125 and ANXA5 are evaluated together, it seems to be more valuable than Ca-125 alone in diagnosing endometriosis.

Physical training for patients with depression and anxiety - a randomized controlled study

IntroductionPharmaceutical treatment and psychotherapy constitute the most common treatment methods for depression and anxiety. Physical training has been shown to have comparable effect to cognitive behavioral therapy in treatment of mild to moderate depression and anxiety. Physically active individuals also show lower risks to develop depression and relapse in depression.ObjectivesThe objectives are to evaluate how physical activity can affect depressive and anxiety symptoms, by examining biomarkers in the blood and from the gut and also by measuring cognitive functions. Hopefully, this can lead to new treatment strategies for patients with depression and anxiety.Methods102 patients are randomized to two groups and undergo 12 weeks intervention as add-on to standard outpatient psychiatric treatment. The first group will participate in physical training three times per week and the other group will receive relaxation therapy on a weekly basis. Daily activity intensity will be measured before and at the last week of intervention with an accelerometer. Blood and faeces sample collection, symptom grading by clinician together with self-rating scales and cognitive screening will be performed at baseline, week 12 and one year of follow-up. The cognitive screenings are performed digitally in cooperation with Mindmore.ResultsThe RCT is currently recruiting patients at the Department of Psychiatry of Örebro University Hospital.Conclusions The project aims to be holistic in its approach, combining the defining clinical psychiatric symptoms in patients who have both depression and anxiety with the finding and evaluation of new biomarkers from blood and gut to improve cognitive functions.DisclosureNo significant relationships.

Diagnosing Dyspneic Older Adult Emergency Department Patients: A Pilot Study.

Dyspnea is the second leading cause of US emergency department (ED) visits and an independent predictor of morbidity and mortality1 in older adult patients aged ≥65 years. Unfortunately, the diagnosis of the cause of dyspnea presents diagnostic challenges to emergency physicians2-4 that disproportionately affects older adults.5 One in 5 dyspneic older adults experience missed diagnosis in the ED2 and 21% are treated for ≥1 pneumonia, acute exacerbation of chronic obstructive pulmonary disease [COPD], and acute exacerbation of heart failure [HF].5 Importantly, some may have multiple causes of their dyspnea but accurate diagnosis remains critical.

Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

Idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbon in human blood serum are new biomarkers of lung cancer

Evaluation of epidemiologic risk factor in relation to lung cancer invoked by polycyclic aromatic hydrocarbons has been inconsistent. To address this issue, we conducted a prospective evaluation of new biomarkers for lung cancer classified according levels of idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbons in human blood serum. The blood serums of 557 lung cancer patients and 227 healthy donors were analysis of these antibodies by ELISA. Collected data were regrouped and analyzed by gender, smoking, and age as predictors of risk lung cancer factors. Also, the data of lung cancer patients were additionally analyzed by stages and types of lung cancer, surgery, and chemotherapy. It was suggested to use ratio of idiotypic and anti-idiotypic antibodies rather than distinguish level each of them separately. The ratio of levels in healthy people was 3.32 times higher than in lung cancer patients. This approach gave more precisely results and great prognostic value. The logistic regression model (AUC = 0.9) and neural networks (AUC = 0.95) were built to compare lung cancer patients and healthy donors by predictors. The ELISA data of 49 people random sampled from the originally ELISA data and ELISA data of 52 coal miners as a group of lung cancer risk were confirmed logistic regression model. So, suggested idiotypic and anti-idiotypic antibodies against polycyclic aromatic hydrocarbons were not only shown difference between healthy donors and lung cancer patients also elicited group of lung cancer risk among healthy people.

Evaluation of new biomarkers of stress in saliva of sheep

Some routine handling procedures can produce stress in farm animals, and an adequate control of these stressors is important to avoid the negative effects on animal health and production. The measurement of biomarkers in saliva can be a suitable tool for the evaluation and control of stress. In this report, lipase, butyrylcholinesterase (BChE), total esterase (TEA) and adenosine deaminase (ADA) activities in the saliva of sheep were evaluated as biomarkers of stress. For this purpose, they were measured after inducing stress by facing a dog (experiment 1) and shearing (experiment 2), and comparing them to other stress salivary biomarkers such as α-amylase (sAA) and cortisol, as well as heart rate (HR). Each analyte was measured at the basal time, and during and just after the end of the stressful stimulus, and at various times for the first hour after the period of stress induction. Values were compared with those obtained from a control group. Lipase was the only analyte that showed significant changes between the stress and the control group in both experiments. Although TEA and ADA increased after stress, no significant differences were seen compared with the control group. Lipase was correlated highly with sAA and HR, in experiment 1; and correlated moderately with cortisol and HR in experiment 2. Lipase showed the greatest percentage increase after the stressful stimuli and less overlap with the control group in the two experiments. From the results of this study it can be concluded that lipase, TEA, BChE and ADA are enzymes present in the saliva of sheep and that they can be measured by using simple and fast colorimetric methods. Further studies should be undertaken with regard to the possible application of lipase as a biomarker of stress in sheep.

ALTEA: A Software Tool for the Evaluation of New Biomarkers for Alzheimer's Disease by Means of Textures Analysis on Magnetic Resonance Images.

The current criteria for diagnosing Alzheimer’s disease (AD) require the presence of relevant cognitive deficits, so the underlying neuropathological damage is important by the time the diagnosis is made. Therefore, the evaluation of new biomarkers to detect AD in its early stages has become one of the main research focuses. The purpose of the present study was to evaluate a set of texture parameters as potential biomarkers of the disease. To this end, the ALTEA (ALzheimer TExture Analyzer) software tool was created to perform 2D and 3D texture analysis on magnetic resonance images. This intuitive tool was used to analyze textures of circular and spherical regions situated in the right and left hippocampi of a cohort of 105 patients: 35 AD patients, 35 patients with early mild cognitive impairment (EMCI) and 35 cognitively normal (CN) subjects. A total of 25 statistical texture parameters derived from the histogram, the Gray-Level Co-occurrence Matrix and the Gray-Level Run-Length Matrix, were extracted from each region and analyzed statistically to study their predictive capacity. Several textural parameters were statistically significant (p < 0.05) when differentiating AD subjects from CN and EMCI patients, which indicates that texture analysis could help to identify the presence of AD.

Three-tiered score for Ki-67 and p16ink4a improves accuracy and reproducibility of grading CIN lesions

AimsTo investigate the accuracy and reproducibility of a scoring system for cervical intraepithelial neoplasia (CIN1–3) based on immunohistochemical (IHC) biomarkers Ki-67 and p16ink4a.Methods115 cervical tissue specimens were reviewed by three...

P.69 - The evaluation of new biomarkers in a case of MELAS

The aim of our study is to evaluate the utility of new biomarkers, FGF-21 and GDF-15, as well as to confirm the efficacy of L-arginine and sodium pyruvate administration in a patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient was 60 years old women with mtT3271C mutation who developed abrupt onset of aphasia and stroke-like episodes. Muscle pathology and laboratory findings were compatible with MELAS. She was treated with L-arginine and sodium pyruvates, but her condition got worsen and died in 2 years. During the clinical course of the patient, we examined FGF-21 and GDF-15 which were reported to be sensitive and specific new biomarkers of mitochondrial diseases. Traditional biomarkers, lactate and pyruvate, were also measured and the relationship between serum levels of biomarkers and clinical severity scale were evaluated. We also performed autopsy and examined pathology. New biomarkers showed consistently high values along with the course and increased with disease progression. Of note, serum degree showed temporal fall when her consciousness was improved with sodium pyruvate therapy. In contrast, traditional biomarkers were increased in early stage and got decreased in advanced period. The intravenous infusion of L-arginine immediately recovered the stroke-like episodes attacks, but oral intake of L-arginine could not prevent the disease progression. Sodium pyruvate administration seemed to be effective, but was discontinued because of digestive dysfunction. In the pathological findings, most of stroke like lesions were on chronic stage, including cortical laminar necrosis and massive spongy change of gray and white matter. In this case, the utility of new biomarkers was demonstrated. Also, the positive effect of L-arginine and sodium pyruvate therapy on the disease progression was suggested.

Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure.

The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos. This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined. Benign pleural plaques were present in 27 (58.3%) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p=0.023, p=0.011, and p<0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p=0.041, p=0.023, p=0.002, and p=0.001, respectively), and significantly lower mean SDC-1 levels (p=0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95% CI0.79-0.92 and p<0.001 for SMRP, and 95% CI0.62-0.81 and p<0.001 for TRX). The cut-off value for SMRP was 0.62nmol/l (sensitivity: 97.6%, specificity: 68.9%, positive predictive value (PPV): 56.2%, and negative predictive value (NPV): 98.3%) and for TRX was 156.67ng/ml (sensitivity: 92.9%, specificity: 77.6%, PPV: 41.4%, and NPV: 92.1%). The combination of the biomarkers reached a sensitivity of 100%, but had lower specificity (as high as 27.7%). Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination.

Diagnostic and economic evaluation of new biomarkers for Alzheimer’s disease: the research protocol of a prospective cohort study

BackgroundNew research criteria for the diagnosis of Alzheimer’s disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model.Methods/designIn a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered.Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers.DiscussionSeveral other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems.Trial registrationNCT01450891

Brain death induced renal injury

The considerable demand in kidney transplantation against a persisting organ donor shortage has forced most centers to nowadays accept of suboptimal donor kidneys. Despite the substantial increase in the past decade in kidney transplantation with grafts retrieved from living donors and after donation from deceased brain dead (DBD) and extended criteria donation (ECD) donors, the supply of donor kidneys still does not meet the actual numbers needed. Moreover, older and more marginal kidney donors following the physiologically abnormal state of brain death do function less well and have a shorter graft survival. In this review, we present an overview of the current knowledge of renal injury induced by pathophysiological effects of brain death and its relevance for renal transplant outcome.The better insight in the role of brain death induced renal injury has clearly demonstrated its detrimental effect on outcome but, also, offers new opportunities for donor management and evaluation of new biomarkers to assess kidney graft quality in the brain dead donor. The option to intervene and selectively block or enhance a pathway as well as identify specific parameters for graft quality at time of organ retrieval in the deceased brain dead donor will ultimately benefit early function and long-term survival.

2326 ENGRAILED-2 (EN2): A URINARY BIOMARKER FOR THE DIAGNOSIS OF PROSTATE CANCER WITHOUT DRE

You have accessJournal of UrologyProstate Cancer: Markers1 Apr 20112326 ENGRAILED-2 (EN2): A URINARY BIOMARKER FOR THE DIAGNOSIS OF PROSTATE CANCER WITHOUT DRE Hardev Pandha, Mohammed Ismail, Angie Boxall, Aagna Bhatt, Stephen Langley, Richard Hindley, and Richard Morgan Hardev PandhaHardev Pandha Guildford, United Kingdom More articles by this author , Mohammed IsmailMohammed Ismail Guildford, United Kingdom More articles by this author , Angie BoxallAngie Boxall Guildford, United Kingdom More articles by this author , Aagna BhattAagna Bhatt Guildford, United Kingdom More articles by this author , Stephen LangleyStephen Langley Guildford, United Kingdom More articles by this author , Richard HindleyRichard Hindley Basingstoke, United Kingdom More articles by this author , and Richard MorganRichard Morgan Guildford, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2573AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. Recently described biomarkers are complex, expensive, often identify ‘high risk' but are not immediately diagnostic and not easily adopted into clinical practice. We have assessed the diagnostic potential of EN2 protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men. Detection of EN2 was simple and inexpensive. METHODS EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine (without prior digital rectal examination (DRE)) was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from 3 relevant control groups. EN2 protein was measured by ELISA in urine from men with PC (n=82) and controls (combined n=102). RESULTS EN2 expression was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE, with an overall AUC of 0.81. There was no correlation with PSA levels. These results we confirmed independently by a second academic centre in the United Kingdom. CONCLUSIONS Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. To date, the limitations of false positive PSA levels due to BPH have not been observed. No DRE was required unlike all other recently described markers, making it attractive as a screening tool in the future. No correlation with PSA was evident. A larger multicentre study to further evaluate the diagnostic potential of EN2 is justified. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e932-e933 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hardev Pandha Guildford, United Kingdom More articles by this author Mohammed Ismail Guildford, United Kingdom More articles by this author Angie Boxall Guildford, United Kingdom More articles by this author Aagna Bhatt Guildford, United Kingdom More articles by this author Stephen Langley Guildford, United Kingdom More articles by this author Richard Hindley Basingstoke, United Kingdom More articles by this author Richard Morgan Guildford, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Engrailed-2 (EN2): A Tumor Specific Urinary Biomarker for the Early Diagnosis of Prostate Cancer

Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men. EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n = 82) and controls (n = 102). EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center. Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified.

123 ENGRAILED-2 (EN2): A HIGHLY SPECIFIC URINARY BIOMARKER FOR THE EARLY DIAGNOSIS OF PROSTATE CANCER

Purpose: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men. Experimental Design: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)]was collected from menpresenting withurinary symptoms (referredto exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n ¼ 82) and controls (n ¼ 102). Results: EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center. Conclusions: Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified. Clin Cancer Res; 17(5); 1090–8. � 2011 AACR.

Development and validation of new biomarkers: major opportunities for health-care scientists

Reflecting significant advances in technology and substantial research investment in discovery programmes, thousands of new biomarkers with diagnostic potential have been identified over the last 30 years. However, only a tiny fraction of these – among them CA125, prostate specific antigen (PSA) and troponin – have successfully joined the routine clinical biochemistry repertoire, and often only after considerable delay. Reasons for this were considered at a multidisciplinary ‘Perspectives in Clinical Proteomics’ conference convened in March 2010 under the auspices of the Wellcome Trust. While primarily focusing on biomarkers identified using proteomic technologies, conclusions developed during the conference and subsequent retreat are equally relevant to the introduction of biomarkers identified by other routes. Among issues highlighted were the pressing need for more thorough and systematic evaluation of new biomarkers and the importance of early involvement of healthcare scientists, both of which are briefly considered here. A more detailed report is available as an open access publication with key points summarized here (Table 1). The proceedings of a recent International Federation of Clinical Chemistry and Laboratory Medicine Bergmeyer Conference on the same topic are also relevant.

Exhaled breath condensate in patients with asthma: implications for application in clinical practice

Exhaled breath condensate (EBC) analysis, a rather appealing and promising method, can be used to evaluate conveniently and non-invasively a wide range of molecules from the respiratory tract, and to understand better the pathways propagating airway inflammation. A large number of mediators of inflammation, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results to date, the introduction of EBC in everyday clinical practice requires the resolution of some methodological pitfalls, the standardization of EBC collection and finally the identification of a reliable biomarker that is reproducible has normal values and provides information regarding the underlying inflammatory process and the response to treatment. So far, none of the parameters studied in EBC fulfils the aforementioned requirements with one possible exception: pH. EBC pH is reproducible, has normal values, reflects a significant part of asthma pathophysiology and is measurable on-site with standardized methodology although some methodological aspects of measurement of pH in EBC (e.g. the effect of ambient CO(2), sample de-aeration, time for pH measurement) require further research. However, EBC pH has not been evaluated prospectively as a guide for treatment, in a manner similar to exhaled NO and sputum eosinophils. EBC represents a simple and totally non-invasive procedure that may contribute towards our understanding of asthma pathophysiology. Besides the evaluation of new biomarkers, the standardization of the already existing procedures is warranted for the introduction of EBC in clinical practice.