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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

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wienerklinischewochenschriftThe Central European Journal of Medicine

123. Jahrgang 2011 Wien Klin Wochenschr (2011) 123/17-18: A1-A34DOI 10.1007/s00508-011-0050-8© Springer-Verlag 2011

Jahrestagung 2011 der Österreichischen Gesellschaft für PneumologieAbstracts

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 AignerPrim. Univ.-Prof. Dr. Otto C. BurghuberUniv.-Prof. Dr. Ernst EberPrim. Dr. Peter ErrhaltOA Dr. Holger FlickPriv. Doz. Dr. Georg-Christian FunkOÄ Dr. Sylvia HartlDr. Peter A. HesseDr. Maximilian Johannes HochmairOA Dr. Hubert Karl KollerOA Dr. Klaus KirchbacherPrim. Univ.-Prof. Dr. Meinhard KneusslOA Dr. Gabor KovacsOÄ Dr. Angelika Kugi

Univ.-Prof. Dr. Horst OlschewskiOÄ Dr. Birgitta PlakolmPrim. Univ.-Prof. Dr. Josef RiedlerPrim. Univ.-Prof. Dr. Peter SchenkPrim. Dr. Herwig A. E. SchinkoPT MSc Ingrid SchmidtDr. Nika Skoro-SajerPrim. Prof. Dr. Michael StudnickaPrim. Dr. Martin TrinkerPriv. Doz. OA. Dr. Arschang ValipourUniv. Doz. Dr. Felix WantkeDGKS Rita WardyBMA Eva Zeitlhofer

abstracts

ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A3

ÖGP

F1

„Das gab’s in Österreich noch nie…“

R. Arnitz1, W. Purkarthofer1, G. Höchtl2, H. Popper3,B. Baumgartner1

1Abteilung für Pneumologie, LKH Vöcklabruck, Vöcklabruck, Österreich

2Institut für Klinische Pathologie, LKH Vöcklabruck, Vöcklabruck, Österreich

3Institut für Pathologie, Medizinische Universität Graz, Graz, Österreich

Wir präsentieren den Fall einer 53-jährigen Patientin, welche im

Februar 2011 aufgrund im Th orax-CT detektierter bilateraler Raum-

forderungen (rechter OL, linker UL) an unserer Abteilung aufgenom-

men 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 unauff ällig, aktiver Ni-

kotinabusus bestand nie, 10 Jahre war sie einer Passivrauchbelastung

ausgesetzt.

Im Routinelabor fi nden sich außer einer erhöhten BSG keinerlei

Auff älligkeiten, an Tumormarkern im Serum lediglich das CA19-9 ge-

ringfügig erhöht.

Es folgt die Bronchoskopie zu Histologiegewinnung, wobei die

feingewebliche Aufarbeitung der gewonnenen Proben ein Pleomor-

phes Karzinom bestehend aus einem Adenokarzinomanteil und

einem spindelzelligen Karzinom ergibt. Der Adenokarzinomanteil ist

aufgrund des Markerprofi ls 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.

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 häufi ge

Zuweisungsdiagnosen an Lungenfachärzte. Die entsprechenden

Ursachen fi nden sich jedoch nicht immer allein im kardiopulmona-

len Bereich.

Ein 77-jähriger Patient wurde aufgrund zunehmender Belastungs-

dyspnoe und Hustenattacken zur weiterführenden Abklärung zuge-

wiesen. Die phasenweise produktiven Hustenanfälle traten teils

zeitlich mit der Nahrungsaufnahme zusammenhängend auf. Zusätz-

lich bestanden zehn Kilogramm Gewichtsverlust innerhalb des vor-

hergehenden Jahres.

Es präsentierte sich ein adipöser Patient mit arrhythmischer Herz-

aktion und mäßigen Beinödemen beidseits.

Die kardialen Untersuchungen zeigten eine de-novo Vorhoffl im-

merarrhythmie, eine Herzinsuffi zienz mit einer echokardiographisch

gemessenen Ejektionsfraktion von 45 % und eine schlecht kontrollier-

te arterielle Hypertonie.

Die pulmonale Abklärung ergab tagsüber ausgeglichene Blutgase

und eine mittelgradige kombinierte Ventilationsstörung mit Beto-

nung der kleinen Atemwege. Ursächlich hierfür waren radiologisch

darstellbare postentzündiche Lungenveränderungen sowie die Herz-

insuffi zienz. Die Schlafuntersuchung zeigte eine zentral-periodische

Schlafatemstörung mit gutem Ansprechen auf nächtliche Sauerstoff -

gabe.

Das Schluckaktröntgen ergab eine Raumforderung dorsal des

Hypopharynx mit gestörtem Kontrastmittelabfl uss. Eine HNO-ärztli-

che Untersuchung bestätigte eine Vorwölbung im Larynx. Die Hals-

Computertomographie zeigte bis zwei Zentimeter große, den

Hypopharynx und den Larynx dorsal imprimierende Spondylophy-

ten als Ursache für die Schluckstörung.

In Zusammenschau der Befunde hatten die Beschwerden unter-

schiedliche Gründe. Ursächlich für die Belastungsdyspnoe war die

kardiale Problematik. Kausal für den Husten waren – durch hochgra-

dige degenerative Halswirbelsäulenveränderungen bedingte –

Schluckstörungen, welche zu rezidivierenden Aspirationen führten.

Der Patient wurde neurochirurgisch vorgestellt, lehnte jedoch

eine angebotene operative Abtragung der Spondylophyten ab. Es er-

folgten eine kardiale Rekompensation, die Adaptierung der antihy-

pertensiven Th erapie sowie das Einleiten einer oralen Antikoagulation.

Eine nächtliche Sauerstoff therapie wurde verordnet.

Dieser Fall zeigt, dass besonders bei multimorbiden Patienten

zeitgleich auftretende Symptome verschiedenste Ursachen haben

können. Umso wichtiger erscheint hier eine interdisziplinäre Abklä-

rung mit besonderer Berücksichtigung fachfremder Diff erentialdiag-

nosen.

Weiters soll das Augenmerk auf ein in der pneumologischen Fach-

literatur unterrepräsentiertes Krankheitsbild gerichtet werden. Dege-

nerative Veränderungen der Halswirbelsäule können eine Vielzahl

respiratorischer Probleme bedingen, sind jedoch fast ausschließlich

Th ema HNO-ärztlicher oder orthopädischer Publikationen.

F3

Husten nach Kaffee und Kuchen – ein interdisziplinäres Rätselraten

J. Bilek1, G. Kühteub1, W. Klepetko2, P. Schnider1,3, P. Schenk1

1Landesklinikum Thermenregion Hochegg, Grimmenstein, Österreich2Univ.-Klinik für Chirurgie, Medizinische Universität Wien, Wien, Österreich

3Abteilung für Neurologie, Landesklinikum Wr. Neustadt, Wiener Neustadt, Österreich

Bei Frau P., 63 Jahre, wurde im Juni 2010 eine Appendektomie

durchgeführt. Anschließend kam es zu einem komplizierten post-

operativem Verlauf mit Peritonitis und Adnexitis, der sich durch eine

Pseudomonas aeruginosa Sepsis aggravierte und einen sechs-mona-

tigen Aufenthalt auf der Intensivstation nach sich zog. Nach an-

schliessendem Weaning und Dekanülierung kam es zu einer solch

ausgeprägten Dysphagie, dass sie mit einer PEG-Sonde versorgt wer-

den musste. Eine Schluckdiagnostik ergab einen unauff älligen Be-

fund.

Fall des Jahres 2011

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA4

ÖGP

Th erapeutisch begannen wir mit einer systemischen Cortisongabe.

In den nachfolgenden Kontrolluntersuchungen war die Patientin

klinisch stabil. Die Th orax-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 unauff ällig, 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: auff älliges 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: uncharak-

teristischer 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 Granu-

lationsgewebspolypen (Abb. 3).

Nach Transferierung zur Neurorehabilitation wegen Critical Ill-

ness Polyneuropathie und Abklärung der Schluckstörung erlitt die

Patientin eine schwere Pneumonie mit Pseudomonas aeruginosa

und E. Coli Isolation. Eine abermalige Videofl uoroskopie ergab wie-

der 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 Dys-

phagie. Also lag ein Zusammenhang mit der Tracheostomienarbe

und eventuellen Strikturen nahe. Die Abklärung an der HNO Abtei-

lung bestätigte zwar die Aspiration sämtlicher Konsistenzen, eine

Ursache im Narbenbereich des Stoma wurde aber ausgeschlossen. In

einer Bronchoskopie konnte der Verdacht auf eine ösophagotrachea-

le Fistel verifi ziert 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

Th orax 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 be-

schriebenen Rundherde durchleutungsgezielt einzustellen, aufgrund

der geringen Größenausdehnung gelang dies jedoch nicht. Es wur-

den Probeexzisionen an der Hauptcarina und im linken Unterlappen

entnommen, beide lieferten unauff ällige Bronchialschleimhautan-

teile. Die brochoskopische Absaugung zeigte keinen Keimnachweis.

Auch mittels CT gezielte Feinnadelpunktion konnte keine Diagnose

gestellt werden.

Somit wurde die chirurgische Exzision eines Rundherdes ange-

strebt. Es erfolgte eine Minithorakotomie. Die Pathologie unseres

Hauses stellte die Verdachtsdiagnose Morbus Castleman – multizent-

rische Form. Dieser Befund wurde vom Institut für Pathologie der

Medizinischen Universität Graz bestätigt.

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

abstracts

ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A5

ÖGP

F6

Vaskulär bedingte pulmonale Infi ltrate bei einer Raucherin

M. Gulesserian¹, H. Koller¹, M. Huber², O. C. Burghuber¹

1I. Interne Lungenabteilung, Otto Wagner Spital, Wien, Österreich2Pathologisch-bakteriologisches Institut, Otto Wagner Spital, Wien, Österreich

Bei einer 53-jährigen Krankenschwester mit 30 pack-years wurde

auswärtig wegen seit Wochen bestehender Belastungsdyspnoe eine

Computertomographie des Th orax durchgeführt, welche beidseitige

zerfallende, fl eckförmige Infi ltrate 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 sauerstoff pfl ichtig.

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

Abb. 2. Sichelförmige Einengung der Trachea

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

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA6

ÖGP

Kurvatur des Magens entsprechend – sowie auch intrapulmonale

kleine, hypermetabole Läsionen darstellen (SUV unter 1,5).

Bei zunehmender Verschlechterung der respiratorischen Situa-

tion 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-Th erapie mit Imatinib.

Im Verlauf konnte im CT-Th orax einerseits eine Regressio, ande-

rerseits ein Neuauftreten von multiplen zerfallenden Rundherden

beobachtet werden.

Konkordant musste im PET eine neuerliche Progredienz der pul-

monalen Manifestationen (steigender SUV 2,7) zur Kenntnis genom-

men werden, der als Primum defi nierte Herd an der Magenkurvatur

kam nicht mehr zur Darstellung (interpretiert als teilweises Anspre-

chen auf die Th erapie). Die Th erapie mit Imatinib wurde somit bei-

behalten.

Im Verlauf der Erkrankung musste akzeptiert werden, dass keine

weitere Abklärung trotz weiterer Progressio der pulmonalen Rund-

herde möglich erschien. Die Patientin verstarb in der respiratorischen

Globalinsuffi zienz.

Im Obduktionsbefund erschienen die Rundherde makroskopisch

primär spezifi sch (ZN negativ), wurden letztlich jedoch als non

rezente Pulmonalembolien unterschiedlichsten Alters klassifi ziert.

Diese Diff erentialdiagnose 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

12. Interne Lungenabteilung, Otto Wagner Spital, Wien, Österreich2Institut für Pathologie, Otto Wagner Spital, Wien, Österreich3Institut für Radiologie, Otto Wagner Spital, Wien, Österreich

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

Th erapie.

Befunde: Labor: CRP 234 mg/l, Mykoplasmen-AK positive.

CT der Th oraxorgane: Links dorsobasal fi ndet sich endobronchial

eine ovaläre Konsolidierung mit etwa 6 : 3 cm Größe. Einzelne zufüh-

rende Bronchien zeigen deutliche Sekretretentionen.

Bronchoskopie: Links fi ndet sich im UL-Abgang ein kugeliger, gel-

blich-weißer weicher tumoröser Prozess, welcher das Ostium des UL-

Stammbronchus komplett obturiert.

Histologie: Man erkennt in den Gewebsanteilen abschnittsweise

Bronchusmucosa mit oberfl ächlich regulärem respiratorischen Epi-

thel mit angrenzenden Anteilen eines reifen Fettgewebes.

Verlauf: Die stationäre Aufnahme erfolgte aufgrund einer Myko-

plasmenpneumonie, welche mit Cefuroxim und Clarithromycin

behandelt wurden. Aufgrund der Anamnese wurde eine Computerto-

mographie des Th orax veranlasst, in welcher sich im posterobasalen UL

links endobronchial ein Tumor zeigte. Endoskopisch zeigte sich en-

doluminal ein gelblicher, oberfl ächlich glatter Tumor. Histologisch

wurde die Diagnose eines endobronchialen Lipoms gestellt, welches in

einer 2. Sitzung endoskopisch komplett reseziert wurde.

Zwei Wochen später musste die Patientin wegen akuter

Verschlechterung und respiratorischer Globalinsuffi zienz (pO2:

45 mmHg, pCO2: 58 mmHg, pH: 7,18) an unserer Intensivstation

aufgenommen und intubiert werden. Nativradiologisch zeigte sich

eine Zunahme der beidseitigen intrapulmonalen Konsolidierungsherde,

sodass eine breite antibiotische Th erapie etabliert wurde. Die

Histologie der Lingula- und Unterlappen-Biopsate, die mittels Video-

assistierter Th orakoskopie (VATS) gewonnen wurde, ergab eine

abszedierende nekrotisierende Pleuropneumonie mit intravasalen

Th rombenbildungen. Aufgrund des Verteilungsmuster der pulmonalen

Abszedierungen und des Th rombennachweises wurde unter Annahme

eines septisch-embolischen Geschehens eine transösophagale

Echokardiographie (TEE) durchgeführt. Diese zeigte eine an der

Trikuspitalklappe fl otierende 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

Th erapie entsprechend modifi ziert. 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 Infi ltrate, die Echokardiographie zeigte eine

Besserung. Der Intensivaufenthalt wurde in weiterer Folge durch eine

Critical-illness Neuro- bzw. Myopathie sowie durch einen septisch-

embolisch 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

Sauerstoffi nsuffl ation auf unsere Normalstation übernommen werden.

Nach 3 Monaten konnte die Patientin Rollator-mobil mit 2 Liter

Langzeitsauerstoff therapie an ein Rehabilitationszentrum transferiert

werden.

Im 3-monatigen Verlauf zeigte die Computertomographie des

Th orax eine deutliche Regredienz der beidseitigen pulmonalen Ver-

änderungen, die Echokardiographiekontrolle war zu diesem Zeit-

punkt unauff ällig.

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 ge-

stellt.

Als Zufallsbefund fand sich – bioptisch verifi ziert – ein gastrointes-

tinaler Stromatumor (GIST) des Magens. Nachdem es sich histolo-

gisch um keinen invasiv wachsenden Tumor handelte, stellte dies

primär keine Kontraindikation zur Transplantation dar.

In Folge zeigten sich im Th orax-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 hyper-

metaboler Herd im Oberbauch links – dem Primum an der kleinen

abstracts

ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A7

ÖGP

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 Eintreff en 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 Th erapie.

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 unauff ällig. Im

Labor fi el einzig eine minimale Hypoproteinämie (Totalprotein 6,2 g/

dl) auf, welche laut Patientin schon aus früheren Routine-

Laborkontrollen bekannt war. Lungenfunktionell bestand keine

Einschränkung.

Radiologie: Das Th orax-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. Auff allend 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, fi brös 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 häufi gsten 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 IgM-

Spiegeln. Somit konnte, nach Ausschluss anderer Ursachen, die

Diagnose einer LIP im Rahmen einer CVID (Common variable

immunodefi ciency) 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.

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 %.

Häufi ger fi nden sich diese Tumore in den größeren Atemwegen und

mit 66 % rechtsseitig. Sie sind farblich gelblich bis weiß-gräulich mit

glatter Oberfl äche. Symptome können persistierender Husten, Dysp-

noe, Hämoptysen sowie rezidivierende Pneumonien sein. Die zuver-

lässigste Diagnosemethode ist die Bronchoskopie, die Th erapie 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 er-

möglicht bzw. persistierende Lungenschäden (Atelektasen, Bron-

chiektasien) entstanden sind. Im Fall unserer Patientin war dies jedoch

nicht notwendig, eine Kontroll-CT ist für Okt. 2011 vorgesehen.

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 Angio-

CT eine Lungenembolie nachzuweisen ist, aber dichte Lungeninfi ltrate,

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 fi brinöse Bronchitis.

Atemfunktionell mäßiggradige kombinierte restriktiv-obstruktive

Ventilations- mit Oxigenations- und volumsdominierter

Diff usionsstörung. 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 Th erapie mit Prednisolon, Unasyn®

und Anaerobex®, später Tazonam®. Bei zögerlicher Besserung ambulante

Fortsetzung der Antibiose und Kortikoidtherapie.

Anfang Juli Normalisierung der CRP und Aufl ockerung der

pulmonalen Infi ltrate. 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

Lymphozyteninfi ltration. 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

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA8

ÖGP

weniger als 1 % aller Lungentumore aus, können sich aber klinisch

und radiologisch wie maligne Tumore präsentieren und sind häufi g

erst postoperativ eindeutig zu diagnostizieren. Dieser Fall mit

Ansprechen auf intravenöse Immunglobuline erweitert die seltenen

Berichte über Th erapieoptionen für unresezierbare Pseudotumoren.

F13

Pulmonale Infektion mit M. szulgai – Fallbericht eines seltenen Pathogens

R. Mikes1, J. M. Kern2, V. Maaß2, R. Hartl3, M. Maaß2, M. Studnicka1

1Universitätsklinik für Pneumologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich

2Institut für Medizinische Mikrobiologie, Hygiene und Infektiologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich

3Institut 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 Th orax-Röntgen zeigten sich ausgedehnte

postspezifi sche Veränderungen beidseits oberfeldbetont sowie eine

Kranialraff ung 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 Th erapie mit Isoniazid, Rifampicin, Ethambutol und

Pyrazinamid.

Die CVID ist charakterisiert durch rezidivierende Infekte,

Splenomegalie, gastrointestinale Beschwerden und progrediente

pulmonale Veränderungen (Bronchiektasien, lymphozytäre

interstitielle Infi ltrate und granulomatöse Veränderungen).

Prognostisch bedeutsam sind die pulmonalen Veränderungen, welche

einzig durch IVIG-Substitution positiv beeinfl usst werden können.

F12

Mediastinale Raumforderung bei einer Patientin mit Z.n. Mammakarzinom

J. Löffl er-Ragg1, J. Bodner2, M. Freund3, M. Steurer4, B. Zelger5, C. M. Kähler1

1Universitätsklinik für Innere Medizin I, Department Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Österreich

2Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie, Department Operative Medizin, Medizinische Universität Innsbruck, Innsbruck, Österreich

3Department Radiologie, Medizinische Universität Innsbruck, Innsbruck, Österreich

4Universitätsklinik für Innere Medizin V, Department Innere Medizin, Medizinische Universität Innsbruck, Innsbruck, Österreich

5Institut für Pathologie, Medizinische Universität Innsbruck, Innsbruck, Österreich

Wir berichten über eine 48-jährige Frau mit Brustkrebsanamnese,

die wegen zunehmender Atemnot, Fieber, trockenem Husten und in-

terskapulären 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-gesteu-

erte Biopsie dieses Tumors im Bereich zwischen viszeraler Pleura und

dem Lungenoberlappen rechts (Abb. 3) ergab keinen Malignitäshin-

weis, zeigte jedoch eine ausgeprägte infl ammatorische Gewebsreak-

tion mit Schaumzellen. Nach einer initialen empirischen antibiotischen

Th erapie kam es vorübergehend zu Fieberfreiheit, Rückgang von Ent-

zündungszeichen und Reduktion der Tumorgröße. Im weiteren Ver-

lauf kam es zu einem Relaps und die Patientin war Th erapie-refraktär

auf weitere antibiotische Th erapie und auf einen Kortisonversuch. Mit

der Arbeitshypothese „Infl ammatorischer 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. Infl ammatorische Pseudotumoren machen

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

abstracts

ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A9

ÖGP

In den letzten Wochen der Schwangerschaft kam es zu zunehmen-

der Belastungsdyspnoe und rezidivierenden Hämoptysen. Die Ent-

bindung erfolgte problemlos. Danach kam es rasch zu einer

Verschlechterung der respiratorischen Situation. Die Patientin wurde

auf Grund multipler pulmonaler Infi ltrate im Lungen-CT an unsere

Abteilung transferiert. Zu diesem Zeitpunkt besteht eine respiratori-

sche Insuffi zienz mit zunehmender Verschlechterung und Indikation

für nicht-invasive Beatmung. Initiale Th erapie mit Verdacht auf Vas-

kulitis und organisierende Pneumonie (Solu Dacortin und Antibiose)

Radiologie: Fleckig disseminierte Infi ltrate mit Hauptausprägung

in den Unterfeldern und nach apikal hin abnehmend. Teilweise kon-

fl uierend. In der CT zeigen sich disseminierte atypische pneumoni-

sche Infi ltrate 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 Schleimhautver-

hältnisse, jedoch keine rezente Blutung, endoluminal kein Tumorhin-

weis. Histopathologisch kein schlüssiger Befund.

Ultraschallgezielten Stanzbiopsie: Der Befund entspricht einem

großzelligen pleomorphen Beta-HCG produzierenden Karzinom,

Chorionkarzinom.

CT-Abdomen: Hämangiom rechter Leberlappen, keine freie intra-

abdominelle Flüssigkeit. Uterus deutlich vergrößert mit Sekret im Ca-

vum beim Z. n. Partum. Das rechte Ovar weist mehrere bis zu 2,5 cm

im DM haltende Zysten auf.

Endgültige Diagnose: Chorionkarzinom (Schwangerschaft-asso-

ziiert).

FIGO-Klassifi kation: Stad. II c, Prognosekriterien: high risk.

Zusammenfassung: 30-jährige Patientin kommt postpartal mit

Infi ltraten, respiratorischer Insuffi zienz und Hämoptysen. Nach der

Abklärung zeigte sich ein Chorionkarzinom mit multiplen intrapul-

monalen Metastasen. Noch unter nicht-invasiver Beatmung wurde

eine Chemotherapie nach dem EMA/CO Schema eingeleitet.

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 infl uenza 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 in-

fection of H1N1 and respiratory syncytial virus (RSV). Th e patient was

admitted to the hospital with infl uenza symptoms extending over

several weeks. H1N1 testing was positive at admission. Th e disease

followed a rapidly progressive course requiring mechanical ventila-

tion and aggressive medical treatment. However, the respiratory situ-

ation 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 there-

fore 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

In drei konsekutiven Sputumkulturen zeigte sich jedoch nach 4

Wochen ein Wachstum atypischer Mykobakterien. Die

molekularbiologische Speziesidentifi zierung mittels Gensonde

(GenoType Mycobacterium AS, Hain Lifesciences) ergab M. szulgai.

Entsprechend der Resistenzbestimmung (Löwenstein-Jensen-

Medium) wurde schließlich die eingeleitete Th erapie 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. Radiografi sch konnte bei einer 2-Mo-

nats-Kontrolle jedoch noch keine wesentliche Befundänderung er-

kannt werden.

F14

Ein Holländer in Salzburg – Lunge, Lacke und Snowboards

F. Oberascher1, I. Stelzmüller1, G. Hutarew2, M. Studnicka1

1Universitätsklinik für Pneumologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich

2Institut 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 berufl ichen Gründen nach Österreich

kam, arbeitet seit einigen Jahren als Lackierer ohne ausreichende

Schutzmaßnahmen in einer Schifabrik.

Bei der Aufnahme waren BGA und Lungenfunktion unauff ällig.

CT: Disseminierte Milchglastrübung aller Lappensegmente mit

fl eckförmigen, kleinnodulären Infi ltraten 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 Th erapie bereits

klinische und radiologische Befundbesserung, in der Lungenfunktion

persistiert eine geringfügige Diff usionsstörung.

Die CT-morphologischen und histologischen Veränderungen

erhärten den Verdacht auf eine akut toxische Alveolitis nach

jahrelanger inhalativer Exposition gegenüber Inhaltsstoff en 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 Infi ltrate und Hämoptysen nach Entbindung

U. Radda1, T. Jaritz1, H. Martinz², E. Isak³, C. Geltner1

1Abteilung für Pulmologie, Klinikum Klagenfurt, Klagenfurt, Österreich2Institut für Pathologie, Klinikum Klagenfurt, Klagenfurt, Österreich31. Medizinische Abteilung (Onkologie), Klinikum Klagenfurt, Klagenfurt, Österreich

Anamnese: 33-jährige Patientin, 2. Schwangerschaft, 1. Schwanger-

schaft unkompliziert. Spontangeburt in der 38. plus 5d SSW (Knabe).

Postpartal verstärkter Husten und Schmerzen im Rippenbereich.

Keine pulmonale Vorerkrankungen, keine Begleiterkrankungen.

Nichtraucherin.

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA10

ÖGP

IGF II fähig sind. Die Prognose ist günstig, Rezidive sind selten v. a. bei

radikaler Tumorresektion. Maligne Transformation ist möglich.

Literatur1. Briselli M, Mark EJ, Dickersin GR. Solitary fi brous 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 fi brous tumors of the pleura. Chirurg 1999;70:949–52.

1519 - 1735 (MW:1643)

Abb. 1. Thorax-Röntgen bei Übernahme

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

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. Th e ECMO could be removed at the end of the LUTX.

Th e patient received a standard immunosuppressive therapy with

cortisone,tacrolimus and mycophenalate. For infection prophylaxis

intravenous administration of tazobactam, ganciclovir, cmv-antibod-

ies and caspofungin was used in combination with amphotericin-b

and gentamicin for inhalation. Th e patient left the ICU on the 24th

postoperative day and could be discharged from the hospital 2 weeks

later. Th e patient is now 3 months post LUTX and no recurrence of

the viral infection has occurred so far.

Th is 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.

F17

Interdisziplinäre Synkopenabklärung

O. Schindler1, A. Ederegger1, N. Neuböck2, H. Langenberger3, G.Wurzinger1

1Abteilung für Lungenkrankheiten, Landeskrankenhaus Hörgas-Enzenbach, Gratwein, Österreich

2Klinische Abteilung für Thorax-Chirurgie, Universitätsklinik für Chirurgie, Medizinische Universität Graz, Graz, Österreich

3Radiologieverbund 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 unauff ällig, der Blutdruck mit 175/

105 mmHg hypertensiv.

Laborchemisch auff ällig waren Hb 8,9 g/dl, Th rombozyten 448 g/l,

CRP 12,4 mg/l (Grenzwert 5 mg/l).

Eine Computertomographie des Schädels war unauff ällig.

Im Th oraxröntgen fi el 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 spindel-

zelliges Tumorgewebe – suspekte Anteile eines sarkomatoiden Me-

sothelioms – beschrieben.

Klinisch auff ällig waren rezidivierende Hypoglykämien (Glucose

bei Aufnahme 126 mg/dl, HbA1c 4,9 %), die kontinuierliche Glucose-

infusionen erforderten.

Zur weiteren Abklärung bei thorakalem Neoplasma wurde der Pa-

tient an unsere Fachabteilung transferiert. Ein schmaler linksseitiger

Pleuraerguss erwies sich als Transsudat, das zytologische Bild war

unspezifi sch.

Endobronchial war der linke Unterlappen subtotal duch Kom-

pression von außen stenosiert, die Zytologie zeigte unklare atypische

Zellverbände, die Histologie eine fi brosierende Bronchitis.

C-Peptid war erniedrigt und Seruminsulin im unteren Normbe-

reich.

Mit der Arbeitsdiagnose rezidivierender paraneoplastischer

Hypoglykämien bei Pleuratumor erfolgte eine linksseitige Pneumon-

ektomie. Histologisch konnte das Vorliegen eines fi brösen Pleuratu-

mors bestätigt werden.

Postoperativ bestand ein normaler Glucose-Stoff wechsel.

Lokalisierte fi bröse Pleuratumoren sind eine seltene, häufi g asym-

ptomatische 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

abstracts

ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A11

ÖGP

F19

Ein PET-Pitfall: eine 39-jährige Patientin mit multiplen pulmonalen und extrapulmonalen Rundherden

I. Stelzmüller1, F. Oberascher1, R. Untersteiner1, L. Rettenbacher2, M. Studnicka1

1Universitätsklinik für Pneumologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich

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

Eine Lungenbeteiligung im Rahmen einer Sarkoidose fi ndet sich

in über 90 % und wird mittels Th orax-Röntgen diagnostiziert und

verlaufskontrolliert. Zur Beurteilung weiterer Organbeteiligungen

erscheint auch das PET-CT besonders innovativ.

Eine 39-jährige Frau mit laufender Th erapie einer atypischen

Mykobakteriose wird aufgrund pathologischer LFP und zunehmender

Infi ltrate 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 unauff ällig.

Th erapie: Beendigung der antituberkulösen Th erapie bei

fehlendem Keimnachweis und radiologischer Verschlechterung,

stattdessen bei V. a. Sarkoidose nun Einleitung einer

Cortisontherapie.

Verlauf: Zunächst gutes Th erapieansprechen 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 Infi ltrate – mykobakterielle Infektion, was sonst?

C. Wohlkönig1, M. Meilinger1, H. Flick1, W. Fritz1, C. Hesse1, R. Wurm1, J. Polachova1, R. Krause1, H. Popper2, H. Olschewski1

1Klinische Abteilung für Lungenkrankheiten, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Österreich

2Institut für Pathologie, Medizinische Universität Graz, Österreich

Granulome können bei vielen Lungenkrankheiten auftreten,

angefangen bei den häufi geren Entitäten bis hin zu den Raritäten.

Dabei kann die Ursache sowohl entzündlich als auch nicht-

entzündlich 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.

F18

Lungenzysten und Gelenksbeschwerden

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

1Pneumologische Abteilung, Landeskrankenhaus Krems, Krems, Österreich

2Institut für Pathologie, Landeskrankenhaus Horn, Horn, Österreich3Chirurgische 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 Th orax-CT weitgehend unauff ällig, lungenfunktionell bestätigte

sich die anamnestisch angegebene COPD Grad III.

Klinisch auff ällig 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 Diagnosesi-

cherung erreicht werden konnte, entschieden wir uns für eine VATS.

Es erfolgte eine atypische Segmentresektion im linken UL, histolo-

gisch zeigte sich eine lymphoide interstitielle Pneumonie (LIP), als

Nebenbefund eine fokale DIP-Reaktion. Somit konnte ein systemi-

scher Lupus erythematodes mit positiver Autoimmunserologie, Z. n.

Pericarditis, monatlich auftretenden Arthralgien und einem Schmet-

terlingserythem gesichert werden. Die pulmonale Manifestation be-

stand in Form einer lymphoiden interstitiellen Pneumonie (LIP),

woraus sich die Indikation zu einer Th erapie mit Endoxan und Corti-

son ergab. Nach 6 Zyklen zeigten sich Lungenfunktionsparameter

(VCmax und FEV1) gebessert, CT-morphologisch war keine wesentli-

che Veränderung eingetreten.

Take home: Eine Lungenbeteiligung bei LE äußert sich typischer-

weise in Form von – meist beidseits basal auftretenden – pulmonalen

Infi ltraten mit/ohne Hämorrhagie, Pleuritis. Die akute Lupuspneu-

monie ist ein seltenes Krankheitsbild, dem histologisch eine -unspe-

zifi sche- generalisierte Vasculitis und Alveolitis zugrunde liegt, die

Alveolitis ist in der BAL in der Regel lymphozytär. Ein pathognomoni-

sches 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.

Literatur1. Swigris JJ, Berry GJ, Raffi n AT, Kuschner WG. Lymphoid Interstitial

Pneumonia. Chest 2002;122;2150–64.

abstracts

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Lungenparenchymveränderungen. Endobronchial waren waren

Candida glabrata sowie Aspergillus candidus nachzuweisen. Eine

antimykotische Th erapie 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 Th erapie mit Lidaprim forte zeigte in den folgenden

Verlaufskontrollen einen sehr guten Erfolg.

F21

Unter Immunsuppression ist nicht jeder zerfallende Lungenprozess eine Pilzpneumonie

S. Zillinger

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

abstracts

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ÖGP

mum therapy were screened from three outpatient heart failure clin-

ics in Vienna. Eligible patients underwent full-night polysomnography,

lung function measurements, arterial blood gas analysis, and assess-

ment of subjective sleep quality and sleepiness.

Results: 73 patients with heart failure and stable disease under-

went polysomnography. Th ree patients were excluded due to airways

obstruction on lung function, leaving 70 patients (95%) for fi nal analy-

sis (50 male, 20 female, age 64 ± 11 yrs, BMI 29 ± 5 kg/sqm). Th e 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% pa-

tients had no evidence of SDB. Patients with SDB and those without

did not diff er with respect to age, body-mass-index, cardiac function,

or pharmacological treatment. Patients with SDB scored signifi cantly

higher on sleepiness and sleep quality scores than heart failure pa-

tients without SDB. Patients with Cheyne-Stokes-Respiration had sig-

nifi cantly lower arterial pCO2 levels compared with the other groups.

Conclusions: Th ere is a high prevalence of sleep disordered

breathing in patients with stable chronic heart failure. Th e latter fi nd-

ings may have important diagnostic and therapeutic implications.

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 transplanta-

tion is de-novo malignancy. Th e immunosuppressive treatment, the

increasing long-time survival and the capacity to reactivate viruses

like Epstein-Barr virus (EBV) with cancer-causing potential are seri-

ous risk factors for the development of malignancies in lung trans-

plant recipients. Th e aim of this study was to determine the incidence

and outcome of patients suff ering 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 pa-

tients (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 suff ered 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. Th e median time to cancer appearance was collectively

1378 ± 1272 days after transplantation [45–5003]. 14 patients with de-

novo malignoma or PTLD underwent surgery, 14 were treated with

chemotherapy and 4 with radiation. 3 patients were treated with che-

motherapy and radiation, 2 additional with surgery. 5 patients re-

ceived no therapy. Th e therapy modalities of 7 patients were unknown.

Th e underlying illness, the status of Cytomegalie-Virus infection, the

P001

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 diff erences in cardiovascular auto-

nomic control and baroreceptor function between patients with sta-

ble 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 diag-

nosed CHF-CSR and 14 age, body-mass-index, and apnea-hypopnea

index (AHI) matched patients with CHF-OSA. Cardiovascular auto-

nomic tone was recorded using power spectral analysis of R-R interval

variability on the morning after polysomnography. Th e slope of the

regression line between beat-to-beat spontaneous systolic blood pres-

sure and pulse interval changes was taken as an index of the sensitiv-

ity of arterial barorefl ex modulation.

Results: Th e two groups did not diff er with respect to left ventricu-

lar 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

signifi cantly higher sympathetically mediated low frequency R-R in-

terval variability (58 16 vs 29 15% normalized units, p < 0.01) and high-

er 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 fi nd-

ings, mean slope of spontaneous baroreceptor activity was signifi -

cantly 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 signifi cant diff erences in both sympa-

thetic 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 mor-

tality. Th e 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 maxi-

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

abstracts

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ÖGP

1Clinical Hospital Center Zagreb – Clinic for Lung Disease Jordanovac, Zagreb, Croatia

2Children’s Hospital Srebrnjak, Zagreb, Croatia

Background: Th e aim of this study was to investigate the relation-

ship 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: Th e 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 coeffi cient for carbon monoxide–Kco, the level of dys-

pnea (Borg scale, Medical Research Council scale–MRC), the level of

fatigue (Borg scale, Fatigue Assessment Scale-FAS), and nutrition sta-

tus parameters (Body Mass Index-BMI, Fat-Free Mass Index-FFMI).

Results: Th ere was a signifi cant diff erence 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)

signifi cantly 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 (% pre-

dicted) signifi cantly 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) signifi cantly associated with spirometric pa-

rameters, gas transfer and coeffi cient, levels of dyspnea and fatigue,

and nutrition status parameters.

P006

Alpha-1-antitrypsin defi ciency screening program in Poland

J. Chorostowska-Wynimko1, R. Struniawski1, P. Kuca1, M. Czajkowska-Malinowska2, P. Śliwiński1, J. Kozielski3

1National Institute of Tuberculosis and Lung Diseases in Warsaw, Poland

2Department of Lung Diseases and Respiratory Failure, Regional Center of Pulmonology, Bydgoszcz, Poland

3Department Lung Diseases and Tuberculosis, Silesian Medical University, Zabrze, Poland

Background: In Poland, the overwhelming majority of individuals

with alpha-1-antitrypsin (AAT) defi ciency still remains undiagnosed.

We estimated the AAT gene frequency and prevalence in a large co-

hort 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-phe-

notype identifi ed by isoelectrofocusing. Th e PI*S and PI*Z alleles were

confi rmed by real-time PCR; rare phenotypes were characterized by

sequencing.

Results: 63 (12.6%) lung disease patients demonstrated AAT defi -

ciency 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). Th e

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

defi ciency among Polish patients with chronic obstructive respiratory

form of immunosuppression (Tacrolimus or Cyclosporin A) and the

induction (with antithymocyte globulin - ATG) had no infl uence on

the incidence of malignoma after lung transplantation. Th e only risk

factors which could be identifi ed were the age at time of transplanta-

tion (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 trans-

plant recipients to achieve an advantageous outcome.

P004

The presence of an acute phase response – refl ected by systemic infl ammatory 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

1Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

2Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

3National Koranyi Institute of TB and Pulmonology, Budapest, Hungary

4Department of Pulmonology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria

5Department of Pneumology, Hospital Hietzing, Karl Landsteiner Institute for Clinical and Experimental Pneumology, Vienna, Austria

Background: Asbestos and its related infl ammatory processes are

suspected to be the main contributors in Malignant Pleural Mesothe-

lioma (MPM) carcinogenesis. Elevated C-reactive protein (CRP), a

systemic infl ammatory parameter (SIP) refl ecting the acute phase re-

sponse (APR), showed prognostic power in a number of non-infl am-

matory diseases including various malignancies. However, only

limited data exist about the infl uence of an APR on the clinical out-

come of MPM patients.

Methods: Accordingly, a retrospective multicenter analysis of 173

pathologically proven MPM patients was performed. Clinical data in-

cluding routine SIP levels, and treatment modalities were collected by

the three participating institutions (Department of Th oracic Surgery,

Medical University of Vienna, Department of Pulmonology,

Landesklinik Hochegg and National Koranyi Institute of Pulmonolo-

gy, 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 signifi cant shorter overall survival when compared to

patients with normal SIP levels (log rank tests: CRP: p < 0.001, leuko-

cytosis: 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 - refl ected by altered CRP and albumin levels - to be prognos-

tic in MPM patients.

P005

Six-minute walk test in diagnosis of COPD patients

B. Butorac Petanjek1, S. Popović-Grle1, F. Pavičić1, D. Plavec2

abstracts

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ÖGP

Notch signalling plays a key role in the development of the im-

mune 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 do-

nors 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 to-

wards fMLP [10–8 M] was evaluated in Boyden chambers. After prein-

cubation with the specifi c gamma secretase inhibitor DAPT [10–6

– 10–12 M], basophils migrated towards fMLP [10–8 M] for 90 min. Th e

cellulose nitrate fi lters were then dehydrated, fi xed 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.

Th e RT-PCR revealed basophils to express both, Notch-1 and the

Notch-2. In comparison to PBMC, human basophils were found to ex-

press Notch-1 to a greater extent, whereas Notch-2 expression was

lower than in PBMC. With regards to the functionality of Notch signal-

ling in human basophils we found that the gamma secretase inhibitor

DAPT [10–6 to 10–8 M] most signifi cantly blocked basophil migration

towards fMLP [10–8 M] (p < 0.0001). Furthermore, after Jagged-1 stimu-

lation an increase of histamine concentration by 8.67 fold could be

determined.

We could show for the fi rst 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.

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

1Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

2Department of Internal Medicine B – Pulmonary Medicine and Infectious Diseases, Medical Faculty of the Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany

Background: Th e aim of the present retrospective study was to

evaluate the suitability of hemodynamic parameters assessed by the

indirect Fick method in patients suff ering from pulmonary arterial hy-

pertension (PAH) and controls.

Methods: For this purpose right heart catheterization was per-

formed 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% suff ered 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 re-

sults obtained by the indirect Fick method were compared to data ob-

tained by the thermodilution method.

Results: Patients and controls did not diff er in age, BSA and heart

rate. Th e 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 (COTh ermo) in PAH patients was consistently higher than COFick

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.

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

1Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

2Rheumatology Laboratory, Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

3Division of Physiology, Department of Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck, Austria

Th e proinfl ammatory peptide endothelin-1 (ET-1) proved to be el-

evated in patients suff ering from asthma. As the impact of ET-1 on ba-

sophils, 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 Mag-

netic Cell Sorting (MACS). For RT-PCR and Western Blot analysis,

RNA and protein were isolated by Trizol. Histamine release was meas-

ured 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 fl uorescence 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 be-

tween ETAR and ETBR signalling the specifi c blockers BQ123 and

BQ788 were applied.

Th e RT-PCR proved basophils to express both, ETAR and ETBR.

Th e migratory eff ect of ET-1 [10–8 M] (p < 0.0001) was signifi cantly in-

hibited 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 eff ectively blocked by the ETBR inhibitor BQ-788 [10–8 M]

(p < 0.05). Th e fl uorescence microscopy revealed ET-1 to be highly ef-

fective in inducing intracellular calcium increase 50 seconds after

ET-1 stimulation and lead to a full recovery of ion fl ux 200 seconds

later. Th e 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 in-

duce long lasting eff ects by activation of, for example, c-myc, c-fos and

c-jun transcription.

Our observations reveal for the fi rst time that ET-1 initiates ba-

sophil migration via ETAR and histamine release by ETBR and that

these eff ects are mediated by calcium signalling and downstream ac-

tivation of p38MAPK. Considering the fact that ET-1 and basophils

have a crucial role in airway infl ammation, targeting the eff ects 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. Löffl er-Ragg1

1Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

2Laboratory of Molecular Cell Biology, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

abstracts

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ÖGP

peutic exercises in patients with chronic obstructive pulmonary

disease (COPD).

Aim: To investigate the complex therapeutic infl uence of special-

ized physical therapy (PT) regarding elderly patients with COPD at dif-

ferent stages of the disease.

Methods: A one year study has been conducted investigating the

eff ect of PT applied in hospital and in ambulatory elderly patients in

Sofi a. Outcome measures were: spirometry, pulse oximetry, six min-

utes walking test, Borg scale, Saints’ George Respiratory Question-

naire, 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 fi rst group. In hospital PT sessions were individually

tailored, on 10 daily consecutive days, duration of 20–25 min. Outpa-

tient PT sessions were in groups of 12–20 patients, 30–60 min. Exercise

therapy includes breathing techniques and breathing retraining: tho-

racic 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 prog-

nosis of COPD in patients of fi rst group. Basic dyspnoea and exertion-

al 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 eff ect on:

bronchopulmonary functional status; breathlessness; physical toler-

ance; health-related quality of life and prognosis of the disease.

P013

Infl uenza 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

1Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

2Department of Virology, Medical University of Vienna, Vienna, Austria

Background: Lung transplant recipients (LTRs) are uniquely pre-

disposed in developing severe complications associated with com-

munity acquired respiratory viral infections (CARV). We report the

outcomes of infl uenza 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 secre-

tion. During this period 245 patients frequented our out patient de-

partment for thoracic surgery. All LTRs (n = 82) with respiratory

symptoms were screened. Th ere were 9 (10, 9%) confi rmed cases.

H1N1 infection was diagnosed in 5, infl uenza 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 infl uenza. 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 admit-

ted. Th e patient with BOS II died due to acute respiratory distress syn-

drome (ARDS). Both patients received no vaccination. Th e other two

(4.9 ± 2.1 L/min) showing a signifi cant diff erence by paired non-para-

metric analysis (p < 0.001). COTh ermo was 5.4 ± 1.4 L/min in controls

without reaching a signifi cant diff erence to COFick in paired non-para-

metric test. Direct comparison of COTh ermo 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 con-

trols) 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 under-

estimates 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–de-

rived endothelial progenitor cells (EPC) might play a key role in the

formation of new vessels. Endothelin-1 (ET-1) modulates diff erent

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 iso-

lated 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+) fl ux 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 fl uorescence intensity were measured

using a microplate reader. For selective inhibition of receptor sub-

types, 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 pat-

terns were similar to those observed in paEC and aEC. Both prepro-

ET-1 and ECE encoding mRNA could be detected in EPC. In

Ca2 + mobilisation experiments addition of ET-1 elicited a signifi cantly

increased intracellular Ca2+ mobilisation (p < 0.001 and p < 0.05, re-

spectively). Calcium increase after stimulation with ET-1 was inhibited

by BQ123 and BQ788 by 96% and 45%, respectively.

Conclusions: We proved for the fi rst 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 at-

tributed to the activation of ETA receptors. In summary, our data re-

veal for the fi rst 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”, Sofi a, Bulgaria

Background: Future trends of pulmorehabilitation refer to appro-

bate an eff ective and individual approach applying diff erent thera-

abstracts

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Background: Bronchopleural fi stula (BPF) result in persistent air

leaks due to communications between the bronchial tree and the

pleural space. Th ey are associated with increased morbidity, mortali-

ty, and prolonged hospital stay. Th e management of BPF includes a

multidisciplinary approach, such as surgery, pleurodesis, antibiotics,

and interventional bronchoscopy. No generally accepted guidelines

for eff ective therapy have been developed yet.

Objectives: In high risk patients interventional bronchoscopy us-

ing 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 per-

sistent air leaks after empyema, pulmonary resection, and radical

pleurectomy. 5 patients had surgical as well as bronchoscopic treat-

ment, 6 patients only underwent bronchoscopy. During bronchosco-

py the suspected segmental bronchus was blocked with a ballon

catheter. After identifying the source of bronchopleural fi stula endo-

bronchial 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 fl ow of 1026 ml/min (± 695 ml/min)

down to 56 ml/min (±71 ml/min). In 1 patient bronchography re-

vealed no contrast enhancement in the pleural space after the proce-

dure. In 2 patients there were no bubbles in the water seal system of

the chest tube any more.

Conclusions: Th e implantation of endobronchial one-way valves

may be a high-potential treatment option in the management of bron-

chopleural fi stula.

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

1Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria

2Department of Medical Statistics, Medical University of Vienna, Vienna, Austria

3Department of Anesthesiology and General Intensive Care Medicine, Medical University of Vienna, Austria

Background: Th ere are no large studies about the epidemiology

and outcome of patients with COPD treated in intensive care units

(ICU). More specifi cally 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 informa-

tion 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 in-

creased morbidity and mortality. Th e objectives of the study were

therefore 1. to describe the epidemiology of COPD in patients admit-

ted 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, surgi-

cal, and mixed ICUs in Austria, using a prospectively collected data-

base 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. Th e risk-

adjusted mortality of patients with COPD was higher compared to pa-

tients without COPD (observed to expected mortality ratio with 95%

confi dence intervals 0.91 [0.90–0.92] vs 1.14 [1.12–1.16], respectively).

Th e presence of COPD was an independent risk factor for increased

mortality in multivariable regression. Prolonged mechanical ventila-

tion occurred more common in patients with COPD (24%) compared

LTRs, one with BOS I the other with BOS II and active vaccination pro-

tection were treated with Oseltamivir at the time of the fi rst clinical

assessment, without any further respiratory complications. Th erapy

with Oseltamivir was only started with clinical assessment within the

fi rst 48 hours.

Conclusions: Our review demonstrates a causal link between pre-

existing BOS, vaccination state and the severeness of respiratory

symptoms after infection with community acquired respiratory vi-

ruses as well as the clinical eff ectiveness of seasonal infl uenza vacci-

nation especially in BOS patients.

P014

Endobronchial one-way valve implantation in patients with heterogeneous emphysema using interlobar fi ssure analysis-a pilot study

I. Firlinger1, P. Germonpre2, M. Meysman3, J. Goldin4, M. Noppen3, O. Burghuber1, A. Valipour1

1Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD, Otto-Wagner-Spital, Vienna, Austria

2Pulmonary Department, University Antwerp, Antwerp, Belgium3Respiratory Division, University Brussels, Brussels, Belgium4Department of Radiological Sciences, UCLA, Los Angeles, United States

Background: Th e aim of the present study was to assess the effi -

cacy of bronchoscopic lung volume reduction (BLVR) using endo-

bronchial 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 fi ssure 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 fi ssure.

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 crite-

ria. BLVR was associated with no signifi cant 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. Th ese pa-

tients had a 26% relative increase in FEV1%, 32% increase in maximum

workload, and a 24% increase in inspiratory capacity. Th ere 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 fi ssures may

be associated with clinical benefi ts in a small subgroup of patients, at

an overall higher risk of serious adverse events

P015

Treatment of bronchopleural fi stula using endobronchial one-way valve implantation – a case series

I. Firlinger1, E. Stubenberger2, M. Müller2, O.C. Burghuber1, A. Valipour1

1Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria

2Department of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria

abstracts

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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

1Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria

2Second Department of Medicine (Pulmology), Wilhelminenspital, Vienna, Austria

3Department of Pneumology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria

4Department 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 Aus-

trian patients with NSCLC.

Methods: From January 2010 to May 2011 tumor tissue from bron-

choscopy, CT-guided and ultrasound guided biopsies and surgical

specimen with histological type of Adenocarcinomas and NSCLC

NOS (Not Otherwise Specifi ed) excluding squamous cell carcinomas

and large cell carcinomas were tested for EGFR mutations from 3 hos-

pitals in Vienna and 1 hospital in Lower Austria. Th e mutation detec-

tion was performed with the Th eraScreen 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: Th ese results indicate that Austrian patients with

NSCLC harbor somatic EGFR mutations at a frequency similar to

other European caucasian patients with NSCLC.

Literatur1. 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

1Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

2Department of Pulmonology, Landesklinikum Thermenregion Hochegg, Grimmenstein, Austria

Background: Malignant Pleural Mesothelioma (MPM) is a devas-

tating 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 re-

ferred to the participating institutions (LKH Grimmenstein n = 14,

AKH Wien n = 84) between 01.01.1994 and 01.01.2011. Patients’ char-

acteristics and their impact on overall survival were analyzed using

the SPSS 17.0 software package.

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 admis-

sion. During the course of eleven years the incidence of acute respira-

tory 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 increas-

ingly common condition in critically ill patients. Th e presence of

COPD is associated with increased mortality and morbidity. Th e im-

provement of risk-adjusted mortality over time may be attributable to

the benefi cial eff ects 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

1Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria2Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria

3Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria

4Institute of Pathology, Statistics and Documentation, Medical University of Graz, Graz, Austria

5Institute for Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria

Lung cancer related and unrelated to smoking is still leading cause

of cancer deaths worldwide with an overall survival rate of 15%. Epi-

dermal growth factor receptor (EGFR) kinase mutations occur in over

60% of NSCLC in never-smokers. Most frequent smoking-related mu-

tations 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 ineff ective against

advanced stage K-Ras mutant tumors. In contrast, EGFR amplifi ca-

tion is frequently found in NSCLC patients with smoking history, indi-

cating 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. Th is 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 upregula-

tion of genes encoding apoptosis inhibitors (Bcl-XL, Bcl-2, Mcl-1, sur-

vivin). 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 tu-

mors, we will cross conditional STAT3 transgenic mice with the K-Ras

lung cancer mouse model. Within the second approach the molecu-

lar mechanisms linking STAT3 and lung cancer will be addressed in

more detail.

abstracts

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ÖGP

1Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

2Institute for Hygiene, Mikrobiology und Environmental Medicine, Medical University of Graz, Graz, Austria

3Medical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria

4Institute of Hospital Hygiene and Mikrobiology, Graz, Austria

In a retrospective study we analysed all PCR-proven H1N1 cases

from the infl uenza season 2009/2010 treated within the styrian “LKH

hospital network”. For this purpose all PCR-postive case fi les were re-

viewed and data regarding clinical presentation, laboratory and radio-

logical fi ndings, 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 pa-

tients, which were tested during the infl uenza season 2009/2010 for

infl uenza-like illness. Th e 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

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

1Department of Pneumology, General Hospital Linz, Linz, Austria2Department 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 bear-

ing joints. With trauma, surgery or implantation of endoprosthesis TB

may arise insidiously.

Case Reports: Two case reports of necrotizing tuberculous arthri-

tis/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 antiinfl ammatory measures failed. But healing did

not occur.

In FEF68 m the histology revealed granulation tissue with granulo-

mas 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 le-

sion of the right cheek pointed towards sarcoidosis. Prednisone

cleared the facial lesion but did not change the hypermetabolic activ-

ity 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-ar-

thritis 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 bi-

opsies 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.

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 pa-

tients, chemo-and/or radiotherapy without curative resection was

performed. Mean overall survival (OS) of all patients was 541 days

(95% confi dence interval [CI]: 442-640 days). Patients undergoing

multimodal therapy had the signifi cant longer survival (OS: 742 days,

CI: 566-919 days) than patients treated with chemo-and/or radiother-

apy alone (OS: 472 days, CI: 359–585 days; log rank: p = 0.018) or pa-

tients undergoing surgery alone (OS: 231 days, CI: 114–349 days; log

rank: p = 0.006). Th e most frequent histological subtype was the epith-

eloid (n = 64), followed by the biphasic (n = 21) and the sarcomatoid

(n = 4; missing: n = 9). Patients with non-epitheloid histology had the

signifi cant 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 signifi cant impact on OS

(Cox regression: p = 0.003).

Conclusions: Treatment modality and histology had a signifi cant

impact on MPM outcome. Postoperative ICU stay was found to be

prognostic within the surgical treated subgroup.

P021

Impact of lymphnode downstaging on the prognosis of pancoast tumors

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

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 pre-

senting 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 re-

sections were performed. Pathological evaluation revealed that in 47%

of patients with initially positive lymph nodes there was still evidence

of a microscopic disease. Th is 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, progno-

sis was independent from the extent of resection (laminectomy, vascu-

lar replacements, resections of the brachial plexus or the clavicula).

Conclusions: Patients with advanced N staging should not be ex-

cluded from a multimodal treatment protocol with curative intent. N

downstaging to pN0 after induction therapy increases median surviv-

al by 17 months, however, patients with initially cN0 disease have by

far the best outcome.

P022

Retrospective comparsion of PCR confi rmed H1N1 infections and PCR-negative infl uenza-like illnesses in Styria – risk factors, clinical features and outcome

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

abstracts

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ÖGP

were found in 34 of 1054 cases (3%). Th e highest percentage of discor-

dance was depicted in chronic obstructive lung diseases (12 of 344),

with the fi nal diagnosis of UIP (n = 4), chronic interstitial fi brosis

(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 diff erent in pa-

tients with diff erent diagnoses, malignancies or implanted infections.

Interestingly all mycobacterial infections and all malignancies oc-

curred in patients with COPD.

Conclusions: On account of this high rate of discrepancies and its

possible infl uence 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

1Landesklinikum Thermenregion Hochegg, Grimmenstein, Österreich2Landeskrankenhaus Vöcklabruck, Österreich3Landeskrankenhaus Krems, Österreich4Landeskrankenhaus Hörgas-Enzenbach, Österreich5Landeskrankenhaus Hohenems, Österreich6Otto-Wagner-Spital, Wien, Österreich7Klinikum Wels-Grießkirchen, Österreich8Wilhelminenspital Wien, Österreich9Krankenhaus Hietzing, Wien, Österreich10Landeskrankenhaus Graz, Österreich

Grundlagen: Beurteilung der Genauigkeit des präoperativen

Stagings beim NSCLC im Routinebetrieb pneumologischer Abteilun-

gen Österreichs sowie Erfassung der verwendeten Untersuchungen

mit Hilfe eines vordefi nierten Datenblattes. Das primäre Ziel war es

die Übereinstimmung von Zytologie/Histologie und TNM-Staging

präoperativ gegenüber postoperativ im Routinebetrieb zu unter-

suchen.

Ergebnisse: Von Februar 2011 bis Juni 2011 wurde in Österreich

an 11 pneumologischen Abteilungen Daten von insgesamt 112 Pa-

tienten (Pat.) in ein vordefi niertes 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 prä-

und postoperativer (pop.) Zytologie/Histologie (ZH) und Tumorsta-

dium 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 postopera-

tiv 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 nie-

driger. 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

P024

Alpha-1 antitrypsin defi ciency: a frequently underestimated cause of COPD

V. Hutya1, K. Schmid-Scherzer2

1cand. med., Medical University of Vienna, Vienna, Austria2Second Department of Medicine, Wilhelminenspital, Vienna, Austria

Alpha-1 Antitrypsin Defi ciency (AATD) is a genetic disorder with

decreased levels of AAT protein causing lung disease among adults.

Th e most common lung disease of AATD-patients is COPD, which oc-

curs with a prevalence of 1,220.000 in Austria, while AATD is thought

to be diagnosed in ~5% of patients with AAT defi ciency. Th us, patients

with the disease are unaware and do not receive the necessary and

lung tissue saving augmentation therapy using human alpha-1 anti-

trypsin. 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. Th e average age of the pa-

tients is 49.8 years, and the average age of patients at the time of diag-

nosis is 45 years. 70.8% of the AATD-patients are or were smokers. Th e

detected comorbidities (hypertension is most common, 11,8%) do

not show any relationship with the underlying disease. 42% of regis-

tered patients receive augmentation therapy with Prolastin®. After

initiation of treatment median FEV1 did not change signifi cantly be-

fore 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 suffi cient data from the registry is available.

Summarizing these data, it can be concluded that Austria has to

enhance its eff orts in order to increase the number of diagnosed cases

and to provide the appropriate therapy to all AATD-patients. Aug-

mentation 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 fi ndings

P. Jaksch1, M. Ernst1, V. Augustin1, A. Scheed1 ,S. Geleff2, G. Dekan2, W. Klepetko1

1Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

2Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria

Background: Lung transplantation is a widely accepted therapeu-

tic option for a range of pulmonary conditions in which the diagnosis

is often based on clinical data or on limited biopsy material. Post-

transplantation 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) . Diag-

noses 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 diff erent or expanded diagno-

sis. Discrepancies between referral diagnosis and histopathology

abstracts

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ÖGP

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

1Department of Anästhesiology, Otto Wagner Hospital, Vienna, Austria2Department of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria

Background: We report the fi ndings on 15 Patients which under-

went tumor resection in the lung using SHFJV. SHFJV is defi ned as

weight based ventilation combined with superposition of two jet-

streams. Th e high frequency jet-stream is responsible for the oxygen-

ation 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 PaO

2

71 mmHg ± 5 mmHg PaCO2 41 mmHg ± mmHg Based upon these facts

conventional single lung ventilation during surgery was considered to

be most likely insuffi cient and therefore ventilation with SHFJV was

prepared for standby. Th e trachea was intubated with a double lung

tube. After one unsuccessful trial of conventional single lung ventila-

tion using 100% oxygen we switched to SHFJV before any signs of hy-

poxic 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 de-

pendent lung by conventional ventilation (IPPV) and the non-depen-

dent lung by jet-ventilation.

Results: Findings: After 10 minutes SHFJV resulted in (mean/SD)

PaO2 114 mmHg, PaCO

2 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 fi re risk (laser safe mode)

Conclusions: SHFJV is a safe and eff ective method of ventilation in

order to achieve suffi cient 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

1Department of Anesthesiology, Otto Wagner Hospital, Vienna, Austria2Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria

We report the fi ndings on 42 patients who underwent diagnostic

and therapeutic interventional rigid bronchoscopy under SHFJV.

SHFJV is defi ned as weight-based ventilation combined with super-

position of two jet-streams in an open system. Th e high-frequency jet-

stream is responsible for the oxygenation; the normo-frequency

jet-stream regulates the CO2.

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-Th orax/OB 111/112; Radiolo-

gische 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 Knochen-

szinitgraphie (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 prä-

und 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.

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 resec-

tion – combined with induction treatment – remains controversial.

Th e 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 under-

going 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 ra-

diotherapy followed by radical surgery, including 11 patients (22.4%)

with pancoast tumors. Th e 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 lobecto-

mies, 3 bilobectomies, and 20 pneumonectomies (11 extra- and 9 in-

trapericardial). 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 confer-

ence. In patients with pneumonectomy 3-year survival was signifi -

cantly 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 re-

sults for patients in advanced stage non-small cell lung cancer can be

achieved. In this series survival in patients undergoing pneumonec-

tomy tended to be superior to patients with lobectomy.

abstracts

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ÖGP

P031

Resting and exercise pulmonary vascular resistances in healthy individuals

G. Kovacs1,4, A. Olschewski2,4, A. Berghold3, H. Olschewski1,4

1Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

2Department of Anesthesia and Intensive Care, Medical University of Graz, Graz, Austria

3Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria

4Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

Th e physiological range of pulmonary vascular resistance (PVR)

and total pulmonary resistance (TPR) and the infl uence 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 stratifi ed

according to age, exercise level and posture.

According to the selection criteria, n = 222 subjects from 24 diff er-

ent 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 signifi cant TPR and PVR de-

crease. In individuals ≥ 70 yr TPR even increased by 17% (p = 0.01),

while PVR did not change signifi cantly. At higher exercise levels, TPR

decreased in all age groups. In the upright position, based on a limit-

ed number of data, resting TPR and PVR were higher than supine and

decreased more prominently during exercise, suggesting the release

of resting pulmonary vasoconstriction.

Th ese data may form a basis to defi ne 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

1Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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

Background: Myelodysplastic syndromes (MDS) are a heteroge-

neous group of disorders that are characterized by ineff ective hema-

topoiesis, morphological dysplasia, peripheral blood cytopenias and

progressive bone marrow failure. Myeloproliferative disorders,

thrombocytosis and thrombocytopenia have been identifi ed as risk

factors for pulmonary hypertension (PH) but it is unknown if MDS

bears an increased risk for PH. Th e aim of this study was to investigate

the prevalence of PH in patients with MDS.

Methods: Consecutive MDS patients of the hematology Outpa-

tient Clinic of the Medical University of Graz were enrolled in a PH

screening program and underwent echocardiography. PH was sus-

pected 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.

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 fi re risk (laser safe mode)

Conclusions: SHFJV in diagnostic and therapeutic rigid bron-

choscopy is a safe and eff ective method of ventilation to achieve suf-

fi cient 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

1Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

2Medical 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 routine-

ly performed in the clinical work-up of patients but its clinical value

has not been defi ned. 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 depart-

ment of pulmonology between 2005 and 2010. Th e indication for in-

vasive 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. Th e investigator was blinded to the right heart catheterization

results. Th e sensitivity and specifi city of RAD to predict PH (mean

PAP ≥ 25 mmHg) was determined.

Results: We included n = 317 patients in this study. RAD was pres-

ent 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. Th e specifi city 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 neg-

ative predictive value to rule out PH was just 35%. In patients with

RAD the likelihood of PH was signifi cantly higher (p < 0,001).

Conclusions: Our retrospective analysis on a relatively large, he-

terogenous cohort of subjects including patients with and without PH

suggests that the presence of RAD in the ECG has a high specifi city

but a low sensitivity for PH. Th is simple method may help to recog-

nize PH patients within a population at risk for PH. In order to deter-

mine its appropriate role in a diagnostic algorithm, prospective,

population based studies are needed.

abstracts

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ÖGP

cating that endogenously-driven cAMP synthesis enables the PDE4

inhibitor to act.

Conclusions: Rofl umilast N-oxide diminished TGFß1-induced

proliferation of human lung fi broblasts. In parallel, rofl umilast N-ox-

ide 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 eff ects on Skp2 and

p27(kip1) account for the inhibition of HLF proliferation by rofl umi-

last N-oxide.

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

1Department of Pulmonary Medicine, Paracelsus Private Medical University, Salzburg, Austria

2Department of Nuclear Medicine and Endocrinology, Paracelsus Private Medical University, Salzburg, Austria

3Institute of Histopathology, Paracelsus Private Medical University, Salzburg, Austria

Objectives: To determine the accuracy and safety of ENB in com-

bination 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 superDimen-

sion/Bronchus System. ROSE was facilitated by the immediate smear-

ing of the specimen onto slides, drying, and fi xation. Th e Papanicolaou

(PAP) test grading system was used for cytopathologic evaluation. Th e

fi nal diagnosis was confi rmed by histopathological evaluation of

specimen obtained either by ENB, or – if ENB was not diagnostic – by

surgery or CT-guided fi ne needle aspiration.

Results: Out of 112 subjects 37 (33%) were female, the mean age

was 66.7 years. Th e mean diameter of peripheral lesions was 27mm

(range: 6 – 46 mm). Th e mean Standard Uptake Value (SUV) recorded

by PET-CT was 6.7, and was signifi cantly 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 es-

tablish a correct diagnosis, as defi ned by the defi nite histopathologi-

cal result. 15.2% (17/112) of SPNs were benign, and 84.8% (95/112)

were malignant.

Th e diagnostic yield in lesions < 20 mm and > 20 mm in diameter

was 75.6% and 89.6%, respectively. No signifi cant diff erence in diag-

nostic yield was seen depending on the localization of the SPNs.

Sensitivity and specifi city of ROSE was 82.1% and 100%, respec-

tively. Th e positive predictive value of a positive PET-CT scan for a di-

agnosis 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 eff ective in the diagnostic work-up of SPNs.

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 pa-

tients 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 di-

astolic dysfunction of the left ventricle was present.

Conclusions: According to our data, increased SPAP values may

be present in about 15% of MDS patients. Th e reason of PAP increase

may be multifactoral, postcapillary factors probably playing a relevant

role.

P033

Rofl umilast-N-Oxide, a PDE4 inhibitor, partially reversed an increase in Skp2, a loss in p27(kip1) and inhibits proliferation in human lung fi broblasts secondary to TGFβ1

C. Lambers1, B. Burian1, P. Binder1, H. Tenor2, K. Vonbank1, L.H. Block1

1Division of Respiratory Medicine, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

2Department of In-Vitro Biology, Nycomed GmbH, Konstanz, Germany

Background: Proliferation of human lung fi broblasts (HLF) may

foster pulmonary remodelling as seen in COPD. Th e cell cycle is tight-

ly controlled by a network of cyclins, cyclin-dependent kinases and

their inhibitors (CDKI) such as p27(kip1). In late G1, p27(kip1) re-

cruits 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. Th is study explores whether the phos-

phodiesterase-4 (PDE4) inhibitor rofl umilast N-oxide, the active me-

tabolite of rofl umilast approved for severe COPD in EU and under

review by the US FDA, modifi es 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 with-

out (control) or with TGFß1 (1 ng ml–1) following preincubation (30

min) with rofl umilast-N-oxide (2 nM or 1 μM), forskolin (10 μM) or

dideoxyadenosine (DDA, 100 μM) or vehicle (DMSO). Rofl umilast N-

oxide at 1 μM completely and selectively blocks PDE4, and 2nM is

close to mean steady state plasma levels in clinical trials. Cell prolif-

eration was determined after 72h by cell counting. To assess eff ects 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 con-

trol. 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). Rofl umilast 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. Rofl umilast N-oxide almost fully rescued the TGFß1-in-

duced 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). Th is eff ect was abolished by DDA indi-

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA24

ÖGP

Weyer. Th e active program consisted of endurance and strength train-

ing each of them three times a week for half an hour and an inspira-

tory 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 par-

ticipating the inpatient rehabilitation in Weyer for 3-4 weeks were col-

lected, 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%.

Th e 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 supple-

mentation and 13.51% had a global insuffi ciency.

19.50% were smokers, 72.33% ex-smokers and 8.18% never have

smoked.

Th e mean of the 6MWT at the beginning resulted in 369.11 m, and

increased to 413.92 m at the end. Th e improvement of 44.81 m ex-

ceeded the minimal important clinical diff erence of 28 meter (Puhan

2011).

Th e CRQ domains were as follows:

Dyspnoe at baseline 3.44 and discharge 3.68 (diff erence 0.24 = clin-

ically not relevant).

Fatigue at baseline 4.23 and at discharge 4.91 (diff erence 0.68 = clin-

ically relevant).

Emotional function at baseline 4.38 and at discharge 5.23 (diff er-

ence 0.85 = clinically relevant).

Mastery at baseline 4.56 and at discharge 5.22 (diff erence

0.66 = clinically relevant).

Conclusions: For three to four-week inpatient rehabilitation clini-

cally relevant benefi ts were found in the CRQ domains fatigue, emo-

tional function, and mastery, as well as in the 6MWT.

P037

Comorbidities in COPD – extended diagnosis in inpatient rehabilitation

A. Lichtenschopf1, W. Kullich2, R. Müller3

1SKA der PVA Weyer/Enns, Weyer/Enns, Austria2Ludwig Boltzmann Institut für Rehabilitation interner Erkrankungen Saalfelden, Cluster für Rheumatologie, Balneologie und Rehabilitation, Saalfelden, Austria

3Pensionsversicherungsanstalt Hauptstelle Chefärztlicher Bereich Wien, Vienna, Austria

Background: Detection of comorbidities in COPD of patients who

attended inpatient rehabilitation for 3 to 4 weeks within an observa-

tion 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%.

Th e 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 supple-

mentation and 13.51% had a global insuffi ciency.

20% were smokers, 72% ex-smokers and the rest never have

smoked.

Th e following comorbidities were found:

Hypertension = 53.38%, Coronary heart disease = 14.29%, Chronic

heart disease = 11.84%, Insulin Dependent Diabetes = 3.01%, Non In-

P035

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

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

1Division of Pulmonology, Department of Internal Medicine, Graz, Austria

2Institute of Pathology, Graz, Austria3Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Graz, Austria

4Core Facility Molecular Biology, Center for Medical Research, Graz, Austria

5Experimental Anesthesiology, University Clinic for Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria

6Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

Background: Hypoxia leads to aggressive cancer growth. To iden-

tify cancer specifi c, hypoxia induced pathways is a major aim. Hypox-

ia not only aff ects neoplastic tumor cells, but also the supporting

stroma. We thus established a novel ex vivo lung cancer model for hy-

poxic adaptation with preserved tumor stroma and 3D-structure.

Experimental design: Non-small cell lung cancer (NSCLC) frag-

ments were cultured ex vivo under hypoxia or normoxia for three

days. cDNA microarray analysis was performed in hypoxic and nor-

moxic lung cancer fragments from ten patients. Association of hypox-

ia 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. Hypoxia-

inducible factor 1α was stabilized and signifi cant upregulation of the

hypoxia marker carbonic anhydrase IX was observed under hypoxia.

Microarray analysis identifi ed 107 signifi cantly regulated genes with

at least two-fold expression change in hypoxic compared to normoxic

fragments. However, only four genes were signifi cantly regulated in

both subtypes, adenocarcinoma and squamous cell carcinoma. We

found an unexpected induction of neprilysin (membrane metallo-

endopeptidase, neutral endopeptidase, NEP, CD10) under hypoxia,

which was confi rmed using quantitative PCR. Neprilysin expression

was signifi cantly associated with poor overall survival in NSCLC pa-

tients treated with surgery (P = 0.002).

Conclusions: Our study demonstrates for the fi rst time that the

membrane bound metallopeptidase neprilysin is upregulated by hy-

poxia and that it is an adverse prognostic factor in lung cancer. Ne-

prilysin might thus serve as a hypoxia related target for anti-cancer

therapy.

P036

Which benefi ts can COPD patients derive from inpatient rehabilitation?

A. Lichtenschopf1, W. Kullich2, R. Müller3

1SKA der PVA Weyer/Enns, Weyer/Enns, Austria2Ludwig Boltzmann Institut für Rehabilitation interner Erkrankungen Saalfelden, Cluster für Rheumatologie, Balneologie und Rehabilitation, Saalfelden, Austria

3Pensionsversicherungsanstalt Hauptstelle Chefärztlicher Bereich Wien, Vienna, Austria

Background: Nearly all studies concerning rehabilitation are per-

formed with selected patients. In order to investigate the benefi ts for

unselected COPD patients we performed a study with all COPD pa-

tients who attended an 3 to 4 weeks inpatient rehabilitation stay in

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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 fi xed or

auto-adjusted CPAP treatment for OSAS at our institution. All patients

underwent a standardized educational session and mask fi tting by ex-

perienced 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%. Th ere was a sig-

nifi cant 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), defi ned 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). Th ere were

no signifi cant diff erences between baseline characteristics, residual

AHI or therapeutic CPAP pressure between groups. Patients with poor

CPAP adherence, however, had signifi cantly higher average mask

leakage fl ow (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 infl uence 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

1Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

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

Th ymomas are rare malign tumors of the mediastinum. We want to

report our experience with the resection of thymomas at our institu-

tion 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), modi-

fi ed 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%). Th e 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%), com-

bined 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.

P041

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

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

sulin Dependent Diabetes = 11.09%, Hyperlipidaemia = 34.40%, Oste-

oporosis = 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 comorbidi-

ties, 8.65% four and 6.57% fi ve or more than fi ve.

Conclusions: Th e inpatient rehabilitation of COPD patients re-

vealed numerous comorbid conditions that require extended therapy

and training.

P038

Bactericidal activity of N-chlorotaurine against Chlamydia pneumoniae and Chlamydia trachomatis

V. Maass1, R. Arnitz2,3, M. Nagl3, M. Maass1

1Institute of Medical Microbiology, Hygiene and Infectious Diseases, Paracelsus Private Medical University, Salzburg, Austria

2Department of Pulmonary Diseases, Hospital Vöcklabruck, Vöcklabruck, Austria

3Department 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 infl amma-

tion. Th e sodium salt of N-chlorotaurine (Cl-HN-CH2-CH

2-SO

3-Na,

NCT) can be synthesized chemically and is very well soluble in water.

Th e 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 diff er-

ent 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. Th ese concentra-

tions 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. Th ese 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 infl uenced by mask leak

M. Meshkat, J. Ebner, O. Burghuber, A. Valipour

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

Aims: To investigate the eff ect of mask leak on adherence with

CPAP therapy in patients with obstructive sleep apnea syndrome

(OSAS).

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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 exer-

cise: R = 0.97, rest vs. eight minutes after exercise: R = 0.95). Th e abso-

lute change of base excess was slightly smaller compared to the

absolute change of lactate concentration from rest to maximal exer-

cise (3.3 ± 2.4 vs. 4.3 ± 2.7 mmol/l), but this diff erence 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. Th e factors age, sex, underlying dis-

ease, lung function or exercise capacity were not signifi cantly associ-

ated with the base excess – lactate diff erences.

Conclusions: Th e change of base excess allows a reliable estima-

tion of the blood lactate increase during exercise.

P044

Effects of inspiratory muscle training on dynamic hyperinfl ation in patients with COPD

M. Petrovic1, M. Reiter2, W. Pohl1, T. Wanke1

1Department of Pneumology, Hospital Hietzing, Karl Landsteiner Institute for Clinical and Experimental Pneumology, Vienna, Austria

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

Background: Dynamic hyperinfl ation is associated with exercise

limitation in patients with chronic obstructive pulmonary disease

(COPD). Inspiratory muscle training (IMT) has been shown to posi-

tively infl uence exercice capacity in COPD. Th e aim of the study was

to analyze the eff ects of IMT on exercise capacity, dyspnea and in-

spiratory fraction (IF) during exercise in patients with COPD.

Methods: Daily inspiratory muscle strength and endurance train-

ing (training device: Respifi t STM) was performed for 8 weeks in 10 pa-

tients 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 dur-

ing resistive breathing manouvers (tlim) served as parameter for in-

spiratory 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 pre-

training incremental test. Endurance time (ET) was defi ned as the

duration of loaded pedalling.

Inspiratory capacity (IC) and therefore inspiratory fraction

(IF = IC/TLC) served as parameter for dynamic hyperinfl ation. BORG

Scale was used for dyspnea evaluation.

Results: Following 8 weeks of IMT there was a statistically signifi -

cant 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 train-

ing group but not in the control group.

Concerning incremental exercise test we could observe following

results: there was a signifi cant increase of IF (from 0.41 ± 0.05 to

0.45 ± 0.05, p < 0.01) indicating decreased dynamic hyperinfl ation.

Further on the ratio of bf/VE decreased signifi cantly (from 0.48 ± 0.11

to 0.46 ± 0.13) indicating improved breathing pattern.

A signifi cant 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 ob-

serve an signifi cant improvement of IC and therefore of IF, improve-

ment of breathing pattern and reduction of dyspnoea sensation.

In addition Endurance time (ET in seconds) was signifi cantly

greater (734 ± 74 sec) than before IMT (597 ± 80.8 sec, p < 0.01)

1Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

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

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 diff erent

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 ana-

lyzed by immunohistochemistry in MPM tissue samples. To analyze

functional implications of activin signals, MPM cell models were ex-

posed 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 ana-

lyzed by scratch and transwell assays, and Smad2 phosphorylation by

Western blot as readout for activation of the activin/TGFbeta signal-

ing pathway.

Results: Expression analysis revealed high expression of activin

βA and activin receptors in most MPM cell lines compared to non-

malignant mesothelial cells. Immunohistochemistry in tissue sec-

tions 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 sub-

set of cell lines. Silencing of INHBA in contrast lead to reduced growth,

clonogenic survival and migration of MPM cell models, demonstrat-

ing the important role of INHBA expression for MPM cells. Targeting

activin receptors with two diff erent kinase inhibitors (SB431542,

A8301) confi rmed these results.

Conclusions: Th ese data suggest that deregulated INHBA expres-

sion 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

1Ludwig Boltzmann Institut for Lung Vascular Research, Graz, Austria;2Division of Pulmonology, Department of Medicine, Medical University of Graz, Graz, Austria

Background: Th e change of blood lactate concentration during

exercise is an important parameter describing metabolic changes of

the circulation and the state of metabolic reserves. Th e goal of this

study was to examine if the change of base excess allows the estima-

tion of the changes in lactate concentration during cardiopulmonary

exercise testing (CPET).

Patients and methods: All CPET examinations in the Pulmonol-

ogy 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. Th e correlation between blood lac-

tate and base excess was examined at each time point in all of the pa-

tients and in subgroups based on the underlying disease, sex, age,

lung function, exercise capacity.

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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

Background: Splenectomy is associated with complex venous

thromboembolism such as recurrent deep venous thrombosis, portal

vein thrombosis, and chronic thromboembolic pulmonary hyperten-

sion (CTEPH). Th e spleen serves not only as a red blood cell fi lter but

also as immunological organ. Th e aim of our study was to decipher the

population of spleen cells responsible for misguided thrombus reso-

lution after splenectomy.

Methods: We utilized a mouse model of stagnant fl ow venous

thrombosis to characterize thrombus resolution. Splenectomy was

performed one month before vena cava ligation. In defi ned 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: Th rombus areas of splenectomized mice were signifi cant-

ly larger than those of controls at all time points (ANOVA, n = 8,

p < 0.03). Reinfusion of autologous whole spleen-homogenates recon-

stituted a normal pattern of thrombus organisation. Reinfusion of

spleen tissue depleted of B-lymphocytes did not aff ect thrombus reso-

lution. 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 sniffi ng of pulverized benzodiazepine tablets

M. Rowhani1, R. Rumetshofer1, E. Stiefsohn2, O. C. Burghuber1

1Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna, Austria

2Department 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

No signifi cant changes during both exercise tests were measured

in the control group.

Conclusions: Th e results of our study show that inspiratory mus-

cle strength and endurance training improve inspiratory pump capa-

city reduce dynamic hyperinfl ation and breathlessness during

exercise. Th us the positive eff ects 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 hyperinfl ation during excercise.

P045

Effi cacy of rofl umilast 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

1Pneumology practice, Gänserndorf, Austria2Pneumology practice, Feldbach, Austria3Department of Pneumology, Hospital Natters, Austria4Department of Medicine, Nycomed, Germany5Department of Medicine, Nycomed, Austria

Background: COPD exacerbations are associated with a substan-

tial patient and healthcare burden, which is greater for frequent exac-

erbations. Th is analysis studied the eff ect of rofl umilast 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, place-

bo-controlled, double-blind, multicentre trials in COPD patients with

severe-to-very severe airfl ow obstruction, a history of exacerbations

and chronic bronchitis. Patients were randomised to rofl umilast 500

μg (n = 1537) or placebo once daily (n = 1554) for 12 months.

Results: Th e rate of frequent exacerbations was lower with rofl u-

milast than placebo: patients with 2 exacerbations: 11.5% with rofl u-

milast 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%. Th e mean exac-

erbation rate per patient per year was signifi cantly lower with rofl umi-

last than placebo in patients with <2 exacerbations in the previous

year (0.96 vs 1.15, –16.5%; p = 0.006). Th e diff erence between rofl umi-

last and placebo was greater in patients with ≥2 exacerbations in the

previous year (1.51 vs 1.95, –22.3%; p = 0.002). A benefi t was also seen

with rofl umilast vs placebo for time to fi rst (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 rofl umilast than placebo. Th e greatest

benefi t from rofl umilast was seen in patients with a history of frequent

exacerbations (≥2/year).

*p<0,05 Error Bars ± 2 SE

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

abstracts

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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 signifi cant 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). Con-

trol group C = patients without BOS (n = 454).

Results: Risk factors for the development of BOS were: cy-

closporine as fi rst 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 rejec-

tion episodes in the fi rst year after LUTX (p ≤ 0.01). Patients with cystic

fi brosis 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 lym-

phocytic bronchitis (p ≤ 0.01). 5-year graft survival from patients with

BOS (52.1%) was signifi cantly lower (log rank ≤ 0.01) compared to pa-

tients without BOS (77.8%) and signifi cantly lower (log rank ≤ 0.01) in

group A (26.0%) compared to group B (77.9%) as well.

Conclusions: Cyclosporine as fi rst line immunosuppression, in-

fections 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 fi broblast 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

1Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

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

Background: Malignant pleural mesothelioma (MPM) is an ag-

gressive malignancy characterized by frequent resistance to chemo-

and 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 FG-

FRs in MPM and to evaluate their potential as therapeutic targets.

Methods: Expression of all known FGF and FGFR genes was as-

sessed by qRT PCR in MPM cell lines (n = 10) and normal mesothelial

cells. FGFR-specifi c tyrosine kinase inhibitors and an adenovirus ex-

pressing dominant-negative FGFR were used to block FGF signal

transduction in these cell models. MTT and clonogenic assays as well

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 infl ammation, without evidence of malignan-

cy or tuberculosis. Th ese fi ndings were further corroborated when tb

culture results showed no growth of mycobacteria. Following bron-

choscopy, the patient admitted to sniffi ng (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, sniffi ng or snorting of tab-

lets 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 na-

sal 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 il-

legal 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: Th e use of a multidisciplinary weaning protocol and

the ensuing assessment corresponding to level A evidence is com-

mon practice in North America. A regime such as this was not previ-

ously implemented at our department. We hypothesized, that

ventilation and weaning time would be reduced by a respective pro-

tocol and that the quality of weaning would be sustainable improved.

Th e objective of this study was to evaluate the implementation of a

multidisciplinary (respiratory therapist, physician, nurse) standard-

ized weaning and extubation regime.

Methods: Setting: 8-bed intensive care unit with intubated surgi-

cal, trauma and medical patients. Inclusion criteria: >48 h mechani-

cal ventilation by tracheal tube. Exclusion criteria: neuromuscular

disease, dysphagia, LTOT and home respiratory care. In this prospec-

tive study a historical control group (n = 20) was used as the compari-

son 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, wean-

ing-assessment, weaning-algorithm with a spontaneous breathing

trial and extubation criteria.

Results: Our regime reduced total time of ventilation (medi-

an = 169.1 h vs. 89.9 h) and weaning time (median = 73.35 h vs. 20.43 h)

signifi cantly (p = 0.00329 and p = 0.0004) in the intervention group.

Th e use of prerequisite extubation criteria in the invention group re-

duced the rate of recent ventilation by 50%. Th e reduction of weaning

and ventilation time is based on multidisciplinary protocolized wean-

ing. Th e main diff erence in weaning algorithm (implementation of a

spontaneous breathing trial and the reduced use of a “comfort venti-

lation mode”) can be discussed as additional reasons for benefi t.

Conclusions: Despite the acknowledgement of methodical limi-

tations of the study and the small sample size it can be assumed that a

standardized, multidisciplinary weaning and extubation regime im-

proves the weaning process by reducing weaning and ventilation

time. Th e study results approach to the implementation of a multidis-

ciplinary protocol into European weaning practice.

abstracts

ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A29

ÖGP

P052

The stress kinase MKK7 functions as lung-specifi c tumor suppressor by coupling oncogenic stress to p53 stability

D. Schramek1, R.-H. Zwick2, V. G. Gorgoulis3, M. Serrano4, J. M. Penninger1

1MBA, Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna, Austria

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

3Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece

4Spanish 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 mu-

tations in single cells and are strongly infl uenced 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 premalig-

nant state in vivo are largely unknown. We found that the MKK7-JNK

stress signaling pathway serves this vital function and show that lung-

specifi c 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 specifi c phosphorylation events, which

is required for cell cycle arrest and suppression of epithelial lung can-

cer. 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 (confi rmed by sequencing) showed even

higher phosphorylation of MKK7 than did tumors harboring wild-

type p53 indicating a deregulated response in more advanced, malig-

nant tumors. Th us, MKK7 is activated in primary human lung tumors

and such hyperactivation seems to depend on p53 status.Th ese 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 anti-

cancer barrier.

P053

Quality of life after lung transplantation in patients with cystic fi brosis: 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 end-

stage pulmonary diseases. Th e 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 fi brosis.

Methods: All German speaking lung transplant recipients with

cystic fi brosis were given a set of questionnaires (n = 45, response rate

95%): St. George’s Respiratory Questionnaire (SGRQ), SF-36, the Hos-

pital Anxiety and Depression Scale (HADS-D), a likert scale of actually

as spheroid formation assays and videomicroscopy were performed

to analyze cell growth, survival and migration. Th e eff ect on down-

stream signal transduction was assessed by immunoblotting with

phosphorylation site-specifi c antibodies.

Results: Expression analysis revealed high levels of FGFR1 togeth-

er with the ligands FGF2 qand FGF18 in all MPM cell lines investigat-

ed. Stimulation with FGF2 showed remarkably increased migration

and signifi cant changes in morphology reminiscent of epithelial mes-

enchymal transition. Inhibition of FGFR1 by the specifi c small mole-

cule kinase inhibitor PD166866 lead to decreased proliferation,

survival, migration and spheroid formation in all cell lines tested. Ad-

enoviral expression of dominant-negative FGFR1 further confi rmed

these results. Combination of FGFR inhibition with chemotherapeu-

tic agents (e.g. cisplatin, gemcitabine, trabectedine) increased cyto-

toxicity.

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 po-

tential new treatment strategy in this devastating malignancy.

P051

Dendritic cell function is affected by endothelin-1 in vitro*

C. Schönherr, K. Cima, S. Desole, J. Löffl er-Ragg, C. M. Kähler

Department of Internal Medicine I (Pneumology), Center of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria

Infl ammatory cells such as mast cells, T-lymphocytes and dendrit-

ic cells have been described in the perivascular lesions in PAH. Th e

strong pro-infl ammatory agent endothelin-1 (ET-1) was shown to be

upregulated in PAH patients. So far, ET-1 has been found to be re-

leased from dendritic cells and to be involved in autocrine cell sur-

vival regulatory loops. However, the chemotactic eff ect 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 den-

dritic 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 fi lters.

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 BQ-

788, 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 humidifi ed atmosphere, fi lters were

dehydrated, stained and fi xed. Cell migration was analysed micro-

scopically.

For the fi rst time ET-1 was shown to induce dendritic cell migra-

tion, displaying [10–8 M] to be most eff ective. Furthermore, the ETAR

inhibitor BQ-123 was proven to inhibit dendritic cell migration most

signifi cantly at 10–6 – 10–8 M. To compare, the ETBR inhibitor BQ-788

blocked the chemotactic eff ect of ET-1 at a broader concentration

range [10–6–10–12 M].

Th us, we conclude that ET-1 is a chemoattractant for human den-

dritic cells despite their origin and that this eff ect is more effi ciently

inhibited by ETBR blockage than that of ETAR, reinforcing ET-1 to be a

good therapeutic strategy for targeting the infl ammatory component

of PAH.

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA30

ÖGP

P055

Quantifi cation 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

1Laboratory of Molecular Diagnostics and Immunology, Warsaw, Poland

2Outpatient Clinic, Warsaw, Poland3Department of Thoracic Surgery, Warsaw, Poland4II Department of Lung Diseases, Warsaw, Poland5III Department of Lung Diseases, Warsaw, Poland6Department of Diagnosis and Treatment of Respiratory Failure, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland

Background: Th e 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

eff ectiveness 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 infl ammation 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 signifi cantly higher mean plasma

DNA concentration with respect to patients with chronic respiratory

infl ammation (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 infl ammatory 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 pa-

tients. Th e eff ect of chemotherapy on plasma DNA in NSCLC IIIB pa-

tients is currently analyzed.

P056

Iron defi ciency in non-anemic patients with chronic obstructive pulmonary disease

M. Urban1, O. C. Burghuber1, W. Hübl2, G.-C. Funk1

1Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria

2Department of Laboratory Medicine, Wilhelminenspital, Vienna, Austria

Background: Iron defi ciency contributes to reduced exercise ca-

pacity in patients with heart failure. Th e repletion of iron improves

cognitive, symptomatic, and exercise performance in these patients

independent of hemoglobin. COPD shares many functional features

of heart failure. Th us iron defi ciency could be a potential therapeutic

target in COPD.

Objectives: Th e aim of this study was to determine the prevalence

of iron defi ciency in non-anemic patients with COPD.

QOL (0%–100%), and a self-report questionnaire concerning social

data, daily activities and adverse eff ects 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 ac-

tivities without problems and exercise diff erent sports regularly like

fi tness training (47%), cycling (43%), swimming and so on. Adverse

eff ects of immunosuppression, however turned out to be a important

factor infl uencing LuTX recipients life quality: 19% suff er in a moder-

ate to severe way of adverse eff ects. 77% have diabetes, 53% hyperten-

sion and 63% osteoporosis. However 93% are highly satisfi ed with the

transplant outcome and 98% would opt for the procedure again.

With regard to the SGRQ the LuTX recipients show signifi cantly

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 diff er signifi cantly 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 eff ects of immunosuppression they report a highly satisfying

quality of life. Th is is refl ected 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 examina-

tion by an interdisciplinary team is essential for selection of qualifi ed

candidates.

Methods: Between 2008 and 2010 data were analyzed from pa-

tients who have been assigned to our pretransplant clinic. Th e aim of

the study was to determine the number of accepted, declined or post-

poned patients. Further we wanted to assess the number of listed pa-

tients, waiting list, diagnoses, waiting time, mortality and the

frequency of high urgency reports.

Results: In a period between 2008 and 2010 744 patients were ex-

amined 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).

Th ese 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. Th e shortest waiting time had patients with IPH and CF,

then IPF. Stable COPD-patients had the longest waiting period. Th e

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 mor-

tality on the waiting list or have to be transplanted from the intensive

care unit (HU-status). Patients with these diagnoses should be evalu-

ated and listed earlier.

abstracts

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ÖGP

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

1Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria

2Department of Internal Medicine, Hospital Rudolfstiftung, Vienna, Austria

3St. Anna Children’s Hospital, Vienna, Austria4Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

Background: Patients with chronic obstructive pulmonary disease

(COPD) are at an increased cardiovascular risk; however, the underly-

ing mechanisms for this relationship are ill defi ned. Altered glucose

metabolism may increase cardiovascular risk via impaired endotheli-

al function. We conducted a longitudinal study to assess the interrela-

tionship 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 cardio-

vascular risk factors were studied. Systemic vascular function was as-

sessed by means of fl ow mediated dilation technique of the brachial

artery. Laboratory measurements included fasting blood glucose lev-

els, circulating concentrations of insulin, C-reactive protein, and fi -

brinogen. Homeostasis Model Assessment of Insulin Resistance

(HOMA-IR) was determined. Measurements were performed at base-

line and were repeated after twelve months.

Results: Flow-mediated dilation signifi cantly 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). Th ere was

a signifi cant 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 cardiovas-

cular risk in patients with COPD.

P059

Asthma treatment with beclomethasone/formoterol: disease control and patient-reported outcomes

N. Vetter1, H. Hinterberger2

1Otto Wagner Spital, Vienna, Austria2Practice for Pneumology, Vienna, Austria

Background: To evaluate data regarding asthma control, tolerabil-

ity 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-fi ne

beclomethasone/6 μg formoterol (BDP/F) of 1–2 inhalations twice

daily over a 12-week period. Overall 237 patients were enrolled. Asth-

ma control was examined before and after the observation period cor-

responding 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. Th e number of asth-

ma attacks (day and night time) as well as the severity of asthma

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 defi ciency was diag-

nosed when the serum ferritin level was either <100 μg/l or was be-

tween 100 and 299 μg/l with the transferrin saturation <20%.

Results: Th e serum ferritin level was <100 μg/l in 20 patients. Th e

serum ferritin level was between 100 and 299 μg/l and transferrin sat-

uration was <20% in 6 patients. Th us iron defi ciency was present in

49% of the patients. Th e median soluble transferrin receptor to log_

ferritin ratio was higher in patients with iron defi ciency (1.7, 1.0 to 1.4)

compared to patients without (1.7, 1.4 to 2.0), p < 0.001.

Conclusions: Iron defi ciency 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 defi ciency.

P057

Structural and biochemical characteristics of subclinical atherosclerosis in COPD

M. Urban1, L. Ay2, G.-C. Funk1, M. Wolzt3, O. C. Burghuber1, A. Valipour1

1Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria

2Department of Internal Medicine, Hospital Rudolfstiftung, Vienna, Austria

3Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria

Background: Patients with COPD are at an increased risk of car-

diovascular morbidity and mortality, however, the underlying mecha-

nisms remain poorly defi ned. Th e present study investigated early

markers of cardiovascular disease in patients with COPD and con-

trols.

Methods: Th e 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 airfl ow obstruction. Both patients and controls were free from

traditional cardiovascular risk factors including hypertension, diabe-

tes, or hyperlipidemia. Study participants underwent measurements

of brachial artery intima-media thickness (bIMT) and circulating lev-

els of the endogenous nitric oxide synthase inhibitor asymmetric dim-

ethylarginine (ADMA).

Results: bIMT was signifi cantly higher in patients with COPD than

controls (0.37 ± 0.08 mm vs. 0.32 ± 0.06 mm; p = 0.007). Th ere was a sig-

nifi cant inverse relationship between bIMT and FEV1% predicted

(r = -0.304; p < 0.002) within the complete study sample. We observed

no signifi cant diff erences 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 signifi cant positive relationship be-

tween bIMT and lnADMA levels in patients with COPD (r = 0.331;

p = 0.013).

Conclusions: Th is study provides evidence of both structural and

biochemical characteristics of subclinical atherosclerosis in patients

with COPD.

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA32

ÖGP

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 rofl umilast vs placebo.

Conclusions: In two 12-month studies, rofl umilast reduced the

frequency of moderate and severe exacerbations independent of con-

comitant maintenance bronchodilator treatment (LABA or SAMA), or

treatment with ICS prior to randomization.

P061

Triple Endoscopy (TRES) with fl exible 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 trans-

esophageal fi ne needle aspirations as well. GER is associated with

chronic cough and explored by esophago-gastroscopy (OGD). Even

the stomach is in the reach of fl exible bronchoscopes.

Aim of the study: Lack of information about simultaneous bron-

cho-esophagoscopy let us explore the feasibility and (dis)advantages

of TRES using fl exible bronchoscopes.

Methods: Olympus bronchoscopes were used for TRES in 16 pa-

tients (7 F, 9 M – age mean ± 2SD 66 ± 13 years). Bronchoscopy was im-

mediately followed by esophago-gastric inspection under local

anaesthesia via nasal or oral route.

Results: 17 broncho- esophago-gastroscopies (TRES) were car-

ried out with the same bronchoscope adjusted by an inserted catheter

for insuffl ation of pressurized air. No adverse event occurred.

P062

Hyperinfl ation 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, Ludwig-Boltzmann-Institute for COPD, Otto-Wagner-Spital, Vienna, Austria

Background: Th ere is evidence of impaired biventricular preload

associated with hyperinfl ation in patients with COPD. A reduction in

cardiac fi lling pressures may result in unloading of baroreceptors. We

therefore investigated baroreceptor sensitivity, an independent pre-

dictor 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, gen-

der, and body-weight matched controls without airfl ow obstruction

were studied. Participants underwent comprehensive hemodynamic

measurements and assessment of arterial barorefl ex modulation of

heart rate during resting conditions and mental stress testing.

Results: Patients with COPD had signifi cantly lower stroke index

(p < 0.001), however, signifi cantly higher heart rate (p < 0.001) and

higher total peripheral resistance compared with controls (p = 0.05).

Th e mean slope of spontaneous baroreceptor sequences was signifi -

cantly lower in patients with COPD than controls during both resting

conditions (p < 0.01) and mental stress testing (p = 0.03). Th ere was a

symptoms (dyspnoea, wheezing, rapid breathing and cough) and ex-

acerbations were assessed. In addition a patient-check (GINA Guide-

lines 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. Signifi cant improvement in

pulmonary function (PEF, FEV1, FVC) was observed in all patients.

Th e 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). Th e median sever-

ity of observed asthma symptoms as well as exacerbations decreased,

latter with the main improvement within the fi rst weeks of treatment.

All results which were collected with the patient-check showed a sig-

nifi cant improvement all over the 12 treatment weeks. Worth to be

mentioned is the signifi cant decrease of the nocturnal awakening

(65% to 10.2%; p > 0.01) under BDP/F. No adverse eff ects were report-

ed during the whole observation period.

Conclusions: Th e results of this NIS show that Beclomethasone/

Formoterol fi xcombination enhances eff ectively patients’ asthma

control by decreasing asthma attacks, symptoms and exacerbations

and by improving lung function (PEF, FEV1, FVC) and patient report-

ed outcomes.

P060

Effi cacy of rofl umilast 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

1Pneumology practice, Feldbach, Austria2Pneumology practice, Gänserndorf, Austria3Department of Pneumology, Hospital Natters, Austria4Department of Medicine, Nycomed, Konstanz, Germany5Department of Medicine, Nycomed, Vienna, Austria6Baylor College Medicine, Houston, USA

Background: Th e oral, selective phosphodiesterase 4 inhibitor

rofl umilast improves lung function and reduces exacerbations in pa-

tients with severe-to-very severe chronic obstructive pulmonary dis-

ease (COPD) and improves lung function and other clinical outcomes

in patients with moderate-to-severe COPD who are receiving con-

comitant long-acting inhaled bronchodilators. We analyzed data

from two 12-month studies that investigated the eff ect of rofl umilast

on the rate of moderate or severe exacerbations in patients with se-

vere-to-very severe COPD. Our aim was to investigate whether the ef-

fect of rofl umilast is infl uenced by concomitant maintenance

treatment with bronchodilators (long-acting beta2 agonist [LABA] or

short-acting muscarinic antagonist [SAMA]) or by treatment with in-

haled corticosteroid (ICS) prior to randomization.

Methods: M2-124 and M2-125 were identically designed, double-

blind, 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 rof-

lumilast 500 μg once daily (n = 1537) or placebo once daily (n = 1554)

for 12 months. Concomitant LABA and regular SAMA use were al-

lowed in all groups, but ICS was discontinued at randomization.

Results: LABAs were used by 749 (49%) patients in the rofl umilast

group and 793 (51%) patients in the placebo group in the pooled data

set. Th e 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. Th e change in exacer-

bation rate with rofl umilast vs placebo was –16.9% (95% confi dence

interval [CI] –25, –8) in the overall population and was not infl uenced

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. Th e corresponding changes in ex-

abstracts

ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A33

ÖGP

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 in-

vestigate 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 fl ow cytometry (PhiPhi-

Lux®) and TUNEL-assay. Expression of HIF-1a was detected with west-

ern blot. Regulation of members of the BCL-2 family was assessed

with qRT-PCR and verifi ed with western blot.

Results: Cisplatin induced concentration-dependent apoptosis in

A549 cells (p < 0.001). Hypoxia almost completely abolished this eff ect

(p < 0.001). Th ese results were confi rmed 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 signifi cantly downregulated in hy-

poxic A549 cells (p < 0.01) whereas the corresponding anti-apoptotic

protein Bcl-2 was not regulated by hypoxia, which was verifi ed 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-regula-

tion of Bax.

Fig. 1.

P065

Effi cacy of Rofl umilast when used with Concomitant ICS from the OPUS/RATIO Studies

J. Würtz1, W. Pohl2, J. Dierlamm3, I. Moll-Schüler4, S. I. Rennard5

1Pneumology practice, Linz, Austria2Pneumology practice Gänserndorf, Austria3Department of Medicine, Nycomed, Konstanz, Germany4Department of Medicine, Nycomed, Vienna, Austria5University Nebraska Medical Center, Omaha, USA

Background: Rofl umilast, 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 exacerba-

tions. Th is post-hoc analysis studied the eff ects of rofl umilast vs pla-

cebo in COPD patients with or without concomitant ICS treatment.

Methods: Th is pooled, post-hoc analysis of two replicate, random-

ized, double-blind, placebo-controlled studies (M2-111 and M2-112)

compared oral rofl umilast 500 μg QD with placebo over 52 weeks.

Stable dose ICS use was permitted. Lung function outcomes and exac-

erbation rates were examined.

Results: Of 2686 randomized patients, 1622 used concomitant ICS

(n = 809 rofl umilast and n = 813 placebo) and 1064 did not (n = 518 and

n = 546, respectively). Among patients receiving concomitant ICS, 65%

signifi cant 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 airfl ow obstruction

and hyperinfl ation.

Conclusions: Impaired cardiac fi lling in patients with COPD may

be related to hyperinfl ation. Our fi ndings furthermore indicate a link

between baroreceptor function and increased lung volumes in COPD.

P063

Loss of receptors CD27 and CCR7 on Mycobacterium tuberculosis-specifi c 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

1Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria

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

Background: Enumeration of Mycobacterium tuberculosis (MTB)-

specifi c, interferon (IFN)-γ expressing CD4+ T cells at the site of infec-

tion accurately identifi es active tuberculosis (TB). To fi nd additional

markers for immune-diagnosis, T cell diff erentiation 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 as-

cites, 1 joint fl uid) 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 confi rmed. As expected, TB

patients were shown to enrich MTB-specifi c, IFN-γ expressing CD4+

T cells at the site of infection when compared to blood (p < 0.05). No

enrichment of MTB-specifi c T cells was found in the 7 patients with

non-TB disease. Both CD27 and CCR7 signifi cantly 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). Th is fi nding was even more striking within the memory

(CD4+/CD45RO+) subset. In contrast, in the non-TB group even an in-

crease of CD27 on the CD4+ and CD4+/CD45RO+ subset in the exu-

dates was noted (p < 0.05).

Conclusions: Active TB can not only be diagnosed by the enumer-

ation of MTB-specifi c, 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

1Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

2Experimental Anesthesiology, Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria

3Lung Cell Laboratory, Medical University of Graz, Graz, Austria

abstracts

ÖGP Jahrestagung 2011 © Springer-Verlag 17–18/2011 wkwA34

ÖGP

Background: Chronic thromboembolic pulmonary hypertension

(CTEPH) is a rare and late possible consequence of venous throm-

boembolism. Th e fi rst pathogenic components of CTEPH are the pri-

mary 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 forma-

tion of vessels is often detected. How these vessels are formed and

from which cell source, however is not well known yet. A bacterial in-

fection might be a major determinant of thrombosis, fi brosis and the

remodelling events, where chemokines might play a critical role in

angiogenesis.

Our aim was to check the presence of infl ammatory markers and

receptors, which play a role in promoting angiogenesis in the PEA

material and their receptors, elucidating the mechanism of angiogen-

esis in CTEPH clots.

Methods: Flow-cytometric analysis: Th e PEA samples were put in

endothelial cell basal medium supplemented with 5% FCS and anti-

biotics. Th e tissue was cut into small pieces and incubated for 18h at

37°C. Th e supernatant was collected and stored at -20°C; afterwards

the tissue was briefl y washed with Hepes buff er and lysed in 150 μl

RIPA buff er with PhosphoStop and Protease Inhibitor Complex. Th e

supernatant and the lysate were checked for infl ammatory 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 Th 1/Th 2 Cytokine Kit).

Immunohistochemistry: Th e PEA material was fi xed in 3% formal-

dehyde for 24 h and embedded in paraffi n blocks. Immunohisto-

chemistry was performed on the 2 μm thick sliced paraffi n tissue

using primary antibodies for von Willebrand factor (Dako), or smα-

Actin (Sigma) and goat-anti-rabbit-HRP secondary antibodies (Santa

Cruz Biotechnologies) or goat-anti-mouse-HRP (Santa Cruz Biotech-

nologies) 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-Poly-

mer (Th ermo Scientifi c).

Results: In the CTEPH surgical material the presence of infl am-

matory markers such as IL6; IL8 and MCP-I were found. Beside these

chemokines, their receptors were also present in the PEA tissue. Ves-

sels 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 ang-

iogenesis and chemotaxis, therefore it might attract the endothelial

cells to the occluded region of the pulmonary artery.

had severe disease vs 68% without ICS; 28% with ICS vs 21% without

ICS had very severe COPD. For the overall population, pre-broncho-

dilator and post-bronchodilator FEV1 improved (mean ± SE) with ro-

fl umilast 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) im-

proved with rofl umilast vs placebo. Without concomitant ICS use,

pre-bronchodilator FEV1 (49 ± 13 mL; p = 0.0002) and post-broncho-

dilator FEV1 (53 ± 13 mL; p < 0.0001) improved with rofl umilast com-

pared to placebo. Rofl umilast + 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 rofl umilast + ICS vs placebo + ICS (36% vs

42%). Without concomitant ICS, the exacerbation rate (rofl umilast

0.42; placebo 0.46; –7.7%; p = 0.55) was not aff ected by rofl umilast; the

percentage of patients experiencing an exacerbation was numerically

lower with rofl umilast vs placebo (23% vs 27%).

Conclusions: Rofl umilast was eff ective at improving lung func-

tion 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. Rofl umilast im-

proves lung function, reduces the rate of exacerbations, and can have

an additive eff ect 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

1Department of Anaesthesia and Intensive Care Medicine, Medical University of Graz, Graz, Austria

2Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

3Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria

4Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

5Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria