wiener klinische

wochenschrift The Central European Journal of Medicine 123. Jahrgang 2011

Wien Klin Wochenschr (2011) 123/17-18: A1-A34 DOI 10.1007/s00508-011-0050-8 © Springer-Verlag 2011

Jahrestagung 2011 der Österreichischen Gesellschaft für Pneumologie Abstracts Präsident: Univ.-Prof. Dr. Horst Olschewski

Kongressleitung: Prim. Univ.-Prof. Dr. Otto C. Burghuber Kongresssekretärinnen: Dr. Marie-Kathrin Breyer und Dr. Robab Breyer-Kohansal

Kongressorganisationskomitee (KOK) Prim. MR Dr. Kurt Aigner Prim. Univ.-Prof. Dr. Otto C. Burghuber Univ.-Prof. Dr. Ernst Eber Prim. Dr. Peter Errhalt OA Dr. Holger Flick Priv. Doz. Dr. Georg-Christian Funk OÄ Dr. Sylvia Hartl Dr. Peter A. Hesse Dr. Maximilian Johannes Hochmair OA Dr. Hubert Karl Koller OA Dr. Klaus Kirchbacher Prim. Univ.-Prof. Dr. Meinhard Kneussl OA Dr. Gabor Kovacs OÄ Dr. Angelika Kugi

Univ.-Prof. Dr. Horst Olschewski OÄ Dr. Birgitta Plakolm Prim. Univ.-Prof. Dr. Josef Riedler Prim. Univ.-Prof. Dr. Peter Schenk Prim. Dr. Herwig A. E. Schinko PT MSc Ingrid Schmidt Dr. Nika Skoro-Sajer Prim. Prof. Dr. Michael Studnicka Prim. Dr. Martin Trinker Priv. Doz. OA. Dr. Arschang Valipour Univ. Doz. Dr. Felix Wantke DGKS Rita Wardy BMA Eva Zeitlhofer

abstracts

Fall des Jahres 2011

„Das gab’s in Österreich noch nie…“ R. Arnitz1, W. Purkarthofer1, G. Höchtl2, H. Popper3, B. Baumgartner1 1

Abteilung für Pneumologie, LKH Vöcklabruck, Vöcklabruck, Österreich 2 Institut für Klinische Pathologie, LKH Vöcklabruck, Vöcklabruck, Österreich 3 Institut für Pathologie, Medizinische Universität Graz, Graz, Österreich

Wir präsentieren den Fall einer 53-jährigen Patientin, welche im Februar 2011 aufgrund im Thorax-CT detektierter bilateraler Raumforderungen (rechter OL, linker UL) an unserer Abteilung aufgenommen wurde. Davor litt sie seit November des Vorjahres an einem unteren Atemwegsinfekt und Globusgefühl, später seien dann auch Hämotysen hinzugekommen. Die Berufs- bzw. Sozialanamnese verbleibt unauffällig, aktiver Nikotinabusus bestand nie, 10 Jahre war sie einer Passivrauchbelastung ausgesetzt. Im Routinelabor finden sich außer einer erhöhten BSG keinerlei Auffälligkeiten, an Tumormarkern im Serum lediglich das CA19-9 geringfügig erhöht. Es folgt die Bronchoskopie zu Histologiegewinnung, wobei die feingewebliche Aufarbeitung der gewonnenen Proben ein Pleomorphes Karzinom bestehend aus einem Adenokarzinomanteil und einem spindelzelligen Karzinom ergibt. Der Adenokarzinomanteil ist aufgrund des Markerprofils einem Adenokarzinom vom enterischen Typ zuzuordnen. Das pleomorphe Karzinom der Lunge gehört in die Gruppe der sarkomatoiden Karzinome und ist charakterisiert durch eine sehr schlechte Prognose. Diese Kombination ist äußerst ungewöhnlich, wenn nicht – auch nach Einschätzung eines renommierten Referenzpathologen – bisher gar einzigartig.

Es präsentierte sich ein adipöser Patient mit arrhythmischer Herzaktion und mäßigen Beinödemen beidseits. Die kardialen Untersuchungen zeigten eine de-novo Vorhofflimmerarrhythmie, eine Herzinsuffizienz mit einer echokardiographisch gemessenen Ejektionsfraktion von 45 % und eine schlecht kontrollierte arterielle Hypertonie. Die pulmonale Abklärung ergab tagsüber ausgeglichene Blutgase und eine mittelgradige kombinierte Ventilationsstörung mit Betonung der kleinen Atemwege. Ursächlich hierfür waren radiologisch darstellbare postentzündiche Lungenveränderungen sowie die Herzinsuffizienz. Die Schlafuntersuchung zeigte eine zentral-periodische Schlafatemstörung mit gutem Ansprechen auf nächtliche Sauerstoffgabe. Das Schluckaktröntgen ergab eine Raumforderung dorsal des Hypopharynx mit gestörtem Kontrastmittelabfluss. Eine HNO-ärztliche Untersuchung bestätigte eine Vorwölbung im Larynx. Die HalsComputertomographie zeigte bis zwei Zentimeter große, den Hypopharynx und den Larynx dorsal imprimierende Spondylophyten als Ursache für die Schluckstörung. In Zusammenschau der Befunde hatten die Beschwerden unterschiedliche Gründe. Ursächlich für die Belastungsdyspnoe war die kardiale Problematik. Kausal für den Husten waren – durch hochgradige degenerative Halswirbelsäulenveränderungen bedingte – Schluckstörungen, welche zu rezidivierenden Aspirationen führten. Der Patient wurde neurochirurgisch vorgestellt, lehnte jedoch eine angebotene operative Abtragung der Spondylophyten ab. Es erfolgten eine kardiale Rekompensation, die Adaptierung der antihypertensiven Therapie sowie das Einleiten einer oralen Antikoagulation. Eine nächtliche Sauerstofftherapie wurde verordnet. Dieser Fall zeigt, dass besonders bei multimorbiden Patienten zeitgleich auftretende Symptome verschiedenste Ursachen haben können. Umso wichtiger erscheint hier eine interdisziplinäre Abklärung mit besonderer Berücksichtigung fachfremder Differentialdiagnosen. Weiters soll das Augenmerk auf ein in der pneumologischen Fachliteratur unterrepräsentiertes Krankheitsbild gerichtet werden. Degenerative Veränderungen der Halswirbelsäule können eine Vielzahl respiratorischer Probleme bedingen, sind jedoch fast ausschließlich Thema HNO-ärztlicher oder orthopädischer Publikationen.

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F2 Husten und Belastungsdyspnoe bei einem älteren Patienten W. Auer¹, H. Reiher¹, R. Einspieler², T. Keck³, V. Stepan¹ ¹Abteilung für Innere Medizin, Krankenhaus der Elisabethinen, Graz, Österreich ²Institut für Radiologie, Krankenhaus der Elisabethinen, Graz, Österreich ³Abteilung für Hals-Nasen-Ohren-Heilkunde, Krankenhaus der Elisabethinen, Graz, Österreich

Husten und Belastungsdyspnoe bei älteren Patienten sind häufige Zuweisungsdiagnosen an Lungenfachärzte. Die entsprechenden Ursachen finden sich jedoch nicht immer allein im kardiopulmonalen Bereich. Ein 77-jähriger Patient wurde aufgrund zunehmender Belastungsdyspnoe und Hustenattacken zur weiterführenden Abklärung zugewiesen. Die phasenweise produktiven Hustenanfälle traten teils zeitlich mit der Nahrungsaufnahme zusammenhängend auf. Zusätzlich bestanden zehn Kilogramm Gewichtsverlust innerhalb des vorhergehenden Jahres. wkw 17–18/2011 © Springer-Verlag

F3 Husten nach Kaffee und Kuchen – ein interdisziplinäres Rätselraten J. Bilek1, G. Kühteub1, W. Klepetko2, P. Schnider1,3, P. Schenk1 1

Landesklinikum Thermenregion Hochegg, Grimmenstein, Österreich Univ.-Klinik für Chirurgie, Medizinische Universität Wien, Wien, Österreich 3 Abteilung für Neurologie, Landesklinikum Wr. Neustadt, Wiener Neustadt, Österreich 2

Bei Frau P., 63 Jahre, wurde im Juni 2010 eine Appendektomie durchgeführt. Anschließend kam es zu einem komplizierten postoperativem Verlauf mit Peritonitis und Adnexitis, der sich durch eine Pseudomonas aeruginosa Sepsis aggravierte und einen sechs-monatigen Aufenthalt auf der Intensivstation nach sich zog. Nach anschliessendem Weaning und Dekanülierung kam es zu einer solch ausgeprägten Dysphagie, dass sie mit einer PEG-Sonde versorgt werden musste. Eine Schluckdiagnostik ergab einen unauffälligen Befund.

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Nach Transferierung zur Neurorehabilitation wegen Critical Illness Polyneuropathie und Abklärung der Schluckstörung erlitt die Patientin eine schwere Pneumonie mit Pseudomonas aeruginosa und E. Coli Isolation. Eine abermalige Videofluoroskopie ergab wieder einen normalen Schluckakt. In der Laryngoskopie fand sich aber eine deutliche intra- und postdeglutitive Dysphagie mit Aspiration. Klinisch-neurologisch gab es keinen Anhalt für eine neurogene Dysphagie. Also lag ein Zusammenhang mit der Tracheostomienarbe und eventuellen Strikturen nahe. Die Abklärung an der HNO Abteilung bestätigte zwar die Aspiration sämtlicher Konsistenzen, eine Ursache im Narbenbereich des Stoma wurde aber ausgeschlossen. In einer Bronchoskopie konnte der Verdacht auf eine ösophagotracheale Fistel verifiziert werden, welche letztendlich operativ verschlossen wurde.

F4 Extrem seltene Ätiologie eines Lungenrundherdes J. Bolitschek, I. Kühtreiber, K. Berger-Steiner Lungenabteilung, Landeskrankenhaus Steyr, Steyr, Österreich

Wir berichten über den Fall einer 56jährigen Patientin, welche aufgrund eines protahierten respiratorischen Infektes mit Dyspnoe und links thorakalen Schmerzen primär einen niedergelassenen Lungenfacharzt aufgesucht hatte. Von diesem wurde auswärts ein Thorax CT veranlasst. Als Befund ergaben sich mehrere teils unscharf abgrenzbare Herde in beiden Lungen mit einer Größe bis 15 mm, weiters mehrere mediastinale Lymphknoten mit einer Größe bis zu 15 mm. Unsererseits wurde zur weiteren Abklärung eine Bronchoskopie durchgeführt. Zur Gewebegewinnung wurde versucht einer der beschriebenen Rundherde durchleutungsgezielt einzustellen, aufgrund der geringen Größenausdehnung gelang dies jedoch nicht. Es wurden Probeexzisionen an der Hauptcarina und im linken Unterlappen entnommen, beide lieferten unauffällige Bronchialschleimhautanteile. Die brochoskopische Absaugung zeigte keinen Keimnachweis. Auch mittels CT gezielte Feinnadelpunktion konnte keine Diagnose gestellt werden. Somit wurde die chirurgische Exzision eines Rundherdes angestrebt. Es erfolgte eine Minithorakotomie. Die Pathologie unseres Hauses stellte die Verdachtsdiagnose Morbus Castleman – multizentrische Form. Dieser Befund wurde vom Institut für Pathologie der Medizinischen Universität Graz bestätigt.

Therapeutisch begannen wir mit einer systemischen Cortisongabe. In den nachfolgenden Kontrolluntersuchungen war die Patientin klinisch stabil. Die Thorax-CT-Befunde zeigten keine Progredienz.

F5 Dyspnoe seit 2 Jahren mit akuter dramatischer Entwicklung C. Großruck, R. Kolb, J. Eckmayr Abteilung für Lungenkrankheiten, Klinikum Wels – Grieskirchen, Österreich

42-jährige Verkäuferin, Struma nodosa mit kaltem Knoten, Z. n. AT, Raucherin (14 Py), rezidivierende Arztbesuche wegen Atembeschwerden. Anamnese: Dyspnoe sowie „pfeifende“ Atemgeräusche seit 2 Jahren mit zunehmender Verschlechterung. Stationäre Aufnahme wegen suspekter Raumforderung in der Trachea (Abb. 1). Status: AZ unauffällig, EZ leicht adipös, stridoröse Atmung. Medikation bei Aufnahme: Foster DA 1-2 Hub bei Bedarf, Prednisolon 5 mg 2-0-0. Tag 1: Spirometrie und Bodyplethysmographie: auffälliges Plateau im Exspirium. Tag 2 – Tag 12 Intensivabteilung: Invasive Beatmung für 10 Tage, Sedierung, Antibiose mit Zienam, Solu Dacortin, Lasix, Euphyllin und Gynipralinfusionen, Inhalationen mit Berodual und Pulmicort, Structocabiven. Bronchialsekret, Nadel und Biopsie: uncharakteristischer Befund. Tag 7: Bronchoskopie in Narkose unter Beatmung mit dem Jetkatheter und anschließender Tumorabtragung mit Argonbeamer und Zange, 2/3 des Gesamtvolumens wurden abgetragen. Biopsien Trachealtumor: Intaktes follikuläres Schilddrüsengewebe ohne Malignitätsnachweis. Tag 9: Extubation auf der Intensivabteilung. Tag 12: Verlegung auf die Normalstation mit anschließender psychologischer Betreuung. Tag 16: MRT: Befundbesserung, möglicherweise Einwachsen der Schilddrüse durch die Pars membranacea. Tag 21: Entlassung. Diagnose: Akute Trachealstenose durch ektopes Schilddrüsengewebe ohne Malignitätsnachweis. Kontrollbronchoskopie nach 3 Monaten: Abtragung von 3 Granulationsgewebspolypen (Abb. 3).

Abb. 1. Ovaläre Raumforderung mit ca. 1,8 × 1,2 cm, sichelförmige Einengung der Trachea

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Tag 2. Diagnostische Bronchoskopie in Narkose (Abb. 2). Nach Extubation starker Hustenreiz mit akuter respiratorischer Insuffizienz bei Trachealkollaps mit Reintubation und Transfer auf die Intensivstation.

Abb. 2. Sichelförmige Einengung der Trachea

F6 Vaskulär bedingte pulmonale Infiltrate bei einer Raucherin M. Gulesserian¹, H. Koller¹, M. Huber², O. C. Burghuber¹ 1

I. Interne Lungenabteilung, Otto Wagner Spital, Wien, Österreich Pathologisch-bakteriologisches Institut, Otto Wagner Spital, Wien, Österreich

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Bei einer 53-jährigen Krankenschwester mit 30 pack-years wurde auswärtig wegen seit Wochen bestehender Belastungsdyspnoe eine Computertomographie des Thorax durchgeführt, welche beidseitige zerfallende, fleckförmige Infiltrate beschrieb. Die Histologie aus einer CT-gezielten transthorakalen Biopsie rechts zeigte eine Perivaskulitis. Eine systemische Vaskulitis mit weiterem Organbefall konnte in Folge ausgeschlossen werden. Laborchemisch zeigte sich ein pathologisch erhöhtes CRP von 138 mg/L. Die Patientin war zu diesem Zeitpunkt nicht sauerstoffpflichtig. wkw 17–18/2011 © Springer-Verlag

Abb. 3. (Abstract F5) Kontrollbronchoskopie nach 3 Monaten: Abtragung von 3 Granulationsgewebspolypen

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Zwei Wochen später musste die Patientin wegen akuter Verschlechterung und respiratorischer Globalinsuffizienz (pO2: 45 mmHg, pCO2: 58 mmHg, pH: 7,18) an unserer Intensivstation aufgenommen und intubiert werden. Nativradiologisch zeigte sich eineZunahmederbeidseitigenintrapulmonalenKonsolidierungsherde, sodass eine breite antibiotische Therapie etabliert wurde. Die Histologie der Lingula- und Unterlappen-Biopsate, die mittels Videoassistierter Thorakoskopie (VATS) gewonnen wurde, ergab eine abszedierende nekrotisierende Pleuropneumonie mit intravasalen Thrombenbildungen. Aufgrund des Verteilungsmuster der pulmonalen Abszedierungen und des Thrombennachweises wurde unter Annahme eines septisch-embolischen Geschehens eine transösophagale Echokardiographie (TEE) durchgeführt. Diese zeigte eine an der Trikuspitalklappe flotierende kugelige Struktur kompatibel mit Trikuspitalendokarditis und ursächlich für die septisch-pyämischen Lungenabszesse. Im Bronchialsekret wurde Pseudomonas aeroginosa kultiviert, mehrfach wiederholte Blutkulturen blieben negativ. Bei Verdacht auf Pseudomonas-Endokarditis wurde die antibiotische Therapie entsprechend modifiziert. Dennoch kam es primär zu einer Verschlechterung mit nachfolgendem septischen Kreislaufversagen, welches jedoch intensivmedizinisch beherrscht werden konnte. Mit Besserung der Klinik kam es auch radiologisch zur Regredienz der beidseitigen pulmonalen Infiltrate, die Echokardiographie zeigte eine Besserung. Der Intensivaufenthalt wurde in weiterer Folge durch eine Critical-illness Neuro- bzw. Myopathie sowie durch einen septischembolisch bedingten beidseitigen Sehverlust, wobei das rechte Auge erblindete, kompliziert. Wegen prolongiertem Weaning musste die Patientin tracheotomiert und zunächst an unserer Respiratory Care Unit (RCU) vom Respirator entwöhnt, und schließlich mit 2 Liter Sauerstoffinsufflation auf unsere Normalstation übernommen werden. Nach 3 Monaten konnte die Patientin Rollator-mobil mit 2 Liter Langzeitsauerstofftherapie an ein Rehabilitationszentrum transferiert werden. Im 3-monatigen Verlauf zeigte die Computertomographie des Thorax eine deutliche Regredienz der beidseitigen pulmonalen Veränderungen, die Echokardiographiekontrolle war zu diesem Zeitpunkt unauffällig.

F7 Rund und doch nicht g‘sund B. Heindl, M. Hubner, M. Kneussl 2. Medizinische Abteilung, Lungenabteilung, Wilhelminenspital, Wien, Österreich

65-jährige Patientin: COPD, GOLD IV. Weitere Diagnosen: • Sekundäres zentrilobuläres Emphysem • Sekundäre pulmonale Hypertension • Substituierte Hypothyreose • Glaukom • Steroidinduzierte Osteoporose • Arterielle Hypertonie Bei FEV1 von 700 ml und gutem allgemeinen Performancestatus wurde im Jahr 2007 die Indikation zur Lungentransplantation gestellt. Als Zufallsbefund fand sich – bioptisch verifiziert – ein gastrointestinaler Stromatumor (GIST) des Magens. Nachdem es sich histologisch um keinen invasiv wachsenden Tumor handelte, stellte dies primär keine Kontraindikation zur Transplantation dar. In Folge zeigten sich im Thorax-CT neben bekannten Granulomen (PPD und Quantiferon negativ, Sputum ZN negativ) neue, dringend sekundärblastomsuspekte bis zu 8 mm große Rundherde. In einer PET-Untersuchung ließ sich ein ausgedehnter hypermetaboler Herd im Oberbauch links – dem Primum an der kleinen

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Kurvatur des Magens entsprechend – sowie auch intrapulmonale kleine, hypermetabole Läsionen darstellen (SUV unter 1,5). Bei zunehmender Verschlechterung der respiratorischen Situation war funktionell weder eine bronchoskopische noch bioptische Abklärung möglich. Bei dringendem Verdacht auf Metastasierung des Magentumors erfolgte ex juvantibus im interdisziplinären Konsens die Etablierung einer TKI-Therapie mit Imatinib. Im Verlauf konnte im CT-Thorax einerseits eine Regressio, andererseits ein Neuauftreten von multiplen zerfallenden Rundherden beobachtet werden. Konkordant musste im PET eine neuerliche Progredienz der pulmonalen Manifestationen (steigender SUV 2,7) zur Kenntnis genommen werden, der als Primum definierte Herd an der Magenkurvatur kam nicht mehr zur Darstellung (interpretiert als teilweises Ansprechen auf die Therapie). Die Therapie mit Imatinib wurde somit beibehalten. Im Verlauf der Erkrankung musste akzeptiert werden, dass keine weitere Abklärung trotz weiterer Progressio der pulmonalen Rundherde möglich erschien. Die Patientin verstarb in der respiratorischen Globalinsuffizienz. Im Obduktionsbefund erschienen die Rundherde makroskopisch primär spezifisch (ZN negativ), wurden letztlich jedoch als non rezente Pulmonalembolien unterschiedlichsten Alters klassifiziert. Diese Differentialdiagnose war aufgrund der Fokussierung auf die onkologische Grunderkrankung sowie den PET-Befund leider nicht in Betracht gezogen worden (CT stets ohne selektive Darstellung der peripheren Gefäße).

F8 Rezidivierende Pneumonie – unbemerkte Fremdkörperaspiration oder „steckt“ doch etwas anderes dahinter? F. Huemer1, P. Cicho1, H. Haber1, M. Huber2, H. Wohlschlager1,3, N. Vetter1 1

2. Interne Lungenabteilung, Otto Wagner Spital, Wien, Österreich Institut für Pathologie, Otto Wagner Spital, Wien, Österreich 3 Institut für Radiologie, Otto Wagner Spital, Wien, Österreich 2

Klinik und Anamnese: Im Oktober 2010 wurde eine 39-jährige Frau aufgrund einer therapieresistenten Pneumonie durch den Hausarzt in unsere Ambulanz überwiesen. Sie klagt über Husten und Fieber. Anamnestisch besteht ein Z.n. rez. Pneumonien – zuletzt 2008 mit ausgedehnter Pneumonie im Bereich des posterolateralen Unterlappen links und verzögertem Ansprechen auf antibiotische Therapie. Befunde: Labor: CRP 234 mg/l, Mykoplasmen-AK positive. CT der Thoraxorgane: Links dorsobasal findet sich endobronchial eine ovaläre Konsolidierung mit etwa 6 : 3 cm Größe. Einzelne zuführende Bronchien zeigen deutliche Sekretretentionen. Bronchoskopie: Links findet sich im UL-Abgang ein kugeliger, gelblich-weißer weicher tumoröser Prozess, welcher das Ostium des ULStammbronchus komplett obturiert. Histologie: Man erkennt in den Gewebsanteilen abschnittsweise Bronchusmucosa mit oberflächlich regulärem respiratorischen Epithel mit angrenzenden Anteilen eines reifen Fettgewebes. Verlauf: Die stationäre Aufnahme erfolgte aufgrund einer Mykoplasmenpneumonie, welche mit Cefuroxim und Clarithromycin behandelt wurden. Aufgrund der Anamnese wurde eine Computertomographie des Thorax veranlasst, in welcher sich im posterobasalen UL links endobronchial ein Tumor zeigte. Endoskopisch zeigte sich endoluminal ein gelblicher, oberflächlich glatter Tumor. Histologisch wurde die Diagnose eines endobronchialen Lipoms gestellt, welches in einer 2. Sitzung endoskopisch komplett reseziert wurde. © Springer-Verlag

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F9 Fast-Ertrinken – und am Ende eine Systemerkrankung S. Klade, J. Zwittag, K. Weiglein, A. Huber, H. A. E. Schinko Abteilung für Lungenheilkunde, Allgemeines Krankenhaus Linz, Linz, Österreich

Erholungsurlaub am Roten Meer getrübt durch ein Fast-Ertrinken. In der Folge Hämoptysen. Spitalsaufnahme nach Rückkehr aus Ägypten wegen nächtlicher Atemnot, Husten und Fieber, ohne dass im AngioCT eine Lungenembolie nachzuweisen ist, aber dichte Lungeninfiltrate, eine Obliteration des Unterlappenbronchus rechts, Stenosierung links und Verdickung der Tracheo-Bronchialwände. Bronchoskopisches Bild einer exophytisch-polypoiden Schleimhautverdickung, Verplumpung der Hauptkarina und allgemeine Einengung der Bronchien. Bronchialbiopsien: hyperplastische fibrinöse Bronchitis. Atemfunktionell mäßiggradige kombinierte restriktiv-obstruktive Ventilationsmit Oxigenationsund volumsdominierter Diffusionsstörung. Ein leicht erhöhter Atemwiderstand in Gegenwart leicht erhöhter IgE undECP-Werte veranlasst eine Inhalationstherapie mit Berodualin, schließlich Foradil. Bei 16,8 g/l Leukozyten und CRP 15,8 mg/dl erfolgt eine kombinierte Therapie mit Prednisolon, Unasyn® und Anaerobex®, später Tazonam®. Bei zögerlicher Besserung ambulante Fortsetzung der Antibiose und Kortikoidtherapie. Anfang Juli Normalisierung der CRP und Auflockerung der pulmonalen Infiltrate. Rebronchoskopie: weiterhin hyper-plastische Tracheobronchitis, allgemeine Bronchialwandverdickung und -einengung. Bei Nasenpassage abnorm dicke Schleimhaut. Rebiopsien: Fibrinöse Bronchitis mit nekrotischem und degeneriertem Bronchialknorpel. ANA-Titer grenzwertig, aber Subtypen und ANCA negativ. Alle TBC-Befunde negativ. Kein bakteriologischer Keimnachweis. Bei fehlender Diagnose nochmalige Bronchoskopie im August mit aggressiver Probengewinnung. Histologisch denudierte Bronchialmukosa mit nodulärem eosinophilen Kongorot pos. Material neben fokaler Kalkinkrustation, Fremdkörperreaktion und Lymphozyteninfiltration. Tracheobronchiale Amyloidose mit interstitiellen AL-Amyloidablagerungen vom λ-Leichtketten-Typ bestätigt durch ein Referenzzentrum. Im PET-CT keine metabolische Aktivität.

F10 IGRA in der Diagnostik einer aktiven Lungen-Tbc D. Krejci, R. Rossi, H. Jamnig Abteilung für Pneumologie, Landeskrankenhaus Natters, Österreich

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Wir berichten über eine 25-jährige Patientin aus dem Kosovo. Klinik: Seit 2 Wochen Glieder,- Gelenks,- und Kopfschmerzen; Fieber bis 38 Grad; Gewichtsabnahme von 2, 3 kg im letzten Monat; kein Husten. Zur Diagnose bei radiologischem V.a. Tbc wird neben den Standardmethoden (Mikroskopie, NAT + Kultur aus Sputum und BAL) bei pos. IGRA aus dem Blut die Tb-Spot-Untersuchung aus der BAL durchgeführt. Durch diese Methode, welche zur Diagnose der aktiven Tbc in Niederprävalenzländer geeignet erscheint, gelingt eine frühzeitige Erhärtung des Verdachts, welcher nach 21 Tagen mit dem Eintreffen der positiven Flüssigkultur (Mycobacterium tuberculosis Komplex) bestätigt wird. In der Folge ist auch die Festkultur positiv (Mycobacterium tuberculosis Komplex). Der Mycobacterium tuberculosis Komplex ist sensibel auf die gängige antituberkulöse Therapie.

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Zusammenfassung: Endobronchiale Lipome sind sehr seltene, vom Fettgewebe der Bronchialwand ausgehende Tumore. Sie repräsentieren 0,1 % aller Lungentumore sowie 13 % aller gutartigen Neoplasien. Prädominant ist das männliche Geschlecht mit 85–90 %. Häufiger finden sich diese Tumore in den größeren Atemwegen und mit 66 % rechtsseitig. Sie sind farblich gelblich bis weiß-gräulich mit glatter Oberfläche. Symptome können persistierender Husten, Dyspnoe, Hämoptysen sowie rezidivierende Pneumonien sein. Die zuverlässigste Diagnosemethode ist die Bronchoskopie, die Therapie der Wahl die endoskopische Resektion. An eine chirurgische Sanierung mittels Lobektomie bzw. Pneumektomie muss gedacht werden, wenn keine eindeutige histopathologische Diagnose gestellt werden kann, die Lokalisation keine vollständige bronchoskopische Resektion ermöglicht bzw. persistierende Lungenschäden (Atelektasen, Bronchiektasien) entstanden sind. Im Fall unserer Patientin war dies jedoch nicht notwendig, eine Kontroll-CT ist für Okt. 2011 vorgesehen.

F11 Rezidivierende sinubronchiale Infekte und interstitielle Veränderungen – 08/15 Diagnosen? A. Lakatos-Krepcik, K. Patocka, W. Pohl Abteilung für Atmungs- und Lungenkrankheiten, Krankenhaus Hietzing, Wien, Österreich

Eine 49-jährige Patientin wurde aufgrund rezidivierender sinubronchialer Infekte und dem radiologischen Verdacht einer interstitiellen Lungenerkrankung an unsere Abteilung zugewiesen. Anamnese: Bei der Patientin waren seit einem Jahr wiederholt Infekte der oberen und unteren Atemwege aufgetreten, die mehrfach antibiotisch behandelt wurden. Es waren keine internen Vorerkrankungen erhebbar, sie war Nichtraucherin, Penicillinallergie war bekannt. Klinik und Befunde: Der klinische Status war unauffällig. Im Labor fiel einzig eine minimale Hypoproteinämie (Totalprotein 6,2 g/ dl) auf, welche laut Patientin schon aus früheren RoutineLaborkontrollen bekannt war. Lungenfunktionell bestand keine Einschränkung. Radiologie: Das Thorax-CT zeigte teils dichte, teils milchglasartige Strukturalterationen in beiden Unterlappen, im Mittellappen und der Lingula, sowohl subpleural als auch zentral gelegen. Zudem bestanden Bronchiektasien im Untergeschoß. Auffallend waren weiters vergrößerte hiläre und mediastinale Lymphknoten sowie eine Splenomegalie. Bronchoskopie: Zur weiteren Abklärung wurde eine Bronchoskopie mit Biopsien und einer bronchoalveolären Lavage (BAL) durchgeführt. Die Histologie zeigte Lymphozytenaggregate im Interstitium, fibrös verbreiterte Alveolarsepten und ein Epitheloidzellgranulom ohne Nekrose. Die BAL ergab ein lymphozytäres Bild (Lymphozyten 38 %, CD4/CD8-Ratio 5,4). In der Immunphänotypisierung war keine Klonalität nachweisbar, somit konnte ein Lymphom ausgeschlossen werden. Insgesamt sprach dieses Bild für eine lymphozytäre interstitielle Pneumonie (LIP). Die häufigsten Ursachen einer LIP sind HIV, Dysproteinämien, Autoimmunerkrankungen (Sjögren-Syndrom, RA, SLE) und Virusinfekte (v.a. EBV). Bei unserer Patientin zeigte die Eiweiß-Elektrophorese eine massive Hypogammaglobulinämie mit niedrigen IgG-, IgA- und IgMSpiegeln. Somit konnte, nach Ausschluss anderer Ursachen, die Diagnose einer LIP im Rahmen einer CVID (Common variable immunodeficiency) gestellt werden. Diese indiziert eine regelmäßige und lebenslange i.v.-Immunglobulin-Substitution (IVIG). Schlussbemerkung: Hinter scheinbar banalen respiratorischen Infekten verbarg sich diese seltene Form einer interstitiellen Lungenerkrankung, die mit immunologischen Systemerkrankungen assoziiert ist.

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Die CVID ist charakterisiert durch rezidivierende Infekte, Splenomegalie, gastrointestinale Beschwerden und progrediente pulmonale Veränderungen (Bronchiektasien, lymphozytäre interstitielle Infiltrate und granulomatöse Veränderungen). Prognostisch bedeutsam sind die pulmonalen Veränderungen, welche einzig durch IVIG-Substitution positiv beeinflusst werden können.

weniger als 1 % aller Lungentumore aus, können sich aber klinisch und radiologisch wie maligne Tumore präsentieren und sind häufig erst postoperativ eindeutig zu diagnostizieren. Dieser Fall mit Ansprechen auf intravenöse Immunglobuline erweitert die seltenen Berichte über Therapieoptionen für unresezierbare Pseudotumoren.

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F12 Mediastinale Raumforderung bei einer Patientin mit Z.n. Mammakarzinom J. Löffler-Ragg1, J. Bodner2, M. Freund3, M. Steurer4, B. Zelger5, C. M. Kähler1 1

Universitätsklinik für Innere Medizin I, Department Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Österreich 2 Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie, Department Operative Medizin, Medizinische Universität Innsbruck, Innsbruck, Österreich 3 Department Radiologie, Medizinische Universität Innsbruck, Innsbruck, Österreich 4 Universitätsklinik für Innere Medizin V, Department Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Österreich 5 Institut für Pathologie, Medizinische Universität Innsbruck, Innsbruck, Österreich

Wir berichten über eine 48-jährige Frau mit Brustkrebsanamnese, die wegen zunehmender Atemnot, Fieber, trockenem Husten und interskapulären Schmerzen überwiesen wurde. Bildgebend zeigte sich eine mediastinale Raumforderung mit ausgeprägtem Pleuraerguß (Abb. 1) und hoher Anreicherung von 18F-Fluordesoxyglucose (FDG) in der nuklearmedizinischen Untersuchung (Abb. 2). Die CT-gesteuerte Biopsie dieses Tumors im Bereich zwischen viszeraler Pleura und dem Lungenoberlappen rechts (Abb. 3) ergab keinen Malignitäshinweis, zeigte jedoch eine ausgeprägte inflammatorische Gewebsreaktion mit Schaumzellen. Nach einer initialen empirischen antibiotischen Therapie kam es vorübergehend zu Fieberfreiheit, Rückgang von Entzündungszeichen und Reduktion der Tumorgröße. Im weiteren Verlauf kam es zu einem Relaps und die Patientin war Therapie-refraktär auf weitere antibiotische Therapie und auf einen Kortisonversuch. Mit der Arbeitshypothese „Inflammatorischer Pseudotumor“ wurde bei der Patientin eine Lungenteilresektion durchgeführt und infolge histologisch die Verdachtsdiagnose bestätigt. Das postoperative Staging mit FDG-PET zeigte residuale Tumoranteile. Nach intravenöser Verabreichung von Immunglobulinen konnte eine anhaltende Remission erzielt werden. Inflammatorische Pseudotumoren machen

Pulmonale Infektion mit M. szulgai – Fallbericht eines seltenen Pathogens R. Mikes1, J. M. Kern2, V. Maaß2, R. Hartl3, M. Maaß2, M. Studnicka1 1

Universitätsklinik für Pneumologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich 2 Institut für Medizinische Mikrobiologie, Hygiene und Infektiologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich 3 Institut für Hygiene, Mikrobiologie und Tropische Medizin, Elisabethinen Spital, Linz, Österreich

M. szulgai ist ein seltenes nicht-tuberkulöses Mykobakterium, welches erstmals 1972 beschrieben wurde. Obwohl pulmonale Infektionen überwiegen, konnte M. szulgai auch aus extrapulmonalen Herden wie Bursitis, Tendosynovitis der Hand, Osteomyelitis, Keratitis, cervikale Lymphadentitis und renalen Infektionen isoliert werden. Eine pulmonale Infektion mit M. szulgai ist in den meisten Fällen als pathologisch zu werten und therapiebedürftig. Zu den Hauptrisikofaktoren zählen Nikotinabusus, COPD, Alkoholismus sowie ein immunkompromittierter Organismus. Eine 47-jährige Frau wurde zur weiteren Abklärung von persistierendem Husten, Schwäche, Müdigkeit, Nachtschweiß sowie Gewichtsverlust unserer Abteilung zugewiesen. Anamnestische konnte erhoben werden, dass die Patientin bereits dreimalig eine pulmonale Tuberkulose durchgemacht hatte (1983, 1995 und 1998). Im Aufnahme Thorax-Röntgen zeigten sich ausgedehnte postspezifische Veränderungen beidseits oberfeldbetont sowie eine Kranialraffung der Hili mit bullösen Aufhellungsareale beidseits apikal. Zudem zeigte sich eine strangförmige Konsolidierung links. Die Ziehl-Neelsen-Färbung von 3 konsekutiven Sputa war negativ auf Mykobakterien. Auch im Bronchialsekret konnte initial kein mikroskopischer Nachweis von Mykobakterien erfolgen. Bei hochgradigem klinischen Verdacht auf eine Infektion mit Mykobakterien sowie mehrmaliger pulmonaler Tuberkulose in der Vorgeschichte, entschieden wir uns dennoch für die Einleitung einer Vierfach Therapie mit Isoniazid, Rifampicin, Ethambutol und Pyrazinamid.

Abb. 1–3. Mediastinale Raumforderung mit ausgeprägtem Pleuraerguss (Abb. 1) und hoher Anreicherung von 18F-FDG (Abb. 2). Abb. 3. Ausgeprägte inflammatorische Gewebsreaktion mit Schaumzellen im CT erkennbar

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F14 Ein Holländer in Salzburg – Lunge, Lacke und Snowboards F. Oberascher1, I. Stelzmüller1, G. Hutarew2, M. Studnicka1 1

Universitätsklinik für Pneumologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich 2 Institut für Pathologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich

Die akut toxische Alveolitis wird durch zahlreiche Substanzen ausgelöst und als Berufserkrankung anerkannt. Primäre Abklärung eines 53-jährigen Mannes auf Sarkoidose. Der ehemalige Raucher berichtet über eine seit Monaten bestehende Belastungsdyspnoe, produktiven Husten, Nachtschweiß und Fieber. Der gebürtige Holländer, der aus beruflichen Gründen nach Österreich kam, arbeitet seit einigen Jahren als Lackierer ohne ausreichende Schutzmaßnahmen in einer Schifabrik. Bei der Aufnahme waren BGA und Lungenfunktion unauffällig. CT: Disseminierte Milchglastrübung aller Lappensegmente mit fleckförmigen, kleinnodulären Infiltraten subpleural. BSK: Saugbiopsate mit gesteigerter Zahl an monomorphen Lymphozyten. Histologie: Leichte interstitielle und peribronchioläre Fibrose mit knotigen Entzündungsresiduen und Muster einer organisierenden Pneumonie ohne Hinweis auf eine epitheloidzellige Granulomatose. Verlauf: Nach einwöchiger Allergenkarenz ohne Therapie bereits klinische und radiologische Befundbesserung, in der Lungenfunktion persistiert eine geringfügige Diffusionsstörung. Die CT-morphologischen und histologischen Veränderungen erhärten den Verdacht auf eine akut toxische Alveolitis nach jahrelanger inhalativer Exposition gegenüber Inhaltsstoffen von Farben und Lacken. Neben der Empfehlung einer absoluten Allergenkarenz bzw. Anwendung entsprechender Arbeitsschutzmaßnahmen wurde auch die ärztliche Meldung einer Berufskrankheit gestellt.

F15 Multiple intrapulmonale Infiltrate und Hämoptysen nach Entbindung U. Radda1, T. Jaritz1, H. Martinz², E. Isak³, C. Geltner1 1

Abteilung für Pulmologie, Klinikum Klagenfurt, Klagenfurt, Österreich Institut für Pathologie, Klinikum Klagenfurt, Klagenfurt, Österreich 3 1. Medizinische Abteilung (Onkologie), Klinikum Klagenfurt, Klagenfurt, Österreich 2

Anamnese: 33-jährige Patientin, 2. Schwangerschaft, 1. Schwangerschaft unkompliziert. Spontangeburt in der 38. plus 5d SSW (Knabe). Postpartal verstärkter Husten und Schmerzen im Rippenbereich. Keine pulmonale Vorerkrankungen, keine Begleiterkrankungen. Nichtraucherin. wkw 17–18/2011 © Springer-Verlag

In den letzten Wochen der Schwangerschaft kam es zu zunehmender Belastungsdyspnoe und rezidivierenden Hämoptysen. Die Entbindung erfolgte problemlos. Danach kam es rasch zu einer Verschlechterung der respiratorischen Situation. Die Patientin wurde auf Grund multipler pulmonaler Infiltrate im Lungen-CT an unsere Abteilung transferiert. Zu diesem Zeitpunkt besteht eine respiratorische Insuffizienz mit zunehmender Verschlechterung und Indikation für nicht-invasive Beatmung. Initiale Therapie mit Verdacht auf Vaskulitis und organisierende Pneumonie (Solu Dacortin und Antibiose) Radiologie: Fleckig disseminierte Infiltrate mit Hauptausprägung in den Unterfeldern und nach apikal hin abnehmend. Teilweise konfluierend. In der CT zeigen sich disseminierte atypische pneumonische Infiltrate mit subpleuraler und apicobasaler Ausbreitung mit dem Bild einer organisierenden Pneumonie. Labor: Leukozyten 12.000 × 103/μl, CRP 12 mg/dl, ANA, ANCA, AntiGBM neg., TBC-Mikroskopisch und PCR neg., Quantiferon neg., HCG im Serum deutlich erhöht (447.483 mIU/ml). Bronchoskopie mit BAL und TBB: Vulnerable Schleimhautverhältnisse, jedoch keine rezente Blutung, endoluminal kein Tumorhinweis. Histopathologisch kein schlüssiger Befund. Ultraschallgezielten Stanzbiopsie: Der Befund entspricht einem großzelligen pleomorphen Beta-HCG produzierenden Karzinom, Chorionkarzinom. CT-Abdomen: Hämangiom rechter Leberlappen, keine freie intraabdominelle Flüssigkeit. Uterus deutlich vergrößert mit Sekret im Cavum beim Z. n. Partum. Das rechte Ovar weist mehrere bis zu 2,5 cm im DM haltende Zysten auf. Endgültige Diagnose: Chorionkarzinom (Schwangerschaft-assoziiert). FIGO-Klassifikation: Stad. II c, Prognosekriterien: high risk. Zusammenfassung: 30-jährige Patientin kommt postpartal mit Infiltraten, respiratorischer Insuffizienz und Hämoptysen. Nach der Abklärung zeigte sich ein Chorionkarzinom mit multiplen intrapulmonalen Metastasen. Noch unter nicht-invasiver Beatmung wurde eine Chemotherapie nach dem EMA/CO Schema eingeleitet.

ÖGP

In drei konsekutiven Sputumkulturen zeigte sich jedoch nach 4 Wochen ein Wachstum atypischer Mykobakterien. Die molekularbiologische Speziesidentifizierung mittels Gensonde (GenoType Mycobacterium AS, Hain Lifesciences) ergab M. szulgai. Entsprechend der Resistenzbestimmung (Löwenstein-JensenMedium) wurde schließlich die eingeleitete Therapie wie folgt adaptiert: Rifampicin (300 mg), Ethambutol (500 mg), Clarythromycin (500 mg). Diese sollte für mindestens 12 Monate fortgeführt werden. Regelmäßige Kontrollen der Patientin zeigten erfreulicherweise eine deutliche klinische Besserung. Radiografisch konnte bei einer 2-Monats-Kontrolle jedoch noch keine wesentliche Befundänderung erkannt werden.

F16 Lungentransplantation bei einem Patienten mit ARDS und ECMO (extracorporal membrane oxygenation) Unterstützung nach H1N1 und RSV Infektion A. Scheed, P. Jaksch, M. B. Ernst, J. Matilla, S. Taghavi, W. Klepetko Division of Thoracic Surgery Department of Surgery, Medical University of Vienna, Vienna, Austria

During the 2009 H1N1 influenza A virus pandemic, some patients developed severe pneumonia leading to acute respiratory distress syndrome(ARDS). Several studies described the need of intensive care or ECMO support in these mostly young and healthy patients. We report the case of bilateral lung transplantation (LUTX) in a 29 year old female bridged with ECMO due to ARDS after combined infection of H1N1 and respiratory syncytial virus (RSV). The patient was admitted to the hospital with influenza symptoms extending over several weeks. H1N1 testing was positive at admission. The disease followed a rapidly progressive course requiring mechanical ventilation and aggressive medical treatment. However, the respiratory situation worsened increasingly and the virological examination revealed a secondary infection with RSV. Ultimately the patient needed ECMO support. Blood cultures were negative at all time. After 10 days on ECMO no improvement of the clinical situation occurred and therefore the patient was transferred to our center for LUTX. At the time of listing, tests for H1N1 and RSV were already negative. A bilateral, size reduced (middle-lobe and lingual resection) LUTX on central ECMO was performed. Ischemic time on the right side was 295 min and ÖGP Jahrestagung 2011

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375 min on the left side. 1200 ml of erythrocyte-concentrates,140 ml of thrombocyte-concentrates and 2000 ml of fresh-frozen-plasma were needed. The ECMO could be removed at the end of the LUTX. The patient received a standard immunosuppressive therapy with cortisone,tacrolimus and mycophenalate. For infection prophylaxis intravenous administration of tazobactam, ganciclovir, cmv-antibodies and caspofungin was used in combination with amphotericin-b and gentamicin for inhalation. The patient left the ICU on the 24th postoperative day and could be discharged from the hospital 2 weeks later. The patient is now 3 months post LUTX and no recurrence of the viral infection has occurred so far. This report demonstrates a fulminate course of a viral infection in a before healthy patient. LUTX in such critically ill patients is an option if virological tests are negative and a single organ failure is present.

IGF II fähig sind. Die Prognose ist günstig, Rezidive sind selten v. a. bei radikaler Tumorresektion. Maligne Transformation ist möglich. Literatur 1. Briselli M, Mark EJ, Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer 1981;47:2678–89. 2. Meyer M, Krause U. Solitary fibrous tumors of the pleura. Chirurg 1999;70:949–52.

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F17 Interdisziplinäre Synkopenabklärung O. Schindler1, A. Ederegger1, N. Neuböck2, H. Langenberger3, G.Wurzinger1 1

Abteilung für Lungenkrankheiten, Landeskrankenhaus HörgasEnzenbach, Gratwein, Österreich 2 Klinische Abteilung für Thorax-Chirurgie, Universitätsklinik für Chirurgie, Medizinische Universität Graz, Graz, Österreich 3 Radiologieverbund Burgenland Mitte – Süd KH Oberwart – Oberpullendorf – Güssing, Österreich

Ein 79-jähriger Patient wurde wegen wiederholter Synkopen und Dyspnoe im Heimatkrankenhaus vorstellig. Das Aufnahme-EKG war unauffällig, der Blutdruck mit 175/ 105 mmHg hypertensiv. Laborchemisch auffällig waren Hb 8,9 g/dl, Thrombozyten 448 g/l, CRP 12,4 mg/l (Grenzwert 5 mg/l). Eine Computertomographie des Schädels war unauffällig. Im Thoraxröntgen fiel eine Verschattung im linken Mittel- und Unterfeld auf (Abb. 1). Computertomographisch fand sich eine Raumforderung nahezu den gesamten linken Unterlappen einnehmend mit Atelektase (Abb. 2). Es folgte eine CT-gezielte Punktion, histologisch wurde spindelzelliges Tumorgewebe – suspekte Anteile eines sarkomatoiden Mesothelioms – beschrieben. Klinisch auffällig waren rezidivierende Hypoglykämien (Glucose bei Aufnahme 126 mg/dl, HbA1c 4,9 %), die kontinuierliche Glucoseinfusionen erforderten. Zur weiteren Abklärung bei thorakalem Neoplasma wurde der Patient an unsere Fachabteilung transferiert. Ein schmaler linksseitiger Pleuraerguss erwies sich als Transsudat, das zytologische Bild war unspezifisch. Endobronchial war der linke Unterlappen subtotal duch Kompression von außen stenosiert, die Zytologie zeigte unklare atypische Zellverbände, die Histologie eine fibrosierende Bronchitis. C-Peptid war erniedrigt und Seruminsulin im unteren Normbereich. Mit der Arbeitsdiagnose rezidivierender paraneoplastischer Hypoglykämien bei Pleuratumor erfolgte eine linksseitige Pneumonektomie. Histologisch konnte das Vorliegen eines fibrösen Pleuratumors bestätigt werden. Postoperativ bestand ein normaler Glucose-Stoffwechsel. Lokalisierte fibröse Pleuratumoren sind eine seltene, häufig asymptomatische Erkrankung (1). Zu paraneoplastischen Hypoglykämien kommt es in <5 % der Fälle (2), insbesondere bei großen Tumoren. Der Tumor nimmt seinen Ausgang von submesothelialen Stammzellen, meist von der viszeralen (etwa 70 %) Pleura, die zur Produktion von

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Abb. 1. Thorax-Röntgen bei Übernahme

Abb. 2. CT-Thorax (Radiologieverbund Burgenland Mitte – Süd)

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F18

M. Speiser1, O. Braun2, M.Gadenstätter3, P. Errhalt1 1

Pneumologische Abteilung, Landeskrankenhaus Krems, Krems, Österreich 2 Institut für Pathologie, Landeskrankenhaus Horn, Horn, Österreich 3 Chirurgische Abteilung, Landeskrankenhaus Krems, Krems, Österreich

Grund der Zuweisung: Bei der 50-jährigen Patientin sind seit 2006 zystische Lungenveränderungen bds. vorbekannt, damals wurden in einem auswärtigen Zentrum eine LAM bzw. eine Histiozytosis-X weitgehend ausgeschlossen und die zystischen Veränderungen als postentzündlich interpretiert. Wegen zunehmender Belastungsdyspnoe sowie Progredienz der zystischen Lungenveränderungen im Jahr 2009 erfolgte eine Vorstellung an der Pneumologie Krems. Anamnese: 2002 Perikarditis unklarer Genese, Struma nodosa, COPD GOLD III. Klinik und Befunde: Bis auf polyzystische Veränderungen mit einer Zystengröße zwischen 5 und 25 mm war das Lungenparenchym im Thorax-CT weitgehend unauffällig, lungenfunktionell bestätigte sich die anamnestisch angegebene COPD Grad III. Klinisch auffällig war ein Schmetterlings-Erythem im Gesicht. Serologisch fanden sich deutlich erhöhte ANA mit erhöhten Subsets passend zu einem Lupus Erythematodes (LE): • ANA 1/5120 (Fluoreszenzmuster homogen, Chromosomen positiv) • Anti-ds-DNA – Antikörper 169,4 I.E./ml Verlauf: Da bronchoskopisch bereits auswärts keine Diagnosesicherung erreicht werden konnte, entschieden wir uns für eine VATS. Es erfolgte eine atypische Segmentresektion im linken UL, histologisch zeigte sich eine lymphoide interstitielle Pneumonie (LIP), als Nebenbefund eine fokale DIP-Reaktion. Somit konnte ein systemischer Lupus erythematodes mit positiver Autoimmunserologie, Z. n. Pericarditis, monatlich auftretenden Arthralgien und einem Schmetterlingserythem gesichert werden. Die pulmonale Manifestation bestand in Form einer lymphoiden interstitiellen Pneumonie (LIP), woraus sich die Indikation zu einer Therapie mit Endoxan und Cortison ergab. Nach 6 Zyklen zeigten sich Lungenfunktionsparameter (VCmax und FEV1) gebessert, CT-morphologisch war keine wesentliche Veränderung eingetreten. Take home: Eine Lungenbeteiligung bei LE äußert sich typischerweise in Form von – meist beidseits basal auftretenden – pulmonalen Infiltraten mit/ohne Hämorrhagie, Pleuritis. Die akute Lupuspneumonie ist ein seltenes Krankheitsbild, dem histologisch eine -unspezifische- generalisierte Vasculitis und Alveolitis zugrunde liegt, die Alveolitis ist in der BAL in der Regel lymphozytär. Ein pathognomonisches histologisches Bild ist nicht beschrieben. Die LIP als pulmonale Manifestation eines LE ist als Rarität in der Literatur beschrieben (1), im vorliegenden Fall wurde die Grunderkrankung über den „Umweg“ der pulmonalen Abklärung erst aufgedeckt. Literatur 1. Swigris JJ, Berry GJ, Raffin AT, Kuschner WG. Lymphoid Interstitial Pneumonia. Chest 2002;122;2150–64.

wkw 17–18/2011 © Springer-Verlag

Ein PET-Pitfall: eine 39-jährige Patientin mit multiplen pulmonalen und extrapulmonalen Rundherden I. Stelzmüller1, F. Oberascher1, R. Untersteiner1, L. Rettenbacher2, M. Studnicka1 1

Universitätsklinik für Pneumologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich 2 Universitätsklinik für Radiodiagnostik, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich

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Lungenzysten und Gelenksbeschwerden

F19

Eine Lungenbeteiligung im Rahmen einer Sarkoidose findet sich in über 90 % und wird mittels Thorax-Röntgen diagnostiziert und verlaufskontrolliert. Zur Beurteilung weiterer Organbeteiligungen erscheint auch das PET-CT besonders innovativ. Eine 39-jährige Frau mit laufender Therapie einer atypischen Mykobakteriose wird aufgrund pathologischer LFP und zunehmender Infiltrate im Mittel- und Oberlappen rechts zur Abklärung aufgenommen. BGA und Lungenfunktion im Normbereich. Aufgrund eines AV-Block III wurde bereits ein Schrittmacher implantiert. In der BSK präsentiert sich makroskopisch das Bild einer Sarkoidose. BAL und Biopsien sind jedoch unauffällig. Therapie: Beendigung der antituberkulösen Therapie bei fehlendem Keimnachweis und radiologischer Verschlechterung, stattdessen bei V. a. Sarkoidose nun Einleitung einer Cortisontherapie. Verlauf: Zunächst gutes Therapieansprechen mit Abnahme der Verschattungen der OL-Basis rechts, im weiteren Verlauf jedoch wieder geringgradige radiologische Progredienz. Es wird daher ein PET-CT nach 24 Stunden Fasten vereinbart: Intensive Mehrspeicherungen in den Lymphknoten mediastinal, bihilär, retroperitioneal, iliacal, in mutiplen Herden in Leber und Milz, in kardialen und pulmonalen Herden und in einzelnen ossären Herden. Neuerliche BSK: nun gelingt die Diagnosesicherung auch histologisch: granulomatöse Entzündung vom Sarkoidosetyp.

F20 Nekrotisierende epitheloidzellige granulomatöse Infiltrate – mykobakterielle Infektion, was sonst? C. Wohlkönig1, M. Meilinger1, H. Flick1, W. Fritz1, C. Hesse1, R. Wurm1, J. Polachova1, R. Krause1, H. Popper2, H. Olschewski1 1

Klinische Abteilung für Lungenkrankheiten, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Österreich 2 Institut für Pathologie, Medizinische Universität Graz, Österreich

Granulome können bei vielen Lungenkrankheiten auftreten, angefangen bei den häufigeren Entitäten bis hin zu den Raritäten. Dabei kann die Ursache sowohl entzündlich als auch nichtentzündlich sein. Wir stellen den Fall eines 71 Jahre alten Mannes mit Hämoptysen, tumorverdächtigen pulmonalen Expansionen in beiden Lungen und nekrotisierenden epithelioid-zelligen Granulomen in der Histologie vor. Wir werden Schwierigkeiten und Stolperfallen des Ausschlusses von infektiösen und nicht-infektiösen Ursachen bei so einem Szenario diskutieren.

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F21 Unter Immunsuppression ist nicht jeder zerfallende Lungenprozess eine Pilzpneumonie S. Zillinger

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Pneumologische Abteilung, Krankenhaus der Elisabethinen, Linz, Österreich

Bei einem Patienten, der primär aufgrund eines Pyoderma gangränosums in dermatologischer Behandlung immunsupprimiert wurde, kam es zum Auftreten eines einschmelzenden Lungenprozesses im rechten Lungenunterlappen mit bilateralen großnodulären

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Lungenparenchymveränderungen. Endobronchial waren waren Candida glabrata sowie Aspergillus candidus nachzuweisen. Eine antimykotische Therapie erfolgte mit gutem Ansprechen. Ein Monat später wurde der Patient mit einer akuten klinischen und bildgebenden Verschlechterung wieder aufgenommen. Man entschied sich aufgrund neuerlicher massiver Fieberschübe zu einer Open-Lung Biopsie. Das histologische Ergebnis dieser und die mikrobiologische Aufarbeitung der Blutkulturen ergaben eine unerwartete Diagnose: Nokardiose pulmonal und invasiv (Blutkultur positiv). Eine Therapie mit Lidaprim forte zeigte in den folgenden Verlaufskontrollen einen sehr guten Erfolg.

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Poster Die mit * markierten Poster wurden in einem anonymisierten Reviewerverfahren als beste Poster ausgewählt.

Cardiovascular autonomic control and baroreceptor sensitivity in patients with stable chronic heart failure and sleep disordered breathing S. Asadi, M. Ruis, S. Radakovic, I. Mikulic, O. Burghuber, and A. Valipour, for the VISIFA study group Ludwig-Boltzmann-Institute for COPD, Otto-Wagner-Spital, Vienna, Austria

Objectives: We hypothesized differences in cardiovascular autonomic control and baroreceptor function between patients with stable chronic heart failure and Cheyne-Stokes-Respiration (CHF-CSR) and heart failure patients with obstructive sleep apnea (CHF-OSA). Methods: We studied 14 patients with polysomnographically diagnosed CHF-CSR and 14 age, body-mass-index, and apnea-hypopnea index (AHI) matched patients with CHF-OSA. Cardiovascular autonomic tone was recorded using power spectral analysis of R-R interval variability on the morning after polysomnography. The slope of the regression line between beat-to-beat spontaneous systolic blood pressure and pulse interval changes was taken as an index of the sensitivity of arterial baroreflex modulation. Results: The two groups did not differ with respect to left ventricular ejection fraction, pharmacologic treatment, or etiology of heart failure. Mean AHI was 33 14/hr in patients with CHF-CSR and 25 15/ hr in patients with CHF-OSA (p > 0.05). Patients with CHF-CSR had significantly higher sympathetically mediated low frequency R-R interval variability (58 16 vs 29 15% normalized units, p < 0.01) and higher low-to-high frequency ratio of R-R interval variability (2.0 1.8 vs. 0.5 0.4, p < 0.01) than patients with CHF-OSA. Consistent with these findings, mean slope of spontaneous baroreceptor activity was significantly lower in patients with CHF-CSR than in CHF-OSA (8.3 3.3 vs 35.6 24.5, p = 0.01). Conclusions: We observed significant differences in both sympathetic activity and baroreceptor sensitivity between patients with CHF-CSR and CHF-OSA despite similar cardiac function impairment and sleep parameters.

P002 Prevalence of sleep-disordered breathing in patients with stable chronic heart failure: results from the VIenna Sleep In heart FAilure (VISIFA) cohort S. Asadi, M. Ruis, S. Radakovic, I. Mikulic, O. Burghuber, and A. Valipour, for the VISIFA study group Ludwig-Boltzmann-Institute for COPD, Otto-Wagner-Spital, Vienna, Austria

Background: Sleep disordered breathing (SDB) in patients with chronic heart failure is associated with increased morbidity and mortality. The prevalence of SDB in Austrian patients with chronic heart failure, however, remains unknown. Objectives: Multi-centre study to assess both prevalence and characteristics of SDB in an Austrian patient sample. Methods: Patients with stable chronic heart failure (NYHA class II-IV) and left ventricular ejection fraction below 35% despite maxiwkw 17–18/2011 © Springer-Verlag

mum therapy were screened from three outpatient heart failure clinics in Vienna. Eligible patients underwent full-night polysomnography, lung function measurements, arterial blood gas analysis, and assessment of subjective sleep quality and sleepiness. Results: 73 patients with heart failure and stable disease underwent polysomnography. Three patients were excluded due to airways obstruction on lung function, leaving 70 patients (95%) for final analysis (50 male, 20 female, age 64 ± 11 yrs, BMI 29 ± 5 kg/sqm). The overall prevalence of SDB was 79% (n = 55) with an apnea-hypopnea-index of 22 ± 18/hour of sleep. 53% of the sample had obstructive sleep apnea, 23% Cheyne-Stokes-Respiration, 3% mixed sleep apnea, and 21% patients had no evidence of SDB. Patients with SDB and those without did not differ with respect to age, body-mass-index, cardiac function, or pharmacological treatment. Patients with SDB scored significantly higher on sleepiness and sleep quality scores than heart failure patients without SDB. Patients with Cheyne-Stokes-Respiration had significantly lower arterial pCO2 levels compared with the other groups. Conclusions: There is a high prevalence of sleep disordered breathing in patients with stable chronic heart failure. The latter findings may have important diagnostic and therapeutic implications.

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P003 Incidence of solid de-novo malignoma and posttransplant lymphoproliferative disorder (PTLD) after lung transplantation – experience in Vienna V. Augustin, M.A. Hoda, P. Jaksch, B. Ghanim, M. Ernst, C. Aigner, G. Lang, S. Taghavi, W. Klepetko Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

Background: A factor limiting the survival after lung transplantation is de-novo malignancy. The immunosuppressive treatment, the increasing long-time survival and the capacity to reactivate viruses like Epstein-Barr virus (EBV) with cancer-causing potential are serious risk factors for the development of malignancies in lung transplant recipients. The aim of this study was to determine the incidence and outcome of patients suffering from de-novo solid tumors and PTLD in a single center cohort. Methods: Between 1989 and 2009 962 patients underwent lung transplantation at the lung transplant center in Vienna/Austria. 50 patients (5.2%) developed a solid tumor or PTLD. All data were collected and retrospectively analysed. Results: 19 (38%) patients were female, 31 (62%) were male. At the time of incidence patients were on average 51 ± 15.9 years [13–73] old. 16 (32%) patients suffered from PTLD, 10 (20%) from lung cancer, 12 (24%) from tumors of the gastrointestinal tract respectively 7 (14%) of the urinary tract. 2 female patients (4%) were detected with breast cancer, 3 patients (6%) with other neoplasms. Overall survival after solid malignoma and PTLD was 53% at 1 year, 32% at 3 years and 29% at 5 years. The median time to cancer appearance was collectively 1378 ± 1272 days after transplantation [45–5003]. 14 patients with denovo malignoma or PTLD underwent surgery, 14 were treated with chemotherapy and 4 with radiation. 3 patients were treated with chemotherapy and radiation, 2 additional with surgery. 5 patients received no therapy. The therapy modalities of 7 patients were unknown. The underlying illness, the status of Cytomegalie-Virus infection, the ÖGP Jahrestagung 2011

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form of immunosuppression (Tacrolimus or Cyclosporin A) and the induction (with antithymocyte globulin - ATG) had no influence on the incidence of malignoma after lung transplantation. The only risk factors which could be identified were the age at time of transplantation (p = 0.005) and sex (p < 0.05). Conclusions: Immunosuppressant induced neoplasms and PTLD are an important cause of mortality. Attention needs to be payed on identifying solid de-novo malignoma and PTLD early in lung transplant recipients to achieve an advantageous outcome.

P004 The presence of an acute phase response – reflected by systemic inflammatory parameters – predicts poor survival in patients with malignant pleural mesothelioma: a retrospective multicenter analysis G. Bahil1, A. Hoda1, M.-P. Winter1, T. Klikovits1, A. Alimohammadi1, B. Hegedus1, 2, B. Dome1,3, M. Grusch2, M. Arns4, P. Schenk4, W. Pohl5, M. Filipits2, W. Klepetko1, W. Berger2 1

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria 3 National Koranyi Institute of TB and Pulmonology, Budapest, Hungary 4 Department of Pulmonology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria 5 Department of Pneumology, Hospital Hietzing, Karl Landsteiner Institute for Clinical and Experimental Pneumology, Vienna, Austria

Background: Asbestos and its related inflammatory processes are suspected to be the main contributors in Malignant Pleural Mesothelioma (MPM) carcinogenesis. Elevated C-reactive protein (CRP), a systemic inflammatory parameter (SIP) reflecting the acute phase response (APR), showed prognostic power in a number of non-inflammatory diseases including various malignancies. However, only limited data exist about the influence of an APR on the clinical outcome of MPM patients. Methods: Accordingly, a retrospective multicenter analysis of 173 pathologically proven MPM patients was performed. Clinical data including routine SIP levels, and treatment modalities were collected by the three participating institutions (Department of Thoracic Surgery, Medical University of Vienna, Department of Pulmonology, Landesklinik Hochegg and National Koranyi Institute of Pulmonology, Budapest, Hungary) and correlated with patients overall survival. Results: Patients with elevated CRP (≥1 mg/dl), leukocytosis (>10.0 g/l), hypoalbuminaemia (<34 g/l) and high (more than 75% of leukocytes are neutrophiles) percentage of neutrophil granulocytes (PNG) had a significant shorter overall survival when compared to patients with normal SIP levels (log rank tests: CRP: p < 0.001, leukocytosis: p < 0.001, hypoalbuminaemia: p = 0.008, PNG: p = 0.001). After multivariate analyses, CRP (p = 0.003) and hypoalbuminaemia (p = 0.015) remained as independent MPM outcome predictors. Conclusions: Following these results, we propose the presence of an APR - reflected by altered CRP and albumin levels - to be prognostic in MPM patients.

P005 Six-minute walk test in diagnosis of COPD patients B. Butorac Petanjek1, S. Popović-Grle1, F. Pavičić1, D. Plavec2

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Clinical Hospital Center Zagreb – Clinic for Lung Disease Jordanovac, Zagreb, Croatia 2 Children’s Hospital Srebrnjak, Zagreb, Croatia

Background: The aim of this study was to investigate the relationship of Six-Minute Walk Test (6MWT) results in patients with COPD with the results of lung function tests, levels of dyspnea and fatigue, and nutrition status parameters. Methods: The study included 82 patients with COPD (46 GOLD stage II and 36 GOLD stage III), 54 men and 28 women, aged 30–80 years (mean ± SD, 63.9 ± 9.6). 6MWTs were conducted according to the ATS guidelines, and the walked distance (m) and the percent of predicted distance were correlated with spirometric parameters (FVC, FEV1, FEV1/FVC ratio), transfer factor for carbon monoxide– DLco, transfer coefficient for carbon monoxide–Kco, the level of dyspnea (Borg scale, Medical Research Council scale–MRC), the level of fatigue (Borg scale, Fatigue Assessment Scale-FAS), and nutrition status parameters (Body Mass Index-BMI, Fat-Free Mass Index-FFMI). Results: There was a significant difference between two groups for 6MWT results (distance walked: group I, 378.6 ± 81.6 m; group II, 337.8 ± 76.9 m; P = 0.023; percent of predicted: group I, 73.3 ± 13.0%; group II, 61.8 ± 12.6%; P = 0.000). 6MWT as the walked distance (m) significantly correlated with patient’s age and height, FVC (L, %), FEV1 (L, %), DLco, oxygen saturation before the test, heart rate change from baseline, MRC, FAS and FFMI (P < 0.05 for all). 6MWT (% predicted) significantly correlated with FVC (L, %), FEV1 (L, %), FEV1/ FVC ratio, DLco, Kco, heart rate change from baseline, dyspnea and fatigue Borg scale change from baseline, MRC, FAS and BMI (P < 0.05 for all). Conclusions: In our investigation 6MWT was in patients with COPD (stage II and III) significantly associated with spirometric parameters, gas transfer and coefficient, levels of dyspnea and fatigue, and nutrition status parameters.

P006 Alpha-1-antitrypsin deficiency screening program in Poland J. Chorostowska-Wynimko1, R. Struniawski1, P. Kuca1, M. Czajkowska-Malinowska2, P. Śliwiński1, J. Kozielski3 1

National Institute of Tuberculosis and Lung Diseases in Warsaw, Poland 2 Department of Lung Diseases and Respiratory Failure, Regional Center of Pulmonology, Bydgoszcz, Poland 3 Department Lung Diseases and Tuberculosis, Silesian Medical University, Zabrze, Poland

Background: In Poland, the overwhelming majority of individuals with alpha-1-antitrypsin (AAT) deficiency still remains undiagnosed. We estimated the AAT gene frequency and prevalence in a large cohort of Polish chronic lung or liver disease patients eligible for AAT testing. Methods: Blood samples were collected prospectively from 500 respiratory patients (COPD, emphysema, bronchiectasis, asthma). AAT serum concentration was measured by turbidimetry and PI-phenotype identified by isoelectrofocusing. The PI*S and PI*Z alleles were confirmed by real-time PCR; rare phenotypes were characterized by sequencing. Results: 63 (12.6%) lung disease patients demonstrated AAT deficiency phenotypes. Calculated frequencies expressed per 1000 were for PI*Z 46.6 (95% CI: 32.3–60.8), PI*S 20,3 (95% CI: 10.8–29.8). The AAT gene prevalence calculated by Hardy-Weinberg equilibrium were: 1/1.16 for MM, 1/26 for MS, 1/2429 for SS, 1/11 for MZ, 1/530 for SZ and 1/462 for ZZ. Conclusions: Our results show relatively high frequency of AAT deficiency among Polish patients with chronic obstructive respiratory © Springer-Verlag

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P007 The effect of endothelin-1 on calcium signalling in human basophils K. Cima1, S. Blunder2, S. Desole1, N. Hobi3, J. Günther1, C. M. Kähler1 1

Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria 2 Rheumatology Laboratory, Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria 3 Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck, Austria

The proinflammatory peptide endothelin-1 (ET-1) proved to be elevated in patients suffering from asthma. As the impact of ET-1 on basophils, which numbers correlate with asthma severity, has yet to be fully understood, our aim was to map the signalling pathway of ET-1 in human basophils. Human basophils were isolated from peripheral blood by Magnetic Cell Sorting (MACS). For RT-PCR and Western Blot analysis, RNA and protein were isolated by Trizol. Histamine release was measured via ELISA and cell migration was analysed in Boyden Chambers. To show the calcium signalling of ET-1 in human basophils, cells were loaded with fura 2-AM and monitored by fluorescence microscopy during stimulation with ET-1 compared to fMLP [10–8 M], ATP [10–4 M] and ionomycin [10–6 M] that served as controls. To discriminate between ETAR and ETBR signalling the specific blockers BQ123 and BQ788 were applied. The RT-PCR proved basophils to express both, ETAR and ETBR. The migratory effect of ET-1 [10–8 M] (p < 0.0001) was significantly inhibited solely by the ETAR inhibitor BQ-123 [10–6–10–12 M]. However, to compare, the histamine release upon ET-1 [10–8 M] (p < 0.0001) could only be effectively blocked by the ETBR inhibitor BQ-788 [10–8 M] (p < 0.05). The fluorescence microscopy revealed ET-1 to be highly effective in inducing intracellular calcium increase 50 seconds after ET-1 stimulation and lead to a full recovery of ion flux 200 seconds later. The Western Blot on the downstream enzyme cascade proved ET-1 stimulated basophils to have an activation of p-p38MAPK and p38MAPK compared to untreated basophils, which is known to induce long lasting effects by activation of, for example, c-myc, c-fos and c-jun transcription. Our observations reveal for the first time that ET-1 initiates basophil migration via ETAR and histamine release by ETBR and that these effects are mediated by calcium signalling and downstream activation of p38MAPK. Considering the fact that ET-1 and basophils have a crucial role in airway inflammation, targeting the effects of ET-1 by receptor antagonists may be a new option in the treatment of allergic airway disease.

P008 Notch signalling in human basophils* K. Cima1, G. Gamerith2, A. Amann2, S. Desole1, C.M. Kähler1, J. Löffler-Ragg1 1

Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria 2 Laboratory of Molecular Cell Biology, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

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Notch signalling plays a key role in the development of the immune system. Recently, Notch was found to confer antigen presenting cell function on mast cells, induce lung allergic responsiveness in CD4 + T-cells and regulate migration and survival of eosinophils. As basophils play a key role in allergic reactions our aim was to analyse, whether basophils express Notch-1 or Notch-2 and whether the Notch signaling pathway has an impact on basophil function. Human basophils were isolated from venous blood of healthy donors via magnetic cell sorting (MACS®). RNA of basophils and PBMC was extracted by trizol and transcribed into cDNA using superscript III (Invitrogen®). Notch-1 and Notch-2 expression was determined by RT-PCR. To explore the functionality of Notch, basophil migration towards fMLP [10–8 M] was evaluated in Boyden chambers. After preincubation with the specific gamma secretase inhibitor DAPT [10–6 – 10–12 M], basophils migrated towards fMLP [10–8 M] for 90 min. The cellulose nitrate filters were then dehydrated, fixed and stained and migration depth was analysed by microscopy. Furthermore, basophils were stimulated with plate-bound Jagged-1 for 24 h before histamine release was measured by ELISA. The RT-PCR revealed basophils to express both, Notch-1 and the Notch-2. In comparison to PBMC, human basophils were found to express Notch-1 to a greater extent, whereas Notch-2 expression was lower than in PBMC. With regards to the functionality of Notch signalling in human basophils we found that the gamma secretase inhibitor DAPT [10–6 to 10–8 M] most significantly blocked basophil migration towards fMLP [10–8 M] (p < 0.0001). Furthermore, after Jagged-1 stimulation an increase of histamine concentration by 8.67 fold could be determined. We could show for the first time that human basophils express Notch-1 and Notch-2 and that the Jagged-1/Notch signalling pathway is involved in basophil functions such as histamine release and cell migration.

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disorders. Estimated frequency for PI*Z and PI*S allele in respiratory group was about four-fold higher than estimated prevalence in healthy Polish population.

P009 The indirect Fick method is an unfeasible method for hemodynamic assessment in pulmonary arterial hypertension patients S. Desole1, S. Czekay2, T. Bollmann2, K. Lau2, R. Ewert2, C.M. Kaehler1 1

Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria 2 Department of Internal Medicine B – Pulmonary Medicine and Infectious Diseases, Medical Faculty of the Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany

Background: The aim of the present retrospective study was to evaluate the suitability of hemodynamic parameters assessed by the indirect Fick method in patients suffering from pulmonary arterial hypertension (PAH) and controls. Methods: For this purpose right heart catheterization was performed in 42 patients (mean-age 61.2 ± 12.7 years, 29 females) with PAH and 9 controls in supine position. 60.5% of the patients revealed the diagnosis of an idiopathic PAH (n = 26), 27.9% suffered from PAH associated with connective tissue diseases (n = 12) and the remaining 9.5% were distributed to drugs and toxins induced PAH (n = 3) and PAH associated with portal hypertension (n = 1). Hemodynamic results obtained by the indirect Fick method were compared to data obtained by the thermodilution method. Results: Patients and controls did not differ in age, BSA and heart rate. The mean cardiac output (CO) determined by the indirect Fick method (COFick) in PAH patients and control population was 4.4 ± 1.8 and 4.7 ± 1.2 L/min, respectively. CO obtained by the thermodilution method (COThermo) in PAH patients was consistently higher than COFick ÖGP Jahrestagung 2011

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(4.9 ± 2.1 L/min) showing a significant difference by paired non-parametric analysis (p < 0.001). COThermo was 5.4 ± 1.4 L/min in controls without reaching a significant difference to COFick in paired non-parametric test. Direct comparison of COThermo with COFick by agreement analysis revealed a comparable bias between the methods in both groups (0.56 ± 1.10 L/min in patients and 0.65 ± 0.82 L/min in controls) with wider limits of agreement for the patient population (–1.60 to 2.72 L/min versus –0.96 to 2.25 L/min in controls). Conclusions: Determination of CO by the indirect Fick method can not be used in PAH patients as this method consequently underestimates CO. It can be suggested that the estimated VO2 parameters are invalid for PAH patients.

P010 Endothelial progenitor cells and the endothelin system* S. Desole, F. Albrecht, H. Vogelsinger, K. Cima, C. M. Kaehler Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

Background: Emerging evidence indicates that bone-marrow–derived endothelial progenitor cells (EPC) might play a key role in the formation of new vessels. Endothelin-1 (ET-1) modulates different stages of neovascularisation, e.g. proliferation, migration, invasion, protease production and changes in morphogenesis of endothelial cells. We investigated a potential link between the ET system and EPC. Methods: For all experiments ex vivo generated, characterized and cultivated rat bone marrow-derived EPC were used. Freshly isolated rat pulmonary artery (paEC) and aortic endothelial cells (aEC) served as positive control. Expression of ETA and ETB receptors and detection of prepro-ET and ET converting enzyme (ECE) mRNA were performed by standard RT-PCR. In calcium (Ca2+) flux assays EPC previously loaded with FURA-2 [5 μM] were exposed to ET-1 [10–6M and 10–8M]. ATP [100 μM] served as positive control. Changes in fluorescence intensity were measured using a microplate reader. For selective inhibition of receptor subtypes, EPC were pre-incubated with ETRA (BQ123) and ETRB (BQ788) antagonists for 20 min before stimulation with ET-1 [10–6M]. Results: EPC express both ET-receptor subtypes. Expression patterns were similar to those observed in paEC and aEC. Both preproET-1 and ECE encoding mRNA could be detected in EPC. In Ca2 + mobilisation experiments addition of ET-1 elicited a significantly increased intracellular Ca2+ mobilisation (p < 0.001 and p < 0.05, respectively). Calcium increase after stimulation with ET-1 was inhibited by BQ123 and BQ788 by 96% and 45%, respectively. Conclusions: We proved for the first time the expression of both ETRA and ETRB and detected mRNA of prepro-ET and of ECE on EPC. Additionally, we found that ET-1 activates Ca2 + mobilisation in EPC. Our results indicate that the increased Ca2+ release is mainly attributed to the activation of ETA receptors. In summary, our data reveal for the first time a link between EPC and the ET system.

P011 The effectiveness of long term physical therapy in elderly patients with chronic obstructive pulmonary disease A. V. Dimitrova, D. Todorova Lubenova Department of Physical Therapy and Rehabilitation, National Sports Academy “Vassil Levski”, Sofia, Bulgaria

Background: Future trends of pulmorehabilitation refer to approbate an effective and individual approach applying different thera-

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peutic exercises in patients with chronic obstructive pulmonary disease (COPD). Aim: To investigate the complex therapeutic influence of specialized physical therapy (PT) regarding elderly patients with COPD at different stages of the disease. Methods: A one year study has been conducted investigating the effect of PT applied in hospital and in ambulatory elderly patients in Sofia. Outcome measures were: spirometry, pulse oximetry, six minutes walking test, Borg scale, Saints’ George Respiratory Questionnaire, BODE index, body mass index, pulse and respiratory rate, blood pressure, apnoic tests. 65 patients with COPD divided into 2 groups according to the stage of the disease were studied. First group includes 33 patients (22 women, 11 men, age 68.6 ± 7.3) with an exacerbation of COPD (II–III GOLD), receiving in hospital and ambulatory PT. Second group includes 32 patients (28 women, 4 men, age 71.7 ± 6.9) without an exacerbation of COPD (I –II GOLD), receiving only ambulatory the same PT as the first group. In hospital PT sessions were individually tailored, on 10 daily consecutive days, duration of 20–25 min. Outpatient PT sessions were in groups of 12–20 patients, 30–60 min. Exercise therapy includes breathing techniques and breathing retraining: thoracic and diaphragm breathing; pursed lips breathing; pronouncing various of sounds during prolonged expiration; rhythmic cuing of breathing; controlled walking or slight jogging. Results: PT improves forced vital capacity, saturation, physical tolerance, apnoic respiratory tests, quality of life and individual prognosis of COPD in patients of first group. Basic dyspnoea and exertional breathlessness decreased. PT improves forced vital capacity, physical tolerance and apnoic respiratory tests in patients of second group. Conclusions: Our PT program has positive therapeutic effect on: bronchopulmonary functional status; breathlessness; physical tolerance; health-related quality of life and prognosis of the disease.

P013 Influenza infection in lung transplant recipients 2010/2011 M.B. Ernst1, P. Jaksch1, T. Popow-Kraupp2, R. Strassl2, C. Honsig2, A. Scheed1, V. Augustin1, C. Aigner1, G. Lang1, S. Taghavi1, W. Klepetko1 1

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Department of Virology, Medical University of Vienna, Vienna, Austria

Background: Lung transplant recipients (LTRs) are uniquely predisposed in developing severe complications associated with community acquired respiratory viral infections (CARV). We report the outcomes of influenza infections in a cohort of 82 screened lung transplant recipients at our center. Methods: Data were collected from December 2010 to March 2011 on using real-time polymerase chain reaction (PCR) from nasal secretion. During this period 245 patients frequented our out patient department for thoracic surgery. All LTRs (n = 82) with respiratory symptoms were screened. There were 9 (10, 9%) confirmed cases. H1N1 infection was diagnosed in 5, influenza B in 4 lung transplant recipients, median age 36 (26–65) years, with a median of 6 (1, 1–12) years post lung transplantation. Results: All patients with BOS grade 0 (bronchiolitis obliterans syndrome, n = 5) were treated symptomatically alone, with no further impact on their lung function. Two patients of this group have been vaccinated for seasonal influenza. Among the group of patients with pre-existing BOS (n = 4), two lung transplant recipients, one with BOS I, the other with BOS II developed pneumonia and had to be admitted. The patient with BOS II died due to acute respiratory distress syndrome (ARDS). Both patients received no vaccination. The other two © Springer-Verlag

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P014 Endobronchial one-way valve implantation in patients with heterogeneous emphysema using interlobar fissure analysis-a pilot study I. Firlinger1, P. Germonpre2, M. Meysman3, J. Goldin4, M. Noppen3, O. Burghuber1, A. Valipour1 1

Department of Respiratory and Critical Care Medicine, LudwigBoltzmann-Institute for COPD, Otto-Wagner-Spital, Vienna, Austria 2 Pulmonary Department, University Antwerp, Antwerp, Belgium 3 Respiratory Division, University Brussels, Brussels, Belgium 4 Department of Radiological Sciences, UCLA, Los Angeles, United States

Background: The aim of the present study was to assess the efficacy of bronchoscopic lung volume reduction (BLVR) using endobronchial one-way valve implantation in patients with emphysema based on a novel radiological treatment algorithm. Methods: Patients were considered radiologically eligible if at least one of the lungs had a complete oblique fissure and a primary target lobe with a destruction score ≥ 55% and a heterogeneity score ≥10%. Patients with a right upper target lobe underwent also right middle lobe treatment in the presence of an incomplete horizontal fissure. Primary endpoint was the mean % change in FEV% predicted at 90 days after valve implantation. Secondary endpoints included mean% change in lung volumes and exercise capacity. Results: A total of 15 patients with severe emphysematous type of COPD (mean FEV1 31%) met clinical and radiological eligibility criteria. BLVR was associated with no significant improvements in primary or secondary endpoints in the overall study population. Five patients (33%) were considered radiological responders with more than 500ml of target lobe volume reduction in HRCT at three months. These patients had a 26% relative increase in FEV1%, 32% increase in maximum workload, and a 24% increase in inspiratory capacity. There was a high rate of serious adverse events including 1 sudden cardiac death within 24 hours and 3 pneumothoraces (20%) during the 3 month period. Conclusions: BLVR using one-way valve implantation in patients with heterogeneous emphysema and closed interlobar fissures may be associated with clinical benefits in a small subgroup of patients, at an overall higher risk of serious adverse events

P015 Treatment of bronchopleural fistula using endobronchial one-way valve implantation – a case series I. Firlinger1, E. Stubenberger2, M. Müller2, O.C. Burghuber1, A. Valipour1 1

Department of Respiratory and Critical Care Medicine, LudwigBoltzmann-Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria 2 Department of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria

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Background: Bronchopleural fistula (BPF) result in persistent air leaks due to communications between the bronchial tree and the pleural space. They are associated with increased morbidity, mortality, and prolonged hospital stay. The management of BPF includes a multidisciplinary approach, such as surgery, pleurodesis, antibiotics, and interventional bronchoscopy. No generally accepted guidelines for effective therapy have been developed yet. Objectives: In high risk patients interventional bronchoscopy using endobronchial one-way valve implantation may be a less invasive treatment option of BPF. Methods: We report on a series of 11 patients who developed persistent air leaks after empyema, pulmonary resection, and radical pleurectomy. 5 patients had surgical as well as bronchoscopic treatment, 6 patients only underwent bronchoscopy. During bronchoscopy the suspected segmental bronchus was blocked with a ballon catheter. After identifying the source of bronchopleural fistula endobronchial one-way valves were implanted. Results: After valve implantation, air leakage ceased immediatly in 5 patients. In 8 patients, who had a digital chest tube monitoring, air leakage decreased from a mean flow of 1026 ml/min (± 695 ml/min) down to 56 ml/min (±71 ml/min). In 1 patient bronchography revealed no contrast enhancement in the pleural space after the procedure. In 2 patients there were no bubbles in the water seal system of the chest tube any more. Conclusions: The implantation of endobronchial one-way valves may be a high-potential treatment option in the management of bronchopleural fistula.

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LTRs, one with BOS I the other with BOS II and active vaccination protection were treated with Oseltamivir at the time of the first clinical assessment, without any further respiratory complications. Therapy with Oseltamivir was only started with clinical assessment within the first 48 hours. Conclusions: Our review demonstrates a causal link between preexisting BOS, vaccination state and the severeness of respiratory symptoms after infection with community acquired respiratory viruses as well as the clinical effectiveness of seasonal influenza vaccination especially in BOS patients.

P016 Prevalence and prognosis COPD in critically ill patients – a prospective cohort study between 1998 and 2008 G. C. Funk1, P. Bauer2, O. C. Burghuber1, A. Fazekas1, S. Hartl1, B. Metnitz2, P. Metnitz3 1

Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria 2 Department of Medical Statistics, Medical University of Vienna, Vienna, Austria 3 Department of Anesthesiology and General Intensive Care Medicine, Medical University of Vienna, Austria

Background: There are no large studies about the epidemiology and outcome of patients with COPD treated in intensive care units (ICU). More specifically it is unknown, whether the presence of COPD is an independent risk factor for prolonged mechanical ventilation, prolonged weaning and eventually a poor prognosis. Such information is valuable for the planning of resources including respiratory care units and weaning facilities. Objectives: We speculated that COPD would be an increasing problem in critically ill patients and would be associated with increased morbidity and mortality. The objectives of the study were therefore 1. to describe the epidemiology of COPD in patients admitted to the ICU, 2. to determine whether COPD is an independent risk factor for unfavorable outcome. Methods: We conducted a retrospective study in 87 medical, surgical, and mixed ICUs in Austria, using a prospectively collected database of 194, 453 adults admitted consecutively over a period of eleven years [1998–2008]. Results: COPD was present in 8.6% of all ICU patients. The riskadjusted mortality of patients with COPD was higher compared to patients without COPD (observed to expected mortality ratio with 95% confidence intervals 0.91 [0.90–0.92] vs 1.14 [1.12–1.16], respectively). The presence of COPD was an independent risk factor for increased mortality in multivariable regression. Prolonged mechanical ventilation occurred more common in patients with COPD (24%) compared ÖGP Jahrestagung 2011

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to those without (13%), p < 0.0001. Prolonged weaning was also more common in patients with COPD (6%) compared to those without (2%), p < 0.0001. Within all ICU patients with a diagnosis of COPD, 29% had acute respiratory failure as the main cause for ICU admission. During the course of eleven years the incidence of acute respiratory failure due to COPD increased from 1.8% to 3.0% (p < 0.0001) and the use of non-invasive ventilation more than doubled (from 15% to 34%, p < 0.0001). Simultaneously the risk-adjusted mortality of COPD patients decreased. Conclusions: Acute respiratory failure due to COPD is an increasingly common condition in critically ill patients. The presence of COPD is associated with increased mortality and morbidity. The improvement of risk-adjusted mortality over time may be attributable to the beneficial effects of non-invasive ventilation.

P018 Role of EGFR-STAT3 signaling in K-RAS induced tumorigenesis B. Grabner1, D. Schramek2, L. Blaas1, R. H. Zwick3, H. Popper4, R. Eferl1, M. Sibilia5, J. Penninger2, E. Casanova1 1

Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria 3 Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria 4 Institute of Pathology, Statistics and Documentation, Medical University of Graz, Graz, Austria 5 Institute for Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria 2

Lung cancer related and unrelated to smoking is still leading cause of cancer deaths worldwide with an overall survival rate of 15%. Epidermal growth factor receptor (EGFR) kinase mutations occur in over 60% of NSCLC in never-smokers. Most frequent smoking-related mutations impair GTP hydrolysis in Kirsten-Ras (K-Ras), a key oncogene downstream of the EGFR pathway, causing persistent cell growth and proliferation in 20–30% of lung adenocarcinomas. Although anti-EGFR therapy with erlotinib and geftinib works within 75% of patients with EGFR tyrosine kinase mutated NSCLC, EGFR activity blockers have been reported to be ineffective against advanced stage K-Ras mutant tumors. In contrast, EGFR amplification is frequently found in NSCLC patients with smoking history, indicating that EGFR plays a role in tumor onset of smoking related adenocarcinomas. First aim of the project will be to identify the role of EGFR in lung tumors of the K-Ras induced lung cancer mouse model. This model allows conditional expression of a constitutive form of K-Ras leading to adenocarcinoma in mice. By crossing conditional EGFR transgenic mice with the K-Ras mutated mice, we will investigate the role of EGFR in onset and progression of lung cancer in more detail. Another key pathway downstream of EGFR signaling is the signal transducers and activators of transcription (STAT) pathway. STAT-3 regulates important pathways in tumorigenesis, through upregulation of genes encoding apoptosis inhibitors (Bcl-XL, Bcl-2, Mcl-1, survivin). In patient samples and NSCLC cell lines nuclear pSTAT3 is upregulated and correlates with subsequent suppression of apoptosis of NSCLC tumors. In order to investigate the role of STAT3 in lung tumors, we will cross conditional STAT3 transgenic mice with the K-Ras lung cancer mouse model. Within the second approach the molecular mechanisms linking STAT3 and lung cancer will be addressed in more detail.

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P019 EGFR-mutation in Austria: a retrospective study M. J. Hochmair1, M. Miler1, U. Setinek1, K. Kirchbacher2, A. Mohn-Staudner1, M. Kaufmann1, I. Kapfhammer1, B. M. Arns3, K. Patocka4, O. C. Burghuber1 1

Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria 2 Second Department of Medicine (Pulmology), Wilhelminenspital, Vienna, Austria 3 Department of Pneumology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria 4 Department of Pneumology, Hospital Hietzing, Vienna, Austria

Background: Mutations of the Epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) predicts the response to tyrosine kinase inhibitors. Commonly mutations occur more in never smokers, adenocarcinomas, women and East Asians. In the largest European screening trial the frequency of caucasian Spanish patients was 16.6% (1). However, the frequency of EGFR mutations in NSCLC from Austrian patients is unknown. Objectives: To evaluate the frequency of EGFR Mutation in Austrian patients with NSCLC. Methods: From January 2010 to May 2011 tumor tissue from bronchoscopy, CT-guided and ultrasound guided biopsies and surgical specimen with histological type of Adenocarcinomas and NSCLC NOS (Not Otherwise Specified) excluding squamous cell carcinomas and large cell carcinomas were tested for EGFR mutations from 3 hospitals in Vienna and 1 hospital in Lower Austria. The mutation detection was performed with the TheraScreen EGFR29MutationKit from DxS on a Light Cycler 480. Results: EGFR mutations were found in 65 of in total 406 patients (16.01%). 52 patients (12.81%) carried an activating Mutation (Exon 19 Deletion and Exon 21 L858R). Conclusions: These results indicate that Austrian patients with NSCLC harbor somatic EGFR mutations at a frequency similar to other European caucasian patients with NSCLC. Literatur

1.

Rosell, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009;361(10):958– 67.

P020 Clinical survival predictors in malignant pleural mesothelioma patients M.A. Hoda1, B. Ghanim1, T. Klikovits1, C. Aigner1, S. Taghavi1, G. Lang1, M. Arns2, B. Hegedus, B. Dome1, P. Schenk2, W. Klepetko1 1

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Department of Pulmonology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria

Background: Malignant Pleural Mesothelioma (MPM) is a devastating disease characterized by poor outcome. Aim of this study was to evaluate clinical and histological MPM survival predictors. Methods: All retrospective analyzed 98 MPM patients were referred to the participating institutions (LKH Grimmenstein n = 14, AKH Wien n = 84) between 01.01.1994 and 01.01.2011. Patients’ characteristics and their impact on overall survival were analyzed using the SPSS 17.0 software package.

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Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 2 Institute for Hygiene, Mikrobiology und Environmental Medicine, Medical University of Graz, Graz, Austria 3 Medical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria 4 Institute of Hospital Hygiene and Mikrobiology, Graz, Austria

In a retrospective study we analysed all PCR-proven H1N1 cases from the influenza season 2009/2010 treated within the styrian “LKH hospital network”. For this purpose all PCR-postive case files were reviewed and data regarding clinical presentation, laboratory and radiological findings, treatment, outcome and preexisting underlying chronic illnesses were systematically collected. In a second step the same data collection was performed in a group of PCR-negative patients, which were tested during the influenza season 2009/2010 for influenza-like illness. The data from the PCR-positive group were compared to the data from the PCR-negative group.

P023 Necrotizing arthritis of right talo-navicular joints – when arthrodesis fails, it’s TB

Impact of lymphnode downstaging on the prognosis of pancoast tumors

R. Hürbe1, B. Ruhs2, M. Riedler1, H. A. E. Schinko1

K. Hoetzenecker, P. Altmann, A. Aliabadi, A. Hoda, G. Lang, C. Aigner, S. Taghavi, W. Klepetko

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Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

Background: Pancoast tumors are a rare disease entity associated with poor prognosis. Induction chemoradio-therapy before surgical resection is the standard treatment nowadays. However, there is little knowledge regarding the impact of advanced N stages on multimodal treatment protocols. Methods and results: We retrospectively evaluated patients presenting with a pulmonary sulcus tumor at our department from 1998 – 2011. A total of 47 patients were included in the analysis. At the time of diagnosis 39% of patients had a positive N staging (7% N1, 23% N2, 9% N3). 88% of patients received an induction chemotherapy or a combined radio-chemotherapy. After induction therapy curative resections were performed. Pathological evaluation revealed that in 47% of patients with initially positive lymph nodes there was still evidence of a microscopic disease. This subtype of patients had an unfavourable prognosis when compared to N stage responders or patients without lymph node involvement at time of diagnosis (median survival: 24 months, 41 months, 145 months, respectively). Interestingly, prognosis was independent from the extent of resection (laminectomy, vascular replacements, resections of the brachial plexus or the clavicula). Conclusions: Patients with advanced N staging should not be excluded from a multimodal treatment protocol with curative intent. N downstaging to pN0 after induction therapy increases median survival by 17 months, however, patients with initially cN0 disease have by far the best outcome.

P022 Retrospective comparsion of PCR confirmed H1N1 infections and PCR-negative influenza-like illnesses in Styria – risk factors, clinical features and outcome

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Results: Out of 98 patients (mean age: 63 ± 9 years, 20 female, 78 male), 65 underwent curative surgery including either resection alone (n = 21) or surgery within multimodality treatment (n = 44). In 33 patients, chemo-and/or radiotherapy without curative resection was performed. Mean overall survival (OS) of all patients was 541 days (95% confidence interval [CI]: 442-640 days). Patients undergoing multimodal therapy had the significant longer survival (OS: 742 days, CI: 566-919 days) than patients treated with chemo-and/or radiotherapy alone (OS: 472 days, CI: 359–585 days; log rank: p = 0.018) or patients undergoing surgery alone (OS: 231 days, CI: 114–349 days; log rank: p = 0.006). The most frequent histological subtype was the epitheloid (n = 64), followed by the biphasic (n = 21) and the sarcomatoid (n = 4; missing: n = 9). Patients with non-epitheloid histology had the significant worse outcome (non-epitheloid: OS: 358 days, CI: 208-508 days vs. epitheloid: OS: 632 days; CI: 495–770 days; log rank: p = 0.016). Furthermore, postoperative ICU stay had a significant impact on OS (Cox regression: p = 0.003). Conclusions: Treatment modality and histology had a significant impact on MPM outcome. Postoperative ICU stay was found to be prognostic within the surgical treated subgroup.

1

Department of Pneumology, General Hospital Linz, Linz, Austria Department of Orthopedic Surgery together with Pathology, Nuclear Medicine, and Radiology, General Hospital Linz, Linz, Austria

Background: TB can occur in any tissue including bones and joints involving most often the spine and monoarticular weight bearing joints. With trauma, surgery or implantation of endoprosthesis TB may arise insidiously. Case Reports: Two case reports of necrotizing tuberculous arthritis/synovitis of the right talo-navicular joint 63–64 years after primary TB are reported – in a male (FEF68m) and female patient (SCr69f ). It was mistaken for noninfectious necrotizing arthritis. Arthrodesis of the talo-navicular joint was performed 20 and 7 months after onset of symptoms when antiinflammatory measures failed. But healing did not occur. In FEF68 m the histology revealed granulation tissue with granulomas like a foreign body reaction, but no material for microbiology was sent. In SCr69f neither histology nor microbiology were done. In FEF68 m IGRA was negative but TST positive twice. In him the histology of non-caseating epitheloid granulomas in a lichenoid lesion of the right cheek pointed towards sarcoidosis. Prednisone cleared the facial lesion but did not change the hypermetabolic activity on PET-CT in the right middle foot. In SCr69f all immunological TB-tests were positive, but a needle biopsy of the necrotized talus and os cuneiforme inconclusive. Delay of 39 and 24 months without combined anti-TB treatment allowed progressive destruction of joints. Conclusions: Paucibacillary tuberculous necrotizing synovio-arthritis of talo-navicular joints can be mistaken to be degenerative. TB at/after arthrodesis could be successfully managed if diagnosed early and treated properly. Decreased morbidity would have resulted, but indicators of TB (history, positive TST) were not appreciated, and biopsies at surgery not worked up with ZN-stain, PCR and TB-culture. Histology might be misleading or misread. MR details the morphology while 18-FDG-PET-CT reveals ongoing metabolic hyperactivity.

M. Hönigl1, J. Prattes1, K. Tovilo1, I. Zollner-Schwetz1, T. Valentin1, H. J. Salzer1, R. Raggam3, A. J. Grisold2, K. Vander4, H. Kessler2, H. Olschewski1, R. Krause1, H. Flick1 wkw 17–18/2011 © Springer-Verlag

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P024 Alpha-1 antitrypsin deficiency: a frequently underestimated cause of COPD V. Hutya1, K. Schmid-Scherzer2 1

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cand. med., Medical University of Vienna, Vienna, Austria Second Department of Medicine, Wilhelminenspital, Vienna, Austria

Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder with decreased levels of AAT protein causing lung disease among adults. The most common lung disease of AATD-patients is COPD, which occurs with a prevalence of 1,220.000 in Austria, while AATD is thought to be diagnosed in ~5% of patients with AAT deficiency. Thus, patients with the disease are unaware and do not receive the necessary and lung tissue saving augmentation therapy using human alpha-1 antitrypsin. An early diagnosis and initiation of the therapy are crucial factors for the later course of disease. Since 2001, Austria is a member of the Alpha One International Registry (AIR). In order to simplify administration and to prevent data loss the Austrian Alpha-1 Lung Registry, a new web-based national registry, was introduced. Within Austria, seven centres of excellence have been established with a direct access to the registry. Until today, the Austrian Alpha-1 Lung Registry includes data of 178 patients, of whom 40.4% are female. The average age of the patients is 49.8 years, and the average age of patients at the time of diagnosis is 45 years. 70.8% of the AATD-patients are or were smokers. The detected comorbidities (hypertension is most common, 11,8%) do not show any relationship with the underlying disease. 42% of registered patients receive augmentation therapy with Prolastin®. After initiation of treatment median FEV1 did not change significantly before and after broncholysis. Further follow-up studies in order to analyse the progression of FEV1 are planned and will be carried out as soon as sufficient data from the registry is available. Summarizing these data, it can be concluded that Austria has to enhance its efforts in order to increase the number of diagnosed cases and to provide the appropriate therapy to all AATD-patients. Augmentation therapy with alpha-1 antitrypsin maintains lung function in AATD-patients.

P025 Comparison between referral and explant diagnoses in lung transplant recipients: Discrepancies and additional findings P. Jaksch1, M. Ernst1, V. Augustin1, A. Scheed1 ,S. Geleff2, G. Dekan2, W. Klepetko1 1

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria

Background: Lung transplantation is a widely accepted therapeutic option for a range of pulmonary conditions in which the diagnosis is often based on clinical data or on limited biopsy material. Posttransplantation complications and recurrence of underlying disease may be related to the primary disease, and an accurate diagnosis is therefore essential. Methods: A pathologic review was performed on 1056 primary lung transplantations over a period of 22 years (1998 to 2010) . Diagnoses of native lungs were compared with referral diagnoses to assess the presence of discrepancies or expanded results like malignancies or infections. Results: 73 (7%) cases presented a different or expanded diagnosis. Discrepancies between referral diagnosis and histopathology

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were found in 34 of 1054 cases (3%). The highest percentage of discordance was depicted in chronic obstructive lung diseases (12 of 344), with the final diagnosis of UIP (n = 4), chronic interstitial fibrosis (n = 4), silicosis (n = 2), LAM (n = 1) and sarcoidosis (n = 1). 16 patients who were referred with the diagnosis of an interstitial lung disease had predominantly emphysema (n = 12), bronchiectasis (n = 2) and histiocytosis X (n = 2). Expanded results included Aspergillus (n = 11) and mycobacterial (n = 16) infections, carcinomas (n = 10), cystic adenomatoid dysplasia (n = 1) and carcinoid (n = 1). However, short- and long-term survival was not different in patients with different diagnoses, malignancies or implanted infections. Interestingly all mycobacterial infections and all malignancies occurred in patients with COPD. Conclusions: On account of this high rate of discrepancies and its possible influence on survival , frequently repeated clinicopathologic investigations should be performed during the waiting list period.

P026 Genauigkeit des präoperativen Stagings beim NSCLC im Routinebetrieb M. Arns1, E. Bitterlich2, S. Handzhiev3, N. Hasenhüttl4, T. Hernler5, M. Hochmair6, I. Kapfhammer6, L. Koch5, R. Kolb7, K. Kirchbacher8, K. Patocka9, J. Polachova10 1

Landesklinikum Thermenregion Hochegg, Grimmenstein, Österreich Landeskrankenhaus Vöcklabruck, Österreich 3 Landeskrankenhaus Krems, Österreich 4 Landeskrankenhaus Hörgas-Enzenbach, Österreich 5 Landeskrankenhaus Hohenems, Österreich 6 Otto-Wagner-Spital, Wien, Österreich 7 Klinikum Wels-Grießkirchen, Österreich 8 Wilhelminenspital Wien, Österreich 9 Krankenhaus Hietzing, Wien, Österreich 10 Landeskrankenhaus Graz, Österreich 2

Grundlagen: Beurteilung der Genauigkeit des präoperativen Stagings beim NSCLC im Routinebetrieb pneumologischer Abteilungen Österreichs sowie Erfassung der verwendeten Untersuchungen mit Hilfe eines vordefinierten Datenblattes. Das primäre Ziel war es die Übereinstimmung von Zytologie/Histologie und TNM-Staging präoperativ gegenüber postoperativ im Routinebetrieb zu untersuchen. Ergebnisse: Von Februar 2011 bis Juni 2011 wurde in Österreich an 11 pneumologischen Abteilungen Daten von insgesamt 112 Patienten (Pat.) in ein vordefiniertes Datenblatt übertragen. Von den 112 Patienten waren 101 für die primäre Zielsetzung verwertbar (entsprechende Daten von 6 Patienten fehlten, 5 Patienten wurden erfolgreich downgestaged). Eine komplette Übereinstimmung in präund postoperativer (pop.) Zytologie/Histologie (ZH) und Tumorstadium fand sich bei 39/101 Pat. (38,6 %). Eine Diskrepanz im T-Faktor fand sich bei 29/101 Pat. (28,7 %). Bei 9/29 Pat. zeigte sich postoperativ ein höheres T-Stadium, bei 6/29 fand sich lediglich ein Wechsel zwischen „a“ und „b“ bei identem T, bei 14/29 Pat. war das pop. T niedriger. Eine Diskrepanz beim N-Faktor zeigte sich bei 32/101 Pat. (31,7 %). Das N pop. war bei 29/32 Pat. höher (17 Pat. N0→N1, 3 Pat. N1→N2, 8 Pat. N0→N2, 1 Pat. N2→N3) und bei 3/29 niedriger (alle N1→N0). Beim M-Faktor fand sich in 3/101 (3 %) eine Diskrepanz. Ein Unterschied der präoperativen (prä) zur pop. ZH fand sich bei 11/101 (10,9 %). Präoperativ lag von 84/112 (75 %) Pat. Gewebe vor. (nur Zyto 20, nur Histo 38, ZH 26). Die Aufteilung war 38 ADC, 29 PEC, 3 großz., 1 ADC/großz., 2 NOS, 3 SCLC, 4 TC, 1 Tu-Zellen und 3mal unterschied sich H und Z. Von den restlichen 28 Pat. war bei 17 kein Gewebe vorhanden, bei 5 fehlten Angaben, 4 inkonklusiv, 1 PN IV und 1 Leiomyosarkom. Die Tumordiagnose wurde mit BSK bei 73

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P027 Multimodality treatment in advanced stage non-small cell lung cancer T. Klikovits, M. A. Hoda, B. Ghanim, C. Aigner, S. Taghavi, G. Lang, J. Matilla, W. Klepetko Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

Background: Advanced stage non-small cell lung cancer (NSCLC) is a fatal disease, characterized by N2/N3 lymph nodes and/or locally advanced tumor. In clinical stage III NSCLC the role of surgical resection – combined with induction treatment – remains controversial. The aim of this study was to retrospectively assess the clinical outcome of patients undergoing a trimodality therapy regime (induction chemoradiotherapy and curative resection) for advanced stage NSCLC. Methods: A retrospective review of all consecutive patients undergoing induction chemoradiotherapy followed by curative resection between 1998 and 2010 at our institution was conducted. Results: A total of 49 patients received induction chemo- and radiotherapy followed by radical surgery, including 11 patients (22.4%) with pancoast tumors. The patients comprised 34 (69.4%) men and 15 (30.6 %) women with a mean age of 54.5 years at the time of resection. Surgical procedures consisted of 3 segmental resections, 24 lobectomies, 3 bilobectomies, and 20 pneumonectomies (11 extra- and 9 intrapericardial). In 48 patients a complete resection (R0) was achieved. 21 (42.9%) patients had a postoperative complication, ranging from 29.2% after lobectomy to 63% after pneumonectomy (p = 0.23). No deaths occurred within 30 days. Overall 3-year survival rate was 45%. Overall disease free survival (DFS) will be presented at the conference. In patients with pneumonectomy 3-year survival was significantly better than in patients with lobectomy (55% vs. 32%, p = 0.039; HR 0.386; 95% CI 0.153 – 0.976). Conclusions: Within a multimodal therapy strategy favorable results for patients in advanced stage non-small cell lung cancer can be achieved. In this series survival in patients undergoing pneumonectomy tended to be superior to patients with lobectomy.

P028 SHFJV (Superimposed High Frequency Jet Ventilation) is a feasible method to achieve adequate oxygenation during lung surgery G. Koller-Halmer1, E. Deusch1, S. B. Watzka2, M. R. Müller2,1, I. Schindler1

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Pat. (65 %), mit CT-Punktion bei 20 Pat. (18 %), durch die Operation bei 13 Pat. (11 %), durch VATS bei 2 Pat. (2 %) gestellt, und bei 4 (4 %) fehlten die Angaben (NA). Staging: CT-Thorax/OB 111/112; Radiologische Abklärung des Gehirns (RG): keine 34/112 (30 %), MR 52/112 (46 %), CT 23/112 (21 %), CT + MR 3/112 (3 %); PET: ja 42/112 (37 %), nein 70/112 (63 %); PET-CT: ja 33/112 (29 %), nein 74/112 (66 %); NA 5/112 (5 %); insgesamt erhielten daher 75/112 (67 %) Pat. entweder ein PET oder eine PET-CT; keine RG und Einsatz von PET-CT: 14/34 ohne RG erhielten ein PET-CT, 1 × NA; daher hatten 19/112 (17 %) Pat. prä keine Abklärung des Gehirns (7 × T1, 7 × T2, 1 × T3, 1 × T4, 3 × N1); PET od. PET-CT und Abdomen: 81/112 (72 %) US oder CT-Abdomen, davon 43 Pat. auch PET od. PET-CT; PET od. PET-CT und Knochenszinitgraphie (GKS): 40/112 (36 %), davon 16 auch PET od. PET-CT; LUFU: 112/112; DLCO 95/112, V/P 15/112, Spiroergometrie 35/112; Schlussfolgerungen: Eine komplette Übereinstimmung in präund postoperativer Zytologie/Histologie und Tumorstadium fand sich nur bei 39 von 101 (38,6 %) auswertbaren Patienten. Ob das mit einer klinischen Relevanz verbunden ist, sollte hinterfragt werden.

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Department of Anästhesiology, Otto Wagner Hospital, Vienna, Austria Department of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria

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Background: We report the findings on 15 Patients which underwent tumor resection in the lung using SHFJV. SHFJV is defined as weight based ventilation combined with superposition of two jetstreams. The high frequency jet-stream is responsible for the oxygenation and the normofrequency jet eliminates the CO2. In all patients preoperatively lung function was severely restricted. Methods: Basic Patient characteristics (mean/SD): FEV1 below 2.1 ± 1 litre O2 saturation below 92% at room air conditions PaO2 71 mmHg ± 5 mmHg PaCO2 41 mmHg ± mmHg Based upon these facts conventional single lung ventilation during surgery was considered to be most likely insufficient and therefore ventilation with SHFJV was prepared for standby. The trachea was intubated with a double lung tube. After one unsuccessful trial of conventional single lung ventilation using 100% oxygen we switched to SHFJV before any signs of hypoxic pulmonary vasoconstriction and desaturation occurred. Oxygenation goals were a PaO2 between 80 mmHg and 100 mmHg and a PaCO2 level between 35 mmHg and 45 mmHg. We ventilated the dependent lung by conventional ventilation (IPPV) and the non-dependent lung by jet-ventilation. Results: Findings: After 10 minutes SHFJV resulted in (mean/SD) PaO2 114 mmHg, PaCO2 41 mmHg. Mean operating time was 41 minutes; 14 patients were transferred to an IMC-ward, 1 patient to an ICU. In no patients pneumonia occurred. Characteristics of SHFJV: - Rapid increase of SaO2 - No CO2 increase - Reduction of shunt volume - No risk of barotrauma (open system conditions) - No airtrapping (open system conditions) - Laserapplication without fire risk (laser safe mode) Conclusions: SHFJV is a safe and effective method of ventilation in order to achieve sufficient oxygenation during lung surgery even in patients with compromised lung functions and therefore can be seen as an optimal approach within the open lung concept.

P029 SHFJV (Superimposed High Frequency Jet Ventilation) – ETCO2 correlation to PaCO2 in diagnostic and therapeutic rigid bronchoscopy G. Koller-Halmer1, I. Schindler1, H. Koller2 1

Department of Anesthesiology, Otto Wagner Hospital, Vienna, Austria Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria

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We report the findings on 42 patients who underwent diagnostic and therapeutic interventional rigid bronchoscopy under SHFJV. SHFJV is defined as weight-based ventilation combined with superposition of two jet-streams in an open system. The high-frequency jetstream is responsible for the oxygenation; the normo-frequency jet-stream regulates the CO2.

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Basic patient characteristics (mean ± SD): Age 59.7 ± 13.8 FEV1 (liter) 2.79 ± 0.58 PaCO2 (mmHg) 35.52 ± 6 Findings after 10 minutes SHFJV: PaCO2 (mmHg) 35.13 ± 11.78* ETCO2 (mmHg) 27.48 ± 4.81 FIO2 (%) 64.76 ± 12.95 *p = 0.001 Characteristics of SHFJV: No CO2 increase No risk of barotrauma (open system conditions) No air trapping (open system conditions) Best ventilation in open system Integrated gas analysis Electronically controlled Laser application without fire risk (laser safe mode) Conclusions: SHFJV in diagnostic and therapeutic rigid bronchoscopy is a safe and effective method of ventilation to achieve sufficient oxygenation without any increase of PaCO2.

P030 The presence of right axis deviation indicates pulmonary hypertension in a risk population G. Kovacs1,2, X. Kqiku2, V. Foris1, M. Tscherner1,2, N. Troester2, S. Scheidl2, C. Hesse2, H. Olschewski1,2 1

Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 2 Medical University of Graz, Graz, Austria

Background: Pulmonary hypertension (PH) is diagnosed by right heart catheterization, but non-invasive methods play an important role in the screening and the follow-up of the disease. ECG is routinely performed in the clinical work-up of patients but its clinical value has not been defined. We hypothesized that a simple parameter, such as the presence of right axis deviation (RAD) in the standard ECG might be a useful tool in the diagnosis and follow up of patients with PH. Methods: We retrospectively analysed all patients who received at least one right heart catheterization and a routine ECG in our department of pulmonology between 2005 and 2010. The indication for invasive hemodynamic assessment was heterogeneous, the pretest probability of PH was about 50%. We determined the ratio of the S and R waves in lead I in each patient, a value ≥1 (≥90°) was considered as RAD. The investigator was blinded to the right heart catheterization results. The sensitivity and specificity of RAD to predict PH (mean PAP ≥ 25 mmHg) was determined. Results: We included n = 317 patients in this study. RAD was present in n = 71 of these patients. Within these, PH was detected in n = 65 patients, and was missing in n = 6 subjects. In n = 246 patients without RAD, PH was present in n = 87 patients. The specificity of RAD for PH was 96%, whereas the sensitivity was merely 43%. Accordingly, the positive predictive value of RAD to predict PH was 92%, while its negative predictive value to rule out PH was just 35%. In patients with RAD the likelihood of PH was significantly higher (p < 0,001). Conclusions: Our retrospective analysis on a relatively large, heterogenous cohort of subjects including patients with and without PH suggests that the presence of RAD in the ECG has a high specificity but a low sensitivity for PH. This simple method may help to recognize PH patients within a population at risk for PH. In order to determine its appropriate role in a diagnostic algorithm, prospective, population based studies are needed.

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P031 Resting and exercise pulmonary vascular resistances in healthy individuals G. Kovacs1,4, A. Olschewski2,4, A. Berghold3, H. Olschewski1,4 1

Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 2 Department of Anesthesia and Intensive Care, Medical University of Graz, Graz, Austria 3 Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria 4 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

The physiological range of pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR) and the influence of exercise, age, and posture have been a matter of debate for many years. We performed a systematic literature review including all right heart catheterisation data where individual PVR and TPR of healthy subjects both at rest and exercise were available. Data were stratified according to age, exercise level and posture. According to the selection criteria, n = 222 subjects from 24 different studies were included into this analysis. Supine resting PVR in subjects < 24 yr, 24–50 yr, 51–69 yr, and ≥70 yr was 61 ± 23, 69 ± 28, 86 ± 15, and 90 ± 39 dyn*s*cm–5. Corresponding TPR was 165 ± 50, 164 ± 46, 226 ± 64, and 223 ± 45 dyn*s*cm–5. During moderate exercise, in subjects ≤50 yr, 85% increase in cardiac output (CO) was associated with 25% decrease in TPR (p < 0.0001) and 12% decrease in PVR (p < 0.01). Between 51–69 yr there was no significant TPR and PVR decrease. In individuals ≥ 70 yr TPR even increased by 17% (p = 0.01), while PVR did not change significantly. At higher exercise levels, TPR decreased in all age groups. In the upright position, based on a limited number of data, resting TPR and PVR were higher than supine and decreased more prominently during exercise, suggesting the release of resting pulmonary vasoconstriction. These data may form a basis to define normal pulmonary vascular resistances at rest and exercise.

P032 Screening for pulmonary hypertension in patients with myelodysplastic syndromes X. Kqiku1, G. Kovacs1, S. Reitter2, H. Sill2, H. Olschewski2 1

Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 2 Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders that are characterized by ineffective hematopoiesis, morphological dysplasia, peripheral blood cytopenias and progressive bone marrow failure. Myeloproliferative disorders, thrombocytosis and thrombocytopenia have been identified as risk factors for pulmonary hypertension (PH) but it is unknown if MDS bears an increased risk for PH. The aim of this study was to investigate the prevalence of PH in patients with MDS. Methods: Consecutive MDS patients of the hematology Outpatient Clinic of the Medical University of Graz were enrolled in a PH screening program and underwent echocardiography. PH was suspected if resting systolic pulmonary arterial pressure (SPAP) exceeded 40 mmHg. Six minute walk distance (6MWD), pulmonary function test (PFT), laboratory tests including N-terminal pro brain natriuretic peptide (NT-proBNP) and WHO functional class were determined in each patient. © Springer-Verlag

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P033 Roflumilast-N-Oxide, a PDE4 inhibitor, partially reversed an increase in Skp2, a loss in p27(kip1) and inhibits proliferation in human lung fibroblasts secondary to TGFβ1 C. Lambers1, B. Burian1, P. Binder1, H. Tenor2, K. Vonbank1, L.H. Block1 1

Division of Respiratory Medicine, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria 2 Department of In-Vitro Biology, Nycomed GmbH, Konstanz, Germany

Background: Proliferation of human lung fibroblasts (HLF) may foster pulmonary remodelling as seen in COPD. The cell cycle is tightly controlled by a network of cyclins, cyclin-dependent kinases and their inhibitors (CDKI) such as p27(kip1). In late G1, p27(kip1) recruits to S-phase kinase-associated protein-2 (Skp2) resulting in p27(kip1) proteasomal degradation facilitating S-phase entry. In smooth muscle cells, cAMP suppresses Skp2, enhances p27(kip1), thus preventing proliferation. This study explores whether the phosphodiesterase-4 (PDE4) inhibitor roflumilast N-oxide, the active metabolite of roflumilast approved for severe COPD in EU and under review by the US FDA, modifies TGFß1-induced proliferation of HLF and the expression of the CDKI p27(kip1) and Skp2. Methods: Normal HLF cultured in 0.5% FCS were incubated without (control) or with TGFß1 (1 ng ml–1) following preincubation (30 min) with roflumilast-N-oxide (2 nM or 1 μM), forskolin (10 μM) or dideoxyadenosine (DDA, 100 μM) or vehicle (DMSO). Roflumilast Noxide at 1 μM completely and selectively blocks PDE4, and 2nM is close to mean steady state plasma levels in clinical trials. Cell proliferation was determined after 72h by cell counting. To assess effects on p27(kip1) and Skp2 protein levels, incubations were terminated at 3h after TGFß1 and cellular proteins were extracted. p27(kip1) and Skp2 were detected by immunoblotting with ß-actin as loading control. Blots were analysed by densitometry and related to the loading control. Results were given as the means ± SD from 3 experiments. Results: Incubation of HLF with TGFß1 (1 ng ml–1) enhanced their proliferation by 1.6 ± 0.1 fold of control (p < 0.05). Roflumilast N-oxide at 2 nM and 1 μM curbed the TGFß1-induced increment by 50% and 58% to 1.3 ± 0.06 fold (p < 0.05) and 1.25 ± 0.05 fold of control (p < 0.05). Forskolin abolished the TGFß1-induced proliferation. Exposing HLF over 3h to TGFß1 (1 ng ml–1) reduced p27(kip1) to 69 ± 20% (p < 0.05) but enhanced SKP2 protein to 149 ± 10% (p < 0.05) of control. Roflumilast N-oxide almost fully rescued the TGFß1-induced loss in p27(kip1) to 92 ± 9% of control at 2 nM and 96 ± 4% at 1 μM (p < 0.05) while it attenuated the increment in Skp2 by 78% (2 nM) and 87% (1 μM) (p < 0.05). This effect was abolished by DDA indiwkw 17–18/2011 © Springer-Verlag

cating that endogenously-driven cAMP synthesis enables the PDE4 inhibitor to act. Conclusions: Roflumilast N-oxide diminished TGFß1-induced proliferation of human lung fibroblasts. In parallel, roflumilast N-oxide reversed the TGFß1-induced loss in p27(kip1) protein perhaps emanating from an observed reduction of Skp2 up-regulated by TGFß1. Future studies shall decipher whether the effects on Skp2 and p27(kip1) account for the inhibition of HLF proliferation by roflumilast N-oxide.

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Results: Fourty two MDS patients (female n = 17; male n = 25, age 70 ± 12 years, disease onset 4 ± 7 years, NYHA functional class I:II:III:IV = 20 : 16 : 6 : 0) underwent echocardiography. SPAP > 40 mmHg was found in 6/42 patients (SPAP: 56 ± 9 mmHg), 36/42 patients had SPAP ≤ 40 mmHg (29 ± 5 mmHg). Compared to patients with normal SPAP, patients with increased SPAP were older (79 ± 9 vs. 69 ± 12 years), had a decreased right ventricular function (TAPSE: 14 ± 2 vs. 16 ± 3), a larger left atrium (46 ± 5 mm vs. 36 ± 9 mm measured in the parasternal long axis), a lower left ventricular systolic function (fractional shortening: 30 ± 11 vs. 39 ± 8%) a lower 6MWD (275 ± 117 vs. 444 ± 100 m) and higher NT proBNP (2708 ± 2845 vs. 313 ± 252 pg/ml). In 4/6 patients with SPAP > 40 mmHg a relevant diastolic dysfunction of the left ventricle was present. Conclusions: According to our data, increased SPAP values may be present in about 15% of MDS patients. The reason of PAP increase may be multifactoral, postcapillary factors probably playing a relevant role.

P034 Work-up of solitary pulmonary nodules: Diagnostic yield of electromagnetic navigation bronchoscopy (ENB) in combination with PET-CT and rapid-on-site cytopathologic evaluation (ROSE) B. Lamprecht1, P. Porsch1, B. Wegleitner1, L. Rettenbacher2, G. Hutarew3, M. Studnicka1 1

Department of Pulmonary Medicine, Paracelsus Private Medical University, Salzburg, Austria 2 Department of Nuclear Medicine and Endocrinology, Paracelsus Private Medical University, Salzburg, Austria 3 Institute of Histopathology, Paracelsus Private Medical University, Salzburg, Austria

Objectives: To determine the accuracy and safety of ENB in combination with PET-CT and ROSE in subjects with solitary pulmonary nodules (SPNs). Methods: In 112 consecutive patients referred to our tertiary care hospital between March 2010 and December 2010 the diagnostic work-up for SPNs included preceding FDG-PET-CT scans and ENB in combination with ROSE. ENB was performed using the superDimension/Bronchus System. ROSE was facilitated by the immediate smearing of the specimen onto slides, drying, and fixation. The Papanicolaou (PAP) test grading system was used for cytopathologic evaluation. The final diagnosis was confirmed by histopathological evaluation of specimen obtained either by ENB, or – if ENB was not diagnostic – by surgery or CT-guided fine needle aspiration. Results: Out of 112 subjects 37 (33%) were female, the mean age was 66.7 years. The mean diameter of peripheral lesions was 27mm (range: 6 – 46 mm). The mean Standard Uptake Value (SUV) recorded by PET-CT was 6.7, and was significantly higher in malignant lesions than in benign lesions (7.4 vs 2.9, p < 0.001). In 83.9% the combination of PET-CT, ENB, and ROSE helped to establish a correct diagnosis, as defined by the definite histopathological result. 15.2% (17/112) of SPNs were benign, and 84.8% (95/112) were malignant. The diagnostic yield in lesions < 20 mm and > 20 mm in diameter was 75.6% and 89.6%, respectively. No significant difference in diagnostic yield was seen depending on the localization of the SPNs. Sensitivity and specificity of ROSE was 82.1% and 100%, respectively. The positive predictive value of a positive PET-CT scan for a diagnosis of malignancy was 92.9%. Two cases (1.8%) of pneumothorax were seen during and up to 24 hours after bronchoscopy, none of them required a chest tube. Conclusions: ENB in combination with PET-CT and ROSE is safe and highly effective in the diagnostic work-up of SPNs.

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P035 Neprilysin is induced by hypoxia and is a prognostic factor in non-small cell lung cancer*

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K. Leithner1, C. Wohlkoenig1, E. Stacher2, J. Lindenmann3, B. Ebner4, C. Guelly4, F.-M. Smolle-Jüttner3, H. H. Popper2, A. Hrzenjak1, A. Olschewski5,6, H. Olschewski1 1

Division of Pulmonology, Department of Internal Medicine, Graz, Austria 2 Institute of Pathology, Graz, Austria 3 Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Graz, Austria 4 Core Facility Molecular Biology, Center for Medical Research, Graz, Austria 5 Experimental Anesthesiology, University Clinic for Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria 6 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

Background: Hypoxia leads to aggressive cancer growth. To identify cancer specific, hypoxia induced pathways is a major aim. Hypoxia not only affects neoplastic tumor cells, but also the supporting stroma. We thus established a novel ex vivo lung cancer model for hypoxic adaptation with preserved tumor stroma and 3D-structure. Experimental design: Non-small cell lung cancer (NSCLC) fragments were cultured ex vivo under hypoxia or normoxia for three days. cDNA microarray analysis was performed in hypoxic and normoxic lung cancer fragments from ten patients. Association of hypoxia regulated genes and survival was assessed in four publically available microarray series including 342 NSCLC patients. Results: Ex vivo cultured lung cancer fragments were viable, apoptosis rates were not increased by hypoxic treatment. Hypoxiainducible factor 1α was stabilized and significant upregulation of the hypoxia marker carbonic anhydrase IX was observed under hypoxia. Microarray analysis identified 107 significantly regulated genes with at least two-fold expression change in hypoxic compared to normoxic fragments. However, only four genes were significantly regulated in both subtypes, adenocarcinoma and squamous cell carcinoma. We found an unexpected induction of neprilysin (membrane metalloendopeptidase, neutral endopeptidase, NEP, CD10) under hypoxia, which was confirmed using quantitative PCR. Neprilysin expression was significantly associated with poor overall survival in NSCLC patients treated with surgery (P = 0.002). Conclusions: Our study demonstrates for the first time that the membrane bound metallopeptidase neprilysin is upregulated by hypoxia and that it is an adverse prognostic factor in lung cancer. Neprilysin might thus serve as a hypoxia related target for anti-cancer therapy.

P036 Which benefits can COPD patients derive from inpatient rehabilitation? A. Lichtenschopf1, W. Kullich2, R. Müller3 1

SKA der PVA Weyer/Enns, Weyer/Enns, Austria Ludwig Boltzmann Institut für Rehabilitation interner Erkrankungen Saalfelden, Cluster für Rheumatologie, Balneologie und Rehabilitation, Saalfelden, Austria 3 Pensionsversicherungsanstalt Hauptstelle Chefärztlicher Bereich Wien, Vienna, Austria 2

Background: Nearly all studies concerning rehabilitation are performed with selected patients. In order to investigate the benefits for unselected COPD patients we performed a study with all COPD patients who attended an 3 to 4 weeks inpatient rehabilitation stay in

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Weyer. The active program consisted of endurance and strength training each of them three times a week for half an hour and an inspiratory muscle training for patients with a PI max below 7 kPsa and, furthermore, a Patient education including 4 lessons. Methods: From 2009 to 2010 data of all 533 COPD patients participating the inpatient rehabilitation in Weyer for 3-4 weeks were collected, especially the CRQ (chronic respiratory questionnaire) and the 6MWT (6-minute walking test) at the beginning and the end of the program. Results: Mean age 62. 7 (40 to 89) years, 64.35% men and 35.65% women. Mean FEV1 was 1.35 or 44.76%. GOLD-stage 0 = 1.5%, stage 1 = 10.13%, stage 2 = 23.08%, stage 3 = 25.33%, stage 4 = 39.96%. The distribution of the BODE-score showed 36.72% of the patients to be in the 1st Quartile, 28.06% in the 2nd Quartile, 19.59% in the 3rd Quartile and 15.63% in the 4th Quartile. 34.52% of the patients were treated with long time oxygen supplementation and 13.51% had a global insufficiency. 19.50% were smokers, 72.33% ex-smokers and 8.18% never have smoked. The mean of the 6MWT at the beginning resulted in 369.11 m, and increased to 413.92 m at the end. The improvement of 44.81 m exceeded the minimal important clinical difference of 28 meter (Puhan 2011). The CRQ domains were as follows: Dyspnoe at baseline 3.44 and discharge 3.68 (difference 0.24 = clinically not relevant). Fatigue at baseline 4.23 and at discharge 4.91 (difference 0.68 = clinically relevant). Emotional function at baseline 4.38 and at discharge 5.23 (difference 0.85 = clinically relevant). Mastery at baseline 4.56 and at discharge 5.22 (difference 0.66 = clinically relevant). Conclusions: For three to four-week inpatient rehabilitation clinically relevant benefits were found in the CRQ domains fatigue, emotional function, and mastery, as well as in the 6MWT.

P037 Comorbidities in COPD – extended diagnosis in inpatient rehabilitation A. Lichtenschopf1, W. Kullich2, R. Müller3 1

SKA der PVA Weyer/Enns, Weyer/Enns, Austria Ludwig Boltzmann Institut für Rehabilitation interner Erkrankungen Saalfelden, Cluster für Rheumatologie, Balneologie und Rehabilitation, Saalfelden, Austria 3 Pensionsversicherungsanstalt Hauptstelle Chefärztlicher Bereich Wien, Vienna, Austria 2

Background: Detection of comorbidities in COPD of patients who attended inpatient rehabilitation for 3 to 4 weeks within an observation period of 1 year. Methods: From 2009 to 2010 we investigated the comorbidities in 533 COPD patients in the rehabilitation centre in Weyer . Results: Mean FEV1 was 44.76%. GOLD-stage 0 = 1.50%, stage 1 = 10.13%, stage 2 = 23.08%, stage 3 = 25.33%, stage 4 = 39.96%. The distribution of the BODE-score showed / resulted in 36.72% in the 1st Quartile, 28.06% in the 2nd Quartile, 19.59% in the 3rd Quartile and 15.63% in the 4th Quartile. 34.52% of the patients were treated with long time oxygen supplementation and 13.51% had a global insufficiency. 20% were smokers, 72% ex-smokers and the rest never have smoked. The following comorbidities were found: Hypertension = 53.38%, Coronary heart disease = 14.29%, Chronic heart disease = 11.84%, Insulin Dependent Diabetes = 3.01%, Non In-

© Springer-Verlag

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P038 Bactericidal activity of N-chlorotaurine against Chlamydia pneumoniae and Chlamydia trachomatis V. Maass1, R. Arnitz2,3, M. Nagl3, M. Maass1 1

Institute of Medical Microbiology, Hygiene and Infectious Diseases, Paracelsus Private Medical University, Salzburg, Austria 2 Department of Pulmonary Diseases, Hospital Vöcklabruck, Vöcklabruck, Austria 3 Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria

Chlamydia pneumoniae causes infections of both the lower and upper respiratory tract, such as pneumonia, bronchitis, pharyngitis and sinusitis. In the last few years, it has also been implicated as an infectious trigger for acute exacerbations of asthma and COPD. N-chlorotaurine, the N-chloro derivative of the amino acid taurine, is a mild endogenous long-lived oxidant, which is thought to exert immune-regulatory and antimicrobial properties during inflammation. The sodium salt of N-chlorotaurine (Cl-HN-CH2-CH2-SO3-Na, NCT) can be synthesized chemically and is very well soluble in water. The 1% aqueous solution of NCT has broad-spectrum bactericidal, fungicidal, virucidal, and protozoocidal activity. NCT proved to be very well tolerated by human tissue and can be used topically at different body sites to treat infections, e.g. in the human eye, on the skin, in the ear and paranasal sinuses, in the oral cavity, and in the urinary tract. NCT at concentrations of 0.1% and 1% completely inactivated C. pneumoniae and C. trachomatis serovars A and D after a minimal incubation time of 1 min thus preventing any further chlamydial growth in culture after exposure to the compound. These concentrations can therefore be considered chlamydiacidal. Exposure to 0.01% (550 μM) NCT for up to 30 min did not interfere with the formation of inclusion bodies. These results were identical for chlamydial inocula of either 103 IFU or 104 IFU. As a conclusion, NCT at concentrations of 0.1 and 1% (5.5. and 55 mM, respectively) leads to inactivation of the obligate intracellular chlamydiae and may be considered for topical treatment of infections caused by these pathogens, too.

P039 Treatment adherence with CPAP for obstructive sleep apnea is influenced by mask leak M. Meshkat, J. Ebner, O. Burghuber, A. Valipour

Methods: We studied 63 patients (mean Age 55 ± 11 yrs, mean BMI 36 ± 7 kg/sqm, mean AHI 48 ± 30/hr, ESS 11 ± 5) who received fixed or auto-adjusted CPAP treatment for OSAS at our institution. All patients underwent a standardized educational session and mask fitting by experienced staff. Data on treatment adherence and mask leakage was collected for approximately 6 months after initiation of CPAP. Results: Mean ± standard deviation days of CPAP use was 176 ± 82 days, percentage of days with CPAP usage 84 ± 18%, and percentage of days with at least 4 hours CPAP use/night 71 ± 24%. There was a significant inverse relationship between CPAP adherence using Kribbs criteria and average time spent with mask leak per night (r = -0.362, p < 0.01). Patients with good adherence (n = 42), defined as CPAP use > 4 hours per night on at least 5 days per week, were compared with those who used their device less frequently (n = 21). There were no significant differences between baseline characteristics, residual AHI or therapeutic CPAP pressure between groups. Patients with poor CPAP adherence, however, had significantly higher average mask leakage flow (39 ± 8 litres/min vs. 34 ± 6 litres/min, p < 0.01) and higher time spent with mask leakage per night (3.7 ± 6 min/night vs. 7.7 ± 10 min/night, p < 0.05) than those with good adherence. Conclusions: Mask leakage may influence treatment adherence with CPAP for OSAS.

P040 Multimodal management of thymomas and thymic carcinomas: a ten year experience B. Moser1, M. Scharitzer1, S. Hacker2, H. Ankersmit1, G. Lang1, C. Aigner1, S. Taghavi1, W. Klepetko1 1

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Division of Plastic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

Thymomas are rare malign tumors of the mediastinum. We want to report our experience with the resection of thymomas at our institution in the years 2001 to 2010. In the indicated time period a total of 84 resections were performed. 72 patients who underwent surgery for thymoma were analyzed for survival (overall, recurrence free), modified Masaoka stage, WHO type, type and completeness of resection, recurrences, the occurrence of myasthenia gravis, neoadjuvant and adjuvant therapy. 9.7% of cases showed tumor recurrence, 6.9% tumor progression. Patients admitted present with Masaoka stage I (29.2%), stage II (43.1%), stage III (13.9%) and stage IV (13.9%). The following WHO types were found: type A (19.4%), type AB (5.6%), type B1 (6.9%), type B2 (22.2%), type B3 (12.5%), thymic carcinoma (19.4%), combined thymomas (12.5%, most frequently B2/B3) and micronodular thymoma (1.4%). Myasthenia Gravis was present in 26.4% of cases. In about 88.9% of cases a complete resection could be reached. Using Overall Survival as outcome measure, the 1 year survival rate was 97%, the 5 year survival rate was 87%. After 1 year 95% of patients were free from recurrence, after 4 years 89% of patients. Progression occurs in 50% of patients one year after incomplete resection. We will discuss the current surgical treatment strategy of thymomas and multimodal approaches for advanced thymomas.

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Department of Respiratory and Critical Care Medicine, Otto-WagnerHospital, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Vienna, Austria

Silencing of INHBA Expression Inhibits Growth of Human Malignant Pleural Mesothelioma Cell Models

Aims: To investigate the effect of mask leak on adherence with CPAP therapy in patients with obstructive sleep apnea syndrome (OSAS).

J. Muenzker1,2, M.A. Hoda1,2, K. Schelch1,2, B. Ghanim1,2, T. Klikovits1, M. Filipits2, B. Hegedus1, B. Dome1, W. Berger2, W. Klepetko1, M. Grusch2

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sulin Dependent Diabetes = 11.09%, Hyperlipidaemia = 34.40%, Osteoporosis = 25.56%, Depression = 18.98%, Aneurysma abdominalis = 2.26%, St p. cerebral stroke = 3.20%, Peripheral Occlusive Disease = 6.95% 17.30% had 1 comorbidity, 23.50% two, 12.78% three comorbidities, 8.65% four and 6.57% five or more than five. Conclusions: The inpatient rehabilitation of COPD patients revealed numerous comorbid conditions that require extended therapy and training.

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1

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria

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Background: Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy-resistant tumor with rising incidence related to asbestos exposure during the 2nd half of the 20th century. Growth factors of the activin family are deregulated in a number of different malignancies including hepatocellular carcinoma, NSCLC and esophageal cancer. Here we present evidence that activin signals may contribute to aggressiveness of MPM cells. Methods: Expression of activin subunits and activin receptors was determined in a panel of 10 MPM cell lines by conventional and real-time PCR. Moreover, activin βA (INHBA) expression was analyzed by immunohistochemistry in MPM tissue samples. To analyze functional implications of activin signals, MPM cell models were exposed to exogenous activin A, siRNA-mediated INHBA silencing or activin receptor inhibitors. MTT and clonogenic growth assays were used to assess cell proliferation and survival. Cell migration was analyzed by scratch and transwell assays, and Smad2 phosphorylation by Western blot as readout for activation of the activin/TGFbeta signaling pathway. Results: Expression analysis revealed high expression of activin βA and activin receptors in most MPM cell lines compared to nonmalignant mesothelial cells. Immunohistochemistry in tissue sections of MPM patients showed intense cytoplasmic staining for activin A in the tumor cells of a subset of the cases analyzed. Treatment with activin A lead to a strong induction of Smad2 phosphorylation in MPM cell models and stimulated growth and clonogenicity in a subset of cell lines. Silencing of INHBA in contrast lead to reduced growth, clonogenic survival and migration of MPM cell models, demonstrating the important role of INHBA expression for MPM cells. Targeting activin receptors with two different kinase inhibitors (SB431542, A8301) confirmed these results. Conclusions: These data suggest that deregulated INHBA expression contributes to the malignant phenotype of MPM cells and that activin signals should be further evaluated as therapeutic targets.

P042 Correlation between blood lactate concentration and base excess during exercise L. M. Nagler1, G. Kovacs1,2, M. Tscherner1,2, X. Kqiku2, H. Olschewski1,2 1

Ludwig Boltzmann Institut for Lung Vascular Research, Graz, Austria; Division of Pulmonology, Department of Medicine, Medical University of Graz, Graz, Austria

2

Background: The change of blood lactate concentration during exercise is an important parameter describing metabolic changes of the circulation and the state of metabolic reserves. The goal of this study was to examine if the change of base excess allows the estimation of the changes in lactate concentration during cardiopulmonary exercise testing (CPET). Patients and methods: All CPET examinations in the Pulmonology Outpatienz Clinic of the Medical University of Graz between 2007 and 2010 were included in this retrospective analysis where both blood lactate and base excess values were available. Blood lactate and base excess were determined at rest, at maximal exercise, at three and at eight minutes after exercise by using an ABL 800 Flex (Radiometer, Copenhagen) blood gas analyser. The correlation between blood lactate and base excess was examined at each time point in all of the patients and in subgroups based on the underlying disease, sex, age, lung function, exercise capacity.

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Results: N = 585 examinations of n = 320 subjects were analysed. In the whole group, there was a very tight correlation between the changes in lactate concentration and base excess at each time point (rest vs. maximal exercise: R = 0.95, rest vs. three minutes after exercise: R = 0.97, rest vs. eight minutes after exercise: R = 0.95). The absolute change of base excess was slightly smaller compared to the absolute change of lactate concentration from rest to maximal exercise (3.3 ± 2.4 vs. 4.3 ± 2.7 mmol/l), but this difference disappeared three (5.2 ± 3.0 vs. 5.4 ± 3.0 mmol/l) and eight minutes (4.8 ± 3.4 vs. 4.7±3.1 mmol/l) after exercise. The factors age, sex, underlying disease, lung function or exercise capacity were not significantly associated with the base excess – lactate differences. Conclusions: The change of base excess allows a reliable estimation of the blood lactate increase during exercise.

P044 Effects of inspiratory muscle training on dynamic hyperinflation in patients with COPD M. Petrovic1, M. Reiter2, W. Pohl1, T. Wanke1 1

Department of Pneumology, Hospital Hietzing, Karl Landsteiner Institute for Clinical and Experimental Pneumology, Vienna, Austria 2 Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria

Background: Dynamic hyperinflation is associated with exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Inspiratory muscle training (IMT) has been shown to positively influence exercice capacity in COPD. The aim of the study was to analyze the effects of IMT on exercise capacity, dyspnea and inspiratory fraction (IF) during exercise in patients with COPD. Methods: Daily inspiratory muscle strength and endurance training (training device: Respifit STM) was performed for 8 weeks in 10 patients with COPD GOLD II and III. 10 patients with COPD II and III served as a control group. Maximal inspiratory pressure (Pi max) and endurance time during resistive breathing manouvers (tlim) served as parameter for inspiratory muscle capacity. Before and after training the patients performed an incremental symptom limited excercise test to maximum and a constant load test on a cycle ergometer at 75% of the peak work rate obtained in the pretraining incremental test. Endurance time (ET) was defined as the duration of loaded pedalling. Inspiratory capacity (IC) and therefore inspiratory fraction (IF = IC/TLC) served as parameter for dynamic hyperinflation. BORG Scale was used for dyspnea evaluation. Results: Following 8 weeks of IMT there was a statistically significant improvement of Pi max from 7.75 ± 0.47 to 9.15 ± 0.73 kPa (p < 0.01) and of tlim from 348 ± 54 to 467 ± 58 s (p < 0.01) in the training group but not in the control group. Concerning incremental exercise test we could observe following results: there was a significant increase of IF (from 0.41 ± 0.05 to 0.45 ± 0.05, p < 0.01) indicating decreased dynamic hyperinflation. Further on the ratio of bf/VE decreased significantly (from 0.48 ± 0.11 to 0.46 ± 0.13) indicating improved breathing pattern. A significant decrease in perception of dyspnoea (BORG Scale) was also measured. Peak work rate (Watt max) remained constant. Concerning constant load cycle ergometer test we could also observe an significant improvement of IC and therefore of IF, improvement of breathing pattern and reduction of dyspnoea sensation. In addition Endurance time (ET in seconds) was significantly greater (734 ± 74 sec) than before IMT (597 ± 80.8 sec, p < 0.01)

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P045 Efficacy of roflumilast in patients with a history of frequent exacerbations: Pooled data from pivotal 12-month studies W. Pohl1, R. Voves2, H. Jamnig3, V. Rechberg4, I. Moll-Schüler5 1

Pneumology practice, Gänserndorf, Austria Pneumology practice, Feldbach, Austria 3 Department of Pneumology, Hospital Natters, Austria 4 Department of Medicine, Nycomed, Germany 5 Department of Medicine, Nycomed, Austria 2

Background: COPD exacerbations are associated with a substantial patient and healthcare burden, which is greater for frequent exacerbations. This analysis studied the effect of roflumilast on moderate or severe exacerbations by exacerbation history using pooled data from two 12-month studies. Methods: M2-124 and M2-125 were replicate, randomised, placebo-controlled, double-blind, multicentre trials in COPD patients with severe-to-very severe airflow obstruction, a history of exacerbations and chronic bronchitis. Patients were randomised to roflumilast 500 μg (n = 1537) or placebo once daily (n = 1554) for 12 months. Results: The rate of frequent exacerbations was lower with roflumilast than placebo: patients with 2 exacerbations: 11.5% with roflumilast vs 13.6% with placebo; with 3: 5.9% vs 6.8%; with 4: 2.4% vs 3.5%; with 5: 1.0% vs 2.1%, and with ≥6: 0.6% vs 1.5%. The mean exacerbation rate per patient per year was significantly lower with roflumilast than placebo in patients with <2 exacerbations in the previous year (0.96 vs 1.15, –16.5%; p = 0.006). The difference between roflumilast and placebo was greater in patients with ≥2 exacerbations in the previous year (1.51 vs 1.95, –22.3%; p = 0.002). A benefit was also seen with roflumilast vs placebo for time to first (hazard ratio [HR] 0.89, p = 0.019), second (HR 0.79, p = 0.001) and third exacerbation (HR 0.73, p = 0.003). Conclusions: Frequency of exacerbations was lower and time to exacerbation was longer with roflumilast than placebo. The greatest benefit from roflumilast was seen in patients with a history of frequent exacerbations (≥2/year).

P046 The Role of B-lymphocytes in thrombus resolution* M. K. Renner, M.-P. Winter, A. Alimohammadi, A. Panzenboeck, D. Bonderman, I. M. Lang Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

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No significant changes during both exercise tests were measured in the control group. Conclusions: The results of our study show that inspiratory muscle strength and endurance training improve inspiratory pump capacity reduce dynamic hyperinflation and breathlessness during exercise. Thus the positive effects of IMT on exercise capacity in COPD are not only the result of improved inspiratory pump capacity but also the result of reduction in dynamic hyperinflation during excercise.

Background: Splenectomy is associated with complex venous thromboembolism such as recurrent deep venous thrombosis, portal vein thrombosis, and chronic thromboembolic pulmonary hypertension (CTEPH). The spleen serves not only as a red blood cell filter but also as immunological organ. The aim of our study was to decipher the population of spleen cells responsible for misguided thrombus resolution after splenectomy. Methods: We utilized a mouse model of stagnant flow venous thrombosis to characterize thrombus resolution. Splenectomy was performed one month before vena cava ligation. In defined groups, whole spleens, spleens depleted of B-lymphocytes or B-lymphocytes alone were reinfused intraperitoneally. On days 3, 7, 14 and 28 after vena cava ligation thrombi were harvested for histology. Results: Thrombus areas of splenectomized mice were significantly larger than those of controls at all time points (ANOVA, n = 8, p < 0.03). Reinfusion of autologous whole spleen-homogenates reconstituted a normal pattern of thrombus organisation. Reinfusion of spleen tissue depleted of B-lymphocytes did not affect thrombus resolution. However, reinfusion of autologous splenic B-lymphocytes in previously splenectomized mice normalized thrombus resolution (Fig. 1). Conclusions: Reinfusion of spleen cells restores normal venous thrombus resolution in a mouse model. Our data demonstrate that spleen B-lymphocytes play a key role in thrombus resolution.

P047 A case of abscedizing pneumonia and pulmonary embolism – after sniffing of pulverized benzodiazepine tablets M. Rowhani1, R. Rumetshofer1, E. Stiefsohn2, O. C. Burghuber1 1

Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria 2 Department of Radiology, Otto Wagner Hospital, Vienna, Austria

Case Report: We present the case of a 41-year old Austrian male smoker who was referred to our tuberculosis ward by a pneumologist

*p<0,05 Error Bars ± 2 SE

Fig. 1. (Abstract P046). Reinfusion of autologous splenic B-lymphocytes in previously splenectomized mice normalized thrombus resolution

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due to suspicion of pulmonary tuberculosis with a cavitating lesion in the right upper lobe. A diagnostic bronchoscopy was performed, with the result of a purulent inflammation, without evidence of malignancy or tuberculosis. These findings were further corroborated when tb culture results showed no growth of mycobacteria. Following bronchoscopy, the patient admitted to sniffing (or „snorting“) prescribed benzodiazepines repeatedly. Discussion: Amongst patients with multiple drug use, alternate routes of administration of prescribed drugs have been observed. While i.v. administration of heroin substitutes such as methadone is a fairly well-known phenomenon in Austria, sniffing or snorting of tablets as described in the present case report seems to be a less common practice. Medical literature only provides individual case reports on the above practice. One Australian investigation of heroin abuse reports that, of 10 heroin related deaths investigated, four occurred after nasal application. A history of polytoxicomania should therefore prompt discussion of drug habits in patients with atypical infections possibly resulting from alternate administration routes of prescribed and of illegal drugs.

P048 A multidisciplinary weaning and extubation regime leads to relevant reduction of weaning and ventilation time P. Schandl, S. Heil, B. Gustorff Department of Anaesthesiology and Intensive Care, Wilhelminenspital, Vienna, Austria

Background: The use of a multidisciplinary weaning protocol and the ensuing assessment corresponding to level A evidence is common practice in North America. A regime such as this was not previously implemented at our department. We hypothesized, that ventilation and weaning time would be reduced by a respective protocol and that the quality of weaning would be sustainable improved. The objective of this study was to evaluate the implementation of a multidisciplinary (respiratory therapist, physician, nurse) standardized weaning and extubation regime. Methods: Setting: 8-bed intensive care unit with intubated surgical, trauma and medical patients. Inclusion criteria: >48 h mechanical ventilation by tracheal tube. Exclusion criteria: neuromuscular disease, dysphagia, LTOT and home respiratory care. In this prospective study a historical control group (n = 20) was used as the comparison group: physician directed weaned without protocol. Standardized weaning in the intervention group (n = 20) was exclusively performed by using the developed protocol: including weaning-criteria, weaning-assessment, weaning-algorithm with a spontaneous breathing trial and extubation criteria. Results: Our regime reduced total time of ventilation (median = 169.1 h vs. 89.9 h) and weaning time (median = 73.35 h vs. 20.43 h) significantly (p = 0.00329 and p = 0.0004) in the intervention group. The use of prerequisite extubation criteria in the invention group reduced the rate of recent ventilation by 50%. The reduction of weaning and ventilation time is based on multidisciplinary protocolized weaning. The main difference in weaning algorithm (implementation of a spontaneous breathing trial and the reduced use of a “comfort ventilation mode”) can be discussed as additional reasons for benefit. Conclusions: Despite the acknowledgement of methodical limitations of the study and the small sample size it can be assumed that a standardized, multidisciplinary weaning and extubation regime improves the weaning process by reducing weaning and ventilation time. The study results approach to the implementation of a multidisciplinary protocol into European weaning practice.

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P049 Risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation A. Scheed, P. Jaksch, B. Ghanim, S. Taghavi, G. Lang, C. Aigner, W. Klepetko Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

Background: Bronchiolitis obliterans syndrome (BOS) remains the most important complication in long-term follow-up after lung transplantation (LUTX) and has significant impact on graft survival. We aimed to identify risk factors for BOS in general and in addition for the early onset (≤2 years post LUTX) of BOS. Methods: All LUTX from 1999 to 2009 and a survival of more than 6 months were retrospectively analyzed (n = 605). Patients with at least BOS 1(n = 151) were divided in 2 groups: A = onset of BOS ≤2 years post LUTX (n = 81); B = onset of BOS after 2 years (n = 70). Control group C = patients without BOS (n = 454). Results: Risk factors for the development of BOS were: cyclosporine as first line immunosuppression, compared to tacrolimus (p ≤ 0.01), aspergillus infection post LUTX (p = 0.015), CMV infection post LUTX (p ≤ 0.01), no induction therapy (p = 0.029) and acute rejection episodes in the first year after LUTX (p ≤ 0.01). Patients with cystic fibrosis are developing BOS less common (p ≤ 0.01) and later (p = 0.034) than patients with other diagnoses. Additional risk factors for an early onset of BOS were: aspergillus infection post LUTX (p ≤ 0.01), age (group A: 48.5 ± 12.9; B: 44.1 ± 14.5; p = 0.041) and lymphocytic bronchitis (p ≤ 0.01). 5-year graft survival from patients with BOS (52.1%) was significantly lower (log rank ≤ 0.01) compared to patients without BOS (77.8%) and significantly lower (log rank ≤ 0.01) in group A (26.0%) compared to group B (77.9%) as well. Conclusions: Cyclosporine as first line immunosuppression, infections with CMV and aspergillus and acute rejections are potential risk factors for the development of BOS. Patients with higher age and lymphocytic bronchitis are at risk for an early onset of BOS and should be observed frequently.

P050 Inhibition of the fibroblast growth factor receptor axis in malignant pleural mesothelioma: potential therapeutic implications K. Schelch1,2, M. A. Hoda1,2, J. Muenzker1,2, B. Ghanim1,2, T. Klikovits1, M. Filipits2, B. Hegedus1, B. Dome1, W. Berger2, M. Grusch2, W. Klepetko1 1

Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria

Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterized by frequent resistance to chemoand radiotherapy. Fibroblast growth factors (FGF) and their receptors (FGFR) contribute to malignant growth in several tumor types but in case of MPM their role is poorly understood so far. Aim of the present study was to investigate the expression and impact of FGFs and FGFRs in MPM and to evaluate their potential as therapeutic targets. Methods: Expression of all known FGF and FGFR genes was assessed by qRT PCR in MPM cell lines (n = 10) and normal mesothelial cells. FGFR-specific tyrosine kinase inhibitors and an adenovirus expressing dominant-negative FGFR were used to block FGF signal transduction in these cell models. MTT and clonogenic assays as well © Springer-Verlag

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P051 Dendritic cell function is affected by endothelin-1 in vitro* C. Schönherr, K. Cima, S. Desole, J. Löffler-Ragg, C. M. Kähler Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

Inflammatory cells such as mast cells, T-lymphocytes and dendritic cells have been described in the perivascular lesions in PAH. The strong pro-inflammatory agent endothelin-1 (ET-1) was shown to be upregulated in PAH patients. So far, ET-1 has been found to be released from dendritic cells and to be involved in autocrine cell survival regulatory loops. However, the chemotactic effect of ET-1 on dendritic cells has yet to be elucidated. Dendritic cells were directly isolated from peripheral venous blood of healthy donors by Ficoll Density Gradient Separation. As a next step Magnetic Cell Sorting (MACS®) for myeloid and plasmacytoid dendritic cells was performed. For the chemotaxis assays 48-well Boyden Chambers were used, of which the lower and upper compartments were separated by 8 μM pore-sized cellulose nitrate filters. Dendritic cells were let to migrate towards ET-1 [10–6 – 10–12M]. In order to specify receptor signalling, dendritic cells were pre-incubated for 30 min with BQ-123, a well established ETAR inhibitor and BQ788, which is a known inhibitor of the ETBR, before migration assays towards ET-1 [10–8M] were performed; fMLP [10–8M] served as positive control. After 4 hours at 37 °C in humidified atmosphere, filters were dehydrated, stained and fixed. Cell migration was analysed microscopically. For the first time ET-1 was shown to induce dendritic cell migration, displaying [10–8 M] to be most effective. Furthermore, the ETAR inhibitor BQ-123 was proven to inhibit dendritic cell migration most significantly at 10–6 – 10–8 M. To compare, the ETBR inhibitor BQ-788 blocked the chemotactic effect of ET-1 at a broader concentration range [10–6–10–12 M]. Thus, we conclude that ET-1 is a chemoattractant for human dendritic cells despite their origin and that this effect is more efficiently inhibited by ETBR blockage than that of ETAR, reinforcing ET-1 to be a good therapeutic strategy for targeting the inflammatory component of PAH.

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P052 The stress kinase MKK7 functions as lung-specific tumor suppressor by coupling oncogenic stress to p53 stability D. Schramek1, R.-H. Zwick2, V. G. Gorgoulis3, M. Serrano4, J. M. Penninger1

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as spheroid formation assays and videomicroscopy were performed to analyze cell growth, survival and migration. The effect on downstream signal transduction was assessed by immunoblotting with phosphorylation site-specific antibodies. Results: Expression analysis revealed high levels of FGFR1 together with the ligands FGF2 qand FGF18 in all MPM cell lines investigated. Stimulation with FGF2 showed remarkably increased migration and significant changes in morphology reminiscent of epithelial mesenchymal transition. Inhibition of FGFR1 by the specific small molecule kinase inhibitor PD166866 lead to decreased proliferation, survival, migration and spheroid formation in all cell lines tested. Adenoviral expression of dominant-negative FGFR1 further confirmed these results. Combination of FGFR inhibition with chemotherapeutic agents (e.g. cisplatin, gemcitabine, trabectedine) increased cytotoxicity. Conclusions: Our data suggest that FGFR signals contribute to proliferation, survival, migration and chemotherapy resistance of MPM cells and their inhibition should be further evaluated as a potential new treatment strategy in this devastating malignancy.

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MBA, Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna, Austria 2 Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria 3 Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece 4 Spanish National Cancer Research Centre (CNIO), Madrid, Spain

Lung cancer is one of the most common malignancies in humans both in terms of frequency and mortality. On average, 1 in 12 men and 1 in 15 women will be diagnosed with lung cancer during their life time in the US and Europe. Most lung cancers are due to sporadic mutations in single cells and are strongly influenced by risk factors such as smoking or pollution. However, most of these preneoplastic cells are quiescent and do not progress to form overt tumors. It has been proposed that oncogenic stress activates the DNA damage response and the key tumor suppressor p53, which prohibits tumor growth. However, the molecular pathways by which cells sense a premalignant state in vivo are largely unknown. We found that the MKK7-JNK stress signaling pathway serves this vital function and show that lungspecific inactivation of MKK7 in a KRas(G12D)-driven NSLCLC mouse model markedly accelerates tumor onset and reduces overall survival. Mechanistically, MKK7 acts through the kinases JNK1 and JNK2, and this signaling pathway directly couples oncogenic and genotoxic stress to the stability of p53 by specific phosphorylation events, which is required for cell cycle arrest and suppression of epithelial lung cancer. To test whether MKK7-JNK signaling is also perturbed in human primary lung tumors, we analyzed MKK7 in samples from human NSLCLC patients. Phosphorylation of MKK7 was upregulated in NSCLCs compared to surrounding healthy tissue indicating that this pathway is actively engaged during tumorigensis. Strikingly, tumors in which p53 was mutated (confirmed by sequencing) showed even higher phosphorylation of MKK7 than did tumors harboring wildtype p53 indicating a deregulated response in more advanced, malignant tumors. Thus, MKK7 is activated in primary human lung tumors and such hyperactivation seems to depend on p53 status.These results show that MKK7 functions as a major tumor suppressor in lung cancer and identify MKK7 as a vital molecular sensor to set a cellular anticancer barrier.

P053 Quality of life after lung transplantation in patients with cystic fibrosis: a cross-sectional study B. Smeritschnig, P. Jaksch, A. Scheed, W. Klepetko Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

Background: Over the last years lung transplantation (LuTX) has become an established procedure for treatment of patients with endstage pulmonary diseases. The aim of the present cross-sectional study was therefore to provide an overview on quality of life and life satisfaction in lung transplant patients with cystic fibrosis. Methods: All German speaking lung transplant recipients with cystic fibrosis were given a set of questionnaires (n = 45, response rate 95%): St. George’s Respiratory Questionnaire (SGRQ), SF-36, the Hospital Anxiety and Depression Scale (HADS-D), a likert scale of actually ÖGP Jahrestagung 2011

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QOL (0%–100%), and a self-report questionnaire concerning social data, daily activities and adverse effects of immunosuppression. Results: Social data about professional life illustrate that after LuTX 49% are employed and 33% in retirement. 75% of the patients are married or in a common law marriage, 16% are living alone and 9% living still with parents. Most of all (98%) are able to do daily activities without problems and exercise different sports regularly like fitness training (47%), cycling (43%), swimming and so on. Adverse effects of immunosuppression, however turned out to be a important factor influencing LuTX recipients life quality: 19% suffer in a moderate to severe way of adverse effects. 77% have diabetes, 53% hypertension and 63% osteoporosis. However 93% are highly satisfied with the transplant outcome and 98% would opt for the procedure again. With regard to the SGRQ the LuTX recipients show significantly better scores, equalling an increased quality of life, compared to the reference value of patients with obstructive pulmonary disease. HADS-D as well as SF-36 did not differ significantly to the published norms at healthy population. At last the actually QOL-scale shows 83 ± 17%. Conclusions: Although lung transplant patients have to cope with adverse effects of immunosuppression they report a highly satisfying quality of life. This is reflected in the daily activities, regularly sports, retirement and the psychosocial situation.

P054 Pretransplant clinical status of LuTX-candidates and waiting list 2008 – 2010 B. Smeritschnig, V. Augustin, P. Jaksch, W. Klepetko Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

Background: Lung transplantation is an established treatment for patients with end stage pulmonary diseases. Preoperative examination by an interdisciplinary team is essential for selection of qualified candidates. Methods: Between 2008 and 2010 data were analyzed from patients who have been assigned to our pretransplant clinic. The aim of the study was to determine the number of accepted, declined or postponed patients. Further we wanted to assess the number of listed patients, waiting list, diagnoses, waiting time, mortality and the frequency of high urgency reports. Results: In a period between 2008 and 2010 744 patients were examined and 981 conversations were conducted with these patients. After additional examinations 20% of the patients were refused and 47% were put on the waiting list. 33% were either in evaluation or had to optimize the clinical status (BMI, rehabilitation, muscular status). These patients were postponed to further examination. In this period 498 patients were put on the waiting list with following diagnoses: COPD 31%, CF 21%, IPF 18%, IPH 8%, A1ATM 6% and re-TX with 6%. Waiting time depends always on urgency, blood group, height and diagnosis. The shortest waiting time had patients with IPH and CF, then IPF. Stable COPD-patients had the longest waiting period. The mortality on the waiting list is stable at the percentage rate of 6% over the years. Death on the waiting list depends on the diagnosis: re-TX 24%, IPF 19%, IPH 17%, CF 10% and at least COPD with 2%. In the period of 2008 to 2010 63 patients were listed with high urgency status primarily patients with CF, IPH and IPF. 51 were transplanted, 7 died before transplantation. Conclusions: Patients with IPF, IPH and CF have the highest mortality on the waiting list or have to be transplanted from the intensive care unit (HU-status). Patients with these diagnoses should be evaluated and listed earlier.

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P055 Quantification of free-circulating DNA in plasma of NSCLC patients A. Szpechcinski1, K. Maszkowska-Kopij2, W. Kupis3, E. Puscinska4, J. Zaleska5, E. Radzikowska5, T. Orlowski3, P. Sliwinski6, K. Roszkowski-Sliz5, J. Chorostowska-Wynimko1 1

Laboratory of Molecular Diagnostics and Immunology, Warsaw, Poland 2 Outpatient Clinic, Warsaw, Poland 3 Department of Thoracic Surgery, Warsaw, Poland 4 II Department of Lung Diseases, Warsaw, Poland 5 III Department of Lung Diseases, Warsaw, Poland 6 Department of Diagnosis and Treatment of Respiratory Failure, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland

Background: The increased amount of free-circulating DNA is present in blood of non-small cell lung cancer (NSCLC) patients, most likely due to up-regulated cell death processes. We believe that dynamics of plasma DNA changes monitored throughout treatment and follow-up period might prove useful for assessment of therapy effectiveness in NSCLC. Methods: We analyzed plasma DNA concentrations in 50 NSCLC patients prior and following the radical treatment (stage I-IIIA) or chemotherapy (IIIB), using qPCR method. In order to determine a potential contribution of chronic respiratory inflammation to this phenomenon the levels of plasma DNA were analyzed in 30 COPD, 30 sarcoidosis and 30 persistent asthma patients as well. Results: Only resectable NSCLC (12.1 ng/ml), but not advanced NSCLC (4.4 ng/ml) group, showed significantly higher mean plasma DNA concentration with respect to patients with chronic respiratory inflammation (3.9 ng/ml) and 30 healthy controls (2.8 ng/ml; p < 0.001). Furthermore, a drastic increase in plasma DNA levels up to mean 68.74 ng/ml was observed a week after primary tumor resection or 24/48 hours after chemotherapy administration (16.4 ng/ml). Most resected NSCLC patients with no disease recurrence during 6–12 month follow-up demonstrated reduced plasma DNA levels (2.4 ng/ ml) with respect to their presurgical values. Conclusions: Increased plasma DNA level in NSCLC patients is due to the cancer but not chronic inflammatory process. Drastic raise in plasma DNA levels observed after radical therapy are most likely due to the surgical trauma. Importantly, a trend towards reduction of free-circulating DNA concentration was observed in relapse-free patients. The effect of chemotherapy on plasma DNA in NSCLC IIIB patients is currently analyzed.

P056 Iron deficiency in non-anemic patients with chronic obstructive pulmonary disease M. Urban1, O. C. Burghuber1, W. Hübl2, G.-C. Funk1 1

Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria 2 Department of Laboratory Medicine, Wilhelminenspital, Vienna, Austria

Background: Iron deficiency contributes to reduced exercise capacity in patients with heart failure. The repletion of iron improves cognitive, symptomatic, and exercise performance in these patients independent of hemoglobin. COPD shares many functional features of heart failure. Thus iron deficiency could be a potential therapeutic target in COPD. Objectives: The aim of this study was to determine the prevalence of iron deficiency in non-anemic patients with COPD. © Springer-Verlag

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P057 Structural and biochemical characteristics of subclinical atherosclerosis in COPD M. Urban1, L. Ay2, G.-C. Funk1, M. Wolzt3, O. C. Burghuber1, A. Valipour1 1

Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria 2 Department of Internal Medicine, Hospital Rudolfstiftung, Vienna, Austria 3 Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria

Background: Patients with COPD are at an increased risk of cardiovascular morbidity and mortality, however, the underlying mechanisms remain poorly defined. The present study investigated early markers of cardiovascular disease in patients with COPD and controls. Methods: The study sample consisted of 60 patients with stable COPD (mean ± SD age 64 ± 8 yrs, FEV1 41 ± 18% predicted, BMI 24 ± 4 kg/sqm) and 20 age, gender, and body-weight matched controls without airflow obstruction. Both patients and controls were free from traditional cardiovascular risk factors including hypertension, diabetes, or hyperlipidemia. Study participants underwent measurements of brachial artery intima-media thickness (bIMT) and circulating levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). Results: bIMT was significantly higher in patients with COPD than controls (0.37 ± 0.08 mm vs. 0.32 ± 0.06 mm; p = 0.007). There was a significant inverse relationship between bIMT and FEV1% predicted (r = -0.304; p < 0.002) within the complete study sample. We observed no significant differences in lnADMA levels between patients with COPD and controls (–0.68 ± 0.30 μmol/l vs. –0.57 ± 0.18 μMol/l; p = 0.057). However there was a significant positive relationship between bIMT and lnADMA levels in patients with COPD (r = 0.331; p = 0.013). Conclusions: This study provides evidence of both structural and biochemical characteristics of subclinical atherosclerosis in patients with COPD.

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P058 Insulin resistance may contribute to systemic vascular dysfunction in patients with COPD M. Urban1, L. Ay2, G.-C. Funk1, O. C. Burghuber1, P. Eickhoff3, M. Wolzt4, A. Valipour1 1

Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria 2 Department of Internal Medicine, Hospital Rudolfstiftung, Vienna, Austria 3 St. Anna Children’s Hospital, Vienna, Austria 4 Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

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Methods: Serum markers of iron status were measured in 53 stable non-anemic (hemoglobin > 12 g/l) COPD patients (53% males; mean age 64 ± 8 years, mean FEV1 predicted 41 ± 18%; GOLD stage II, III, and IV was 34%, 32%, and 34%, respectively). Iron deficiency was diagnosed when the serum ferritin level was either <100 μg/l or was between 100 and 299 μg/l with the transferrin saturation <20%. Results: The serum ferritin level was <100 μg/l in 20 patients. The serum ferritin level was between 100 and 299 μg/l and transferrin saturation was <20% in 6 patients. Thus iron deficiency was present in 49% of the patients. The median soluble transferrin receptor to log_ ferritin ratio was higher in patients with iron deficiency (1.7, 1.0 to 1.4) compared to patients without (1.7, 1.4 to 2.0), p < 0.001. Conclusions: Iron deficiency is present in half of the patients with stable COPD. A randomized, placebo-controlled trial should clarify whether repletion of iron stores improves functional performance in COPD patients with iron deficiency.

Background: Patients with chronic obstructive pulmonary disease (COPD) are at an increased cardiovascular risk; however, the underlying mechanisms for this relationship are ill defined. Altered glucose metabolism may increase cardiovascular risk via impaired endothelial function. We conducted a longitudinal study to assess the interrelationship between systemic vascular function, glucose metabolism, and lung function in patients with COPD. Methods: 18 non-smoking patients with stable moderate to severe COPD (67% male; median [1st to 3rd quartiles] FEV1 % predicted 38% [28–55%]; body mass index 26 kg/m2 [24–28 kg/m2]) free from cardiovascular risk factors were studied. Systemic vascular function was assessed by means of flow mediated dilation technique of the brachial artery. Laboratory measurements included fasting blood glucose levels, circulating concentrations of insulin, C-reactive protein, and fibrinogen. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was determined. Measurements were performed at baseline and were repeated after twelve months. Results: Flow-mediated dilation significantly decreased from 13.5% [11–15%] at baseline to 9.8% [6–12%] (p = 0.002) at the follow-up visit, whereas both fasting blood glucose concentrations increased from 94 mg/dl [86–103 mg/dl] to 102 mg/dl [94–111 mg/dl] (p = 0.027) and HOMA-IR from 1.2 [0.8–2.1] to 1.7 [1.2–3.0] (p = 0.023). There was a significant relationship between changes in endothelial function with changes in fasting serum glucose (r = –0.483, p = 0.009), HOMA-IR (r = –0.441, p = 0.019), and FEV1 (r = 0.336, p = 0.05). Conclusions: Altered glucose metabolism may be associated with progression of endothelial dysfunction and thus increased cardiovascular risk in patients with COPD.

P059 Asthma treatment with beclomethasone/formoterol: disease control and patient-reported outcomes N. Vetter1, H. Hinterberger2 1

Otto Wagner Spital, Vienna, Austria Practice for Pneumology, Vienna, Austria

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Background: To evaluate data regarding asthma control, tolerability and compliance with beclomethasone/formoterol (Foster®) under real-life conditions, a prospective, multicenter, non-interventional study (NIS) was conducted in pneumologic and general practices all over Austria in 2010. Methods: Treatment consisted of 100 μg extra-fine beclomethasone/6 μg formoterol (BDP/F) of 1–2 inhalations twice daily over a 12-week period. Overall 237 patients were enrolled. Asthma control was examined before and after the observation period corresponding to a 3-point scale (controlled/partly controlled/non controlled). Pulmonary function (PEF, FEV1, FVC) was measured at the beginning, in week 4–8 and 12 of the therapy. The number of asthma attacks (day and night time) as well as the severity of asthma ÖGP Jahrestagung 2011

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symptoms (dyspnoea, wheezing, rapid breathing and cough) and exacerbations were assessed. In addition a patient-check (GINA Guidelines 2009) was performed to gain important asthmarelevant data. Results: After 12-week treatment with BDP/F 81.4% of patient population showed good asthma control. Significant improvement in pulmonary function (PEF, FEV1, FVC) was observed in all patients. The number of asthma attacks was reduced from 1.3 weekly to 0.1 weekly at day time (1.0 to 0.1 weekly at night time). The median severity of observed asthma symptoms as well as exacerbations decreased, latter with the main improvement within the first weeks of treatment. All results which were collected with the patient-check showed a significant improvement all over the 12 treatment weeks. Worth to be mentioned is the significant decrease of the nocturnal awakening (65% to 10.2%; p > 0.01) under BDP/F. No adverse effects were reported during the whole observation period. Conclusions: The results of this NIS show that Beclomethasone/ Formoterol fixcombination enhances effectively patients’ asthma control by decreasing asthma attacks, symptoms and exacerbations and by improving lung function (PEF, FEV1, FVC) and patient reported outcomes.

P060 Efficacy of roflumilast in patients receiving concomitant treatments for chronic obstructive pulmonary disease over 12 months R. Voves1, W. Pohl2, H. Jamnig3, C. Schmid-Wirlitsch4, I. Moll-Schüler5, N. A. Hanania6 1

Pneumology practice, Feldbach, Austria Pneumology practice, Gänserndorf, Austria 3 Department of Pneumology, Hospital Natters, Austria 4 Department of Medicine, Nycomed, Konstanz, Germany 5 Department of Medicine, Nycomed, Vienna, Austria 6 Baylor College Medicine, Houston, USA 2

Background: The oral, selective phosphodiesterase 4 inhibitor roflumilast improves lung function and reduces exacerbations in patients with severe-to-very severe chronic obstructive pulmonary disease (COPD) and improves lung function and other clinical outcomes in patients with moderate-to-severe COPD who are receiving concomitant long-acting inhaled bronchodilators. We analyzed data from two 12-month studies that investigated the effect of roflumilast on the rate of moderate or severe exacerbations in patients with severe-to-very severe COPD. Our aim was to investigate whether the effect of roflumilast is influenced by concomitant maintenance treatment with bronchodilators (long-acting beta2 agonist [LABA] or short-acting muscarinic antagonist [SAMA]) or by treatment with inhaled corticosteroid (ICS) prior to randomization. Methods: M2-124 and M2-125 were identically designed, doubleblind, randomized studies. Patients with severe-to-very severe COPD associated with cough and sputum production (chronic bronchitis) and a history of exacerbations were randomly assigned to either roflumilast 500 μg once daily (n = 1537) or placebo once daily (n = 1554) for 12 months. Concomitant LABA and regular SAMA use were allowed in all groups, but ICS was discontinued at randomization. Results: LABAs were used by 749 (49%) patients in the roflumilast group and 793 (51%) patients in the placebo group in the pooled data set. The corresponding numbers for regular SAMA use were 537 (35%) and 569 (37%), respectively; 650 (42%) and 657 (42%), respectively, were treated with ICS prior to randomization. The change in exacerbation rate with roflumilast vs placebo was –16.9% (95% confidence interval [CI] –25, –8) in the overall population and was not influenced by LABA use, with changes in exacerbation rates of –20.7% (95% CI –31, –9) and –14.6% (95% CI –26, –1) in the subgroups of LABA users and non-LABA users, respectively. The corresponding changes in ex-

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acerbation rates for concomitant SAMA use vs non-SAMA use were –13.1% (95% CI –24, –1) and –19.8% (95% CI –30, –8), respectively. In patients with and without prior ICS treatment, exacerbations changed by –19.3% (95% CI –30, –7) and –16.8% (95% CI –28, –4), respectively, with roflumilast vs placebo. Conclusions: In two 12-month studies, roflumilast reduced the frequency of moderate and severe exacerbations independent of concomitant maintenance bronchodilator treatment (LABA or SAMA), or treatment with ICS prior to randomization.

P061 Triple Endoscopy (TRES) with flexible bronchoscopes – feasible or not feasible W. Weinwurm, R. Kropfmüller, W. Duller, H. Schinko Department of Pneumology, General Hospital Linz, Linz, Austria

Background: Triple or panendoscopy evaluates larynx, trachea and proximal oesophagus in cancer of the larynx and thyroid gland. Trachea, mainstem bronchi, and esophagus lay next to each other and so do their cancers, causing stenosis. EBUS can be used for transesophageal fine needle aspirations as well. GER is associated with chronic cough and explored by esophago-gastroscopy (OGD). Even the stomach is in the reach of flexible bronchoscopes. Aim of the study: Lack of information about simultaneous broncho-esophagoscopy let us explore the feasibility and (dis)advantages of TRES using flexible bronchoscopes. Methods: Olympus bronchoscopes were used for TRES in 16 patients (7 F, 9 M – age mean ± 2SD 66 ± 13 years). Bronchoscopy was immediately followed by esophago-gastric inspection under local anaesthesia via nasal or oral route. Results: 17 broncho- esophago-gastroscopies (TRES) were carried out with the same bronchoscope adjusted by an inserted catheter for insufflation of pressurized air. No adverse event occurred.

P062 Hyperinflation associated with COPD is associated with impaired cardiac function and spontaneous baroreceptor sensitivity V. Wieser, R. Breyer-Kohansal, I. Firlinger, I. Franke, O. C. Burghuber, A. Valipour Department of Respiratory and Critical Care Medicine, LudwigBoltzmann-Institute for COPD, Otto-Wagner-Spital, Vienna, Austria

Background: There is evidence of impaired biventricular preload associated with hyperinflation in patients with COPD. A reduction in cardiac filling pressures may result in unloading of baroreceptors. We therefore investigated baroreceptor sensitivity, an independent predictor of cardiovascular morbidity and mortality, in patients with COPD and controls. Methods: 25 patients with COPD free from clinical cardiovascular disease (age 58 ± 7yrs, FEV1 28 ± 7%, TLC 137 ± 20%) and 12 age, gender, and body-weight matched controls without airflow obstruction were studied. Participants underwent comprehensive hemodynamic measurements and assessment of arterial baroreflex modulation of heart rate during resting conditions and mental stress testing. Results: Patients with COPD had significantly lower stroke index (p < 0.001), however, significantly higher heart rate (p < 0.001) and higher total peripheral resistance compared with controls (p = 0.05). The mean slope of spontaneous baroreceptor sequences was significantly lower in patients with COPD than controls during both resting conditions (p < 0.01) and mental stress testing (p = 0.03). There was a © Springer-Verlag

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abstracts

P063 Loss of receptors CD27 and CCR7 on Mycobacterium tuberculosis-specific T cells at the site of infection marks active tuberculosis S. Winkler1, J. Nemeth1, C. Müller1, R. Rumetshofer2, A. Valipour2, O. C. Burghuber2, H.-M. Winkler1 1

Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria 2 Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria

Background: Enumeration of Mycobacterium tuberculosis (MTB)specific, interferon (IFN)-γ expressing CD4+ T cells at the site of infection accurately identifies active tuberculosis (TB). To find additional markers for immune-diagnosis, T cell differentiation markers CD27 and CCR7 were studied on T cells from both peripheral blood and the site of infection in patients with suspected active TB. Methods: 13 patients with lymphocytic exudates (10 pleural, 2 ascites, 1 joint fluid) suspicious for TB were prospectively studied. Flow cytometry for intracellular detection of IFN-γ in CD4+ T cells as well as surface receptor staining (CD27, CCR and CD45RO) were performed after overnight stimulation of mononuclear cells from peripheral blood and the site of disease with early secretory antigenic target (ESAT)-6. Results: In 6 patients active TB was confirmed. As expected, TB patients were shown to enrich MTB-specific, IFN-γ expressing CD4+ T cells at the site of infection when compared to blood (p < 0.05). No enrichment of MTB-specific T cells was found in the 7 patients with non-TB disease. Both CD27 and CCR7 significantly decreased on CD4+ T cells in TB patients (CD27, median: blood 94.1%, site of infection 63.6%; CCR7, median: blood 79.9%, site of infection 43.9%; p < 0.05, respectively). This finding was even more striking within the memory (CD4+/CD45RO+) subset. In contrast, in the non-TB group even an increase of CD27 on the CD4+ and CD4+/CD45RO+ subset in the exudates was noted (p < 0.05). Conclusions: Active TB can not only be diagnosed by the enumeration of MTB-specific, IFN-γ expressing T cells at the site of infection additional signatures such as the decrease of T cell associated CD27 and CCR7 hold promise as new markers for immune-diagnosis of TB.

P064 Down-regulation of the pro-apoptotic BCL-2 family member protein Bax by hypoxia may contribute to hypoxia-induced chemotherapy resistance in A549 lung cancer cells* C. Wohlkoenig1,3, K. Leithner1,3, A. Hrzenjak1,3, A. Olschewski2,3, H. Olschewski1,3 1

Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 2 Experimental Anesthesiology, Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria 3 Lung Cell Laboratory, Medical University of Graz, Graz, Austria

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Background: Hypoxia is known to play a role in chemoresistance and tumor progression and is frequently found in solid tumors. It is widely accepted that the hypoxia-inducible factor 1-alpha (HIF-1a) is a key-regulator of hypoxia-induced chemotherapy resistance but downstream mechanisms are not entirely known. We wanted to investigate if regulation of pro- or antiapoptotic proteins is involved in hypoxia-induced chemoresistance. Methods: A 549 cells were treated with cisplatin under normoxia and hypoxia (1% O2). Viability was assayed with electronic pulse area analysis (CASY®). Apoptosis was assessed via flow cytometry (PhiPhiLux®) and TUNEL-assay. Expression of HIF-1a was detected with western blot. Regulation of members of the BCL-2 family was assessed with qRT-PCR and verified with western blot. Results: Cisplatin induced concentration-dependent apoptosis in A549 cells (p < 0.001). Hypoxia almost completely abolished this effect (p < 0.001). These results were confirmed using the PhiPhiLux® assay and 32 μM cisplatin (62.1 ± 3.7% apoptosis rate in normoxia vs. 21.7 ± 1.2% in hypoxia; p = 0.0005). HIF-1a was upregulated in hypoxia time-dependently. Bax mRNA was significantly downregulated in hypoxic A549 cells (p < 0.01) whereas the corresponding anti-apoptotic protein Bcl-2 was not regulated by hypoxia, which was verified by western blot (Fig. 1). Conclusions: Cisplatin-resistance in hypoxic A549 cells is due to a direct inhibition of apoptosis and is associated with a down-regulation of Bax.

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significant relationship between stroke index with FEV1% predicted (r = 0.588, p < 0.001), total lung capacity (r = –0.391, p = 0.01) and RV/ TLC ratio (r = –0.491, p = 0.002). Similar associations were observed between baroreceptor sensitivity and markers of airflow obstruction and hyperinflation. Conclusions: Impaired cardiac filling in patients with COPD may be related to hyperinflation. Our findings furthermore indicate a link between baroreceptor function and increased lung volumes in COPD.

Fig. 1.

P065 Efficacy of Roflumilast when used with Concomitant ICS from the OPUS/RATIO Studies J. Würtz1, W. Pohl2, J. Dierlamm3, I. Moll-Schüler4, S. I. Rennard5 1

Pneumology practice, Linz, Austria Pneumology practice Gänserndorf, Austria 3 Department of Medicine, Nycomed, Konstanz, Germany 4 Department of Medicine, Nycomed, Vienna, Austria 5 University Nebraska Medical Center, Omaha, USA 2

Background: Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, reduces exacerbation rates and improves lung function in COPD patients. Inhaled corticosteroids (ICS) are commonly used to manage COPD, particularly among individuals at risk for exacerbations. This post-hoc analysis studied the effects of roflumilast vs placebo in COPD patients with or without concomitant ICS treatment. Methods: This pooled, post-hoc analysis of two replicate, randomized, double-blind, placebo-controlled studies (M2-111 and M2-112) compared oral roflumilast 500 μg QD with placebo over 52 weeks. Stable dose ICS use was permitted. Lung function outcomes and exacerbation rates were examined. Results: Of 2686 randomized patients, 1622 used concomitant ICS (n = 809 roflumilast and n = 813 placebo) and 1064 did not (n = 518 and n = 546, respectively). Among patients receiving concomitant ICS, 65% ÖGP Jahrestagung 2011

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had severe disease vs 68% without ICS; 28% with ICS vs 21% without ICS had very severe COPD. For the overall population, pre-bronchodilator and post-bronchodilator FEV1 improved (mean ± SE) with roflumilast compared to placebo by 51 ± 7 mL (p < 0.0001) and 53 ± 8 mL (p < 0.0001) and exacerbations were decreased by 14.3% (p = 0.026). With concomitant ICS use, pre-bronchodilator FEV1 (53 ± 9 mL; p < 0.0001) and post-bronchodilator FEV1 (54 ± 9 mL; p < 0.0001) improved with roflumilast vs placebo. Without concomitant ICS use, pre-bronchodilator FEV1 (49 ± 13 mL; p = 0.0002) and post-bronchodilator FEV1 (53 ± 13 mL; p < 0.0001) improved with roflumilast compared to placebo. Roflumilast + ICS reduced the moderate/severe exacerbation rate vs placebo + ICS (rate ratio 0.72 vs 0.89; –18.8%; p = 0.014); the percentage of patients experiencing an exacerbation was numerically lower with roflumilast + ICS vs placebo + ICS (36% vs 42%). Without concomitant ICS, the exacerbation rate (roflumilast 0.42; placebo 0.46; –7.7%; p = 0.55) was not affected by roflumilast; the percentage of patients experiencing an exacerbation was numerically lower with roflumilast vs placebo (23% vs 27%). Conclusions: Roflumilast was effective at improving lung function independent of concomitant ICS use and reduced exacerbation rates in patients taking concomitant ICS, who may be recognized by clinicians as more likely to experience exacerbations. Roflumilast improves lung function, reduces the rate of exacerbations, and can have an additive effect in patients receiving concomitant ICS.

P066 High chemokine levels are present in PEA tissue of CTEPH patients D. Zabini1, Z. Bálint2, A. Heinemann3, P. Nierlich4, I. Lang5, A. Olschewski1,2 1

Department of Anaesthesia and Intensive Care Medicine, Medical University of Graz, Graz, Austria 2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 3 Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria 4 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 5 Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

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Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and late possible consequence of venous thromboembolism. The first pathogenic components of CTEPH are the primary obstruction of the central pulmonary arteries by accumulation of thrombotic material and the second is severe pulmonary vascular remodeling. In the surgical tissue from CTEPH patients, the formation of vessels is often detected. How these vessels are formed and from which cell source, however is not well known yet. A bacterial infection might be a major determinant of thrombosis, fibrosis and the remodelling events, where chemokines might play a critical role in angiogenesis. Our aim was to check the presence of inflammatory markers and receptors, which play a role in promoting angiogenesis in the PEA material and their receptors, elucidating the mechanism of angiogenesis in CTEPH clots. Methods: Flow-cytometric analysis: The PEA samples were put in endothelial cell basal medium supplemented with 5% FCS and antibiotics. The tissue was cut into small pieces and incubated for 18h at 37°C. The supernatant was collected and stored at -20°C; afterwards the tissue was briefly washed with Hepes buffer and lysed in 150 μl RIPA buffer with PhosphoStop and Protease Inhibitor Complex. The supernatant and the lysate were checked for inflammatory factors such as IL-8, RANTES, MIG, MCP-1, IP-10, IL-2, IL-4, IL-6, IL-10, TNF, IFN-g (Human Chemokine and Th1/Th2 Cytokine Kit). Immunohistochemistry: The PEA material was fixed in 3% formaldehyde for 24 h and embedded in paraffin blocks. Immunohistochemistry was performed on the 2 μm thick sliced paraffin tissue using primary antibodies for von Willebrand factor (Dako), or smαActin (Sigma) and goat-anti-rabbit-HRP secondary antibodies (Santa Cruz Biotechnologies) or goat-anti-mouse-HRP (Santa Cruz Biotechnologies) for double staining. For CD31 staining the DAB detection kit from R & D Systems was applied. IL6(1:200), IL8(1:250), CCR2(1:250), CXCR3(1:250) and CXCR2(1:100) (abcam) stainings were performed with the UltraVision LP Large Volume Detection System HRP-Polymer (Thermo Scientific). Results: In the CTEPH surgical material the presence of inflammatory markers such as IL6; IL8 and MCP-I were found. Beside these chemokines, their receptors were also present in the PEA tissue. Vessels formed in the CTEPH clots were detected and stained for vWF, smooth muscle alpha-actin and CD31. Conclusions: IL8 and its receptor are known to play a role in angiogenesis and chemotaxis, therefore it might attract the endothelial cells to the occluded region of the pulmonary artery.

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