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Purpose: Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods: VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results: We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =−0.393, p = 0.013), %VC (r =−0.569, p < 0.001), FVC (r = −0.440, p = 0.004), %FVC (r =−0.539, p < 0.001), DLco (r =−0.394, p = 0.018), and %DLco (r =−0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion: We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.
Engineering of large vascularized adipose tissue constructs is still a challenge for the treatment of extensive high-graded burns or the replacement of tissue after tumor removal. Communication between mature adipocytes and endothelial cells is important for homeostasis and the maintenance of adipose tissue mass but, to date, is mainly neglected in tissue engineering strategies. Thus, new coculture strategies are needed to integrate adipocytes and endothelial cells successfully into a functional construct. This review focuses on the cross-talk of mature adipocytes and endothelial cells and considers their influence on fatty acid metabolism and vascular tone. In addition, the properties and challenges with regard to these two cell types for vascularized tissue engineering are highlighted.
Online measurement of drug concentrations in patient's breath is a promising approach for individualized dosage. A direct transfer from breath- to blood-concentrations is not possible. Measured exhaled concentrations are following the blood-concentration with a delay in non-steady-state situations. Therefore, it is necessary to integrate the breath-concentration into a pharmacological model. Two different approaches for pharmacokinetic modelling are presented. Usually a 3-compartment model is used for pharmacokinetic calculations of blood concentrations. This 3-compartment model is extended with a 2-compartment model based on the first compartment of the 3-compartment model and a new lung compartment. The second approach is to calculate a time delay of changes in the concentration of the first compartment to describe the lung-concentration. Exemplarily both approaches are used for modelling of exhaled propofol. Based on time series of exhaled propofol measurements using an ion-mobility-spectrometer every minute for 346 min a correlation of calculated plasma and the breath concentration was used for modelling to deliver R2 = 0.99 interdependencies. Including the time delay modelling approach the new compartment coefficient ke0lung was calculated to ke0lung = 0.27 min−1 with R2 = 0.96. The described models are not limited to propofol. They could be used for any kind of drugs, which are measurable in patient's breath.
In the era of precision medicine, digital technologies and artificial intelligence, drug discovery and development face unprecedented opportunities for product and business model innovation, fundamentally changing the traditional approach of how drugs are discovered, developed and marketed. Critical to this transformation is the adoption of new technologies in the drug development process, catalyzing the transition from serendipity-driven to data-driven medicine. This paradigm shift comes with a need for both translation and precision, leading to a modern Translational Precision Medicine approach to drug discovery and development. Key components of Translational Precision Medicine are multi-omics profiling, digital biomarkers, model-based data integration, artificial intelligence, biomarker-guided trial designs and patient-centric companion diagnostics. In this review, we summarize and critically discuss the potential and challenges of Translational Precision Medicine from a cross-industry perspective.
Standardisation of breath sampling is important for application of breath analysis in clinical settings. By studying the effect of room airing on indoor and breath analytes and by generating time series of room air with different sampling intervals we sought to get further insights into room air metabolism, to detect the relevance of exogenous VOCs and to make conclusions about their consideration for the interpretation of exhaled breath. Room air and exhaled breath of a healthy subject were analysed before and after room airing. Furthermore a time series of room air with doors and windows closed was taken over 84 h by an automatic sampling every 180 min. A second times series studied room air analytes over 70 h with samples taken every 16.5 min. For breath and room air measurements an IMS coupled to a multi-capillary column (IMS/MCC) [Bio-Scout® - B&S Analytik GmbH, Dortmund, Germany] was used. The peaks were characterized using the Software Visual Now (B&S Analytik, Dortmund Germany) and identified using the software package MIMA (version 1.1, provided by the Max Planck Institute for Informatics, Saarbrücken, Germany) and the database 20160426_SubstanzDbNIST_122 (B & S Analytik GmbH, Dortmund, Germany). In the morning 4 analytes (Decamethylcylopentasiloxane [541-02-6]; Pentan-2-one [107-87-9] – Dimer; Hexan-1-al [66-25-1]; Pentan-2-one [107-87-9]) – Monomer showed high intensities in the room air and exhaled breath. They were significantly but not equally reduced by room airing. The time series about 84 h showed a time dependent decrease of analytes (limonen-monomer and -dimer; Decamethylcylopentasiloxane, Butan-1-ol, Butan-1-ol) as well as increase (Pentan-2-one [107-87-9] – Dimer). Shorter sampling intervals exhibited circadian variations of analyte concentrations for many analytes. Breath sampling in the morning needs room airing before starting. Then the variation of the intensity of indoor analytes can be kept small. The time series of indoor analytes show, that their intensities have a different behaviour, with time dependent declines, constant increases and circadian variations, dependent on room airing. This has implications on the breath sampling procedure and the intrepretation of exhaled breath.
Ecuador, traditionally an agricultural based economy, has a great potential for valorizing their industrial residues. This study, presents a techno-economic analysis for applying a novel biomass oxidation method to produce formic and acetic acids from coffee husk residues in Machala, Ecuador. The analysis determined that the time of return of investment was lower than 5 years, making this project economically feasible, when producing approx. 1000 tons of formic acid per year, which is enough for supplying the Ecuadorian market. This production, would reduce imports costs and develop the chemical industry in the country.
Stronger than they look
(2019)
Children undergoing systemic chemotherapy often suffer from severe immunosuppression usually associated to severe neutropenia (neutrophils < 0.5 x 109/l). Clinical courses during those periods range from asymptomatic to septic general conditions. Development of septic symptoms can be very fast and life-threatening. Swift detection of risk factors in those patients is therefore needed. So far no early, rapid and reliable marker or tool exists. Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column (IMS-MCC) can analyze more than 600 volatile components from exhaled air within a few minutes and hence is a potential, rapid detection-tool. As a proof of concept we measured the exhaled breath of 11 patients with neutropenia and 10 healthy controls ranging from 3 to 18 years of age at the time of measurement. Ten milliliters breath samples were taken at the outpatient clinic and analyzed with an onsite IMS-MCC (BreathDiscovery, B&S Analytik, Dortmund, Germany). Dead-space-volume was adapted to two groups (small 250 ml, large 500 ml). Interestingly 59 differing peaks were measured. Eleven were significantly different (p ≤ 0.05), three of which highly significant (p ≤ 0.01) in Mann-Whitney-Rank-Sum-testing. The corresponding analytes used in the decision tree are 2-Propanol, D-Limonene and Acetone. The analytes with the lowest rank sum identified are 2-Hexanone, Iso-Propylamine and 1-Butanol. Eventually we were able to show a three-step-decision-tree, which discerns the 21 samples except one from each group. Sensitivity was 90 % and specificity was 91 %. Naturally these findings need further confirmation within a bigger population. Our pilot-study proves that Ion-Mobility-Spectrometry coupled with a Multi-Capillary-Column is a feasible rapid diagnostic tool in the setting of a pediatric oncology out-patient clinic for patients 3 years and older. Our first results furthermore encourage additional analysis as to whether patients at risk for septic events during immunosuppression can be diagnosed in advance by rapidly assessing risk factors such as Neutropenia in exhaled breath.
Several diseases occur due to asbestos exposure. Until today, asbestos predicted mortality and morbidity will increase because of the long latency period. Actually, the methods to investigate asbestos related disease are mostly invasive. Therefore, the aim of the present paper was to investigate, whether signals in human breath could be correlated to Asbestos related lung diseases using a multi-capillary column (MCC) connected to an ion mobility spectrometer (IMS) as non-invasive method. Here, the breath samples of 10 mL of 25 patients suffering from asbestos related diseases. This group includes patients with asbestos related pleural thickening with and without pulmonary fibrosis. Twelve healthy persons constitute the control group and the breath samples are compared with those of the BK4103 patients. In total 83 peaks are found in the IMS-Chromatogram. A discrimination was possible with p-values <0.001 for two peaks (99.9 %), <0.01 (99 %) for 5 peaks and <0.05 (95 %) for 17 peaks. The most discrimination peaks alpha pinene and 4-ethyltoluol were identified among some others with lower p-values. The corresponding Box-and-Whisker-Plots comparing both groups are presented. In addition, a decision tree including all peaks was created that shows a differentiation with alpha pinene between BK4103 (pleural plaques group) and the control group. In addition, the sensitivity was calculated to 96 %, specificity was 50 %, positive and negative predictive values were 80 % and 86 %. Ion mobility spectrometry was introduced as non-invasive method to separate both groups Asbestos related and healthy. Naturally, the findings need further confirmation on larger population groups, but encourage further investigations, too.
This article provides a general overview of the most promising candidates of bio based materials and deals with the most important issues when it comes to their incorporation into PF resins. Due to their abundance on Earth, much knowledge of lignin-based materials has already been gained and uses of lignin in PF resins have been studied for many decades. Other natural polyphenols that are less frequently considered for impregnation are covered as well, as they do also possess some potential for PF substitution.