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Ha H.,St. Marianna University School of Medicine | Usuba A.,St. Marianna University School of Medicine | Maddula S.,BandS Analytik | Baumbach J.I.,Reutlingen University | And 2 more authors.
PLoS ONE | Year: 2014

Background: Conventional methods for lung cancer detection including computed tomography (CT) and bronchoscopy are expensive and invasive. Thus, there is still a need for an optimal lung cancer detection technique.Methods: The exhaled breath of 50 patients with lung cancer histologically proven by bronchoscopic biopsy samples (32 adenocarcinomas, 10 squamous cell carcinomas, 8 small cell carcinomas), were analyzed using ion mobility spectrometry (IMS) and compared with 39 healthy volunteers. As a secondary assessment, we compared adenocarcinoma patients with and without epidermal growth factor receptor (EGFR) mutation.Results: A decision tree algorithm could separate patients with lung cancer including adenocarcinoma, squamous cell carcinoma and small cell carcinoma. One hundred-fifteen separated volatile organic compound (VOC) peaks were analyzed. Peak-2 noted as n-Dodecane using the IMS database was able to separate values with a sensitivity of 70.0% and a specificity of 89.7%. Incorporating a decision tree algorithm starting with n-Dodecane, a sensitivity of 76% and specificity of 100% was achieved. Comparing VOC peaks between adenocarcinoma and healthy subjects, n-Dodecane was able to separate values with a sensitivity of 81.3% and a specificity of 89.7%. Fourteen patients positive for EGFR mutation displayed a significantly higher n-Dodecane than for the 14 patients negative for EGFR (p<0.01), with a sensitivity of 85.7% and a specificity of 78.6%.Conclusion: In this prospective study, VOC peak patterns using a decision tree algorithm were useful in the detection of lung cancer. Moreover, n-Dodecane analysis from adenocarcinoma patients might be useful to discriminate the EGFR mutation. © 2014 Handa et al.

Baumbach J.I.,Microfluidics | Maddula S.,Microfluidics | Sommerwerck U.,University of Duisburg - Essen | Besa V.,University of Duisburg - Essen | And 5 more authors.
International Journal for Ion Mobility Spectrometry | Year: 2011

Exhaled breath of patients suffering non-small bronchial carcinoma contains volatile organic compounds (VOC) different from healthy people. VOCs could be detected using ion mobility spectrometry down to the pg/L range even in air directly. To date, the origin of the different VOCs found is insecure. Such VOCs could be a direct product of the metabolism of the tumor or relatable to mostly present co-factors like infections or necrosis or a reaction of the human organism to the tumor (e.g. oxidativ stress). In the present study the breath of 19 patients suffering from confirmed NSCLC (non-small-cell lung carcinoma) with different histological types was investigated. In all cases flexible video-chip bronchoscopy was realized. Before taking samples for histological investigations in the lung on both main bronchi, samples of air were taken using a polytetrafluoroethylene (PTFE or Teflon) tube as catheter directly from the working channel of a bronchoscope and connected directly to the inlet of the ion mobility spectrometer. The measurement was started immediately. In total, 72 common peaks could be identified. 5 Peaks were significantly varying between the tumor site and the collateral lung. Considering adenocarcinoma, one peak separates both sites clearly and was relatable to the dimer of n-Dodecane. Two peaks were found on squamous cell carcinoma and relatable to 2-Butanol or 2-Methylfuran and Nonanal. The sensitivity, specificity, positive and negative predictive values were, for adenocarcinoma 100%, 75%, 80% and 100%, respectively - for squamous cell carcinoma 78%/78%, 67%/78%, 70%/80% and 75%/88%, for 2-Butanol and Nonanal respectively. Therefore, VOCs obtained from bronchoscopic sampling of breath could be detected using ion mobility spectrometry. The present study suggests that lung carcinoma with different histology will be represented by different volatile analytes. © 2011 Springer-Verlag.

Rabis T.,University of Duisburg - Essen | Sommerwerck U.,University of Duisburg - Essen | Anhenn O.,University of Duisburg - Essen | Darwiche K.,University of Duisburg - Essen | And 5 more authors.
International Journal for Ion Mobility Spectrometry | Year: 2011

Diseases of the lung, e. g. chronic obstructive pulmonary disease (COPD), interstitial lung diseases, bronchiectasis or cystic fibrosis, often lead to recurrent severe respiratory infections that cause exacerbations of the underlying disease. These acute or chronic inflammatory processes can result in a progressive destruction of the lung and in an ongoing decline in lung function. Therefore longer inpatient stays for intravenous antibiotic treatment are necessary and the quality of life in these patients is severely limited. A rapid detection of infectious agents in human lungs is often crucial, because the choice of the appropriate therapeutic regime depends at first on the identification of the infecting species. Standard methods for detection and identification are either time consuming, of low sensitivity or expensive. It is known that bacteria, and also mitosporic fungi, produce volatile organic compounds (VOCs) that can be detected in exhaled breath by ion mobility spectrometry (IMS), were a distinct detection of a specific VOC is related to a "peak". We investigated, whether the detection and characterisation of VOCs by Multi-capillary column coupled to IMS in exhaled breath of patients whose airways are either infected or colonized by Pseudomonas aeruginosa compared to healthy non-smoker controls is capable of identifying those infectious agents. To realize a non invasive identification of pathogens, the exhaled breath of 53 persons (24 patients suffering chronic or infectious on Pseudomonas and 29 healthy controls) was investigated using an ion mobility spectrometer type BioScout. In total 224 different signals were found. Actually, 21 different signals are able to differentiate the two groups, Control and Pseudomonas, with rank sum values less than 0.2. For all 224 signals Box-and-Wisker plots were realized. The peaks with the lowest rank sum values F (0,107) and PS0 (0,112) show rather good separation of both groups. Our preliminary results demonstrate that distinct patterns of a small number of IMS-peaks are sufficient for the identification of these infectious agents. Therefore MCC-IMS seems to be a promising method for the non-invasive identification of patients which are colonized or infected with bacteria such as Pseudomonas aeruginosa. © 2011 Springer-Verlag.

Furtwangler R.,Saarland University | Hauschild A.-C.,Max Planck Institute for Informatics | Hubel J.,Saarland University | Rakicioglou H.,Saarland University | And 5 more authors.
International Journal for Ion Mobility Spectrometry | Year: 2014

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. © 2014 Springer-Verlag Berlin Heidelberg.

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