TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls (original) (raw)
Respiratory research, 2017
Researchers investigating lung diseases, such as asthma, have questioned whether certain compounds previously reported in exhaled breath condensate (EBC) originate from saliva contamination. Moreover, despite its increasing use in 'omics profiling studies, the constituents of EBC remain largely uncharacterized. The present study aims to define the usefulness of EBC in investigating lung disease by comparing EBC, saliva, and saliva-contaminated EBC using targeted and untargeted mass spectrometry and the potential of metabolite loss from adsorption to EBC sample collection tubes. Liquid chromatography mass spectrometry (LC-MS) was used to analyze samples from 133 individuals from three different cohorts. Levels of amino acids and eicosanoids, two classes of molecules previously reported in EBC and saliva, were measured using targeted LC-MS. Cohort 1 was used to examine contamination of EBC by saliva. Samples from Cohort 1 consisted of clean EBC, saliva-contaminated EBC, and clean ...
Airway Monitoring by Collection and Mass Spectrometric Analysis of Exhaled Particles
Analytical Chemistry, 2009
We describe a new method for simultaneously collecting particles in exhaled air for subsequent chemical analysis and measuring their size distribution. After forced exhalation, particles were counted and collected in spots on silicon wafers with a cascade impactor. Several phospholipids were identified by time-of-flight secondary ion mass spectrometric analysis of the collected spots, suggesting that the particles originated from the lower airways. The amount of particles collected in ten exhalations was sufficient for characterizing the phospholipid composition. The feasibility of the technique in respiratory research is demonstrated by analysis of the phospholipid composition of exhaled particles from healthy controls, patients with asthma, and patients with cystic fibrosis. We believe this technology will be useful for monitoring patients with respiratory disease and has a high potential to detect new biomarkers in exhaled air. (3) Phillips, M.; Cataneo, R. N.; Cummin, A. R.; Gagliardi, A. J.; Gleeson, K.; Greenberg, J.; Maxfield, R. A.; Rom, W. N. Chest 2003, 123, 2115-23. (4) Phillips, M.; Cataneo, R. N.; Ditkoff, B. A.; Fisher, P.; Greenberg, J.; Gunawardena, R.; Kwon, C. S.; Rahbari-Oskoui, F.; Wong, C. Breast J. 2003, 9, 184-91. (5) Scheideler, L.; Manke, H. G.; Schwulera, U.; Inacker, O.; Hammerle, H.
Comparison of Exhaled Endogenous Particles from Smokers and Non-Smokers Using Multivariate Analysis
Respiration, 2013
sition of RTLF. The discriminating ions identified by OPLS were then used as explanatory variables in traditional regression analysis. Results: There was a clear discrimination between smokers and non-smokers according to the chemical composition, where phospholipids from smokers were protonated and sodiated to a larger extent. Poor lung function showed a strong association with higher response from all molecular phosphatidylcholine species in the samples. Furthermore, the accumulated amount of tobacco consumed was associated with variations in mass spectra, indicating a dose-response relationship. Conclusion: The chemical composition of PEx differs between smokers and nonsmokers, reflecting differences in the RTLF. The results from this study may suggest that the composition of RTLF is affected by smoking and may be of importance for lung function.
A European Respiratory Society technical standard: exhaled biomarkers in lung disease
The European respiratory journal, 2017
Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampli...
Exhaled breath condensate volatilome allows sensitive diagnosis of persistent asthma
Allergy, 2018
The diagnosis and phenotyping of paediatric asthma is particularly complex due to the lack of currently available sensitive diagnostic tools. This often results in uncertainties associated with inhaled steroid therapy prescription. Therefore, this study aimed to investigate if volatile organic compounds measured in exhaled breath condensate can be used as biomarkers for asthma diagnosis in the paediatric population. A total of 64 participants, aged 6 to 18 years, were recruited on a random basis during visits to an outpatient allergy clinic and to a juvenile football team training session. Lung function, airway reversibility and skin prick tests were performed. Exhaled breath condensate samples were collected and breathprints were assessed using an electronic nose. Information on medical diagnosis of asthma, rhinitis and atopic dermatitis was retrieved for each participant. A hierarchical cluster model based on the volatilome profiles was then created. A two-cluster exhaled volatile...
A new approach to study exhaled proteins as potential biomarkers for asthma
Clinical & Experimental Allergy, 2011
Background Asthma is a complex clinical disease characterized by airway inflammation. Recently, various studies reported on the analysis of exhaled breath condensate (EBC) in the search for potential biomarkers for asthma. However, in a complex disease such as asthma, one biomarker might not be enough for early diagnosis or follow-up. Objective The use of proteome analysis may reveal disease-specific proteolytic peptide or protein patterns, and may lead to the identification of novel proteins for the detection of asthma. Methods Liquid chromatography and mass spectrometry were used to separate and detect proteins (proteolytic peptides) present in EBC samples from 30 healthy children and 40 children with asthma in the age group of 6-12 years. Results Support vector machine analysis resulted in differentiating profiles based on asthma status. These proteolytic peptide patterns were not correlated to some well known (spirometry, exhaled nitric oxide) and more recently described exhaled markers (EBC pH, LTB 4). The more abundant proteins in EBC were identified as cytokeratins, albumin, actin, haemoglobin, lysozyme, dermcidin, and calgranulin B. Conclusion Although the exact role in the disease development or physiological state of the airways of the proteins described in the presented pattern is not clear at this moment, this is an important step in the search for exhaled biomarkers for asthma. This study shows that EBC contains proteins that are of interest for future non-invasive asthma diagnosis or follow-up.
Biomarker as a Research Tool in Linking Exposure to Air Particles and Respiratory Health
BioMed Research International, 2015
Some of the environmental toxicants from air pollution include particulate matter (PM10), fine particulate matter (PM2.5), and ultrafine particles (UFP). Both short- and long-term exposure could result in various degrees of respiratory health outcomes among exposed persons, which rely on the individuals’ health status.Methods. In this paper, we highlight a review of the studies that have used biomarkers to understand the association between air particles exposure and the development of respiratory problems resulting from the damage in the respiratory system. Data from previous epidemiological studies relevant to the application of biomarkers in respiratory system damage reported from exposure to air particles are also summarized.Results. Based on these analyses, the findings agree with the hypothesis that biomarkers are relevant in linking harmful air particles concentrations to increased respiratory health effects. Biomarkers are used in epidemiological studies to provide an unders...
AJP: Lung Cellular and Molecular Physiology, 2009
Exhaled breath condensate (EBC) analyses promise simple and noninvasive methods to measure airway biomarkers but pose considerable methodological challenges. We utilized mass spectrometry to measure EBC purine biomarkers adenosine and AMP plus urea to control for dilutional variability in two studies: 1) a cross-sectional analysis of 28 healthy, 40 cystic fibrosis (CF), and 11 asthmatic children; and 2) a longitudinal analysis of 26 CF children before and after treatment of a pulmonary exacerbation. EBC adenosine, AMP, and urea were readily detected and quantified by mass spectrometry, and analysis suggested significant dilutional variability. Using biomarker-to-urea ratios to control for dilution, the EBC AMP-to-urea ratio was elevated in CF [median 1.3, interquartile range (IQR) 0.7–2.3] vs. control (median 0.75, IQR 0.3–1.4; P < 0.05), and the adenosine-to-urea ratio was elevated in asthma (median 1.5, IQR 0.9–2.9) vs. control (median 0.4, IQR 0.2–1.6; P < 0.05). Changes in...
Clinical chemistry, 2015
Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the pot...
Diagnostic value of a pattern of exhaled breath condensate biomarkers in asthmatic children
Allergologia et immunopathologia, 2017
Background: Diagnosing asthma in children is a challenge and using a single biomarker from exhaled breath condensate (EBC) showed the lack of improvement in it. Objective: The aim of this study was to assess the diagnostic potential of a pattern of simple chemical biomarkers from EBC in diagnosing asthma in children in a real-life setting, its association with lung function and gastroesophageal reflux disease (GERD). Methods: In 75 consecutive children aged 5-7 years with asthma-like symptoms the following tests were performed: skin prick tests, spirometry, impulse oscillometry (IOS), exhaled NO (F E NO), 24-hour oesophageal pH monitoring and EBC collection with subsequent analysis of pH, carbon dioxide tension, oxygen tension, and concentrations of magnesium, calcium, iron and urates. Results: No significant differences were found for individual EBC biomarkers between asthmatics and non-asthmatics (p > 0.05 for all). A pattern of six EBC biomarkers showed a statistically significant (p = 0.046) predictive model for asthma (AUC = 0.698, PPV = 84.2%, NPV = 38.9%). None to moderate association (R 2 up to 0.43) between EBC biomarkers and lung function measures and F E NO was found, with IOS parameters showing the best association with EBC biomarkers. A significantly higher EBC Fe was found in children with asthma and GERD compared to asthmatics without GERD (p = 0.049). Conclusions: An approach that involves a pattern of EBC biomarkers had a better diagnostic accuracy for asthma in children in real-life settings compared to a single one. Poor to moderate association of EBC biomarkers with lung function suggests a complementary value of EBC analysis for asthma diagnosis in children.