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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
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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
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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
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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
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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
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Wir berichten über eine 25-jährige Patientin aus dem Kosovo.
Klinik: Seit 2 Wochen Glieder,- Gelenks,- und Kopfschmerzen; Fieber
bis 38 Grad; Gewichtsabnahme von 2, 3 kg im letzten Monat; kein
Husten.
Zur Diagnose bei radiologischem V.a. Tbc wird neben den
Standardmethoden (Mikroskopie, NAT + Kultur aus Sputum und BAL)
bei pos. IGRA aus dem Blut die Tb-Spot-Untersuchung aus der BAL
durchgeführt. Durch diese Methode, welche zur Diagnose der aktiven
Tbc in Niederprävalenzländer geeignet erscheint, gelingt eine frühzeitige
Erhärtung des Verdachts, welcher nach 21 Tagen mit dem 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
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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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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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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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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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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
ÖGP Jahrestagung 2011wkw 17–18/2011 © Springer-Verlag A23
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.
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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