A Hattesohl

Philipps-Universität Marburg, Marburg, Hesse, Germany

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Publications (15)15.65 Total impact

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    ABSTRACT: Diagnosis of obstructive sleep apnoea syndrome (OSAS) is technically demanding, cost-intensive and time-consuming. The measurement of volatile organic compounds by an electronic nose is an innovative method that determines distinct molecular patterns of exhaled breath in different patient groups. We addressed the following questions: What is the diagnostic accuracy of an electronic nose in the detection of OSAS and the ability to detect effects of standard therapy in patients with OSAS? Are these results related to changes in distinct markers of airway inflammation and extracellular remodelling?We included 40 OSAS patients and 20 healthy controls. Exhaled breath of all participants was analysed using the Cyranose 320™. Pharyngeal washings were performed to sample the upper airway compartment. For statistical analysis linear discriminant analysis was employed.We identified a Linear Discriminant function separating OSAS from control (p<0.0001). The corresponding area under the Receiver Operating Curve was 0.85 (95%CI 0.75-0.96; sensitivity 0.93; specificity 0.7). In pharyngeal washing fluids of OSAS patients we observed higher levels of alpha-1-antitrypsin and markers of extracellular remodelling compared to controls.The electronic nose can distinguish between OSAS patients and controls with high accuracy.
    European Respiratory Journal 10/2012; · 6.36 Impact Factor
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    ABSTRACT: Purpose/Objective: The objective of our study was to evaluate whether the frequency of B and T lymphocytes and of natural killer cells in peripheral blood is influenced by moderate exercise in competitive athletes and in non-athletes, respectively. Material and methods: Blood samples from 11 competitive athletes and 6 non-athletes were obtained before, directly after, and 1 h after moderate exercise. Peripheral blood mononuclear cells (PBMCs) were isolated by density centrifugation and analysed by four-colour flow cytometry. Results: Whereas the frequency distribution of B lymphocyte subpopulations (CD19+ cells, class-switched/non class-switched memory cells, plasmablasts) was maintained in both groups, we found considerable differences in the T cell subpopulations: While T cell subpopulations in the athletes group did not change compared to pre-exercise baseline, we found a significant induction of cytotoxic T cells (Tc; CD3+CD8+; p < 0.05, compared to pre-exercise baseline), activated Tc (CD3+CD8+CD69+; p < 0.05), and natural killer T cells (NKT; CD3+CD56+; p < 0.05) in the non-athletes group directly after exercise, which returned to baseline within 1 h. In contrast, numbers of T helper cells (Th; CD3+CD4+; p < 0.01) and regulatory T cells (Treg; CD3+CD4+CD25+CD127-; p < 0.05) were reduced 1 h after exercise in non-athletes. Interestingly, even at baseline level Treg numbers in athletes were significantly reduced compared to non-athletes (p < 0.001). The frequency of natural killer cells (NK; CD3-CD16+CD56+Nkp46+; p < 0.01) increased in athletes and non-athletes after exercise. However, the increase in NK numbers was significantly alleviated in athletes compared to non-athletes (p < 0.01). Conclusion: We found significant temporary changes in the frequency of Tc, Th, Treg, NKT, and NK cells in PBMCs from non-athletes, whereas cell frequencies in athletes, except for NK cells, did not change. Reduced Treg numbers in athletes imply a putative role of Treg cells in the immune regulation during chronic exercise and might contribute to the increased susceptibility to infections in competitive athletes.
    3. European Congress of Immunology, Glasgow; 01/2012
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    ABSTRACT: Fragestellung: B1-Zellen produzieren bereits beim Feten und Neugeborenen spontan Immunglobuline der Klasse M, die häufig gegen Polysaccharid- und Lipid- Antigene von Mikroorganismen gerichtet sind und als „angeborene Antikörper“ bezeichnet werden. Kürzlich wurden anhand funktioneller Studien die B1-Zellen beim Menschen neu definiert (B1: CD20+,CD27+,CD43+,CD69-; alte Definition: CD19+,CD5+). Unser Ziel war es, die B1-Zellen im fetalen und adulten zu quantifizieren. Material und Methoden: Aus Nabelschnurblut (NSB) von 10 gesunden Reifgeborenen und aus peripherem Blut von 10 gesunden Erwachsenen wurden die mononukleären Zellen mit Ficoll-Gradient aufgereinigt, mit fluoreszierenden Antikörpern gefärbt und im Durchflusszytometer analysiert. Ergebnisse: Der Anteil von B1-Zellen an CD20+ B-Zellen betrug im NSB 1,1 ± 0,2% und bei Erwachsenen 1,6 ± 0,3% (n.s.). Naive B-Zellen (CD27-,IgD+, IgM+) machten mit 50,0 ± 4,6% (NSB) bzw. 42,0 ± 3,9% (Erwachsene, n.s.) den größten Anteil an B-Zellen aus. Unreife B-Zellen (CD27-,IgD-,IgM-), Maginalzonen-ähnliche B-Zellen (CD27+, IgD+, IgM+), IgM-Gedächtnis-B-Zellen (CD27+,IgD-,IgM+), Plasmablasten (CD38++,IgM-), Transitionale B-Zellen (CD21+,CD38+,IgM+), sowie klassengewechselte Gedächtnis-B-Zellen (CD27+,IgD-,IgM-) waren im fetalen gegenüber adulten Blut seltener (p< 0,05). Diskussion: Während nach der alten Definition mehr B1 Zellen im fetalen als im adulten Blut vorkamen, war die neu definierte B1-Zellpopulation in beiden Gruppen gleich häufig. Die alte am Mausmodell orientierte Definition umfasst beim Menschen keine einheitliche Zellpopulation, was z.T. widersprüchliche Ergebnisse zur Häufigkeit und Funktion der B1-Zellen erklärt. Weitere Untersuchungen sollten den molekulargenetischen Vergleich fetaler und adulter B1-Zellen umfassen.
    Jahrestagung der Deutschen Gesellschaft für Kinderheilkunde und Jugendmedizin, Hamburg; 01/2012
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    ABSTRACT: BACKGROUND: The major concept behind augmentation therapy with human α(1)-antitrypsin (AAT) is to raise the levels of AAT in patients with protease inhibitor phenotype ZZ (Glu342Lys)-inherited AAT deficiency and to protect lung tissues from proteolysis and progression of emphysema. OBJECTIVE: To evaluate the short-term effects of augmentation therapy (Prolastin(®)) on plasma levels of AAT, C-reactive protein, and chemokines/cytokines. MATERIALS AND METHODS: Serum and exhaled breath condensate were collected from individuals with protease inhibitor phenotype ZZ AAT deficiency-related emphysema (n = 12) on the first, third, and seventh day after the infusion of intravenous Prolastin. Concentrations of total and polymeric AAT, interleukin-8 (IL-8), monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein were determined. Blood neutrophils and primary epithelial cells were also exposed to Prolastin (1 mg/mL). RESULTS: There were significant fluctuations in serum (but not in exhaled breath condensate) levels of AAT polymers, IL-8, monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor within a week of augmentation therapy. In general, augmented individuals had higher AAT and lower serum levels of IL-8 than nonaugmented subjects. Prolastin added for 3 hours to neutrophils from protease inhibitor phenotype ZZ individuals in vitro reduced IL-8 release but showed no effect on cytokine/chemokine release from human bronchial epithelial cells. CONCLUSION: Within a week, augmentation with Prolastin induced fluctuations in serum levels of AAT polymers and cytokine/chemokines but specifically lowered IL-8 levels. It remains to be determined whether these effects are related to the Prolastin preparation per se or to the therapeutic efficacy of augmentation with AAT.
    International Journal of COPD 01/2012; 7:687-696.
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    ABSTRACT: To compare the volatile organic compound patterns of patients with COPD with and without alpha 1-antitrypsin (AAT) deficiency using electronic nose technology. Exhaled breath condensate and pure exhaled breath of patients with COPD with (n=10) and without (n=23) AAT deficiency and healthy controls (n=10) were analysed. The effect of human recombinant AAT on the volatile organic compound profile of 11 AAT-deficient patients was also examined. Exhaled breath condensate and pure exhaled breath were measured using the Cyranose 320. Smell prints were analysed by linear discriminant analysis (LDA) using Mahalanobis distance (MD) and cross-validation values (CVVs). Smell prints of patients with AAT-deficiency were different from those with COPD in exhaled breath condensate (LDA: P<0.0001, sensitivity of 1.00, specificity of 1.00, CVV 82.0%, MD 2.37) and in pure exhaled breath (LDA: P<0.0001, sensitivity of 1.00, specificity of 1.00, CVV 58.3%, MD 2.27). Smell prints of AAT-deficient patients before and after human recombinant AAT augmentation were different (LDA: P=0.001, sensitivity of 1.00, specificity of 1.00, CVV 53.3%, MD 1.79). An electronic nose can detect differences in smell prints of COPD patients with and without AAT deficiency. Augmentation therapy changes the volatile organic compound pattern. The electronic nose may be helpful in the diagnosis of AAT deficiency.
    Respirology 08/2011; 16(8):1258-64. · 2.78 Impact Factor
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    ABSTRACT: One hallmark of COPD is colonization and infection of the lung. Acute exacerbations of COPD (AECOPD) are acute deteriorations of the chronic disease and are associated with a change of the pulmonary microbial balance. The collection of exhaled breath condensate (EBC) can be used to non-invasively determine markers of lung disease. The aim of the present study was to compare the results of assays based on the detection of microbial nucleic acids from EBC and from spontaneous sputum in patients with AECOPD. EBC and sputa of 29 adults with AECOPD were obtained. Isolated DNA or RNA were used as starting material for the PCR assays to detect Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, influenza viruses (AH 1, AH 3) and respiratory syncytial virus. Bacterial or viral nucleic acids were identified in 14 EBC and 21 sputa from 29 patients. Results from EBC did not correlate well with those from sputum. Viral and S. pneumoniae nucleic acids were detected only in sputum, whereas L. pneumophila DNA was only found in EBC. In three EBC and 10 sputa nucleic acids of more than one microorganism was detected. Bacterial nucleic acids can be identified in EBC of COPD patients with exacerbations. The results obtained from EBC and sputum did not correlate well.
    Respirology 04/2011; 16(6):932-8. · 2.78 Impact Factor
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    ABSTRACT: Non-invasive pulmonary diagnostics is a promising and interesting field in respiratory medicine. Beside exhaled breath condensate, there is an increasing interest in alternative and faster techniques such as electronic noses (EN). EN aim to mimic or improve the sense of smelling. Different types of EN have been employed in research so far. In addition to ion mobility spectrometry and mass spectrometry, ENs that consist of various biopolymer sensors for the sensing of volatile organic compounds (VOCs) have been tested. VOCs bind to the sensors depending on size, structure, hydrogen binding and polarity. This leads to physical alterations, e. g., swelling resulting in a change of resistance. The smell print represents composite patterns in contrast to single compounds, and the distinction between different categories is achieved by pattern recognition algorithms. Other types of EN like mass spectrometry and ion mobility spectrometry are capable of identifying even single analyte fractions provided that their characteristics have been saved in data repositories. The non-invasive nature, onsite availability and relatively cheap sampling are advantages of ENs that underly the increasing interest in their use for medical purposes. Some promising results have already been published. This review aims to describe the state of the art in brief form.
    Pneumologie 03/2011; 65(7):401-5.
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    ABSTRACT: Volatile organic compounds (VOCs) can be used as biomarkers in exhaled air. VOC profiles can be detected by an array of nanosensors of an electronic nose. These profiles can be analysed using bioinformatics. It is, however, not known whether different devices of the same model measure identically and to which extent different set-ups and the humidity of the inhaled air influence the VOC profile. Three different measuring set-ups were designed and three healthy control subjects were measured with each of them, using four devices of the same model (Cyranose 320™, Smiths Detection). The exhaled air was collected in a plastic bag. Either ambient air was used as reference (set-up Leipzig), or the reference air was humidified (100% relative humidity) (set-up Marburg and set-up Munich). In the set-up Marburg the subjects inhaled standardised medical air (Aer medicinalis Linde, AGA AB) out of a compressed air bottle through a demand valve; this air (after humidification) was also used as reference. In the set-up Leipzig the subjects inhaled VOC-filtered ambient air, in the set-up Munich unfiltered room air. The data were evaluated using either the real-time data or the changes in resistance as calculated by the device. The results were clearly dependent on the set-up. Apparently, humidification of the reference air could reduce the variance between devices, but this result was also dependent on the evaluation method used. When comparing the three subjects, the set-ups Munich and Marburg mapped these in a similar way, whereas not only the signals but also the variance of the set-up Leipzig were larger. Measuring VOCs with an electronic nose has not yet been standardised and the set-up significantly affects the results. As other researchers use further methods, it is currently not possible to draw generally accepted conclusions. More systematic tests are required to find the most sensitive and reliable but still feasible set-up so that comparability is improved.
    Pneumologie 03/2011; 65(8):465-70.
  • Pneumologie. 01/2011;
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    International Journal for Ion Mobility Spectrometry 01/2011; 14.
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    ABSTRACT: Analysis of exhaled breath condensate (EBC) is a noninvasive method to access the epithelial lining fluid of the lungs. Due to standardization problems the method has not entered clinical practice. The aim of the study was to assess the comparability for two commercially available devices in healthy controls. In addition, we assessed different breathing patterns in healthy controls with protein markers to analyze the source of the EBC. EBC was collected from ten subjects using the RTube and ECoScreen Turbo in a randomized crossover design, twice with every device--once in tidal breathing and once in hyperventilation. EBC conductivity, pH, surfactant protein A, Clara cell secretory protein and total protein were assessed. Bland-Altman plots were constructed to display the influence of different devices or breathing patterns and the intra-class correlation coefficient (ICC) was calculated. The volatile organic compound profile was measured using the electronic nose Cyranose 320. For the analysis of these data, the linear discriminant analysis, the Mahalanobis distances and the cross-validation values (CVV) were calculated. Neither the device nor the breathing pattern significantly altered EBC pH or conductivity. ICCs ranged from 0.61 to 0.92 demonstrating moderate to very good agreement. Protein measurements were greatly influenced by breathing pattern, the device used, and the way in which the results were reported. The electronic nose could distinguish between different breathing patterns and devices, resulting in Mahalanobis distances greater than 2 and CVVs ranging from 64% to 87%. EBC pH and (to a lesser extent) EBC conductivity are stable parameters that are not influenced by either the device or the breathing patterns. Protein measurements remain uncertain due to problems of standardization. We conclude that the influence of the breathing maneuver translates into the necessity to keep the volume of ventilated air constant in further studies.
    PLoS ONE 01/2011; 6(11):e27467. · 3.73 Impact Factor
  • Pneumologie 01/2010; 64.
  • Pneumologie 01/2010; 64.
  • Pneumologie 01/2009; 63.
  • Pneumologie 01/2009; 63(12).