Nachweis von Alpha-1-Antitrypsin in exhaliertem Atemwegskondensat

Der Alpha-1-Antitrypsin-Mangel (AAT-Mangel) ist eine genetische Erkrankung, die den Träger für die Entwicklung einer chronisch obstruktiven Lungenerkrankung (COPD) sowie einer Leberzirrhose prädisponiert. Die Hauptfunktion von Alpha-1-Antitrypsin besteht darin, das Lungengewebe gegen den Einfluss von Neutrophiler Elastase (NE) zu schützen. Es ist sehr schwierig, die Konzentration von Alpha-1-Antitrypsin in den verschiedenen Kompartimenten der Lunge zu bestimmen. Die Bronchoskopie gilt bisher als Goldstandard, um den unteren Atemwegstrakt und den bronchialen Flüssigkeitsfilm zu untersuchen. Die Gewinnung und Untersuchung von Exhaliertem Atemwegskondensat (EBC) stellt die Möglichkeit dar, nicht invasiv wichtige Inhaltsstoffe des epithelialen Atemwegsflüssigkeitsfilms zu beurteilen und Veränderungen der physiologischen Homöostase zu detektieren. Ziel dieser Arbeit war es zu zeigen, dass AAT nicht invasiv in EBC gemessen werden kann. Dazu wurde sowohl ein AAT-ELISA als auch ein AAT-Western Blot etabliert. Es konnte weiterhin gezeigt werden, dass AAT auch im EBC von Patienten mit AAT-Mangel nachgewiesen werden kann. Eine Korrelation der gemessenen AAT-Werte im EBC zu den AAT-Werten im Serum konnte jedoch nicht nachgewiesen werden. Als weiteres Ziel dieser Arbeit wurden die AAT-Konzentrationen im EBC von gesunden Kontrollpersonen mit den AAT-Konzentrationen im EBC von Patienten mit stabiler COPD, exazerbierter COPD sowie substituierten und nicht substituierten Patienten mit AAT-Mangel verglichen. Es zeigten sich signifikant höhere AAT-Werte im EBC von Patienten mit exazerbierter COPD gegenüber Patienten mit stabiler COPD und Gesunden. Auch substituierte Patienten mit AAT-Mangel hatten signifikant höhere AAT-Werte im EBC als Gesunde und Patienten mit stabiler COPD. Nicht substituierte Patienten mit AAT-Mangel zeigten signifikant höhere AAT-Werte im Vergleich zu substituierten Patienten mit AAT-Mangel. Als letzter Punkt dieser Arbeit wurde das Verhalten von pH-Wert und Interleukin-8 (IL-8) als Marker der pulmonalen Inflammation im EBC von Patienten mit stabiler und exazerbierter COPD, substituierten und nicht substituierten Patienten mit AAT-Mangel und von Gesunden untersucht. Es zeigten sich signifikant niedrigere pH-Werte im Exhalat von Patienten mit stabiler sowie exazerbierter COPD im Vergleich zu Gesunden. Die IL-8 Werte im EBC der Patienten mit AAT-Mangel waren signifikant höher als im EBC der Patienten mit COPD und der Gesunden. Die Ergebnisse machen deutlich, dass die Methode des exhalierten Atemwegskondensats eine nicht invasive, einfach durchzuführende und günstige Methode darstellt. Sie könnte besonders für eine individuelle Messung von Patienten mit stabilen und auch exazerbierten Krankheitsstadien geeignet sein. Es konnte gezeigt werden, dass AAT eine Rolle als Akute-Phase-Protein und Inflammationsmarker besitzt. Besonders bei inflammatorischen Prozessen in der Lunge kommt ihm eine wichtige Bedeutung zu. Bis jetzt ist jedoch noch nicht sicher geklärt, ob die erhöht gemessenen AAT-Werte auf eine lokale oder eine systemische Reaktion zurückzuführen sind. Für eine routinemäßige Anwendung der beschriebenen Methode sowohl in der Forschung als auch in der klinischen Praxis sind jedoch noch umfangreiche weiterführende Experimente und Untersuchungen notwendig

Acute and Chronic Effects of Smoking on Inflammation Markers in Exhaled Breath Condensate in Current Smokers

Background: Long-term cigarette smoking is associated with pulmonary inflammation, but the acute effects of smoking have been less well studied. Analysis of the exhaled breath condensate (EBC) can provide noninvasive markers that might be indicative of inflammation. Objectives: The aim of the study was to determine whether the pH, electrical conductivity and the levels of ammonium and interleukin 8 (IL-8) of EBC were altered in smokers and whether they changed after smoking a single cigarette. Methods: We included 19 healthy nonsmokers (controls), 29 asymptomatic smokers, 10 patients with stable chronic obstructive pulmonary disease (COPD) {[}Global Initiative for Chronic Obstructive Lung Disease stages (GOLD) stages II-III], and 10 patients with exacerbated COPD. In 13 smokers, EBC was also analyzed before and after smoking. EBC was obtained during 10 min tidal breathing with a cooled RTube (TM). pH was determined after deaeration with argon. Results: Acute smoking did not alter the pH or ammonium and IL-8 levels, but raised conductivity. As in COPD patients, the pH was significantly decreased in chronic smokers with a history of at least 10 pack-years compared to controls. Conclusions: EBC can be used to detect the acute and chronic effects of smoking. The increased conductivity of EBC after smoking suggests acute inflammatory effects. The reduced pH in chronic smokers shows cigarette-induced inflammation. Copyright (C) 2009 S. Karger AG, Base

Comparison of two devices and two breathing patterns for exhaled breath condensate sampling.

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

CFHT Legacy Ultraviolet Extension (CLUE): Witnessing Galaxy Transformations up to 7 Mpc from Rich Cluster Cores

Using the optical data from the Wide component of the CFHT Legacy Survey, and new ultraviolet data from GALEX, we study the colours and specific star formation rates (SSFR) of ~100 galaxy clusters at 0.16<z<0.36, over areas extending out to radii of r~7Mpc. We use a multicolour, statistical background subtraction method to study the galaxy population at this radius; thus our results pertain to those galaxies which constitute an excess over the average field density. We find that the average SSFR, and its distribution, of the star-forming galaxies (with SFR>0.7 M_sun/yr at z~0.2 and SFR>1.2 M_sun/yr at z~0.3) have no measurable dependence on the cluster-centric radius, and are consistent with the field values. However, the fraction of galaxies with SFR above these thresholds, and the fraction of optically blue galaxies, are lower for the overdense galaxy population in the cluster outskirts compared with the average field value, at all stellar masses M*>10^{9.8} M_sun and at all radii out to at least 7Mpc. Most interestingly, the fraction of blue galaxies that are forming stars at a rate below our UV detection limit is much higher in all radial bins around our cluster sample, compared with the general field value. This is most noticeable for massive galaxies M*>10^{10.7} M_sun; while almost all blue field galaxies of this mass have detectable star formation, this is true for less than 20% of the blue cluster galaxies, even at 7Mpc from the cluster centre. Our results support a scenario where galaxies are pre-processed in locally overdense regions, in a way that reduces their SFR below our UV detection limit, but not to zero.Comment: MNRAS accepte

History of Galaxy Interactions and their Impact on Star Formation over the Last 7 Gyr from GEMS

We perform a comprehensive estimate of the frequency of galaxy mergers and their impact on star formation over z~0.24--0.80 (lookback time T_b~3--7 Gyr) using 3698 (M*>=1e9 Msun) galaxies with GEMS HST, COMBO-17, and Spitzer data. Our results are: (1) Among 790 high mass (M*>=2.5e10 Msun) galaxies, the visually-based merger fraction over z~0.24--0.80, ranges from 9%+-5% to 8%+-2%. Lower limits on the major and minor merger fractions over this interval range from 1.1% to 3.5%, and 3.6% to 7.5%, respectively. This is the first approximate empirical estimate of the frequency of minor mergers at z<1. For a visibility timescale of ~0.5 Gyr, it follows that over T_b~3--7 Gyr, ~68% of high mass systems have undergone a merger of mass ratio >1/10, with ~16%, 45%, and 7% of these corresponding respectively to major, minor, and ambiguous `major or minor' mergers. The mean merger rate is a few x 1e-4 Gyr-1 Mpc-3. (2) We compare the empirical merger fraction and rate for high mass galaxies to a suite of Lambda CDM-based models: halo occupation distribution models, semi-analytic models, and hydrodynamic SPH simulations. We find qualitative agreement between observations and models such that the (major+minor) merger fraction or rate from different models bracket the observations, and show a factor of five dispersion. Near-future improvements can now start to rule out certain merger scenarios. (3) Among ~3698 M*>=1e9 Msun galaxies, we find that the mean SFR of visibly merging systems is only modestly enhanced compared to non-interacting galaxies over z~0.24--0.80. Visibly merging systems only account for less than 30% of the cosmic SFR density over T_b~3--7 Gyr. This suggests that the behavior of the cosmic SFR density over the last 7 Gyr is predominantly shaped by non-interacting galaxies.Comment: Accepted for Publication in the Astrophysical Journal. 17 pages of text, 21 figures, 3 tables. Uses emulateapj5.st

The SINS/zC-SINF survey of z~2 galaxy kinematics: Outflow properties

Based on SINFONI Ha, [NII] and [SII] AO data of 30 z \sim 2 star-forming galaxies (SFGs) from the SINS and zcSINF surveys, we find a strong correlation of the Ha broad flux fraction with the star formation surface density of the galaxy, with an apparent threshold for strong outflows occurring at 1 Msun yr^-1 kpc^-2. Above this threshold, we find that SFGs with logm_\ast>10 have similar or perhaps greater wind mass loading factors (eta = Mdotout/SFR) and faster outflow velocities than lower mass SFGs. This trend suggests that the majority of outflowing gas at z \sim 2 may derive from high-mass SFGs, and that the z \sim 2 mass-metallicity relation is driven more by dilution of enriched gas in the galaxy gas reservoir than by the efficiency of outflows. The mass loading factor is also correlated with the SFR and inclination, such that more star-forming and face-on galaxies launch more powerful outflows. For galaxies that have evidence for strong outflows, we find that the broad emission is spatially extended to at least the half-light radius (\sim a few kpc). We propose that the observed threshold for strong outflows and the observed mass loading of these winds can be explained by a simple model wherein break-out of winds is governed by pressure balance in the disk. Using the ratio of the [SII] doublet in a broad and narrow component, we find that outflowing gas has a density of \sim10-100 cm^-3, significantly less than that of the star forming gas (600 cm^-3).Comment: 7 pages, 3 figures, accepted by Ap

Prevalence of Buruli Ulcer in Akonolinga Health District, Cameroon: Results of a Cross Sectional Survey

As long as there is no strategy to prevent Buruli ulcer, the early detection and treatment of cases remains the most promising control strategy. Buruli ulcer is most common in remote rural areas where people have little contact with health structures. Information on the number of existing cases in the population and where they go to seek treatment is important for project planning and evaluation. Health structure based surveillance systems cannot provide this information, and previous prevalence surveys did not provide information on spatial distribution and coverage. We did a survey using centric systematic area sampling in a Health District in Cameroon to estimate prevalence and project coverage. We found the method was easy to use and very useful for project planning. It identified priority areas with relatively high prevalence and low coverage and provided an estimate of the number of existing cases in the population of the health district. The active case finding component of the method used served as an awareness campaign and was an integrated part of the project, creating a network of health delegates trained on Buruli ulcer

Krüppel-like zinc finger proteins in end-stage COPD lungs with and without severe alpha1-antitrypsin deficiency

ABSTRACT: BACKGROUND: Chronic obstructive pulmonary disease (COPD) is influenced by environmental and genetic factors. An important fraction of COPD cases harbor a major genetic determinant, inherited ZZ (Glu342Lys) alpha1-antitrypsin deficiency (AATD). A study was undertaken to investigate gene expression patterns in end-stage COPD lungs from patients with and without AATD. METHODS: Explanted lungs of end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy) and "normal" MM COPD, and liver biopsies from patients suffering from liver cirrhosis with and without ZZ AATD were used for gene expression analysis by Affymetrix microarrays or RT-PCR. RESULTS: A total of 162 genes were found to be differentially expressed (p-value [less than or equal to] 0.05 and |FC| [greater than or equal to] 2) between MM and ZZ COPD patients. Of those, 134 gene sets were up-regulated and 28 were down-regulated in ZZ relative to MM lung tissue. A subgroup of genes, zinc finger protein 165, snail homolog 1 (Drosophila) (SNAI1), and Kruppel-like transcription factors (KLFs) 4 (gut), 9 and 10, perfectly segregated ZZ and MM COPD patients. The higher expression of KLF 9 and KLF10 has been verified in the replication cohort with AATD-related end-stage lung emphysema and liver cirrhosis. Furthermore, higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy. CONCLUSIONS: These results reveal the involvement of transcriptional regulators of the zinc-finger family in COPD pathogenesis and provide deeper insight into the pathophysiological mechanisms of COPD with and without AATD

Radio-quiet quasars in the VIDEO survey : evidence for AGN-powered radio emission at S-1.4 GHz<1 mJy

Understanding the interplay between black-hole accretion and star formation, and how to disentangle the two, is crucial to our understanding of galaxy formation and evolution. To investigate, we use a combination of optical and near-infrared photometry to select a sample of 74 quasars from the VISTA Deep Extragalactic Observations (VIDEO) survey, over 1 deg2. The depth of VIDEO allows us to study very low accretion rates and/or lower-mass black holes, and 26 per cent of the candidate quasar sample has been spectroscopically confirmed. We use a radio-stacking technique to sample below the nominal flux-density threshold using data from the Very Large Array at 1.4 GHz and find, in agreement with other work, that a power-law fit to the quasar-related radio source counts is inadequate at low flux density. By comparing with a control sample of galaxies (where we match in terms of stellar mass), and by estimating the star formation rate, we suggest that this radio emission is predominantly caused by accretion activity rather than star-formation activityPeer reviewe

The WiggleZ Dark Energy Survey: High Resolution Kinematics of Luminous Star-Forming Galaxies

We report evidence of ordered orbital motion in luminous star-forming galaxies at z~1.3. We present integral field spectroscopy (IFS) observations, performed with the OH Suppressing InfraRed Imaging Spectrograph (OSIRIS) system, assisted by laser guide star adaptive optics on the Keck telescope, of 13 star-forming galaxies selected from the WiggleZ Dark Energy Survey. Selected via ultraviolet and [OII] emission, the large volume of the WiggleZ survey allows the selection of sources which have comparable intrinsic luminosity and stellar mass to IFS samples at z>2. Multiple 1-2 kpc size sub-components of emission, or 'clumps', are detected within the Halpha spatial emission which extends over 6-10 kpc in 4 galaxies, resolved compact emission (r<3 kpc) is detected in 5 galaxies, and extended regions of Halpha emission are observed in the remaining 4 galaxies. We discuss these data in the context of different snapshots in a merger sequence and/or the evolutionary stages of coalescence of star-forming regions in an unstable disk. We find evidence of ordered orbital motion in galaxies as expected from disk models and the highest values of velocity dispersion (\sigma>100 km/s) in the most compact sources. This unique data set reveals that the most luminous star-forming galaxies at z>1 are gaseous unstable disks indicating that a different mode of star formation could be feeding gas to galaxies at z>1, and lending support to theories of cold dense gas flows from the intergalactic medium.Comment: 25 pages, 11 figures, accepted for publication in MNRA