wiener klinische wochenschrift The Central European Journal of Medicine Wien Klin Wochenschr (2016) 128:751–784 DOI 10.1007/s00508-016-1103-9 Online publiziert: 26 September 2016 © Springer-Verlag Wien 2016

40. Jahrestagung der Österreichischen Gesellschaft für Pneumologie in Kooperation mit der Österreichischen Gesellschaft für Thoraxchirurgie Wien, 6.–8. Oktober 2016

Abstracts Präsident: Univ.-Prof. Dr. Meinhard Kneussl Kongresssekretäre: Dr. Marie-Theres Czerny, MSc. DI Dr. Daniel Doberer Kongressorganisationskomitee (KOK): MR Dr. Kurt Aigner Dr. Wolfgang Auer Dr. Bernhard Baumgartner Dr. Anna Haider Dr. Maximilian Hochmair Univ.-Prof. Dr. Friedrich Horak Dr. Jörg Hutter Dr. Eveline Kink Priv.-Doz. Dr. Bernd Lamprecht Univ.-Prof. Dr. Christian Prior Univ.-Prof. Dr. Peter Schenk

Dr. Otmar Schindler Dr. Wolfgang Schreiber PD Dr. Ingrid Stelzmüller Univ.-Prof. Dr. Michael Studnicka DGKP Helmut Täubl Dr. Karin Vonbank Marlies Wagner PD Dr. Angela Zacharasiewicz

Fall des Jahres 2016 F01 Perforation des rechten Vorhofs nach Zementembolie und Wirbelsäulen-OP Harald Baumer*, Michael Laschitz, Wolfgang Wandschneider Abteilung für Herz-, Thorax- und Gefäßchirurgie, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Österreich Wir berichten über eine 62-jährige Patientin, bei der im Rahmen einer dorsalen Spondylodese Th11 bis L3 mit zementierten Schrauben eine beidseitige Pulmonalarterienembolie aufgetreten ist. Postoperativ wurde die Patientin auf der Intensivstation betreut. Ein CT zeigte periphere Embolien sowie ein 8 cm langes Zementstück im rechten Vorhof. Ein Pneumothorax wurde mit einer Buelau Drainage versorgt, die Hämodynamik war stabil. Regelmäßige echokardiographische Kontrollen ergaben bis zum 14. Tag keine Auffälligkeiten, bis sich ein zunehmendes Haematoperikard zeigte. Eine operative Entfernung mittels Sternotomie, Bergung des Fremdkörpers und einer Patchnaht des rechten Vorhofs durch unsere Abteilung war komplikationslos möglich. Die OP und der weitere stationäre Aufenthalt verliefen zufriedenstellend. Auf eine interventionelle Bergung des Zementstückes wurde in Anbetracht der Perforation des rechten Vorhofs verzichtet. Vereinzelt gibt es in der Literatur Fallberichte über Zementembolien, allerdings stellen Perforationen des rechten Herzens eine Rarität dar. Literatur Habib N, et al. Cement pulmonary embolism after percutaneous vertebroplasty and kyphoplasty: an overview. Heart Lung 2012;41(5):509–11.

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Nebenwirkungsprofil. Kontrolle der deutlich erhöhten Tumormarker. 11/2013: Switch auf Exemestan und Everolimus, weiterhin keine viszerale Metastasierung. 11/2014: Radiotherapie der linken Mamma und BWK7; die weiteren ossären Metastasen in Remission. 11/2014: Switch auf Faslodex. Chirurgische Vorstellung an der Universitätsklinik Innsbruck. Empfehlung einer Resektion mit plastischer Deckung. 10/2015: lokaler Progress des Primärtumors. 01/2016: 1–2 mm große RH im Oberlappen bds. Einleitung von Capecitabine Monotherapie. Mammaboardvorstellung. Aufgrund drohender Blutungsgefahr des Tumors lokal Entschluss zu einem chirurgischen Vorgehen. Therapie:  Durchführung einer Thoraxwandresektion; 20 cm Thoraxwanddefekt; Ersatz mit Goretexnetz; Thoraxdrainage für 2 Tage; Ersatz mit myokutanem Lattissimuslappen; ypT4b pNx R0 ER/PR+, Her2neu neg., Ki67 < 10 %. Entlassung am 7. postoperativen Tag. Weiterführende Capecitabine Therapie. Schlussfolgerungen:  Große allschichtige Defekte der Thoraxwand, die adäquate Sicherheitsabstände erfordern, in Verbindung mit der Wiederherstellung von Stabilität und Funktionalität, benötigen ausreichende thoraxchirurgische Erfahrung und einen kompetenten Partner. Literatur 1. Abbott DE, Halverson AL, Wayne JD, Kim JYS, Talamonti MS, Dumanian GA. The oblique rectus abdominal myokutaneous flap for complex pelvic wound reconstruction. Dis Colon Rectum 2008;51(8):1237–41. 2. Alderman AK, Kuzon WM, Wilkins EG. A two-year prospective analysis of trunk function in TRAM breast reconstructions. Plast Reconstr Surg 2006;117(7):2131–8. 3. Alderman AK, Wilkins EG, Kim HM, Lowery JC. Complications in postmastectomy breast reconstruction; two-year results of the Michigan breast reconstruction outcome study. Plast Reconstr Surg 2002;109(7):2265–74. 4. Atisha D, Alderman AK. A systematic review of abdominal wall function following abdominal flaps for postmastectomy breast reconstruction. Ann Plast Surg 2009;63(2):222–30.

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Chirurgische Herausforderungen in der Mammachirurgie?

Nekrotisierende Pneumonie – der Pneumektomie entkommen

Nadina Roth*

Andreas Trobisch*, Andreas Pfleger, Manfred Modl, Ernst Eber

Abteilung für Allgemeine Chirurgie, Viszeral-, Thorax-, Gefäß- und Transplantationschirurgie, Krankenhaus der Elisabethinen Linz, Österreich Patient:  05/2012 Patientin 56a, primär ossär metastasiertes Mammakarzinom links (HWS, BWS, Rippen, palliative Situation, cT4c, cN3a cM1 UICC IV. Invasiv ductal mäßig differenziert GII, ER 95 %/PR 80 %; Her2neu neg, Ki67 < 10 %; negative Familienanamnese; keine Hormonersatztherapie; postmenopausal; ECOG 0; Viszeralorgane unauffällig (CT und MR). Diagnostik/DD:  Beginn einer endokrinen Therapie (Letrozol) und Zometa alle 4 Wochen, engmaschige klinische Verlaufskontrollen. BWK1-5 und BWK  12 Bestrahlung unter endokriner Therapie sofort möglich (5–6/2012); geringeres Die mit Sternchen (*) markierten Autoren sind die korrespondierenden Autoren.

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Klinische Abteilung für Pädiatrische Pulmonologie und Allergologie, Universitätsklinik für Kinder- und Jugendheilkunde Graz, Medizinische Universität Graz, Österreich Ein 13-jähriges Mädchen wird in reduziertem Allgemeinzustand, mit Fieber bis 40 °C und starkem Husten an einer auswärtigen Abteilung vorstellig. Neben fortgeleiteten Atemgeräuschen sowie Giemen beidseits basal zeigt sich ein deutlich abgeschwächtes Atemgeräusch links; Sauerstoffsättigung in Luft 92–96 %. Labor: Leukozyten 1,95 G/​l; CRP 87,4 mg/​l; PCT 85,8 ng/ ml; IL-6 3878 pg/ml. Thorax-Röntgen:  homogene Eintrübung des linken Mittelund Unterfeldes und fleckige Transparenzminderung im linken Oberfeld.

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Abb. 1 Thorax-CT: vollständige Konsolidierung des linken Lungenflügels sowie ausgeprägte Schleimobstruktion des gesamten linken Bronchialsystems; 1,2 cm breiter parapneumonischer Pleuraerguss; Streuinfiltrate in der rechten Lunge. Trotz unverzüglicher i. v. antibiotischer Therapie muss die Patientin auf die auswärtige Intensivstation verlegt werden, wo eine Thoraxdrainage angelegt wird. Nach weiterer Befundverschlechterung mit progredienten Einschmelzungen links und der Ausbildung eines Pleuraempyems Transfer an unsere Klinik. Trotz initial dringlichster Empfehlung zur linksseitigen Pneumektomie wird nach interdisziplinären Besprechungen ein konservatives Vorgehen favorisiert. Nach Therapiemodifikationen zeigen sich die Entzündungswerte rückläufig, und die Patientin kann vier Tage nach Übernahme extubiert werden. Radiologisch zeigt sich der linke Lungenunterlappen nach Extubation nicht belüftet, jedoch perfundiert, weshalb eine bronchoskopische selektive Intubation und Ventilation des Unterlappens durchgeführt wird. Nach langsamer klinischer und radiologischer Besserung und i. v. antibiotischer Therapie über 36 Tage sowie konsequenter Physiotherapie kann die Patientin in gutem Allgemeinzustand wieder in häusliche Pflege entlassen werden.

F04 Trau keinem Lungensequester Melanie Fediuk*, Nicole Neuböck, Jörg Lindenmann, Alfred Maier, Paul Swatek, Freyja-Maria Smolle-Jüttner Klinische Abteilung Thorax- und Hyperbare Chirurgie, Universitätsklinik für Chirurgie, Medizinische Universität Graz, Graz, Österreich Patientin:  Eine 46-jährige Frau, Nichtraucherin, gab rezidivierende Fieberschübe bis 39 °C, Nachtschweiß sowie Abgeschlagenheit innerhalb der letzten 3 Monate an. Kein Gewichts-

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verlust. Unauffälliger Status physicus. Das Routinelabor war abgesehen von während der Fieberschübe erhöhtem CRP (bis 40,5 G/dl) und Leukozytose bis 12,5 G/l unauffällig. Virusstatus und immunpathologisches Laborprofil waren unauffällig, Blutkulturen und Sputum blieben steril. Diagnostik:  Das PET ergab eine rundliche, epidiaphragmale Speicherung, suspekt auf Abszess, die mediastinalen Lymphknoten waren unauffällig. Das CT zeigte konkordant eine 4 × 3 × 8 cm große, cystisch imponierende, intralobäre Sequestration im posterobasalen Segment des rechten Unterlappens, dem Zwerchfell unmittelbar aufsitzend. Eine aberrante System­arterie aus dem Truncus coeliacus verlief transdiaphragmal in den Sequester. Die venöse Drainage erfolgte in die untere Lungenvene. Die Bronchoskopie war unauffällig. Die Resektion wurde geplant. Therapie:  Über Thoracotomie erfolgten Ligatur der atypischen Arterie, Resektion des Sequesters en bloc mit dem dicht verwachsenen, angrenzenden Zwerchfellanteil und Zwerchfelldirektnaht. Der intraoperative Schnellschnitt ergab Abscessformationen. In der Definitivhistologie fand sich jedoch in der von Abscessen durchsetzten, intralobären Sequestration ein Adenokarzinom pG3, pT3 mit inzipienter Infiltration des Diaphragma. Entsprechend den onkologischen Guidelines erfolgten über Re-Thoracotomie die Lobektomie des rechten Unterlappens und die mediastinale Lymphknotendissektion. Die Histologie ergab keinen Resttumor pulmonal sowie nodale Negativität. Adjuvante Chemotherapie mit 4 Zyklen Navelbine wurde angeschlossen. In Sequestern wurden wiederholt unerkannte Malignome beschrieben. Der Resektion sollte daher gegenüber der Therapie durch Coiling aberranter Systemarterien der Vorzug gegeben werden. Literatur Okamoto T, Masuya D, Nakashima T, et al. Successful treatment for lung cancer associated with pulmonary sequestration. Ann Thorac Surg 2005;80(6):2344–6. Ganeshan A, Freedman J, Hoey ET, et al. Transcatheter coil embolisation: a novel definitive treatment option for intralobar pulmonary sequestration. Heart Lung Circ 2010;19(9):561–5.

F05 Nachtschweiß, Fieber, Gewichtsverlust – alles klar!? Karin Wurzinger* LKH-Enzenbach, Österreich Anamnese: 61-jährige Patientin, seit ca. 5 Wochen trockener Husten, subfebrile Temperaturen – v. a. nachmittags ansteigend, Nachtschweiß, Gewichtsverlust, neg. Reiseanamnese, keine Dyspnoe, keine AP-Symptomatik. Vorerkrankungen: art. Hypertonie, chron. Nikotinabusus. Familien-Anamnese: Großmutter Tbc. Erhobenen Befunde: Physikalischer Status: unauffällig. Vitalparameter, EKG und BGA: o. B. Labor: Leukozyten: 9000, Hb 10,4, Thrombozytose 528.000, CRP 218 mg/L (0 – 8), PCT < 0,02. Thorax-Röntgen: li. Sinus dorsal eingeschattet, V. a. Pleuraerguss, keine Infiltrate. Thorax-CT: bis 1 cm tiefer Pleuraerguss links, kein rezentes Infiltrat, semizirkumferenzieller Perikarderguss (7 mm), kein Hinweis auf PAE, Dystelektase in der Lingula. Echokardiographie: global gute Linksventrikelfunktion, diast. Funktionsstörung. I°, Klappen zart, Perikarderguss

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max. 5 mm, keine hämodynamische Wirksamkeit. Bodyplethysmographie: altersentsprechend unauffällige Lungenfunktion. Bronchoskopie: Bis Subsegmentebene bds. frei einsehbar, geringgradige Bronchitiszeichen. Weitere Untersuchungen: Legionellen, Mycoplasmen, Nocardien, Galactomannan, Quantiferron Test neg. Spezifische Immunologie inkl. ANA, ANCA im Normbereich. Bakterien-, Pilz-, und Tbc-Kultur aus Bronchialsekret und Antikörperstatus im Serum neg. Eine Probepunktion aus dem Pleuraerguss lehnt die Patienten strikt ab. Aufgrund der stark erhöhten Entzündungswerte Beginn mit einer antibiotischer und antipyretischer Therapie, darunter kam es jedoch zu keiner klinischen Verbesserung – weiterhin stark erhöhtes CRP, ausgeprägter Nachtschweiß und subfebrile Temperaturen v. a. abends. Trotz Erweiterung der AB-Therapie keine klinische Verbesserung, CRP und BSG weiterhin stark erhöht. PET-CT: gesteigerter Tracer-Uptake im Aortenbogen, langstreckig in der Aorta thoracalis und abdominalis sowie der großen supraaortalen Äste – vereinbar mit Vaskulitis. Angiologischer Fachbefund: Duplexsonographisch kein Halo der Temporalaterien nachweisbar, FCDS der Carotiden unauff. – somit Biopsie nicht erfolgversprechend. Unter Berücksichtigung des PET-CTs, des Fiebers ohne Keimnachweis, des ausgeprägten Nachtschweißes, des Gewichtsverlusts der Thrombozytose und der hohen Entzündungsparameter ohne Leukozytose und normalem PCT ist in erster Linie eine Riesenzellarteriitis mit extrakranieller Manifestation anzunehmen. Anmerkung: Klassischerweise ist bei der Riesenzellarteriitis die A. temporalis betroffen und die Pat. leiden meist an Kopfschmerzen sowie teils an Sehstörungen. In diesem Fall empfiehlt sich eine Biopsie aus dieser Arterie. Bei dieser Patientin liegt der seltene Fall einer extrakraniellen Manifestation vor. Da keine oberflächlichen, der Biopsie zugängigen Arterien betroffen sind, beruht die Diagnosesicherungen auf rein klinische, laborchemische und radiologische Befunde. Therapie: Aprednislon 75 mg 1 × tgl., T-ASS 100 mg 1 × tgl. unter Magenschutz und Osteoporoseprohylaxe. 5 Tage später: CRP rückläufig auf 29 mg/L, deutliche klinische Besserung.

67,1 mmHg, SO2 96,2 %), in der Lungenfunktion keine Restriktion, keine Obstruktion, jedoch eine Diffusionsstörung (VCmax 83,3 %, FVC 83,9 % (4L), FEV1 81,9 %, Tiffeneau 97,7 %, RV 82 %, TLC 83,3 %, TLCO SB 49,7 %, TLCO/VA 64,3 %). Das Thorax-Röntgen zeigt beidseits ein feinretikuläres, interstitielles Bild und im weiterführenden Thorax-CT präsentieren sich ein mikro- und makronoduläres Verschattungsmuster beidseits und eine bihiläre und mediastinale Lymphadenopathie mit deutlich vergrößerten, grobscholligen Verkalkungen aufweisenden Lymphknoten. Der ACE-Wert ist mit 41 U/L nicht erhöht. Die Ergebnisse aus der Bronchoskopie zeigen in der BAL eine mäßig erhöhte CD4/CD8-Ratio, in der peripheren Biopsie Lungengewebe mit epitheloidzelliger, granulomatöser Entzündung ohne Nekroseareale – vereinbar mit Sarkoidose. Aufgrund der Sonographie der Niere (Nephrokalzinose) ist eine Nierenbeteiligung der Sarkoidose sehr wahrscheinlich. Auf eine bioptische Abklärung wird jedoch aufgrund deutlich verkleinerter Nieren verzichtet. Therapie: Eine Kortisontherapie (5 Tage 50 mg Prednisolon, 21 Tage 25 mg Prednisolon) führt zu einer Verbesserung der respiratorischen (BGA in Ruhe: pH 7,38, pC02 38,3 mmHg, p02 82,8 mmHg, S02 98 %; BGA bei Belastung: pH 7,33, pC02 33,2 mmHg, p02 104 mmHg, S02 98,5 %; TLCO SB 58,2 %, TLCO/ VA 75,2 %) Situation und zu einer deutlichen Verbesserung der Nierenfunktion (Kreatinin 2,8 mg/dl) sowie Remission der Hyperkalzämie. Aufgrund der effektiven Therapie ist bei dem Patienten in den nächsten zwei Jahren bei stabiler Nierenfunktion (Kreatinin 2,2 mg/dl) keine Nierenersatztherapie notwendig gewesen. Literatur Bergner R, Hoffmann M, Waldherr R, Uppenkamp M. Frequency of kidney disease in chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2003;20:126. Löffler C, Löffler U, Tuleweit A, et al. Renal sarcoidosis: epidemiological and follow-up data in a cohort of 27 patients. Sarcoidosis Vasc Diffuse Lung Dis 2014;31:306. Berliner AR, Haas M, Choi MJ. Sarcoidosis: the nephrologist’s perspective. Am J Kidney Dis 2006;48:856.

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Entzugsprogramm auf pulmologische Art

Wie ein Thorax-Röntgen eine Nierentransplantation vermeidet …

Valentin Hirzoiu, Felix Hüttinger, Anna Kropfmüller, Rudolf Pokorny, M. Haumer, Peter Schenk

Johannes Kollegger, Michael Kaltenbrunner, Christoph Schwarz

Pulmologische Abteilung, LK Hochegg, Österreich

Abteilung für Lungenheilkunde, LKH Steyr, Österreich Patientencharakteristik, Anamnese und Symptome: Ein 50-jähriger Exraucher, in der Kunststoffverarbeitung tätig, wird an der Urologie wegen erhöhten Harndranges, erektiler Dysfunktion, anschließend wegen einem Kreatinin von 4,6 mg/dl und sonographischem Verdacht auf Markschwammnieren bei Nephrokalzinose und Hyperkalzämie an der Nephrologie vorstellig. Wegen zunehmender Nierenfunktionseinschränkung erfolgen die Abklärung zur Nierentransplantation und der Erstkontakt mit der Lungenabteilung. Diagnostik und Diagnose: Es präsentieren sich in der BGA in Ruhe eine geringe Ruhehypoxämie (pH 7,387, pCO2 37,6 mmHg, pO2 58,6 mmHg, SO2 96,6  %), bei Belastung eine Zunahme des pO2 (pH 7,357, pCO2 33,8 mmHg, pO2

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Ein 38-jähriger Patient, dreifacher Vater und selbständiger Geschäftsführer, litt unter Ruhedyspnoe, anamnestisch war eine seit vielen Jahren bestehende, extreme Tagesschläfrigkeit auffällig. Der Patient konnte seinen beruflichen Verpflichtungen nicht mehr nachgehen und nahm seit mehreren Jahren N-Metamphetamin, auch Crystal Meth genannt. In auswärts durchgeführten Untersuchungen fanden sich im Lungenröntgen Stauungszeichen und ein stark vergrößertem Herzschatten, in einer Echokardiographie eine massive konzentrische linksventrikuläre Hypertrophie mit einer interventrikulären Septumdicke von 25 mm. Nach einem pulmologischen Konsil erfolgte die Einweisung ins KH Hochegg. Die nicht gerade überraschende Diagnose: ein hochgradiges obstruktives Schlafapnoesyndrom (OSAS) mit einem AHI von 137.

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abstracts Einige Wochen nach der CPAP-Einstellung kam es zu einer erheblichen Besserung der Tagesmüdigkeit, so dass der Patient den Drogenkonsum einstellte. Nach 1,5 Jahren ergab die Echokardiographie-Kontrolle eine deutliche Reduktion der linksventrikulären Wandstärke (Septumdurchmesser von 25 mm auf 14 mm). Auffallend bei unserem Patienten war der langwierige, jedoch vermeidbare Leidensweg und die damit verbundene Drogensucht. Mit einer einfachen Diagnostik und Therapie konnten die Symptomatik, die kardialen Veränderungen [1] und die Drogensucht erfolgreich behandelt werden. Einer aktuellen Studie zufolge nehmen 50 % der Konsumenten Crystal Meth hauptsächlich aus beruflichen Gründen [2], wobei die Tendenz auch in Österreich steigend ist. Abschließend stellt sich die spannende Frage, ob Patienten mit einem undiagnostizierten OSAS häufig zu aufputschenden Substanzen greifen, um sich zu kurieren, oder ob es sich bei unserem Patienten lediglich um einen „Fall des Jahres“ handelt. Literatur 1. Cloward T, Walker J, Farney R, Anderson TJ. Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure. Chest 2003;124:594–601 2. Zentrum für interdisziplinäre Suchtforschung der Universität Hamburg, März 2014

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– Exstirpation einer zerebralen Metastase 05/2014 – 2 × neoadjuvante PCT Cisplatin/Navelbine 05–06/2014 – OL-Lobektomie und Lymphadenektomie rechts 07/2014 – (Tu Stadium G3pT2PN2pL1V1R0) – Ganzhirnbestrahlung 08–09/2014 wegen PD – 2. Therapielinie: palliative MCT mit Pemetrexed 09/2014 wegen PD (Abbruch wegen Sepsis) – 3. Therapielinie mit Tarceva 10/2014–01/2015 – Radiofrequenz-Ablation bei bekannten Lebermetastasen 12/2014 – 4. Therapielinie mit Gemzar bei PD in supraclaviculären und mediastinalen LK li. 02/2015–04/2105 Trotz PD-L1 Negativität wurde eine 5. Linientherapie mit Nivolumab gestartet. Bereits innerhalb des ersten Monats kam es zu einer deutlichen Verbesserung des AZ. Die Mittels Gamma-Knife behandelten Hirnmetastasen waren weiterhin stabil. Computertomographisch zeigte sich eine Vollremission der Hals- und Mediastinalen LK sowie Lebermetastasen (Abb.  1). Der Patient befindet sich auch bis zur Erstellung dieses Fallberichtes im August 2016 in radiologischer und klinischer Vollremission. Fazit:  Neue Therapieoptionen sollten selbst bei scheinbar aussichtslosen Fällen in Erwägung gezogen werden. Biomarker sind wichtig für die neuen Therapieformen, sollten jedoch derzeit noch nicht die Therapieentscheidung leiten.

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Immuntherapie entgegen der Biomarker Susanne Pfeiffer *, Jana Polachova , Christoph Wohlkoenig1, Horst Olschewski1 1

Vom Kinderwunsch zur ZNS-Tuberkulose

1

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

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Ein 65-jähriger Patient wird im April 2014 an einer Neurologie wegen plötzlichem Schwindel und Schwäche im rechten Bein vorstellig. Schließlich wird die Diagnose eines adenosquamösen Karzinoms der Lunge gestellt. Die Symptomatik

Abb. 1  PET zu Beginn der Immuntherapie und aktuell

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rührte von einer solitären Metastase im Gehirn her. Es folgten daraufhin mehrere Behandlungslinien:

Verena Jakob*, Michael Mandl, Petra Lichtenberger, Bernd Lamprecht Klinik für Lungenheilkunde, Med Campus III, Kepler Universitätsklinikum Linz, Österreich Patienten-Charakteristik, Anamnese und Symptome:  Beim vorliegenden Fall handelt es sich um eine 31-jährige Patientin aus Afghanistan, die seit sechs Monaten in Österreich lebt und im Jänner 2016 aufgrund einer Synkope ein Krankenhaus in Niederösterreich aufsuchte. Am Aufnahmetag zeigte die Patientin während eines Telefongespräches plötzlich einsetzende Sprachstörungen, unnatürliches Lachen und Gedächtnisverlust von wenigen Stunden im Sinne einer retrograden Amnesie. Die mithilfe eines Dolmetschers erstellte Anamnese ergab seit drei Tagen aufgetretene Sprachstörungen sowie seit vier Monaten stark zunehmende Kopfschmerzen links fronto-temporal und Tinnitus. Vor sechs Jahren war die Patientin wegen unerfüllten Kinderwunsches von Afghanistan in den Iran gereist, wo eine Gebärmutter-TBC diagnostiziert und für sechs Monate behandelt worden war. Bei Aufnahme am 13. Jänner 2016 zeigte sich die Patientin klinisch unauffällig und fieberfrei bei normotensiver Blutdrucklage, das Labor zeigte eine geringe Entzündung (CRP 4 mg/dl, Leukozyten 10,57 G/l). Diagnostik und Diagnose:  Die Computertomographie des Schädels ergab ein Ödem links temporal, eine Felsenbein- und Schläfenbein-CT zeigte eine Mastoiditis links. Am 14. Jänner 2016 erfolgte eine Mastektomie und Paukendrainage links, mit dem histologischen Ergebnis einer entzündlich infiltrierenden Zylinderepithelschleimhaut und Granulationsgewebe. Wegen fokal symptomatisch epileptischer Anfälle erfolgte auch eine

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Lumbalpunktion. Labor sowie Borrelienserologie waren unauffällig, ebenso verlief die Testung des Liquors auf Mycobacterium tuberculosis negativ. Aufgrund eines Wohnsitzwechsels wurde die Patientin an die Klinik für Neurologie des Kepler Universitätsklinikums Linz transferiert, die ihrerseits wegen eines positiven T-Spot-Tests Kontakt zur Klinik für Lungenheilkunde aufnahm. Dort wurde ein MMT mit 2 cm und ein positiver Quantiferon-Test erhoben. Therapie:  Bei hoch positivem MMT und Verdacht auf tuberkulöse Meningoenzephalitis links hemisphärisch wurde eine tuberkulostatische Therapie eingeleitet, die auch eine Befundbesserung und Symptomlinderung bewirkte. Bis Ende Juni 2016 wurde die viermonatige antituberkulöse Dreifachtherapie mit Pyrafat, Rifoldin und INH konsequent durchgeführt, danach auf Zweifachbehandlung mittels Rifoldin und INH umgestellt. Die nächste Kontrolle ist für Herbst 2016, die Therapie insgesamt für ein Jahr geplant. Literatur: infektiologie-hygiene.universimed.com/artikel/tuberkulose-des-zentralnervensystems Checkliste XXL – Pneumologie, 3. Auflage, Joachim Lorenz Taschenlehrbuch Medizinische Mikrobiologie, 11. Auflage, Fritz H. Kayser, Erik C.Böttger, Rolf M. Zinkernagel, Otto Haller, Johannes Eckert, Peter Deplazes Pathologie, 3. Auflage, Böcker, Denk, Heitz MLP, Duale Reihe – Neurologie, 6. Auflage, Karl F. Masuhr, Marianne Neumann www.der-arzneimittelbrief.de/Jahrgang2007/Ausgabe10Seite73.htm https://www.uke.de/extern/dgln/neurotuberkulose.htm medicalforum.ch/docs/smf/archiv/de/2010/2010-16/2010–16189.pdf

im Jahr 2012 mittels CT und PET zeigte sich die RF im RUL auf 3,5 cm größenprogredient, jedoch weiter FDG negativ. Eine operative Resektion wurde diskutiert, jedoch wegen funktioneller Inoperabilität ausgeschlossen. Im Februar 2013 war die RF weiter größenkonstant, jedoch gering FDG avid (SUV 2,3), im Juli 2013 geringgradig größenprogredient und vermehrt FDG avid (SUV 2,7). Es wurde weiterhin Observanz empfohlen. Die durchgeführte Lungenfunktion und Blutgasanalyse zeigte FEV1: 1,75 l (78,5 %), FEV1/VC max: 58,15 (73,9 %). Eine im Juni 2014 erneute CT gezielte Biopsie der RF im RUL ergab nun ein hochdifferenziertes Adenokarzinom der Lunge. Therapie:  Nach Komplettierung des Stagings und Ausschluss von Lymphknoten- und Fernmetastasen mittels PET/ CT wurde zunächst eine operative Korrektur der Phrenicusparese links (Zwerchfellraffung) zur Verbesserung der Atemmechanik vor der kurativen Resektion des kontralateralen Adenokarzinoms durchgeführt (September 2014). Dies führte zu einer klaren Verbesserung der Lungenfunktion, sodass ein Monat später eine kurative Resektion des Adenokarzinoms im RUL mittels Lobektomie durchgeführt werden konnte (Stadium pT2a, pN0, L0, V0, R0). 2 Jahre später ist die Patientin tumorfrei und in gutem funktionellen Zustand. Zusammenfassung:  Dieser Fall zeigt einen Spontanverlauf eines unbehandelten Adenokarzinoms über 5 Jahre mit zunehmendem Größenwachstum und PET Positivität. Die lange als Kontraindikation für eine operative Entfernung angesehene kontralaterale Phrenicusparese konnte in einem ersten Schritt mittels Zwerchfellraffung behoben werden und die Patientin damit in einen operablen Zustand gebracht werden. Trotz des langen Verlaufs konnte eine kurative Resektion erzielt werden.

F11 Ein 24-jähriger Patient mit Ureterstein

F10 Kurative Resektion eines über 5 Jahre progredienten Adenokarzinoms im rechten Unterlappen bei einer funktionell eingeschränkten Patientin mit linksseitiger Phrenicusparese Thomas Klikovits1*, Mir Alireza Hoda1, Walter Klepetko1 Klinische Abteilung für Thoraxchirurgie, Universitätsklinik für Chirurgie, Medizinische Universität Wien, Österreich

1

Patientencharakteristik, Anamnese und Symptome: Eine 67-jährige Patientin mit St.p. Mammakarzinom 1987 und einer idiopathischen Phrenicusparese links (bekannt seit 1998) präsentierte sich erstmalig 2009 mit rezidivierenden Synkopen und progredienter Belastungsdyspnoe. Diagnostik und Diagnose:  Im Rahmen der Durchuntersuchung wurde eine Computertomographie (CT) durchgeführt, in welcher sich eine 2,7 cm große Raumforderung (RF) im rechten Unterlappen (RUL) darstellte. Zusätzlich zeigten sich erhöhte Serum-Tumormarker (CEA, CA 15–3). Im PET/CT zeigte sich die RF als nicht FDG avid, weitere malignomsuspekte Läsionen kamen nicht zur Darstellung. Als Zusatzbefund zeigte sich die bekannte Phrenicusparese links, die zu einer Teilatelektase des linken Unterlappens und beträchtlicher funktioneller Einschränkung führte. Zur Klärung der Dignität der RF wurde 10/2010 eine CT-gezielte Biopsie im RUL durchgeführt, welche keinen Hinweis auf Malignität ergab. Somit wurde weitere Observanz mittels CT empfohlen. In einer Verlaufskontrolle

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Philip Tesik*, Gernot Seebacher, Elisabeth Stubenberger Abteilung für Allgemein- und Thoraxchirurgie, Universitätsklinikum Krems, Österreich Patientencharakteristik, Anamnese und Symptome: Es handelt sich um einen männlichen 24-jährigen Patienten von asthenischem Habitus (176 cm, 68 kg) und gutem Allgemeinzustand ohne Zusatzerkrankungen. Er präsentiert sich mit einem Flankenschmerz rechts, einer Dysurie und reduziertem Appetit. Er hat kein Fieber. Alkohol trinkt er gelegentlich, kein Nikotinabusus. Die tägliche Trinkmenge beträgt einen Liter. Die stationäre Aufnahme des Patienten erfolgt aufgrund einer Nierenkolik im Krankenhaus Horn. Sonographisch zeigt sich eine Nephrolithiasis bzw. ein Ureterstein. Laborchemisch zeigen sich keine erhöhten Entzündungswerte, jedoch auffallend sind ein erhöhtes Serumkalzium und ein erhöhter Parathormonspiegel. Aufgrund dessen wird eine Szintigraphie der Nebenschilddrüse veranlasst, in der sich der Verdacht auf ein Nebenschilddrüsenadenom bei Anreicherung im Mediastinum links äußert. Im CT Thorax zeigt sich eine 1,7 cm messende Struktur paratracheal im aortopulmonalen Fenster bzw. caudal des Aortenbogens mit Verdacht auf ein ektopes Nebenschilddrüsenadenom. Differentialdiagnostisch kommen ein ektopes Schilddrüsengewebe, bzw. Nebenschilddrüsenadenom oder eine Lymphadenopathie in Betracht.

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abstracts Nach Transfer an die urologische Abteilung unseres Hauses war kein Stein mehr nachweisbar, sodass von einem Spontanabgang auszugehen ist. Zur weiteren Abklärung der Raumforderung erfolgte die Zuweisung zum EBUS, welcher keinen relevanten mikrobiologischen Befund ergeben hat. Somit wurde der Patient der Thoraxchirurgie zur Diagnosesicherung und Therapie zugewiesen. Er erhielt über eine videoassitierte Thorakoskopie links eine Resektion des vermeintlichen Tumors, welcher in der definitiven Histologie als ektopes Nebenschilddrüsenadenom bestätigt werden konnte. Leider kam es intraoperativ zu einer Verletzung des N. laryngeus recurrens mit konsekutiver Stimmlippenlähmung links und Heiserkeit. Unter logopädischer Betreuung ist der Patient mittlerweile weitgehend beschwerdefrei und hat die Stimmbandparese gut kompensiert.

F12 Spontaner atraumatischer Hämatothorax Birgit Stark1*, Marianne Hubner1, Meinhard Kneussl1, Thomas Klikovits2, W. Klepetko2 2. Medizinische Abteilung, Wilhelminenspital, Wien, Österreich 2 Klinische Abteilung für Thoraxchirurgie, Universitätsklinik für Chirurgie, Medizinische Universität Wien, Österreich 1

Anamnese: Vierzigjährige Patientin präsentiert sich mit zunehmender Müdigkeit. Husten, Schmerzen, Gewichtsabnahme werden nicht angegeben. Verlauf und Befunde:  Als Substrat für die Symptomatik findet sich eine ausgeprägte Anämie (Hb 7,2 g/dl). Radiologisch zeigt sich eine subtotale Verschattung des rechten Hemithorax. Computertomographisch erscheint diese Veränderung aufgrund ihrer dreifachen Dichteschichtung und des fehlenden Kontrastmittelenhancements als Hämatothorax. Es erfolgt an der Thoraxchirurgie des AKH eine VATS, die das histologische Ergebnis eines malignen, plump spindeligen Tumors, in erster Linie passend zu einem sarkomatoiden Mesotheliom ergibt. Ein Synovialsarkom wird molekularpathologisch ausgeschlossen. In der PET CT wird eine Speicherung mit einem SUV von 4,3 an der visceralen, parietalen Pleura, mit langstreckigem Kontakt zum Diaphragma und der rechten Zirkumferenz des Perikards ohne weitere Zeichen der extrapleuralen Infiltration beschrieben, T1, N0, M0 entsprechend. Lungenfunktionell ergibt sich kein Hinweis für eine Restriktion oder Diffusionsstörung. Es wird nach thoraxonkologischem Konsil (siehe Literatur) vorerst eine Induktions IMRT (insgesamt 25 Gray) veranlasst und 5 Tage danach eine extrapleurale Pneumektomie mit Resektion des Pericards komplikationslos durchgeführt. Epikrise:  Der Befund der histologischen Untersuchungen ergibt keinen Hinweis für ein Malignom, insbesondere das primär verifizierte sarkomatöse Pleuramesotheliom kann nicht nachgewiesen werden. In Zusammenschau aller Befunde gibt es vorerst keine Erklärung für den unerwarteten Befund. Ob die Radiatio präoperativ bereits einen „kurativen“ Effekt erzielt hat, ist als eher unwahrscheinlich anzunehmen. Es erfolgt derzeit keine weitere Therapie. Ein PET CT ist in drei Monaten vorgesehen.

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Literatur Cho BC, et al. A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the „SMART“ approach for resectable malignant pleural mesothelioma. J Thorac Oncol. 2014;9(3):397–402.

F13 Wenn Sitzen Dyspnoe verursacht Andreas Kos*, Peter Errhalt Pneumologische Abteilung, Universitätsklinikum Krems, Österreich 1954 geborene Patientin mit Vorbehandlung in einem auswärtigen Zentrum: November 2015 Pneumonektomie rechts bei Adenokarzinom (pT2apN1cM0), danach 2 Zyklen Cisplatin/ Alimta adjuvant. Februar 2016: Lungenembolie links, die Chemotherapie wird im Anschluss wegen zu langem Therapieintervall vorzeitig beendet. Im März 2016 stellt sich die Patientin mit vermehrter Dyspnoe erstmals in unserer Notaufnahmevor. BGA bei Raumluft: pO2 46,5 mmHg, pCO2 20,5 mmHg, pH 7,543, SO2 84,9 %.Unter NIV Therapie und Antibiose bei Pneumonie links kann die respiratorische Situation stabilisiert werden. Mitte März weist die Patientin dann einen O2 Bedarf von 3 L/min in Ruhe und 15 L/min bei Belastung (25 Watt) auf. Das wird auf die stattgehabte Pulmonalembolie in Kombination mit dem Z. n. Pneumonektomie zurückgeführt und eine ambulante Nachkontrolle vereinbart. Mit einer neuerlichen akuten Verschlechterung stellt sich die Patientin im Juli bei uns vor, in der BGA zeigt sich ein pO2 von 53 mmHg unter 15 L/min O2 Gabe! Auffällig waren die Beschwerden der Patientin und divergierende Sättigungswerte am Pulsoxymeter: im Bett liegend ging es Patientin deutlich besser als im Sitzen, daraufhin führten wir entsprechende Blutgasmessungen durch und es zeigten sich folgende Werte: Im Sitzen: pO2 52,3 mmHg, pCO2 24,9 mmHg, pH 7,54 Im Liegen: pO2 81,9 mmHg, pCO2 30,9 mmHg, pH 7,46 Unter 100 % Sauerstoffatmung: Im Sitzen: pO2 150 mmHg, pCO2 33,8 mmHg, pH 7,44 Im Liegen: pO2 455 mmHg, pCO2 36,1 mmHg, pH 7,43 Somit konnte eindeutig ein beträchtlicher Shunt nachgewiesen werden, in der TEE wurde erwartungsgemäß ein lageabhängig weit offenes Foramen ovale mit Rechts-Links Shunt im Sitzen detektiert. Als Diagnose ergibt sich somit ein Orthodeoxie-Platypnoe-Syndrom. Dieses tritt sehr selten als Folge einer (meist rechts-seitigen) Pneumonektomie auf: Voraussetzung ist ein persistierendes Foramen ovale, das im Sitzen oder Stehen durch die veränderte Geometrie im Vorhofbereich funktionell wirksam wird. Therapie der Wahl ist der operative Verschluss. Dieser führte auch bei unserer Patientin zu einer Normalisierung des Gasaustausches. Literatur Cheng TO. Platypnea-orthodeoxia syndrome: etiology, differential diagnosis, and management. Catheter Cardiovasc Interv 1999;47:64. Cheng TO. Mechanisms of platypnea-orthodeoxia: what causes water to flow uphill? Circulation 2002;105:e47.

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F14 Endobronchialer Tumor bei einem 26-Jährigen – eine Rarität S. Zettelbauer1*, B. Rainer2, T. Schmid3, A. Kreczy4, B. Zelger5, H. Jamnig1 Abteilung für Pneumologie, LKH Hochzirl- Natters, Standort Natters 2 BKH Schwaz, Abteilung für Innere Medizin, Schwaz 3 Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie, Innsbruck 4 Institut für Pathologie, Zytologie und Molekulare Diagnostik, Klinikum Coburg, Deutschland 5 Institut für Pathologie, Medizinische Universität Innsbruck 1

Ein 26- jähriger Patient wird uns im November 2015 vom KH Schwaz zur bronchoskopischen Abklärung bei rezidivierenden Pneumonien im linken Oberlappen zugewiesen. Anamnestisch berichtet der Pat. über rezidivierende Pneumonien seit Herbst 2014 und während des gesamten Jahres 2015. Zwischenzeitlich wird der Pat. im Jänner 2015 einem niedergelassenen Pneumologen vorgestellt. Im Rahmen der Untersuchung wird ein inzipientes Asthma bronchiale festgestellt und in der Folge eine inhalative Therapie mit Foster begonnen. Als Kind leidet der Pat. an spastischer Bronchitis, zu diesem Zeitpunkt hat der Pat. zudem eine atopischen Dermatitis. Im weiteren Verlauf hat der Pat. keine resp. Probleme. Vom 16. bis zum 24. Lebensjahr ist der Pat. als Tischler tätig (inhalative Noxen schlecht toleriert). Diagnostik:  Bereits im KH Schwaz wurde eine CT-Thorax-Untersuchung (Oktober 2014) durchgeführt, hierbei wird eine bronchiektatische Erweiterung im linken Oberlappen inkl. chronischer Mucus Retention beschrieben. Im November 2015 entwickelt der Pat. eine vermehrte bronchitische Symptomatik mit Husten, gelb/dunklem Sputum, Belastungsdyspnoe und begleitender Symptomatik mit starkem Nachtschweiß, Fiebergefühl und Schüttelfrost. Im CT-Thorax zeigt sich nun ein pneumonisches Infiltrat im linken Oberlappen inkl. ausgeprägter Mucus Retention (nun deutlich vermehrt als in den Vorbefunden). In der Folge wird eine antibiotische Therapie mit Unasyn eingeleitet, woraufhin es zu einer raschen Besserung der Symptome kommt. Lungenfunktionell zeist sich eine diskrete Obstruktion der kleinen Atemwege. Bronchoskopisch zeigt sich ein Tumorverschluss im inferioren Lingulasegment. In der Folge werden mehrere Biopsien entnommen. Anschließend entleert sich eitriges Sekret. In der Bronchiallavage wird ein steriles Pilzmyzel gezüchtet. Pathologisch-histologisches Gutachten vom 4.  11.  2015: Zehn bis 2 mm große Biopsate, überwiegend eingenommen von spindelzelligen und hyalinisierten Gewebe, partiell finden sich auch Bronchialwandanteile mit Bild einer chron. Bronchitis. Das Gewebe ist zum Teil auch etwas myxoid mit mäßig reichlichen Gefäßen und angedeuteten Antoni A und B Muster. Diagnose:  Biopsate aus einem Schwannom ohne Hinweis auf Malignität im vorliegenden Material. Therapie:  Am 1.  12.  2015 erfolgt die komplikationslose VATS-Lingularesektion an der Thoraxchirurgie der Klinik Innsbruck. In der histologischen Aufarbeitung des Lingularesektates wird die Diagnose Schwannom bestätigt. In einer Kontrolle am 20. 6. 2016 berichtet der Pat. über keine respiratorischen Probleme. Lungenfunktionell kein Hinweis auf obstruktive oder restriktive Ventilationsstörung.

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Im CT-Thorax zeigt sich eine kleine narbige Veränderung cranial der Absetzungsnaht, jedoch kein Hinweis auf Rezidiv oder Neutumor. Schwannome sind gutartige Tumoren, die peripher, viszeral, intraspinal und intrakraniell lokalisiert sein können. Ausgangspunkt sind die Schwannschen Zellen, diese bilden eine Hüllund Stützzelle, um das Axon einer Nervenzelle im peripheren Verlauf zu umhüllen und bei markhaltigen Fasern durch eine Myelinhülle elektrisch zu isolieren. Zumeist kommt der Tumor im Bereich der Beugeseiten der Extremitäten, im Nacken, Mediastinum, Retroperitoneum, hintere Spinalwurzel und im Kleinhirnbrückenwinkel vor. Das Schwannom der Lunge ist extrem selten, und wird mit ca. 0,2 % aller intrapulmonalen Tumoren beziffert. Immunhistologisch exprimieren die Tumorzellen das S-100 Protein. In seltenen Fällen (weniger als 1 % der Fälle) ist eine maligne Transformation möglich. Die Expression von Ki 67 bedeutet eine erhöhtes Risiko für maligne Transformation. Das typische histologische Bild zeigt spindelförmige neoplastische Schwannzellen mit länglichen plumpen, teilweise zigarrenförmigen Zellkernen. Kompakte Tumorareale (Antoni A) können neben lockeren retikulären Bezirken (Antoni B) und lipidhaltigen Zellgruppen vorkommen. Literatur Ackerman L, Rosai J. Ackermans surgical pathology Ohtsuka T, Nomori H, Naruke T, Orikasa H, Yamazaki K, Suemasu K. Intrapulmonary Schwannoma. Jpn J Thorac Cariovasc Surg 2005;53:154–156. Kindblom LG, Ahlden M, Meis-Kindblom JM, Stenman G. Immunhistochemical and molecular analysis of p53; MDM2, proliferating cell nuclear antigen and Ki67 in benign and malignant peripheral nerve sheath tumors. Virchows Arch 1995;427:19–26. Deutsches Ärzteblatt 2002;99:A928–933 (Heft 14).

F15 Finde die Ursache der Progression (FIP) Sheila Steger, Christian Weippert, Georg Hutarew, Michael Studnicka Universitätsklinik für Pneumologie, Universitätsinstitut für Pathologie, Paracelsus Medizinische Privatuniversität Salzburg Wir berichten über eine 55-jährige Patientin, die wegen progressiver Dyspnoe und Verschlechterung der Belastbarkeit vorstellig wurde. Die Patientin wurde vom niedergelassenen Facharzt zur Abklärung bei Vd auf pulmonale Beteiligung im Rahmen einer chronischen Arthritis (laufende Therapie mit Ebetrexat und Cortison) und auf Grund fibrotischer Veränderungen im Thorax-Röntgen zugewiesen. Beruflich war die Patientin Landwirtin, sodass differentialdiagnostisch auch an eine EAA gedacht werden konnte. In der Lungenfunktion zeigte sich eine restriktive Ventilationsstörung und eine eingeschränkte Diffusionskapazität (FEV1 58 %, FVC 48 %; FEV1 %FVC 98; DLCO 58 %). Im HRCT zeigten sich untypische fibrotische Veränderungen in beiden Lungen. Im langfristigen Verlauf wurde eine Zunahme der retikulären Strukturverdichtungen beider Lungen beschrieben. In der Blutgasanalyse der Erstbegutachtung zeigte sich eine schwere Hypoxämie mit einem pO2 von 43 mmHg, entsprechend wurde eine LTOT verordnet.

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abstracts Zur weiteren Diagnostik wurde eine videoassistierte Thorakoskopie durchgeführt. Der histo-pathologische Befund lautete: „Muster einer gewöhnlichen interstitiellen Pneumonie mit chronischem und floridem Entzündungsinfiltrat, in erster Linie postinfektiös, differentialdiagnostisch sollten eine Kollagenose und eine Hypersensitivitätsreaktion ausgeschlossen werden. Differentialdiagnostisch sollte auch an eine idiopathische Form mit bakterieller Superinfektion gedacht werden.“ Im Verlauf kommt es zur weiteren klinischen und lungenfunktionellen Verschlechterung. Fünf Monate nach der Erstbegutachtung erfolgte eine Doppellungentransplantation. Vor dem Eingriff wurde eine HLA-Typisierung durchgeführt, wo zwei HLA-Allele nachgewiesen werden konnten, die ein hohes Risiko für eine Lungenfibrose darstellen (DQB1*06 und DRB1*15). Bei der Schwester und dem Bruder von der Patientin erfolgte ebenfalls eine Lungentransplantation, sodass wir die Diagnose einer FIP stellen konnten. Literatur Fingerlin TE, et al. Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia. BMC Genetics (2016) 17:74. DOI 10.1186/s12863-016-0377-2

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P01 Disturbances in composition, structure and function of the vascular basement membrane in pulmonary hypertension** Katharina Jandl1,2*, Julia Hoffmann1, Wilhelm Bloch3, Bahil Ghanim1,4, Walter Klepetko4, Gabor Kovacs1,5, Horst Olschewski5, Andrea Olschewski1,6, Grazyna Kwapiszewska1,6

Bence Nagy1,2*, Chandran Nagaraj1,2, Andreas Meinitzer3, Rita Papp1, Laszlo Foris1,4, Bahil Ghanim1,5, Grazyna Kwapiszewska1,2, Gabor Kovacs1,4, Walter Klepetko5, Thomas Pieber6, Harald Mangge3, Horst Olschewski1,4, Andrea Olschewski1,2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria, Graz, Austria 2 Institute of Physiology, Medical University of Graz, Graz, Austria 3 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria 4 Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria 5 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 6 Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Austria 1

Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 2 Institute of Experimental and Clinical Pharmacology, Medical University Graz, Graz, Austria 3 Department of Molecular and Cellular Sports Medicine, German Sports University Cologne, Cologne, Germany 4 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 5 Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Austria 6 Institute of Physiology, Medical University of Graz, Austria 1

Background:  The basement membrane (BM) is a layer of core extracellular matrix (ECM) proteins and ECM associated structural proteins that underlie the endothelium of all pulmonary arteries (PA). Pulmonary hypertension is characterized by excessive vascular remodelling of PAs, and an imbalance of ECM proteins is implicated to contribute to this process. Furthermore, endothelial dysfunction – one of the initial events in the pathogenesis of PH – is directly influenced by disturbances in BM composition. Therefore, the aim of this study is to analyse and compare the composition of BM in remodelled small and large pulmonary arteries in diverse PH forms namely idiopathic pulmonary arterial hypertension (IPAH), and PH associated with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Methods:  To characterize the endothelial BM immunohistochemical staining for collagen IV, XIV and XVIII was performed. BM gene expression profiles of donor, IPAH, COPD and IPF lungs were determined on both small pulmary arteries (50–500 µm diameter) generated from laser capture microdissected material and larger (2 – 4 mm diameter) isolated pulmonary arteries. Structural disintegrity of the BM was visualized by electron microscopy and immunohistochemical stainings Results:  Immunohistochemistry of BM-associated collagens revealed remodelling of the BM in IPAH, COPD and IPF patients compared to healthy donors. Concomitant, using electron microscopy, thickening and splitting of the BM was observed in vessels from PH samples. Gene expression analysis of BM components displayed a distinct profile associated with PH that was further dependent on PA size. Cleavage products of BM components, such as ColXVIII-derived endostatin, were elevated in PH and its levels correlated with worse patients’outcome. Conclusions: PH is associated with changes in structure and composition of the BM. Those changes in the BM might be implicated in disease pathogenesis of PH. Thus restoring the BM to normal conditions might stop or reverse pulmonary vasuclar remodelling.

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Kynurenine is a predictive metabolite for pulmonary hypertension**

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Jene 6 Poster, die mit einem doppelten Asterix (**) gekennzeichnet sind, wurden für den Posterpreis nominiert.

Background:  Recent evidence show that pulmonary hypertension (PH) patients exhibit dysregulated energy metabolism with altered amino acid-, glucose-, and fatty acid homeostasis. The objective of this study was to investigate circulating tryptophan and its metabolites in idiopathic pulmonary arterial hypertension (IPAH) and to examine whether the observations are specific for IPAH or can also be seen in other PH-related diseases. Furthermore, we aimed to explore how tryptophan metabolite-kynurenine modulates pulmonary vascular tone in pulmonary hypertension. Methods:  Tryptophan and its metabolites kynurenine and kynurenic-acid were measured by HPLC in serum samples from 60 subjects of which 20 were IPAH, 20 were age+sex matched healthy controls, 10 chronic lung disease patient-without PH and 10 metabolic syndrome patient-without PH. Kynurenine effect was investigated on human pulmonary arterial smooth muscle cells (hPASMCs), and on intact isolated pulmonary arteries by myograph. The impact of kynurenine on pulmonary arterial pressure was measured using isolated-perfused lungs. In vivo kynurenine effect on hemodynamics was assessed in monocrotaline (MCT)- and hypoxia (HOX)-induced animal models of PH. Results: Kynurenine level was elevated preferentially in IPAH patients (3.6 ± 0.2 µM vs. 2.6 ± 0.1 µM, p < 0.0001) where it significantly correlated with mean pulmonary arterial pressure (ρ: 0.770, p < 0.0001) and had strong predictive value for the disease (AUC = 0.86). Tryptophan level was significantly decreased, and kynurenic-acid was unaltered in IPAH. Kynurenine increased intracellular cAMP and cGMP in hPASMCs, and showed to be vasoactive as it induced the relaxation of preconstricted intrapulmonary arteries and decreased pulmonary arterial pressure in the ex vivo animal system. In both in vivo animal models of PH, kynurenine caused significant decrease in RVSP by 16.7 ± 6.1 mmHg in MCT (p = 0.012) and by 3.3 ± 0.9 mmHg in HOX groups (p = 0.014). Conclusions:  These results suggest that tryptophan-derived kynurenine is a vasoactive metabolite for the pulmonary circulation and the increased levels of this metabolite might be predictive for IPAH.

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P03 Antiinflammatory properties of PAH drugs Kathrin Watzinger1*, Ivan Tancevski1, Thomas Sonnweber1, Judith Löffler-Ragg1 University Hospital of Internal Medicine VI, Pneumology, Medical University of Innsbruck, Innsbruck, Austria

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In patients suffering from pulmonary arterial hypertension (PAH) elevated levels of monocyte-derived cytokines have been described in early stage of disease. Beside vasodilatory potential, specific anti-inflammatory activities of current PAH drugs might contribute to their therapeutic efficacy. We studied the anti-inflammatory properties of different classes of PAH drugs in human cultured monocytes. CD14+ monocytes were isolated from blood taken from healthy donors with their informed consent. Peripheral mononuclear cells were isolated via density gradient centrifugation, following by magnetic cells sorting with an anti-CD-14+ specific antibody. Cultured cells were stimulated with different concentrations of macitentan, riociguat, prostacyclin I2 analogues (iloprost, treprostinil) w/​o LPS [100 ng/ml] for 24 h. For blocking experiments of the Toll-like receptor 4 pathway cells were pretreated with an inhibitor of NfκB or MAPK activation, followed by incubation with LPS and the medications. The IL-6, IL-10 and TNF-α concentration of cell supernatants were measured with a commercially available ELISA based assay system. Only monocytes stimulated with iloprost or treprostinil showed a significant reduction of TNF-α, but no effect on the IL-6 and IL-10 release. The effect of treprostinil compared to iloprost was much stronger. TNF-α suppression by prostacyclines has been described in various cell types and disease models. The detailed interaction between the cyclooxygenase system and the toll-like-receptor-4 pathway (TLR4) still has to be elucidated. We show that PGI2 analogues pronounced suppress TLR4dependent TNF-α expression in human monocytes via the MAPK and NFκB pathway. This observation suggests a specific anti-TNF class effect of prostacyclin analogues in PAH therapy.

P04 Expressional regulation of Cytoplasmic/non-receptor tyrosine kinase Src family in pulmonary circulation Nagaraj Chandran1,2*, Rita Papp1, Bence Nagy1,2, Bahil Ghanim3, Walter Klepetko3, Horst Olschewski4, Andrea Olschewski1,2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 2 Department of Physiology, Medical University Graz, Graz, Austria 3 Division of Thoracic Surgery, Department of Surgery, Medical University Vienna, Vienna, Austria 4 Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 1

Background:  Pulmonary circulation is a low pressure and resistance system. The vascular tone of the pulmonary arteries is in-part regulated by the membrane potential of the smooth

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muscle cells. We have previously shown that non-receptor tyrosine kinase Src family is critical for maintaining resting membrane potential (Em) of the human pulmonary artery smooth muscle cells (hPASMCs). Additionally we have also demonstrated that selective inhibition of the Src family or dasatinib increased the mean pulmonary artery pressure (mPAP) in the isolated perfused mouse lungs. In the current study we investigated the expression and regulation of Src family (C-Src, Fyn, Lyn, Yes, Lck, Hck, Blk and CSK) in pulmonary arteries and PASMCs isolated from of the donor and IPAH patients. Methods: Pulmonary arteries (intima along with medial layers) from donors and IPAH patients were isolated using Laser capture microdissection (LCM) to investigate the compartmental expression of Src family non-receptor tyrosine kinase. These findings were further confirmed on hPASMCs isolated from donor and IPAH lungs. The membrane potential of PASMCs from both groups was measured with the patch-clamp technique Results:  Non-receptor tyrosine kinase Src family was significantly down-regulated in the LCM material and in the PASMCs isolated from IPAH patients. In particular, c-Src is significantly down-regulated in remodeled pulmonary arteries of IPAH patients (n = 8) compared to the healthy donors (n = 8). Accordingly, in the primary PASMCs isolated form IPAH patients, expression of c-Src, Fyn, Lyn and Yes were lower. Measurement of the resting membrane potential showed that the PASMCs from IPAH patients were more depolarized compared to the donors. Conclusions:  Our data suggest that SrcTK family is downregulated in the PASMCs isolated from IPAH patients and it could be a vital cause for the depolarized Em of PASMCs, which might explain the excessive vasoconstriction exhibited in the remodeled pulmonary arteries of these patients.

P05 Fra-2 induces IL-1/IL-6-driven parenchymal and vascular remodelling in systemic sclerosis Anna Gungl1*, Slaven Crnkovic1,2, Valentina Biasin2, Leigh Marsh2, Anita Sahu-Osen2, Elvira Stacher-Priehse2,3, Luka Brcic3, F Schneider4, N Cikes5, Bahil Ghanim2,6, Walter Klepetko6, Balazs Odler2,7, Gabor Kovacs2,8, Robert Eferl9, Horst Olschewski8, Andrea Olschewski1,2, Grazyna Kwapiszewska1,2 Department of Physiology, Medical University of Graz, Graz, Austria 2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 3 Department of Pathology, Medical University of Graz, Graz, Austria 4 Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, USA 5 Division of Clinical Immunology and Rheumatology, University Hospital Centre Zagreb, Zagreb, Croatia 6 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 7 Department of Pulmonology, Semmelweis University, Budapest, Hungary 8 Division of Pulmonology, Medical University of Graz, Graz, Austria 9 Institute of Cancer Research of the Medical University of Vienna, Vienna, Austria 1

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P06 Female prevalence in systemic sclerosis is mirrored in Fra-2 over-expressing mice Valentina Biasin1*, Anna Gungl1,2, Leigh M. Marsh1, Slaven Crnkovic1,2, Andrea Oslchewski1,2, Grazyna Kwapiszewska1,2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria, 2Institute of Physiology, Medical University of Graz, Graz, Austria

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Background:  Systemic sclerosis is a multifactorial disease which shows higher prevalence in female. Lung involvement in systemic sclerosis is characterized by inflammation, fibrosis and development of pulmonary hypertension. Fra-2 overexpressing (fra-2 tg) mice have been described as a model for systemic sclerosis as they show several features of the disease, such as lung inflammation, fibrosis and increase right ventricular systolic pressure (RVSP) accompanied by vascular remodelling. In this study we hypothesized that gender differences can influence progression and disease severity between fra-2 tg males and female. Methods and Results: Analysis of the cell count in the bronchial alveolar lavage (BAL) and histological assessment revealed that female have higher number of inflammatory cells in comparison to male fra-2 tg mice. The RVSP did not show any difference between female and male fra-2 tg mice however fra-2 tg female mice had a worse lung function parameter (static compliance, Cst), higher amount of fibrosis, tissue density and inflammatory infiltrates than male fra-2 tg mice. The protein expression level of fra-2 was not different between female and male fra-2 tg mice, suggesting that fra-2 protein level is not responsible for the different phenotype.

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Conclusions:  These results suggest that fra-2 together with sex hormones could influence the phenotype of fra-2 tg female mice. Therefore, understanding of how gender differences influence the molecular mechanism underlying systemic sclerosis can open new avenues for targeted therapies.

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Background: Systemic sclerosis (SSc) is a progressive fibrotic disorder with frequent lung involvement that correlates with clinically poor outcome and mortality. The exact pathomechanisms are unknown but a strong inflammatory component, including cytokines IL-1α and IL-1β, and AP-1 transcription factor member Fra-2 have been associated with diseases pathogenesis. In this study we aimed to assess the role of Fra-2 and IL-1 in pulmonary vascular and interstitial remodelling. Methods:  Human pulmonary arterial smooth muscle cells (PASMCs) and parenchymal fibroblast (PFs) were stimulated with IL-1α or IL-1β to determine gene expression, intracellular signalling pathway involvement and proliferation. The Fra-2 transgenic (TG) animal model of SSc was used to confirm the findings in vivo. The localization of investigated molecules was assessed in human lung tissue slides from SSc patients and donors. Results:  IL-1 stimulation downregulated collagen production of PASMCs and PFs. Factors associated with tissue remodelling, such as extracellular matrix (ECM) protein Tenascin C or IL-6 were strongly upregulated upon IL-1 stimulation. Interestingly, distinct signalling pathways led to these effects in PASMCs and PFs. In line with our in vitro data, we observed enhanced IL-1α levels in Fra-2 TG mice, followed by increased IL-6 and Tnc expression in later time points. Conclusions: In this study, we have shown in vitro and in vivo that IL-1α and IL-1β, despite of being primarily antifibrotic indirectly exert fibrotic properties by inducing factors such as IL-6 and Tnc, thereby promoting parenchymal and vascular remodelling in SSc.

Evaluation of activin A as a novel circulating prognostic marker in non-small cell lung cancer patients Anita Rozsas1,2*, Mir Alireza Hoda1, Thomas Klikovits1, Elisabeth Lang3, Balazs Hegedus1,4, Walter Berger3, Walter Klepetko1, Michael Grusch3, Balazs Dome1,2,5, Viktoria Laszlo1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Department of Tumor Biology, National Koranyi Institute of Pulmonology, Hungary 3 Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna, Austria 4 MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Hungary 5 Thoracic Surgery, National Institute of Oncology, Hungary 1

Background: Identification of biomarkers that predict therapeutic efficacy in non-small cell lung cancer (NSCLC) is urgently needed. Expression of the growth factor activin A is deregulated in a number of malignancies. However, to date there is no data on circulating activin A levels in NSCLC. Methods:  In a cohort of NSCLC patients (lung adenocarcinoma (ADC, n = 87) and squamous cell carcinoma (SCC, n = 37) and in a sex- and age-matched control cohort (n = 66), plasma samples were collected and the levels of circulating activin A were measured by ELISA. In five ADC cell lines, the in vitro activin A expression was measured by ELISA and the activin receptor mRNA levels were determined by qRT-PCR. The bioactivity of the secreted activin A was investigated by Western blot analysis. Results: Elevated plasma activin A levels were found in patients with lung ADC and SCC (vs. controls) and activin A levels were increased in a TNM stage-dependent manner in both NSCLC subtypes. Moreover, high activin A levels were associated with significantly shorter overall survival in ADC and SCC patients. Multivariate analysis showed that plasma activin A concentration is an independent negative prognostic factor in both groups. In vitro secretion of activin A was observed in 3 of 5 ADC cell lines, while activin receptors were expressed in all of them. Furthermore, the supernatants of these cell lines induced Smad2 phosphorylation in HepG2 cells, demonstrating that the activin A produced by ADC cells is biologically active. Conclusions:  Our findings suggest that plasma activin A is significantly elevated in NSCLC and that increased activin A is associated with poor prognosis in both ADC and SCC patients.

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Elucidating the biomarker potential of circulating fibroblast growth factor 18 in malignant pleural mesothelioma – a multi-institutional study Yawen Dong1*, Thomas Klikovits1, Paul Stockhammer1, Luka Brcic5, Marko Jakopovic2, Glen Reid3, Walter Berger4, Viktoria Laszlo1, Balazs Döme1, Walter Klepetko1, Michael Grusch4, MA Hoda1,4 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Department of Pneumology, University of Zagreb, Zagreb, Croatia 3 Asbestos Diseases Research Institute, University of Sydney, Sydney, Australia 4 Institut of Cancer Research, Medical University of Vienna, Vienna, Austria 5 Department for Pathology, Medical University of Graz, Graz, Austria 1

Background:  Malignant pleural mesothelioma (MPM) is a rare but devastating malignancy that originates from the mesothelial lining of the pleura. Despite the development of new promising treatment approaches, the outcome of MPM still remains dismal. Therefore, the identification of novel non-invasive biomarkers is urgently needed in order to identify patients with a better prognosis and to make the best personalized therapeutic decision. In our previously published study, we were able to show that fibroblast growth factor 18 (FGF18) is overexpressed in MPM tissue specimens. The objective of this study is the evaluation of FGF18 as a circulating biomarker in MPM. Methods:  Plasma was collected from 107 MPM patients at the time of diagnosis or before surgical resection. Samples from 49 healthy participants and from 8 patients with non-malignant pleural diseases served as controls. Circulating FGF18 was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological parameters. Results: Plasma FGF18 level was significantly elevated in MPM patients when compared to healthy controls (P < 0.0001). A slight increase of circulating FGF18 level was also detected in patients with pleuritis or fibrosis (versus control, P = 0.0067). Sarcomatoid (n = 7, P = 0.0064) morphology was associated with high FGF18 levels when compared to the epithelioid (n = 77) histology. Importantly, MPM patients with below median FGF18 levels had a significantly longer overall survival when compared to those with high FGF18 levels (median survival 625 versus 382 d, P = 0.0038). Data on multivariate analysis, diseasefree survival and correlation with other published biomarkers (by our group) and tumor volume will be presented at the conference. Conclusions:  Our findings suggest that FGF18 is a suitable candidate for a blood-derived biomarker in MPM which may support the histological classification of MPM and the identification of MPM patients with poor prognosis.

P09 In vitro evaluation of repurposed drugs in lung cancer and malignant pleural mesothelioma Mai-Quyen Nguyen1*, Mir Alireza Hoda1, Judit Ozsvar1, Walter Klepetko1, Balazs Dome1,2,3, Viktoria Laszlo1 Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria 2 Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary 3 Thoracic Surgery, National Institute of Oncology, Budapest, Hungary 1

Background:  Repositioning non-antineoplastic drugs with potential anti-cancer activities into new therapeutic indications offers the possibility of overcoming chemoresistance and improving clinical outcome. Our knowledge on the impact of such drugs in thoracic malignancies is limited. In this study, we investigated the anti-cancer effect of doxazosin (an alphaadrenergic blocking agent used to treat hypertension) and fluoxetine (an antidepressant belonging to the selective serotonin reuptake inhibitors) in lung cancer and malignant pleural mesothelioma (MPM). Methods:  The short-term effect of fluoxetine and doxazosin on the vitro growth of lung adenocarcinoma (ADC, n = 2), squamous cell carcinoma (SCC, n = 1), small cell lung cancer (SCLC, n = 1) and MPM cell lines (n = 2) was analyzed with SRB assay and IC50 values were determined. The long-term effect was investigated by clonogenic assay. Drugs were combined with cisplatin and combination index values were calculated using CalcuSyn software. Results: Both agents inhibited the growth of lung cancer and MPM cells in a dose-dependent manner. The IC50 values for doxazosin were 20.4 µM and 15.6 µM in ADC, 20.4 µM in SCC, 12.9 µM in SCLC, 16.9 µM and 24.3 µM in MPM cells. Fluoxetine had an IC50 value of 21.6 µM and 14.6 µM in lung ADC cells, 22.7 µM in SCC, 15.7 µM in SCLC and 10.8 µM and 16.2 µM in MPM cells. The clonogenic growth of lung cancer and MPM cells was also inhibited by doxazosin and fluoxetine. Both drugs enhanced the anti-tumor effect of cisplatin in lung ADC cells. Conclusions: Doxazosin and fluoxetine may represent a novel therapeutic strategy in thoracic malignancies. Further investigation is needed to clarify the mode of action of these drugs in lung cancer and MPM and, moreover, to reveal potential impact on clinical outcome.

P10 The expression of cyclooxygenase-2 and prostaglandin-E2 in colorectal-cancer lung metastases and corresponding primary tumors Christian Lang1*, Emilie Hrdliczka1, Thomas Schweiger1, Olaf Glück1, Gerrit Lewik1, Stefan Schwarz, Alberto Benazzo, Georg Lang1, Walter Klepetko1, Konrad Hoetzenecker1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

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Background: Pulmonary metastasectomy (PM) is an important treatment option in patients with oligometastases from primary colorectal cancer (CRC). Currently, the outcome of patients receiving PM is hard to predict. There is a lack of knowledge on variables reflecting the tumor biology of CRC lung metastases, which might be useful to determine patients’ prognosis. One of the hallmarks of cancer is the interaction of a tumor with the immune system. Thus, we sought to assess expression pattern and the possible prognostic impact of cyclooxygenase-2 (COX-2) and prostaglandin-E2 (PGE2) in pulmonary metastases from CRC. Methods: Between April 2009 and June 2014 57 patients receiving PM at the Division of Thoracic Surgery, Medical University of Vienna were included in this study. Using immunohistochemistry, lung metastases and corresponding primary tumors were assessed regarding their expression of COX-2 and PGE2. The immunohistochemical phenotype was correlated with the clinical outcome reflected by recurrence-free survival and overall survival. Results:  COX-2 and PGE2 expression was detectable in all pulmonary metastases (57/57) and primary CRC (28/28). After dichotomizing the patients according the COX-2 and PGE2 expression of the pulmonary metastases into two groups, PGE2 overexpression conferred a better recurrence free survival after metastasectomy (P = 0. 040; median recurrence free survival 11 months vs 19 months. Otherwise no significant impact on recurrence-free survival and overall survival was found. Conclusions:  In conclusion, the COX-2/PGE2 axis impacts the clinical outcome after PM. Thus, the expression of COX2/ PGE2 reflects a highly metastatic phenotype of tumor cells capable to form distant metastases. In the future, further studies need to clarify the possible therapeutic impact of inhibiting the COX-2/PGE2 pathway.

P11 Adherence to inhaled therapy and its impact on Chronic Obstructive Pulmonary Disease (COPD) Magdalena Humenberger1*, Anna Labek2, Bernhard Kaiser2, Rupert Frechinger3, Bernd Lamprecht1 Department of Pulmonary Medicine, Faculty of Medicine, Kepler-University-Hospital, Johannes Kepler University, Linz, Austria 2 OÖGKK, Linz, Austria 3 Medical Controlling, Faculty of Medicine, Kepler-UniversityHospital, Johannes Kepler University, Linz, Austria 1

Background:  COPD is a treatable disease with increasing prevalence worldwide. Treatment aims to stop disease progression, to improve quality of life, and to reduce exacerbations. Objective:  To evaluate adherence to inhaled therapy and its impact on COPD. Methods:  A retrospective analysis of patients hospitalized for COPD and discharged with a guideline conform inhaled therapy (in 2012) was performed and follow-up data on medical utilization, was recorded for the subsequent 24 months. Adherence to inhaled therapy was classified as complete (> 80 %), partial (50–80 %) or minor (< 50 %). Results:  Out of 357 patients, 65.8 % were male and 34.2 % were female, with a mean age of 66.5 years and a mean FEV1 of 55.0 % pred. Overall, 35.3 % were current smokers, and only 3.9 % were never smokers. In 79.3 % inhaled triple therapy (LAMA+LABA+ICS) was prescribed. 33.6  % had complete

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adherence to their therapy (33.2 % in men, 34.4 % in women), with a mean age of 67 years and a mean FEV1 of 49.2 % pred. Subjects with complete adherence to therapy had a significantly lower FEV1 compared to those with minor adherence (49.2 % pred. vs 59.2 % pred., p < 0.001). The risk of exacerbations leading to hospitalisation is 10-fold higher in GOLD stage IV compared to GOLD stage I. Especially for female patients in GOLD stage III and IV the rate of exacerbations was markedly lower (1.4 vs 3.1/12 months of observation) when adherence to inhaled therapy was complete compared to partial. Conclusions:  Complete adherence to inhaled therapy was only seen in 33.6 % and was higher among those with more severe COPD. In COPD III-IV exacerbations/hospitalisations are reduced when adherence is complete compared to partial.

P12 Carbon-dioxide partial pressure trends during six-minute walk test in patients with very severe COPD Vasileios Andrianopoulos1,2*, Lowie E. G.W  Vanfleteren2,4, Inga Jarosch1, Rainer Gloeckl1,3, Emiel F. M. Wouters2,4, Martijn A. Spruit2,5, Klaus Kenn1,6 Department of Respiratory Medicine and Pulmonary Rehabilitation, Schön Klinik Berchtesgadener Land, Schönau Am Königssee, Germany 2 Department of Research and Education; CIRO+, Centre of Expertise for Chronic Organ Failure, Horn, Netherlands 3 Department for Prevention, Rehabilitation and Sports Medicine, Klinikum Rechts der Isar, Technische Universität München (TUM), Munich, Germany 4 Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands 5 REVAL – Rehabilitation Research Center, BIOMED – Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium 6 Pulmonary Rehabilitation, Philipps University Marburg, Marburg, Germany 1

Background:  Transcutaneous carbon-dioxide partial-pressure (PtcCO2) can be reliably measured and may be of clinical relevance in COPD. Changes in PtcCO2 levels and exerciseinduced hypercapnia (EIH) during six-minute walk test (6MWT) need further investigation. We aimed (1) to define patterns of PtcCO2 trends during 6MWT and (2) to study determinants of CO2-retention and EIH. Methods:  Sixty-two COPD patients (age: 63 ± 8 years, FEV1: 33 ± 10 % pred.) were recruited and PtcCO2 was recorded by the SenTec digital-monitoring system during 6MWT. Results: Half of patients (50 %) exhibited CO2-retention (ΔPtcCO2 > 4 mmHg); 26 % preserved and 24 % reduced PtcCO2 in 6 MWT. Nineteen (31 %) out of 62 patients presented EIH (PtcCO2 > 45 mmHg). EIH was associated to higher baselinePaCO2, lower inspiratory-pressures, underweight/normal BMI, worse FEV1 % pred., and pre-walk dyspnea. Stronger determinants of CO2-retention were pre-walk dyspnea and FEV1 % pred. whereas pre-walk dyspnea and baseline-PaCO2 better predict EIH. Conclusions:  PtcCO2 response to 6MWT is highly heterogeneous; however, pre-walk dyspnea and high baseline-PaCO2 are associated to EIH. Increased BMI seems to carry a protective effect against EIH in very severe COPD.

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Cytokine expression in chronic lung allograft dysfunction and end-stage pulmonary fibrosis** Jonathan Kliman1*, Philipp Hacker1, Stefan Janik1, Peter Jaksch2, Jessica Didcock1, Walter Klepetko2, Hendrik Jan Ankersmit1,2, Bernhard Moser1,2 Christian Doppler Laboratory for the Diagnosis and Regeneration of Cardiac and Thoracic Diseases, Medical University of Vienna, Vienna, Austria 2 Department of Thoracic Surgery, Division of Surgery, Medical University of Vienna, Vienna, Austria 1

Background:  Chronic lung allograft dysfunction (CLAD) is the main reason for adverse long term outcome of lung transplantation (LTX). Bronchiolits obliterans syndrome (BOS), the clinical correlate of obliterative bronchiolitis after lung transplantation, has been used synonymously for CLAD. But recently a novel phenotype of CLAD has been described: Restrictive Allograft Syndrome (RAS). Methods: We enrolled 134 patients who underwent LTX: with CLAD (n = 56) and without signs of chronic rejection (LTXstable, n = 72). The CLAD patient group is divided into BOS (n = 43) and RAS (n = 13) subtypes. Furthermore we enrolled patients with end-stage idiopathic pulmonary fibrosis (IPF, n = 31) and cystic fibrosis (CF, n = 15) listed for lung transplantation, as well as 65 healthy volunteers. We performed immunoassays to determine serum concentrations of Lipocalin-2, Matrix Metalloproteinase-9 (MMP-9), Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1), Activin A and Follistatin. Results:  We found significantly elevated concentrations of Lipocalin-2 in sera of patients with CLAD compared to healthy volunteers (p = 0.013) and stable-LTX compared to healthy (p = 0.011). MMP-9 was significantly higher in CF and IPF patients compared to other groups (p < 0.001). TIMP-1 was significantly lower in healthy compared to any other group (LTXstable: p = 0.010, BOS: p = 0.014, IPF: p = 0.033, CF: p < 0.001). Follistatin concentrations were higher in BOS compared to healthy (p = 0.054). In CLAD subtype analysis RAS showed significantly elevated concentrations of Lipocain-2 compared to healthy (p < 0.001), IPF (p = 0.015) and BOS (p = 0.037) patients. Conclusions: The differential expression of Lipocalin-2 in different forms of CLAD may indicate different pathogenic mechanisms. Further investigations are warranted for a better understanding of distinct forms of CLAD.

P14 Pulmonary hypertension in hypersensitivity pneumonitis Adrienn Tornyos1,2*, Martin Trinker1,3, Vasile Foris1, Susanne Pfeiffer1,4, Balazs Odler4,5, Philipp Douschan1, Alexander Avian6, Andrea Olschewski4,7, Gabor Kovacs1,4, Horst Olschewski1,4, Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 2 Department of Interventional Cardiology, Heart Institute, University of Pécs, Pécs, Hungary 3 Rehabilitation Clinic of Respiratory and Metabolic Disorders, Bad Gleichenberg, Austria 1

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Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 5 Department of Pulmonology, Semmelweis University, Budapest, Hungary 6 Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria 7 Institute of Physiology, Medical University of Graz, Graz, Austria 4

Background: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease which may lead to irreversible lung fibrosis and pulmonary hypertension (PH). According to recent data, PH may be a complication of HP but its exact prevalence and prognostic role is not fully explored. Aims:  We aimed to assess the prevalence and clinical relevance of increased pulmonary arterial pressure (PAP) and right heart strain (RHS) in HP patients. Methods: HP patients undergoing rehabilitation between December 1997 and June 2015 at the Rehabilitation Clinic Bad Gleichenberg were enrolled in this single centre retrospective study. Demographic data, comorbidities and therapy as well as echocardiography data (systolic PAP (SPAP) and signs of RHS) and electrocardiography (ECG) data (right axis deviation (RAD)) were evaluated. The primary endpoint of the study was all-cause mortality. The impacts of baseline characteristics on event-free survival were analysed by using Kaplan- Meier and Cox regression analysis. Results:  423 patients (283 male, 140 female) were enrolled in this study (mean age: 53.4 ± 10.1). During the follow-up period (median 7.0 years) 5.2 % of the patients died. 165 patients underwent echocardiography and SPAP was assessed in 84 cases. Mean SPAP was 42.1 ± 12.7 mmHg and 50 patients had SPAP > 35 mmHg. 94 patients had evidence of RHS by echocardiography. Patients presenting with both SPAP > 35 mmHg and RHS (n = 42) had worse survival (p = 0.02; 5 years: 91 % vs. 96 %, 15 years: 65 % vs. 88 %). In patients with ECG (n = 419), RAD was present in 32 (7.6 %) subjects, which was strongly associated with worse survival (p < 0.001; 5 years: 81 % vs. 98 %, 15 years: 70 % vs. 94 %). Conclusions:  Based on our retrospective analysis, elevated PAP values and RHS is present in a considerable proportion of HP patients and they are associated with a poor prognosis. Further investigation of the pulmonary hemodynamic in patients with HP is warranted.

P15 Iron deficiency in pulmonary arterial hypertension: a matter of definition! Thomas Sonnweber1*, Eva Susanne Rieger1, Kathrin Watzinger1, Miriam Deri1, Katharina Cima2, Günter Weiss1, Judith Löffler-Ragg1 University Hospital of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria 2 Department of Pulmology, Hospital Natters, Austria 1

Background:  Iron deficiency (ID) plays an important role in chronic disease modulation. There is increasing interest in the role of iron homeostasis in the natural history of pulmonary arterial hypertension (PAH). Methods:  In 84 PAH patients the presence of ID was assessed according to six different definitions: (1) soluble transferrin receptor (sTfR) > 2.07 mg/l, (2) ferritin < 30 µg/l and transferrin

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P16 Red cell distribution width predicts survival in pulmonary arterial hypertension Victor Immanuel Scheu1*, Vasile Foris1, Gabor Kovacs1,2, Philipp Douschan1, Alexander Avian2,3, Andrea Olschewski2,4, Horst Olschewski1,2 Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 2 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 3 lnstitute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria 4 Institute of Physiology, Medical University of Graz, Graz, Austria 1

Background:  There is a need for simple prognostic biomarkers in pulmonary hypertension (PH). Iron homeostasis is often disturbed in pulmonary arterial hypertension (PAH), however, little is known about other forms of PH. Red cell distribution width (RDW) plays an important role in the differential diagnosis of anemia and was significantly elevated in idiopathic PAH. Objectives: In this retrospective analysis we investigated the prognostic value of RDW in treatment-naïve PH patients. Methods: We included n = 351 right heart catheterization patients and assessed their RDW at diagnosis and during follow-up (Group 1 PAH: n = 86; Group 2 PH (heart): n = 70; Group 3 PH (lung): n = 101; Group 4 PH (chronic thromboembolic): n = 63; Group 5 PH (multifactorial): n = 31). Mann Whitney U Test was used for comparison between groups. Kaplan Meier analysis was used for survival. Results:  Patients were followed for a median of 45 months. RDW ≤ 15 was significantly associated with a better 5-year overall survival (p = 0.042). RDW predicted survival in PAH and

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group 5 PH (p < 0.009 and p < 0.041, respectively), however, not in other forms of PH. During follow-up, RDW significantly increased in PAH (p < 0.04) and in Group 3 PH (p < 0.026), but not in other PH forms. Conclusions:  Our results suggest that RDW, a simple lowcost parameter, automatically determined with every blood count, has prognostic relevance in patients with group 1 PAH and group 5 PH but not in other forms of PH.

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Saturation (TSAT) < 15 %, (3) ferritin < 100 µg/l and TSAT < 20 % and (4) functional ID (ferritin 100–300 µg/l) and TSAT < 20 %, (5) ferritin < 100 µg/l or 100–299 µg/l and TSAT < 20 % and (6) an elevated ferritin-index (sTfR/logFerritin). The impact of ID on exercise capacity, hemodynamic measurements and blood analyses was assessed. In a subgroup of 66 patients serum levels of hepcidin were measured via ELISA. Results:  The frequency of ID varied depending on its definition. All PAH patients displayed elevated sTfR, whereas according to the stringent definition (2) only 9.9 % of the patients were iron deficient. The criteria for ID in (3) demonstrated 37.0 % iron deficient patients, in (4) 7.2 %, in (5) 76.5 % and according to ferritin index (6) in 38.3 %. In contrast to definition (1), (2) and (4) the use of criteria (3), (5) and (6) showed a significant difference between patients with normal iron status and patients lacking iron in exercise capacity as reflected by differences in 6MWD and NYHA FC, hemodynamic parameters such as PVR and blood testing with significant differences in hemoglobin and NT-proBNP levels. All patients with evidence of absolute iron deficiency displayed elevated hepcidin levels. Conclusions: The frequency of ID in our cohort of PAH patients shows pronounced differences depending on its definition. The issue of the most suitable definition of ID in PAH complicates the interpretation of the role of iron homeostasis in the pathophysiology of PAH.

P17 Mutation analysis of Austrian patients with pulmonary arterial hypertension Elisabeth Maurer1*, Martina Witsch-Baumgartner1, Regina Steringer-Mascherbauer2, Günter Weiss3, Johannes Zschocke1, Judith Löffler-Ragg3 Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria 2 Department of Internal Medicine 2, Public Hospital Elisabethinen Linz, Linz, Austria 3 University Hospital of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria 1

Background: Pulmonary arterial hypertension (PAH) is a rare disease with increased pulmonary arterial pressure and consecutively fatal right heart failure. The pathogenesis of PAH is complex and includes both genetic and environmental factors that alter vascular structure. Mutations in BMPR2 are the single most common causal factor for hereditary cases and have been identified in familial PAH (FPAH, 70 %), as well as in idiopathic PAH (IPAH, 10–40 %). Mutations in KCNK3, CAV1 or in members of the SMAD family are rare (< 3 %). Hemorrhagic telangiectasia accompanied by PAH is caused by mutations in ACVRL1 or ENG. Methods:  We analyzed the genes BMPR2, ACVRL1 and ENG in 25 patients with PAH by next generation sequencing method. Target exonic regions and adjacent exon-flanking regions were enriched from genomic DNA by Nextera® Rapid Capture (Illumina®) and underwent massive parallel sequencing (MiSeq, Illumina®). Sequences were aligned to the human reference sequence GRCh37 (hg19). Data analysis was performed with NextGENe® and Geneticist AssistantTM (Softgenetics®). Relevant variants were confirmed by Sanger sequencing or MLPA. Results: We identified two different mutations in BMPR2 and one mutation in ENG, while no mutations were found in ACVRL1. Patient 1 (21a female) with FPAH carried the BMBP2 mutation c.637C>T, leading to a premature stop-codon p.Arg213Ter in exon 6. Patient 2 (27a female) with IPAH harbored a heterozygous deletion of whole BMPR2. Patient 3 (64a male) with IPAH carried the ENG mutation c.-9G>A. Further, we detected two ENG variants (c.7C>T and c.524–12G>A) with unknown significance. Conclusions: The genetics of PAH are complex due to incomplete penetrance and genetic heterogeneity. In our patient cohort we found a mutation frequency of 12 % (8 % BMPR2 and 4 % ENG) and confirm BMPR2 as major genetic determinant underlying PAH. We have established an interdisciplinary team for genetic and clinical counselling and a screening of further candidate genes is ongoing.

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NLR predicts prognosis in pulmonary arterial hypertension Vasile Foris1,2*, Gabor Kovacs1,2, Alexander Avian1,2, Philipp Douschan1,2, Andrea Olschewski1,2, Horst Olschewski1,2 Medical University of Graz, Graz, Austria Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

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Background:  Differential blood count is routinely done at the time of diagnostic work-up and during follow-up of pulmonary arterial hypertension (PAH), however it is unknown if specific cell types are of prognostic relevance. Aims:  We aimed to analyse white cell differential counts of PAH patients and to assess if specific cell types may be of prognostic relevance. Methods: In this retrospective study we included n = 83 newly diagnosed PAH patients and n = 71 patients who underwent right heart catheterization and had normal hemodynamics. White blood cell differential counts of these two groups were analysed and compared using Mann Whitney U test. Area under the curve was calculated for each cell type as well as for neutrophil-to-lymphocyte ratio (NLR). Survival analysis was performed based on the best cut-off values. Data are presented as mean ± standard deviation. Results:  The relative and absolute number of lymphocytes in patients with PAH was decreased as compared to controls (22.3 ± 10 % vs. 25.4 ± 8.8 %, p < 0.006, 1.5 ± 0.7 vs. 1.6 ± 0.6, p < 0.025 respectively). There was a significant elevation in the relative neutrophil counts in PAH as compared to controls (66.8 ± 11.5 % vs. 64.4 ± 10.7 %, p < 0.037). There were no differences in monocyte or eosinophil counts between the two groups. NLR was elevated in PAH as compared to controls (3.8 ± 2.5 vs. 3.3 ± 2.7, p < 0.008). A cut-off for NLR of ≥ 2.62 identified patients with PAH with a sensitivity of 69 % and specificity of 56 %. Overall 5-year survival of PAH patients with NLR ≤ 2.62 was significantly better as compared to those below cut-off (69 % vs. 47 %, p < 0.038). Conclusions:  Neutrophil- to- lymphocyte ratio (NLR) is a simple tool which is of prognostic relevance for PAH.

P19 Diffusion capacity for nitric oxide: a novel marker for pulmonary hemodynamics and exercise capacity? Balazs Odler1,2*, Phillip Douschan3, Susanne Pfeiffer1,3, Vasile Foris3, Adrienn Tornyos3, Alexander Avian5, Andrea Olschewski1,4, Horst Olschewski3, Gábor Kovács1,3 Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria 2 Semmelweis University, Department of Pulmonology, Budapest, Hungary 3 Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 4 Department of Physiology, Medical University of Graz, Graz, Austria 5 Department of Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria 1

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Background: Diffusion capacity of the lung for carbon monoxide (DLCO) is widely used in the clinical practice. Nitric oxide has much higher affinity for hemoglobin, than CO and the diffusion capacity of the lung for nitric oxide (DLNO) is less influenced by changes in capillary blood volume and may better represent the true membrane diffusing capacity. However, its potential role in the differential diagnosis of pulmonary hypertension (PH) and other pulmonary diseases as well as its relationship with prognostic parameters such as six minute walking distance (6MWD) and hemodynamic variables is unknown. Methods:  Combined DLCO and DLNO, including capillary blood volume (Vc) and alveolar membrane diffusion (Dm) were measured in n = 47 patients with PH (idiopathic pulmonary arterial hypertension (IPAH): n = 20; chronic thromboembolic pulmonary hypertension (CTEPH): n = 27), n = 31 patients with chronic obstructive pulmonary disease (COPD), n = 38 patients with interstitial lung disease (ILD) and n = 20 healthy controls. In addition n = 58 patients underwent right heart catheterization (RHC) and DLNO measurement during the study period. Comparisons between groups were evaluated using one-way ANOVA followed by Bonferonni post hoc comparison. Results:  DLNO was significantly lower in all patient groups as compared to healthy controls (control: 34.4 ± 7.3 vs IPAH: 18.2 ± 6.3 vs CTEPH: 19.6 ± 5.8 vs COPD: 17.8 ± 5.6 vs ILD: 16.2 ± 6.7 ml/min/mmHg, p < 0.01; respectively). DLNO was 4 to 5 times larger as DLCO in all patient groups and the DLNO/ DLCO ratio differed significantly between all patient groups except between IPAH and CTEPH. DLNO was correlated correlated with pulmonary vascular and total pulmonary resistance (r = –0.307 and r = –0.307; p = 0.02, respectively) and 6MWD (r = 0.71; p < 0.01). While DLCO was not significantly correlated with these parameters. Conclusions: DLNO is decreased in patients with IPAH, CTEPH, COPD and ILD. DLNO may represent a novel marker for pulmonary hemodynamics and exercise capacity.

P20 Bronchial carcinoids – epidemiology and prognostic factors Anneliese Strießnig*, Julia Lovsin, Jörg Lindenmann, Nicole Fink-Neuböck, Alfred Maier, Freya-Maria Smolle-Jüttner Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria Background: Bronchial carcinoids are neuroendocrine tumours. They are subdivided into typical and atypical carcinoids. In this retrospective study the overall survival time, sex, epidemiological factors (age, smoking habits, obesity) comorbidities (COPD, coronary heart disease, vascular disease, recurrent pneumonia), surgical methods (minimal resection versus lobar resection; lymph node dissection) and localization (lobe; peripheral or central tumour) were evaluated concerning differences between the two histological subtypes. Methods:  Between 1971 and 2012 180 patients with bronchial carcinoids were treated at the Division of Thoracic and Hyperbaric Surgery, Medical University of Graz. 86 of them were evaluable for the retrospective analysis. Informations were drawn from the Hospital-Information-System “MEDOCS” and from records of the respective family doctors. Results:  69 (84 %) out of the 86 patients were alive when last followed up. The 5- and 10-year survival rates of typical carci-

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P21 EGFR, EML4-ALK, ROS 1 and BRAF testing in Austrian patients with NSCLC: a multicentre study Sophia Holzer1*, Rosemarie Rumbold1, Ulrike Setinek2, Dagmar Krenbek2, ­Andrea Mohn-Staudner1, Klaus Kirchbacher3, Nina Dworan1, Britt-Madelaine Arns1, Tatjana Bundalo4, Kurt Patocka5, Otto Chris Burghuber1, Maximilian Hochmair1 Department of Respiratory and Critical Care Medicine, and Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, Otto Wagner Spital, Vienna, Austria 2 Pathological-Bacteriological Institute, Otto Wagner Spital, Vienna, Austria 3 Department of Medicine 2 – Pneumology, Wilhelminenspital, Vienna, Austria 4 Department of Pneumology, Landeskrankenhaus Hochegg, Grimmenstein, Austria 5 Department of Pneumology, Krankenhaus Hietzing, Vienna, Austria 1

Background:  Targeted therapy is becoming increasingly important and has improved the overall survival for patients with NSCLC. EGFR and BRAF mutations, EML4-ALK and ROS1 translocations are current allocatable targets. The incidence of these druggable targets in Austria is unknown. Methods: Tumour tissue from bronchoscopy, CT- and ultrasound guided biopsies as well as surgical specimen with histological type of adenocarcinoma and NSCLC NOS (Not Otherwise Specified) were routinely analyzed independent of the tumour stage and clinical characteristics (reflex testing) for these genetic alterations. Since January 2010 the EGFR mutation detection was performed with the EGFR Mutation Test Kit from ROCHE on a COBAS4800. Since August 2011 tumour tissue was analyzed for EML4-ALK with a two-step procedure. First an immunohistochemical staining was done with the Ventana anti ALK(D5F3), OptiView DAB IHC DetectionKit and OptiViewAmplifikationKit® and further on positive cases were tested by PCR (AmoyDx®EML4-ALK FusionGeneDetectionKit) or ALK FISH (dual colour breakapart FISH/Abbott Vysis®). Since January 2014 the tumour tissue was analyzed for ROS1 with a two-step procedure. First an immunohistochemical staining was done with ROS1 D4D6, cell signaling® and further on positive cases were tested by PCR (AmoyDx®ROS1 GeneFusionDetectionKit) or ROS1 FISH (ROS1-6q22.1 dual colour breakapart probe ZytoVision®). BRAF testing was performed with the cobas®4800BRAF V600Mutation Test from Roche since March 2016. Results:  An EGFR Mutation was found in 340 out of 2776 patients (12.2 %). 253 patients (9.1 %) carried an activated mutation (Exon 19 Deletion, Exon 21 L858R). EML4-ALK positive translocation was found in 100 out of 2212 patients (4.5 %). ROS1 positive translocation was found in 5 out of 1060 patients (0.5 %). BRAF mutation was found in 3 patients out of 40 (7.5 %).

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Conclusions:  Frequency of these genetic alterations in Austrian patients with NSCLC was quite similar to other Caucasian peers. Therefore reflex testing is recommended independent of any clinical characterization.

P22 EGFR T790M resistance mutation in NSCLC: Real-life data of Austrian patients treated with osimertinib

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noids were 96 % compared to 59 % in atypical ones (p > 0.05; not significant). Lobar resections and lymph-node dissection were done significantly more frequent in atypical than in typical carcinoids. Typical carcinoids were preferably localized peripherally, whereas atypical ones were found in the central region. Moreover, the TNM-stages of atypical bronchial carcinoids were more advanced than those of the typical tumours. There were no statistically significant differences concerning age, sex, epidemiological factors and comorbidities.

Sophia Holzer1*, Maximilian Hochmair1, Martin Filipits2, Andrea Mohn-Staudner1, Peter Errhalt3, Gudrun Absenger4, Tatjana Bundalo5, Britt-Madelaine Arns1, Ulrike Setinek1, Romana Mikes6, Rainer Kolb7, Michael Schumacher8, Sabine Zöchbauer-Müller2, Kurt Patocka9, Ferdinand Haslbauer10, Jakob Rudzki11, Otto Chris Burghuber1 Department of Respiratory and Critical Care Medicine, and Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria 2 Department of Medicine I, Medical University of Vienna, Vienna, Austria 3 Department of Pneumology, University Hospital Krems, Krems, Austria 4 Divison of Clinical Oncology, Department of Medicine, Medical University of Graz, Graz, Austria 5 Department of Pneumology, Landeskrankenhaus Hochegg, Grimmenstein, Austria 6 Department of Pulmology Medicine, Paracelsus Private Medical University, Salzburg, Austria 7 Department of Pneumology, Landeskrankenhaus Wels, Wels, Austria 8 Department of Pneumology, Hospital Elisabethinen, Linz, Austria 9 Department of Pneumology,Krankenhaus Hietzing, Vienna, Austria 10 Department of Internal Medicine, Salzkammergut Klinikum Vöcklabruck, Vöcklabruck, Austria 11 University Hospital of Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, Innsbruck, Austria 1

Background:  Somatic mutations in the epidermal growth factor receptor (EGFR) are detected in approximately 13 % of the Austrian non-small cell lung cancer (NSCLC) patients. The EGFR T790M resistance mutation located on Exon 20 is the most common mechanism of drug resistance to EGFR tyrosine kinase inhibitors (TKI). The mutation can be detected by re-biopsy as well liquid biopsy. Osimertinib (AZD9291), a 3rd generation EGFR-TKI, showed a highly clinical activity in these patients. We report about our experience with Osimertinib in patients, who became resistant to first or second generation TKI’s due to EGFR T790M mutation. Methods:  From April 2015 to June 2016 we administered osimertinib 80 mg daily to 82 patients who had disease progression after previous treatment with an EFGR TKI. The T790M mutation status was assessed by re-biopsy and/or liquid biopsy. For liquid biopsies, blood samples were collected in EDTA-containing vacutainer tubes. Cell-free plasma DNA was extracted by using the QIAamp circulating nucleic acid kit (Qiagen) according to the manufacturer’s instructions.

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abstracts Results: The T790M mutation status was assessed in 48 patients by liquid biopsy only and in 13 patients by re-biopsy of the tumor. In 21 patients the T790M mutation was detected by both methods. 70 patients showed a clear clinical and radiographic response. 14 patients reached a complete remission, 56 (68 %) patients showed partial response and in 5 patients, a stable disease after treatment with osimertinib was observed. Five patients had symptomatic brain metastasis initaly without any further option of local treatment, and showed a clear clinical benefit and a remission radiographically. Conclusions:  Osimertinib was highly active in our patients, while showing good safety profile. Therefore, re-biopsy or liquid biopsy should be performed in clinical routine to detect the T790M mutation. With the above described method, liquid biopsy could replace re-biopsy in clinical practice in the future.

metastatic cases (n = 362); 32 % v 27 %; p = 0.32). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35 % v 26.5 %, p = 0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17 % (p < 0.001) and 16 % (p = 0.02) vs 33 %, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRASwild-type vs KRAS-mutant; median OS 9.7 v 3.7 months; HR, 0.49; 95 % CI, 0.31 to 0.79; p = 0.003). Conclusions:  KRAS mutation frequency in LADC patients shows a metastatic site dependent variation. The presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.

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P23 KRAS mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS mutation and bone metastasis Thomas Klikovits1*, Zoltan Lohinai2, Judit Moldvay2, Gyula Ostoros2, Erzsebet Raso3, Jozsef Timar4, Katalin Fabian5, Ilona Kovalszky6, Istvan Kenessey3, Clemens Aigner7, Ferenc Renyi-Vamos8, Walter Klepetko1, Mir Alireza Hoda1, Balazs Hegedus7, Balazs Döme1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 National Koranyi Institute of Pulmonology, Budapest, Hungary 3 2nd Department of Pathology, Semmelweis University, Budapest, Hungary 4 Molecular Oncology Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary 5 Department of Pulmonology, Semmelweis University, Budapest, Hungary 6 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary 7 Department of Thoracic Surgery, Ruhrlandklinik Essen, University Hospital of University Duisburg-Essen, Essen, Germany 8 Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary 1

Background:  Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. Methods:  In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were included. Patients with EGFR mutations were excluded. Results:  KRAS mutation incidence was 28.6 %. The most frequent metastatic sites were lung (45.6 %), bone (26.2 %), adrenal gland (17.4 %), brain (16.8 %), pleura (15.6 %) and liver (11 %). Patients with multiple-organ metastases had inferior median OS compared to those with single-organ dissemination (6.8 vs 11.6 months; HR, 0.63; 95 % CI, 0.498 to 0.788; p < 0.001). Multiple-organ metastatic patients (n = 138) also showed a non-significant increase in KRAS mutation incidence (vs single-organ

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Circulating level of the complement component 4d (C4d) correlates with chemotherapeutic response and survival in MPM patients Paul Stockhammer1*, Thomas Klikovits1, Viktoria Laszlo1, Yawen Dong1, Mir Alireza Hoda1, Isabelle Opitz-Schmitz2, Thomas Frauenfelder3, Thi Dan Linh Nguyen-Kim3, Walter Klepetko1, Balazs Dome1, Rudolf Oehler4, Balazs Hegedus1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland 3 Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland 4 Department of Surgery, Medical University of Vienna, Vienna, Austria 1

Background:  Circulating levels of the degradation complement product C4d were found to be prognostic in lung adenocarcinoma patients. Since there is limited information available about the role of complement activation in the progression of MPM we analyzed the circulating and tissue levels of C4d in a cohort of MPM patients. Methods: Plasma samples from 55 MPM patients were measured by ELISA for C4d. 21 healthy volunteers and 14 patients with non-malignant pleural diseases were also included. Tissue specimens from 32 patients were analyzed by C4d immunohistochemistry. Radiologically assessed tumor volumetry was available in 20 patients. We correlated C4d levels with clinicopathological characteristics of the MPM patients. Results:  We found no evidence of C4d labeling on MPM tumor cells. However, germinal lymphoid centers within the stroma showed C4d positivity. MPM patients showed a heterogeneous pattern of circulating C4d with several individuals showing high levels. The majority showed similar levels as controls or patients with non-malignant pleural diseases (1.24 ± 0.14 versus 1.17 ± 0.34 µg/mL and 1.30 ± 0.37 µg/mL, p = 0.833 and p = 0.851). Among MPM patients, those with advanced disease showed a tendency to have higher C4d levels (IMIG stage I/II versus III/IV: 0.92 ± 0.17 versus 1.43 ± 0.22 µg/mL, p = 0.079). After using 1.5 µg/mL as cutoff, high circulating C4d levels were associated with a higher tumor load (366.7 ± 72.67 cm3 versus 190.3 ± 46.69 cm3, p = 0.047) Furthermore, patients with low C4d levels had a significantly better prognosis (HR 7.33, CI 1.71– 31.44, p = 0.007). Plasma C4d levels following induction chemo-

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P26 Complete remissions in afatinib-treated NSCLC patients with symptomatic brain metastases Maximilian Hochmair1, Sophia Holzer1*, Hannah Fabikan1, Arshang Valipour1, Georg Christian Funk1, Otto Chris Burghuber1

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therapy were higher in patients with stable disease or progressive disease when compared to patients with positive response (2.02 ± 0.42 µg/mL versus 0.52 ± 0.13 µg/mL, p = 0.005). Conclusions: Circulating plasma level of C4d is a potential new prognostic biomarker in MPM patients. Since restaging and stratifying MPM patients for individual response after induction chemotherapy remain challenging tasks, our data suggest that measuring circulating C4d levels may help to riskstratify patients following induction chemotherapy.

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

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P25 Prognostic fibrinogen/leucocyte score at diagnosis predicts survival and benefit from multimodality treatment in MPM Thomas Klikovits1*, Pietro Bertoglio2, Marcello Carlo Ambrogi2, Paul Stockhammer1, Yawen Dong1, Balazs Döme1, Viktoria Laszlo1, Walter Klepetko1, Alfredo Mussi2, Mir Alireza Hoda1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Division of Thoracic Surgery, University Hospital of Pisa, Pisa, Italy 1

Background:  The aim of this study was to identify and validate prognostic and predictive biomarkers in a large cohort of patients with malignant pleural mesothelioma (MPM). Methods: We performed a retrospective chart review, including all patients with histologically confirmed MPM, treated at two specialized centers between 1994 and 2014. The effect of different clinical and pathological characteristics and laboratory values on outcome was investigated by using uniand multivariate logistic and cox regression models Results:  Two-hundred ninety-one patients were enrolled (222 males and 69 females). Main histological subtype was epitheloid (n = 199, 68 %). Median overall survival (OS) was 17.7 months from diagnosis. In the multivariate cox regression model, leucocyte count at diagnosis (continuous, hazard ratio (HR) 1.087, p = 0.04), fibrinogen at diagnosis (continuous, HR 1.002, p = 0.002), histological subtype (epitheloid vs. nonepitheloid, HR 0.064, p = 0.006) and age (continuous, HR 1.035, p = 0.001) remained as independently significant co-factors influencing OS. ROC curve analyses for predicting 1-year survival revealed an area under the curve (AUC) of 0.72 (p = 0.001) for fibrinogen and 0.65 (p = 0.001) for leucocytes. Dichotomizing fibrinogen and leucocytes at the median values (550 mg/dl and 8 G/l) revealed a sensitivity of 0.65 and 0.55 and a specificity of 0.69 and 0.61 for predicting 1-year survival, respectively. Combining dichotomized fibrinogen/leucocytes to an inflammation based prognostic score (none, one or both elevated) significantly influenced 1-year survival (p < 0.001) and OS (score 0 vs. I, p = 0.005; I vs. II, p = 0.03). When introducing to the multivariate cox regression model, the fibrinogen/leucocytes score remained as independently prognostic for OS (I vs. O, HR 1.48, p = 0.02; II vs. 0, HR 2.26, p < 0.001). Conclusions: The inflammation based fibrinogen/leucocytes score predicts OS independently from sex, age, stage, subtype and treatment modality. Multimodality treatment including surgery increases survival selectively in patients with low fibrinogen/leucocytes score.

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Background:  Brain metastases are a frequent complication of NSCLC, with detrimental effects on patient prognosis. TKI therapy appears to represent a new approach in patients with EGFR-mutation-positive tumours that have spread to the central nervous system (CNS). In contrast to cytotoxic treatment, TKIs have been shown to cross the blood-brain barrier. Methods:  We report on six patients with NSCLC and multiple symptomatic brain metastasis. The Table lists the patient characteristics pertaining to age, sex, TNM stage, EGFR mutation type, and number and size of the CNS lesions. As well as cough and dyspnoea, the patients presented with headache and dizziness. All patients declined whole-brain radiation therapy (WBRT). Therefore, it appeared reasonable to treat them with afatinib only, an irreversible ErbB family blocker (Giotrif, Boehringer Ingelheim). Results:  In all six patients, afatinib therapy induced complete remission that lasted at least 6 months, according to magnetic resonance imaging monitoring of the brain, with clear clinical benefit. Conclusions:  Study evidence suggests beneficial effects of afatinib in this respect, underlining these clinical observations. Afatinib might be incorporated into current treatment algorithms, allowing for the omission of radiotherapy, provided that larger phase III trials confirm the potential of EGFR TKIs in this respect.

P27 Nodal upstaging in cN0 lung cancer is more influenced by tumor size than the surgical approach Gregor Laimer1*, Cäcilia Ng1, Magdalena Sacher1, Florian Kocher2, Herbert Maier1, Paolo Lucciarini1, Thomas Schmid1, Florian Augustin1 University Hospital for Visceral, Transplant and Thoracic Surgery, Department of Surgery, Medical University of Innsbruck, Innsbruck, Austria 2 University Hospital for Internal Medicine V (Hematology and Oncology), Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria 1

Background: Several studies reported a lower rate of nodal upstaging in patients undergoing Video-assisted-thoracoscopic-surgery (VATS) anatomic resections compared to patients treated with an open resection. Aim of this analysis was to investigate nodal upstaging in cases treated by VATS or an open approach and to delineate predictive factors in a large consecutive cohort of patients. Methods:  NSCLC patients with cN0 status treated between 2004 and 2015 were included in this retrospective analysis.

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abstracts Tumors were reevaluated with regards to tumor location: a tumor was classified “central”, if it had contact to the main bronchus or first segmental branch in a CT scan or was visible during bronchoscopy. All others were classified “peripheral”. Results: Surgery was performed in 370 cN0 patients: 257 (69.5 %) VATS and 113 (30.5 %) open resections. 49 lesions (13.2 %) were classified as central tumors. Nodal upstaging was detected in 73 (19.7 %) patients. The rate of upstaging was 19.1 % and 21.2 % in VATS and open resection, respectively (p = 0.629). There was significantly more upstaging in centrally located tumors with thoracotomy (33.3 % vs. 10.3 %, p = 0.045). No difference was found in peripherally located tumors (18.5 % vs. 20.2 %, p = 0.73). cT stage was significantly higher in thoracotomy patients (p < 0.001) and was also associated with a higher rate of upstaging. No difference between VATS and open resection was observed in the different tumor stages (cT1: 14.7 % vs. 10.9 %, p = 0.478, cT2: 30.5 % vs. 27.1 %, p = 0.698, cT3: 28.6 % vs. 50, p = 0.285). However, there was a trend towards larger tumorsize in centrally located tumors with thoracotomy (p = 0.062). Conclusions:  According to our analysis VATS is not associated with reduced rates of nodal upstaging. cT status was a predictive factor for nodal upstaging. The higher rate of nodal upstaging in centrally located tumors with open resection might be biased by a larger tumor size.

P28 Incidence, local distribution and impact of pN2 skip metastasis in patients undergoing curative resection for NSCLC Ariane Steindl1, Sabrina Tahon1*, May Nguyen1, Balazs Döme1, Viktoria Laszlo1, Walter Klepetko1, Mir Alireza Hoda1, Thomas Klikovits1 Division of Thoracic Surgery, Departmant of Surgery, Medical University of Vienna, Vienna, Austria

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Background:  The presence of N2 lymph node (LN) involvement has strong impact on therapy and prognosis in non-small cell lung cancer (NSCLC). N2 LN metastasis may occur by skipping N1 LN stations (N2skip-met). We aim to analyze incidence, local distribution and impact of N2skip-mets in a large cohort of patients undergoing curative resection for NSCLC. Methods: A retrospective non-interventional singe-center cohort study was conducted, assessing all patients undergoing curative resection for NSCLC between 2006 and 2013 at our institution by reviewing medical charts. Incidence of N2skip-mets among these patients was the primary endpoint. Subsequent secondary correlation of clinical parameters was performed using uni- and multivariate logistic and cox regression models. Results:  In total, 1110 patients were enrolled, with the following pathological LN status: 789 (71 %) pN0, 211 (19 %) pN1, 105 (9.5 %) pN2, 5 (0.5 %) pN3. Histological subtype was: adenocarcinoma, n = 675 (61 %); squamous cell carcinoma, n = 309 (28 %); other, n = 126 (11 %). Incidence of N2skip was 55 % (47/105). N2skip-mets occurred more frequently in right sided tumors (odds ratio (OR) 2.14, p = 0.058) and patients with adenocarcinoma (vs. other, OR 1.54, p = 0.19). Presence of N2skipmets did not correlate with tumor size (ROC, area under curve (AUC) 0.44, p = 0.32). Strikingly, presence of N2skip-mets was significantly increased in smokers (OR 3.5, 95 % CI 1.38–8.83, p = 0.006). Moreover, patients with N2skip-mets were more likely to develop subsequent brain mets (OR 4.13, p = 0.06). Overalland recurrence free survival will be presented at the conference.

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Conclusions: N2skip-mets occur in a high number of patients with N2 disease, with distinct differences in clinicopathologic features. Considering the results of this study, subclassification of N2 disease as recently proposed by the IASLC may have clinical impact in patients with resectable NSCLC.

P29 Palliative resection for stage IV non-small-cell lung cancer Paul Swatek* Department of Thoraxic Surgery, Hospital Wolfsberg, Wolfsberg, Austria Background: Critical situations such as tumor-induced sepsis or bleeding may develop in the course palliative treatment. When non-surgical methods have no effect, it is mainly in young patients, that palliative resection is discussed in these cases. In other, rare instances the palliative – but resectable – constellation is not diagnosed but intraoperatively. The question whether palliative resection is beneficial or merely an additional burden for incurable patients was investigated. Methods:  In a retrospective data analysis 800 patients who underwent resection of lung cancer at the Division of Thoracic and Hyperbaric Surgery between January 2005 and December 2014 were reviewed. 24 patients with non-small cell lung cancer in whom the resection was carried out under palliative intent due to M1 (M1a: 13; M1b: 11) were identified. The prognostic impact of histology, T and N stage, surgical technique, post/ preoperative therapy, as well as preoperative albumin, CRP, monocytes and neutrophils was analysed. Results:  The mean survival time was 14.9 months. Patients undergoing pneumonectomy had 7.4 mo. median survival compared with 15.7 months after lobectomy (n. s.). Extremely poor results with median survival of 10.5 days only were found after urgent resection because of tumor-related sepsis. No significant influence of pre- and postoperative therapy, T and N stage, histological subtype, age, or sex on survival was found. Preoperatively elevated CRP, neutrophil granulocytes and monocytes, as well as decreased albumin negatively correlated with the survival time. Conclusions: Palliative resection of non-small-cell lung cancer in stage IV has to be considered with extreme caution. If the extent of disease would require pneumonectomy, or in presence of severe sepsis resection should be avoided because of detrimental results.

P30 Is it safe to use NSAIDs for pain control during che­ mical pleurodesis for malignant pleural effusion? Maria Anna Smolle1*, Holger Flick2, Martin Pichler3, Horst Olschewski2, Jörg Lindenmann4, Armin Gerger3 Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria 2 Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 3 Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria 4 Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria 1

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P31 Incidence and outcome of female patients with previous breast cancer undergoing curative resection for lung cancer Sabrina Tahon1*, Ariane Steindl1, Mai Nguyen1, Balazs Döme1, Viktoria Laszlo1, Walter Klepetko1, Thomas Klikovits1, Mir Alireza Hoda1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

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Background:  Due to recent improvements in breast cancer (BC) therapy and outcome, female patients with BC may be at higher risk of developing secondary malignancies such as lung cancer (LC). The aim of this study is to evaluate the incidence and outcome of previous BC in female patients with resectable lung cancer. Methods: A retrospective non-interventional singe-center cohort study was conducted, assessing all female patients undergoing curative resection for LC between 2006 and 2013 at our institution by reviewing medical charts. Follow-up will be completed in September 2016. Incidence of previous BC among these patients was the primary endpoint. Subsequent secondary correlation of clinical parameters was performed using uniand multivariate logistic and cox regression models. Results:  Allover, 463 female patients with LC were identified. The incidence of previous BC was 8.6 % (40/463). Mean age was 64.1 years (SD ± 11.5) and was not different between patients with LC and LC/BC. Main histological LC subtype was adeno-carcinoma (64 %; squamous cell, 23 %; other, 13 %). Stage (TNM-7) distribution was: I, 64.5 %; II, 22 %; III, 12.5 %. Lobectomy was the preferred anatomical resection and mean hospital stay was 8.3 days. Complication rate was 7.6 %. Recurrence free and overall survival will be presented at the conference. There

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were no statistical differences between patients with LC/BC and LC with regard to main clinical parameters and short term outcome. Conclusions:  Due to improvements in breast cancer therapy, a reasonably number of patients developing subsequent lung cancer is observed. Short-term outcome of patients with LC/BC is similar to those with LC.

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Background: Malignant pleural effusion (MPE) develops in advanced stages of malignant diseases. The injection of sclerosing agents into the pleural cavity induces inflammatory processes, thus leading to adhesion of pleural layers. Pain medication may be based on the WHO three-step analgesic ladder for cancer pain. Experimental studies, however, indicate that the anti-inflammatory effect of NSAIDs negatively influences the efficacy of chemical pleurodesis. The emphasis of this study was to retrospectively analyse the impact of NSAIDs on chemical pleurodesis in MPE. Methods:  Demographic, pathological and treatmentrelated parameters of 120 patients (68 females, 52 males) with MPE undergoing chemical pleurodesis were retrospectively analysed. Factors were correlated with outcome following chemical pleurodesis. Failure of the procedure was determined as recurrent ipsilateral MPE exceeding the hilus and/or an effusion requiring re-drainage. Results: Recurrent MPE developed in 25.8 % of patients (n = 31) during a mean follow-up of 7.9 months. The effect of chemical pleurodesis was not impaired following peri-interventional use of NSAIDs (univariate analysis; p = 0.133). Chemotherapy applied after the procedure was the only independent factor reducing the hazard for recurrent MPE (multivariate analysis; HR:0.399, 95 %CI: 0.121–0.948, p = 0.039). Conclusions: Based on the present study, the efficacy of chemical pleurodesis is not impaired by NSAIDs. Therefore, the schedule for pain management as proposed by the WHO may be safely used in patients with MPE during chemical pleurodesis.

CRP, albumin, vitamin D and monocyte/ lymphocyte ratio. No prognostic impact for progression-free survival after pulmonary metastasectomy for colorectal- and renal cell carcinoma Melanie Fediuk*, B Breul, Nicole Fink-Neuboeck, Paul Swatek, Alfred Maier, Joerg Lindenmann, Freyja Maria Smolle-Juettner Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, Graz, Austria

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Background:  In spite of well-known prognostic factors like number and laterality of lesions, type of tumor and interval since treatment of the primary lesion the course after pulmonary metastasectomy is difficult to predict. CRP, vitamin D3, albumin, the rate of monocytes/lymphocytes and thrombocytes have been described as predictive parameters either as single factors or combined as scores for the prognosis of a variety of malignancies either in curative or in palliative settings. Up to this time, very little is known about pulmonary metastasectomy in this context. Methods: In a retrospective analysis in 101 patients who underwent pulmonary metastasectomy at the Division of Thoracic and Hyperbaric Surgery in Graz between 2010 and 2014 (renal cell carcinoma N = 29; colorectal carcinoma N = 72) the influence of CRP, albumin, vitamin D3, monocyte/lymphocyte ratio and thrombocytes as well as further factors (age, sex, single or multiple lesions, smoking habits, haemoglobin, LDH) were assessed for their prognostic impact on progression-free survival (5-year pf survival). Results: Overall 5-year pf survival was 27.3 % (median: 20  ±  4.3 Mo). The 5-year pf survival rates of renal-cell (8.9 %; median: 14 ± 4.6 Mo) and colorectal carcinoma (35.4 %; median: 22  ±  7.9 Mo) were significantly different (p = 0.016). The only significant prognostic factors for the 5-year pf survival in the overall collective were the number of metastases (single lesion: 28.3 %; multiple lesions: 17.4 %; p = 0.07) and thrombocytes < 140.000 (normal thrombocytes: 25.3 %; thrombocytopenia: 0 %; p = 0.005). Thrombocytopenia was a significant predictor for worse outcome in the colorectal metastasis subgroup as well (p = 0.001), whereas age below the median predicted an unfavourable course for metastases of renal-cell carcinoma (p = 0.048). Conclusions:  CRP, vitamin D3, albumin and the monocyte/ lymphocyte ratio as single parameters or in combination had neither prognostic impact in the total collective nor in the two subgroups.

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Vitamin D, CRP and Albumin in thoracic surgical patients Melanie Fediuk1*, Thomas Fuchs, Nicole Fink-Neuböck1, Jörg Lindenmann1, Alfred Maier1, Freyja-Maria Smolle-Jüttner1 Department of Thoracic Surgery and Hyperbaric Medicine, Department of Surgery, Medical University of Graz, Graz, Austria

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Background:  The prognostic value of CRP and albumin in malignancies of the lung or esophagus is already documented: High levels of CRP or low levels of albumin are associated with a poor prognosis.So far there are no data on the possible correlation of vitamin D3 levels, CRP and albumin in a patient population that includes not only all ages, but also a wide range of malignant and benign diseases of the thoracic cavity. Methods:  In a retrospective analysis of thoracic surgical patients seen in the last 2 years at the division of thoracic surgery a correlation of vitamin D, CRP and albumin at the time of admission was evaluated. The data of all in- patients (age: 18 to 90 years) with benign or malignant tumours at or within the chest between October 2012 to October 2014 were analysed. Exclusion criteria were severe renal diseases and vitamin D substitution at the time of admission. 1343 cases where found. In the end there were 515 cases with a complete set of data. Results:  A statistically significant association between CRP, albumin and vitamin D3 levels was shown. Further analysis yielded significant associations between low vitamin D3, high CRP and low albumin and the presence of or poor prognosis of malignant diseases. Conclusions:  The shown relationship between vitamin D3, albumin and CRP might be of prognostic value in malignant disease. Further studies on this combination of parameters are required.

P34 VATS lobectomy: learning curve in the field of experienced VATS surgery Gernot Seebacher1,2*, Milos Brndiar1, Jan Tripsky1, Tomas Bohanes1, Elisabeth Stubenberger1 Department of General and Thoracic Surgery, Universitätsklinikum Krems, Krems, Austria, 2Karl Landsteiner Institute for Clinical Surgery, Krems, Austria

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Background: VATS lobectomy is widely accepted as a standard procedure for the treatment of early stage lung cancer nowadays, but the method is not implemented that widely. A lot of colleagues are afraid of taking this hurdle. Methods:  Four experienced thoracic surgeons, well trained in VATS surgery but having almost no experience in VATS lobectomy started a VATS lobectomy program. One surgeon with experience in VATS lobectomies worked as a supervisor. After the period of January 2014 until April 2016 we retrospectively analyzed our performance. Results:  Within given period we had done 117 lobectomies, 53 with anterolateral incision, 64 by VATS access (54.7 %). We had to convert for 3 times; first due to a recurrent bleeding from a pulmonary segmental vein, second due to pleural adhesions

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and third due to a patient with severe COPD with a lack of collapse of the lung. No mortality was seen in both groups. The mean operating time was 173 minutes for VATS access (minimum: 106 min, maximum: 333 min) and 129 for open access (minimum: 63 min, maximum 253 min). As well as in several studies reported there was a trend for less pain and earlier discharge in the VATS group. Regarding operation time we saw a reduction in 3 of the four surgeons in the first half of operations done compared to the second: 178.3 min vs. 170 min (–4.5 %, n = 25), 203 min vs. 179.3 min (–11.7 %, n = 8), 202.4 vs. 171.8 min (–15.2 %, n = 10). The fourth started faster (148.9 min), but lost time within the observation period (162 min) (+8.8 % %, n = 20). Conclusions:  VATS lobectomy is much easier to learn than expected. Substantial experience of endoscopic lung surgery prior to VATS lobectomy was helpful. Complications could be kept very low despite the fact, that four guys started the same time.

P35 Reduced postoperative morbidity for octogenarians after VATS lung resection compared to an open approach Cäcilia Ng1*, Herbert Maier1, Florian Kocher2, Paolo Lucciarini1, Thomas Schmid1, Florian Augustin1 University Hospital for Visceral, Transplant and Thoracic Surgery, Department of Surgery, Medical University of Innsbruck, Innsbruck, Austria 2 University Hospital for Internal Medicine V (Hematology and Oncology), Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria 1

Background: Due to prolonged life expectancy, more patients aged 80 years or older will undergo anatomic lung resection for lung cancer. This study was performed to evaluate perioperative morbidity and mortality in these patients and differences due to the surgical technique (thoracotomy vs. videoassisted thoracoscopic surgery – VATS). Methods:  A retrospective analysis of patients aged 80 years or older who underwent anatomical lung resection between 2001 and 2015 was performed. Results:  47 patients were found in the database. Resection was performed by VATS technique in 27 patients and an open technique in 20 patients. Median age was 81 years and did not differ between the VATS and thoracotomy group. UICC staging was stage I in 29 patients, stage II in 13 patients and stage III in 4 patients; one patient had metastatic disease requiring lobectomy. 40 patients had one or more comorbidities (COPD, coronary artery disease with intervention, diabetes mellitus or renal insufficiency) with no differences between the VATS and thoracotomy group. Types of resection were lobectomy in 38 patients, segmentectomy in three, bilobectomy in five and pneumonectomy in one patient. Chest drain duration was 6.5 days in median in the thoracotomy group and 5 days in the VATS group (p = 0.07). 12 patients had postoperative complications, with significantly less complications in the VATS group (11.1 % vs. 45 %, p = 0.0161). Median length of hospital stay for all patients was 12 days, with a significant shorter stay in the VATS group (10 vs 13 days, p = 0.008). There was no in-hospital mortality. Conclusions: Lung resection can safely be performed in selected octogenarians with acceptable morbidity and low mortality rates. The use of a VATS technique can significantly reduce the rate of perioperative complications and length of hospital stay.

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P36 Development of a robotic program for general thoracic surgery at the current scenario: is it worth? Jose Ramon Matilla1*, Bernhard Moser1, Axel Scheed1, Thomas Schweiger1, Walter Klepetko1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

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Background:  In the last two decades, many new advances at general thoracic surgery are focused in minimal invasive procedures; in this scenario robotic surgery also plays an important role, even more with the development of the latest robot models. High costs remain the first barrier for many institutions who have no access to robotic technology and open a discussion regarding costs increase for apparently similar results.We present our data regarding the establishment of a robotic program in our institution since 2013, to clarify if the start of such a program has a clear benefit among all other minimal invasive procedures. Methods:  At the beginning of our program thymus procedures were the ideal operations to get skills at the console, at the same time cervicotomies were no longer necessary for thymus removal. After many successful thymus procedures we also include lung cancer in our indication list. Results:  In total we performed 64 procedures using robotic technology, 57 thymectomies and 7 lobectomies for lung cancer. Regarding mediastinal procedures, in 45 cases, patients were suffering from myasthenia gravis (4 paediatric patients). We registered one conversion due to pleural adhesions and no intra/pos operative morbidity/mortality. Mean operative time was 54 minutes. In the lung cancer group of patients, 7 lobectomies were performed. One conversion due to calcified lymph node was registered and one prolonged post-operative air leak solved without re-intervention after 2 weeks of drainage. Mean operative time was 192 minutes and no mortality in the lobectomy group. Conclusions:  The superior motility of robotic instruments can make thoracic surgeons achieve higher level of radicality in some procedures even more when transition from VATS to robotic procedures requires not prolonged learning curves. At our institution left side robotic thymectomy is nowadays the standard approach for patients suffering myasthenia gravis and small thymomas. Robotic instruments allow perfect radical dissection of the thymus from the cervical region down to the lower part of the pericardium.

P37 To induce or not to induce after lung transplantation? Vienna experience** Alberto Benazzo1*, Stefan Schwarz1, Gabriela Murakozy1, Cristopher Lambers1, Gyorgy Lang1, Jose Matilla1, Shahrokh Taghavi1, Walter Klepetko1, Peter Jaksch1 Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria

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Background:  According to the Registry of ISHLT (1), about 50 % of patients transplanted in the last 10 years received some

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type of induction therapy. The most used agents are IL2R Antagonists but interest for Alemtuzumab is increasing. In our study we reviewed all adult lung transplantations from 2007 to 2014 to understand the impact of induction immunosuppression on transplantation outcomes. Methods:  Medical records of 780 patients were reviewed. The following outcomes were examined: patient survival, ACR, LB and CLAD incidence, malignancies and kidney function. Infection incidence and long-term comorbidities were also examined. Results: 446 Patients were included in our analysis. 231 received Alemtuzumab (51.80 %), 50 Thymoglobulin (11.20 %) and 165 no induction (37 %). Alemtuzumab group had the least rate of kidney insufficiency (no: 52.2 %; ATG: 60 %; Alemtuzumab: 36.6 %; p = 0.001) and in parallel, at a linear mixed model, Alemtuzumab group showed by better Creatinine (p < 0.001). ATG and No induction groups showed an higher infection rate in the first year (No: 35.3 %; ATG: 36.2 %; Alemtuzumab: 21.4 %; p < 0.001). Alemtuzumab had a greater freedom from ACR (p < 0.001) and LB (p < 0.01). Moreover it showed a better freedom from CLAD compared to the other groups (p < 0.01). Patients receiving Alemtuzumab had a better 5-years survival: 62.9 % for No induction, 70.7 % for ATG and 77 % for Alemtuzumab (p = 0.004). At the multivariable analysis, independent from other covariates, Alemtuzumab improved survival (HR = 0.619; CI = 409–937; p = 0.023) and along with ATG, it was protective against CLAD (ATG: HR = 0.301, CI = 0.144–631, p = 0.001; Alemtuzumab: HR = 0.556, CI = 0.356–0.868, p = 0.01). Conclusions:  From our retrospective analysis, we deduce that any induction therapy improves long-term results and survival after transplantation. In particular Alemtuzumab seems to improve patient survival, ACR, LB and CLAD incidence independent from other factors. Moreover, in our cohort, Alemtuzumab with reduced maintenance IS was associated with better kidney function and less infections in the first year.

P38 The Laryngotracheal Program Vienna – five-year experience and results Konrad Hoetzenecker1, Thomas Schweiger1, Stefan Schwarz1, Immer Roesner2, Matthias Leonhard2, Berit Schneider-Stickler2, Wolfgang Bigenzahn2, Doris-Maria Denk-Linnert2, Walter Klepetko1* Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Division of Phoniatrics-Logopedics, Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria 1

Background:  Benign and malignant diseases of the trachea are rare and their surgical treatment is sometimes challenging. If the laryngotracheal border is involved, diagnosis, therapy and postoperative rehablitiation is even more complex and requires a multidisciplinary approach. Methods: A dedicated laryngotracheal team consisting of thoracic surgeons, phoniatricians, logopedics was established in 2011 at the Medical University Vienna. Every patient referred to the Laryngotracheal Program Vienna was seen, treated and followed-up by this interdisciplinary team in a structured way. Results:  A total of 120 patients were operated by the Laryngotracheal Team Vienna since 2011. The majority of patients

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abstracts were referred for correction of a benign airway stenosis, which had developed on the basis of a long-term intubation or a tracheostomy. 25 % of our patient cohort suffered from a primary or secondary airway tumor. We performed 50 tracheal resections (predominantly cervical resections) and 45 laryngotracheal resections for lesions extending to the subglottic airway or even intralaryngeally. In about half of these laryngotracheal problems, extended resection methods e. g. cricotracheal resection + dorsal mucosal flap; cricotracheal resection + ant laryngeal split; cricotracheal resection + lateral thyroidectomy; modified Couraud technique) had to be performed. The remaining surgical interventions included dorsal stabilizations for tracheobronchomalacia, carinal resections, repair of a tracheoesophageal fistulas or special pediatric reconstruction techniques. Median follow-up after surgery was 28 months. Results were excellent or acceptable in 83 % of cases (based on endoscopic follow-up, functional status, voice examination and swallowing function). Conclusions:  This preliminary experience of our laryngotracheal team shows that excellent results can be achieved in the treatment of complex airway problems by a multidisciplinary approach. A centralization of these highly demanding patients should be considered in order to offer patients optimal treatment.

P39 Segmental tracheal resection in a patient with chondrodysplasia punctata and early posttracheostomy tracheal stenosis Stefan Schwarz *, Thomas Schweiger , Alberto Benazzo1, Konrad Hötzenecker1, Imme Roesner2, Doris-Maria Denk-Linnert2, Walter Klepetko1 1

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Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria 2 Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria 1

Background: Posttracheostomy stenosis is the most frequent indication for tracheal resection today. Typically, a slowly progressing cicatricial narrowing in the area of the former tracheostomy leads to stenosis of a short segment – often years after successful decannulation. In experienced centers, excellent long-term results can be achieved with resection of the affected segment. Chondrodysplasia punctata refers to a genetically heterogenic group of disorders characterized by a defect of chondrocyte function. The different subtypes all involve focal calcifications in the cartilaginous tissue of epiphyses, joints, the larynx and the trachea. Presentation of a case:  We present the case of a 27-year-old patient with an unspecified subtype of chondrodysplasia punctata. After an orthopedic operation, the patient developed bilateral pneumonia. In the course of the subsequent stay on intensive care, surgical tracheostomy was performed. Subsequently, the stoma spontaneously closed after decannulation. As early as 4 months after decannulation, the patient complained of increasing inspiratory and expiratory stridor, which led to the diagnosis of a slit-shaped tracheal stenosis. A cervical, segmental tracheal resection of 20 mm length was performed under laryngeal mask – and intermittent cross-table ventilation. End-to-end anastomosis was achieved by single sutures for the anterior cartilaginous part and running sutures for the posterior pars membranacea. The postoperative course was uneventful and the patient could be discharged on the 5th post-

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operative day. The histological work-up of the resected segment revealed collapsed tracheal rings with focal areas of calcification. Routine check-ups confirmed an excellent result. Conclusions: The patient we present in this case report developed tracheal stenosis just 19 weeks after tracheostomy. Even though a possible causal link to her chondrodysplasia remains unclear, in our opinion the decision for tracheostomy should be made carefully and restrictively in these patients.

P40 Altitude and COPD prevalence and other determinants: analysis of the PREPOCOLPLATINO-BOLD-EPISCAN study** Andreas Horner1,2*, Joan B Soriano3, Milo A Puhan4, Michael Studnicka5, Bernhard Kaiser2, Lowie Vanfleteren6,7, Louisa Gnatiuc8, Peter Burney8, Marc Miravitlles9, Francisco García-Rio10, Julio Ancochea11, Ana M Menezes12, ­Rogelio  Perez-Padilla13, Maria Montes de Oca14, Carlos A Torres-Duque15,16, Andres Caballero16,17, Mauricio González-García15, Sonia Buist18, Bernd Lamprecht1,2, for the BOLD Collaborative Research Group, the EPI-SCAN Team, the PLATINO Team, and the PREPOCOL Study Group Department of Pulmonary Medicine, Kepler University Hospital, Linz, Austria 2 Faculty of Medicine, Johannes-Kepler-University, Linz, Austria 3 Instituto de Investigación Hospital Universitario de la Princesa (IISP), Universidad Autónoma de Madrid, Cátedra UAM-Linde, Madrid, Spain 4 Institute for Social and Preventive Medicine, University of Zurich, Zurich, Switzerland 5 Department of Pulmonary Medicine, Paracelsus Medical University, Salzburg, Austria 6 Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands 7 Program Development Centre, CIRO+, Centre of Expertise for Chronic Organ Failure, Horn, The Netherlands 8 Respiratory Epidemiology and Public Health, Imperial College, London, United Kingdom 9 Servicio de Neumología, Hospital Universitari Vall d’Hebron. Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain 10 Servicio de Neumología, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain 11 Servicio de Neumología, Hospital La Princesa, Universidad Autónoma de Madrid, Madrid, Spain 12 Programa de Pós-Graduacão em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil 13 Institute of Respiratory Diseases, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico 14 Servicio de Neumonología, Hospital Universitario de Caracas, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela 15 Departamento de Investigación, Fundación Neumológica Colombiana, Bogotá, Colombia 16 Asociación Colombiana de Neumología y Cirugía de Tórax, Bogotá, Colombia 17 Clínica Reina Sofía, Bogotá, Colombia 18 Oregon Health and Science University, Portland, USA 1

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Background: COPD is highly heterogeneous, and factors beyond age and smoking can partly explain its population variability. Geographical altitude has been linked to COPD prevalence, yet with conflicting results. Methods:  A pooled analysis of individual data of the PREPOCOL-PLATINO-BOLD-EPISCAN study (n = 30,874) was used to disentangle the population effect of geographical altitude on COPD prevalence and other population and individual determinants. Post-bronchodilator FEV1/FVC less than the lower limit of normal (LLN) is used to define chronic airflow limitation consistent with COPD. High altitude was defined as > 1500 m above sea level. Undiagnosed COPD was considered when participants had post-bronchodilator FEV1/FVC < LLN but did not report a prior diagnosis of COPD. Results:  Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8 % were women, and 49.6 % neversmokers. 12.9 % or 3,978 subjects were residing at elevations above 1500 meters. COPD prevalence was significantly lower in participants living at high altitude with prevalence rates of 8.5 % compared to 9.9 %, respectively. However, known risk factors for COPD were significantly less frequent at high altitudes. Hence, the results of the multivariate analysis adjusted for sex, age, BMI, level of education, smoking status, and history of a dusty job indicate that altitude itself has no significant influence on the prevalence of COPD. Though, living at high altitude was associated with a significantly increased risk of undiagnosed COPD. This might be due to the fact that subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude. Conclusions: Living at high altitude is associated with a lower COPD prevalence. However, altitude itself did not prove to reduce the risk of COPD but to increase the risk of undiagnosed disease.

Finding a systemic biomarker that reliably predicts disease course after acute exacerbation displays a major challenge. Serum HSP27 has been previously studied in COPD; however, its dynamic as well as prognostic value in urine after an exacerbation episode is not known. Methods: To assess HSP27 urine excretion, prospectively sampled urine and serum of 225 patients admitted to the hospital due to acutely exacerbated COPD were analysed using a commercially available ELISA Kit (DYC1580, R&D Systems). Samples were obtained at admission, discharge and 180 days after discharge. The dynamic of HSP27 urine excretion after an exacerbation episode was analysed and correlated with clinicopathological and survival data. Results:  Mean patient age was 70.5 years, 28 % were female and 180 day mortality was 11.6 %. HSP27 urine excretion increased after an exacerbation episode (1.79 % admission, 1.75 % discharge, 2.27 % 180 days after discharge (p = 0.04)). In GOLD IV patients this course was even more distinct (1.59 % admission, 2.12 % discharge, 2.77 % 180 days after discharge (p < 0.01)). Furthermore HSP27 urine excretion at discharge was increased in GOLD IV patients (p < 0.01) and female patients (p < 0.01). Using two different cut off values admission HSP27 urine excretion levels could both predict short-term (30 day, 90 day, 180 day; cut off = 0.845 %) and long-term (2 year, 3 year; cut off = 2.27 %) survival in Kaplan Meier survival analyses and Cox regression models. No cut off value that predicted hospital readmission within 180 days could be identified. Conclusions:  Our findings provide novel information about HSP27 urine excretion in COPD patients with acute exacerbation. HSP27 urine excretion increases after an exacerbation episode with an even more distinct course in severe COPD and predicts survival suggesting it to be a prognostic factor.

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Vitamin D and 1,25-dihydroxycholecalciferol in smokers and nonsmokers of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC)

HSP27 urine excretion levels and outcome in acute COPD exacerbation Denise Traxler1,2, Jerneja Farkas5, Matthias Zimmermann1, Robert Marcun6, Elisabeth Simader1,2*, Pika Mesko Brguljan6, Olaf Michael Glueck1,2, Christine Bekos2,3, Elisa Einwallner4, Walter Klepetko2, Hendrik Jan Ankersmit1,2, Mitja Lainscak7,8

Graciela Delgado1, Rüdiger Siekmeier2*, Laurin Titze3, Stefan Pilz4, Winfried März1,4,5, Marcus Kleber1,6

Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria 2 Department of Thoracic Surgery, Medical University of Vienna, Austria, Vienna, Austria 3 Department of Gynaecology and Gynaecological Oncology, Gynecologic Cancer Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria 4 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria 5 National Institute of Public Health, Ljubljana, Slovenia 6 University Clinic Golnik, Golnik, Slovenia 7 Department of Cardiology and Department of Research and Education, General Hospital Celje, Celje, Slovenia 8 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 1

Background:  COPD is a major cause of morbidity and mortality and is characterised by episodes of acute exacerbations.

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Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 2 Drug Regulatory Affairs, Pharmaceutical Institute, University Bonn, Bonn, Germany 3 Department of Throacic Surgery, University of Freiburg, Freiburg, Germany 4 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria 5 Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany 6 Institute for Nutrition, University of Jena, Jena, Germany 1

Background: Cardiovascular disease (CVD) is an important cause of morbidity and mortality worldwide. Vitamin D (25OHD) has pleiotropic effects beyond its effect in calcium metabolism and 25OHD deficiency serves as marker for CVD. Recently reports showed evidence for lower 25OHD concentration in active smokers (S). Aim of our study was to analyze 25OHD and its active metabolite 1,25-dihydroxycholecalciferol [1,25(OH)2D] in S and life-time nonsmokers (NS) of the LURIC Study and to investigate their association with incident chronic obstructive pulmonary disease (COPD).

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abstracts Methods:  We determined plasma concentrations of 25OHD and 1,25(OH)2D in 3316 LURIC patients with coronary angiography. Individual smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration. Incident COPD was assessed by a Follow-up questionnaire. Results: 777 LURIC participants were S and 1178 NS. From 1723 study participants that returned the questionnaire 22 participants reported an incident COPD (9 S, 13 NS). The concentration of 25OHD was similar in S and NS (15.2 (9.90–22.3) vs. 15.2 (9.90–23.2) µg/L whereas concentration of 1.25(OH)2D was lower in S (33.7 ± 14.1 vs. 35.2 ± 14.1 ng/L, p = 0.022) and correlated to cotinine concentration (rS = 0.120, p = 0.001). After adjustment for age, sex, eGFR and the season of blood sampling the estimated marginal means (95 % CI) of 1.25(OH)2D were 32.5 (31.5 – 33.5) and 36.0 (35.2 – 36.8) for S and NS, respectively. 1.25(OH)2D was associated with COPD incidence in S with an odds ratio (95 % CI) of 0.937 (0.888–0.989) and remained significant after adjustment with an OR of 0.943 (0.890–0.999). Conclusions:  Our results show reduced concentrations of 1.25(OH)2D, i. e. active vitamin D but not 25OHD in S, indicating a potential effect of smoking on vitamin D metabolism which might be followed by consecutive effects of vitamin D deficiency. The predictive value of 1.25(OH)2D for COPD in S should be investigated in more detail in further studies.

P43 Status quo of the non smoker protection in the catering industry of Graz Melanie Fediuk1*, Markus Andreas Lernbass, Nicole Fink-Neuböck1, Jörg Lindenmann1, Alfred Maier1, Freyja-Maria Smolle-Jüttner1 Division of Thoracic Surgery and Hyperbaric Medicine, Department of Surgery, Medical University of Graz, Graz, Austria

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Background: Austria is “world champion” concerning teenage smokers. The proportion of smokers in relation to the total population lies clearly above the OECD average whereas the proportional decreasing number of active smokers is far below the European average. The current Austrian regulation (Tobacco Amendment 2008) concerning non smoker protection in the catering industry does not follow the European trend of a general ban on smoking. With exceptions, it is still permitted to smoke in restaurants, cafes, etc. as long as architectural steps have been taken to seperate smoking and non smoking areas. Methods:  300 eating places in Graz were visited in order to find out the quantitative relation of smoking-, non smoking-, and mixed places and the current observance of the law. Results:  Only 34 % of the visited restaurants, etc. are non smoking catering businesses. About one third of the smokers’ places violate the size regulation which, according to the law, would allow smoking. In about two thirds of the mixed places smoking and non smoking areas are not seperated in an appropriate way and in 81 % the non smoking areas were contamined with tobacco fumes. In 57 % the passage from the non smoking area to the toilet is not possible without crossing the smoking area. All in all, 74 % of the visited gastronomy facilities in Graz violate the current non smoker protection law in one way or another.

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Conclusions:  The study results show impressively how the non smoker protection law is not implemented sufficiently in Graz and it has to be assumed that the situation is similar in the whole country. Therefore, the current law not only has to be questioned but a general ban on smoking should be considered in order to fight the increasing tobacco addiction and protect the non smokers appropriately.

P44 Role of vitamin D deficiency in asthma bronchiale – an overview Rüdiger Siekmeier1*, Graciela Delgado2, L. Titze3, Tanja Grammer2, Stefan Pilz4, Marcus Kleber5, Winfried März6 Drug Regulatory Affairs, Pharmaceutical Institute, University Bonn, Bonn, Germany 2 Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany 3 Department of Throacic Surgery, University of Freiburg, Freiburg, Germany 4 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria 5 Institute of Nutrition, University of Jena, Jena, Germany 6 Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany 1

Background: Since decades vitamin D is known to be essential for prevention and treatment of rickets in children and osteomalacia and osteoporosis in adults. In the last years other important pleiotropic effects of vitamin D, e. g. regulation of immune response and inflammation, obesity, musculoskeletal development, growth and development were in the focus of interest and it was observed that low vitamin D plasma concentrations are a risk factor, e. g. for cardiovascular disease, cancer, type 2 diabetes mellitus, airway inflammation and acute respiratory infection as well as bronchial asthma and chronic obstructive pulmonary disease (COPD). Aim of our study was a literature review on the role of vitamin D in asthma. Methods: A PUBMED search was made for publications regarding the role of vitamin D deficiency in asthma pathogenesis and the effect of vitamin D supplementation. Results:  In brief, vitamin D affects lung growth and maturation before birth and in the first years of childhood, plays an important role in the development of the adaptive immune system affecting both, cells (e. g. T-helper cells) and regulatory cytokines (i. g. IL-10), influences airway remodelling by suppression of bronchial airway muscle cell proliferation, reduces the risk of respiratory tract infections and may act in synergy with steroids. Clinically, vitamin D deficiency correlates with an increased risk for asthma and asthma exacerbation mainly in children. On the other hand there was some evidence for a protective effect of vitamin D supplementation more pronounced in children than in adults. Conclusions:  Despite numerous but not all epidemiological and clinical studies as well as meta-analyzes demonstrated vitamin D deficiency to be a risk factor for asthma and a possible protective role of vitamin D supplementation (mainly in children) further controlled clinical studies should be performed to confirm the evidence in different patient subgroups.

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P45 Severity of respiratory syncytial virus bronchiolitis is increased in children with passive smoking exposure** Clemens Mädel1*, Katharina Kainz1, Angela Zacharasiewicz1, Thomas Frischer1 Department of Pediatrics, Wilhelminen-Hospital, Vienna, Austria

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Background:  Respiratory syncytial virus (RSV) bronchiolitis is one of the most common causes for hospitalization in the first year of life. Second-hand cigarette smoke (SHS) has been shown to increase the severity of respiratory illnesses but the magnitude of its effect on RSV bronchiolitis is still unknown. As a major metabolite of Nicotine, urinary Cotinine has been shown to be a reliable marker for SHS exposure. Aim of this study was to compare severity of RSV bronchiolitis in children with and without increased urinary Cotinine levels. Methods: A prospective study was performed including children aged below 12 months who were hospitalized with RSV bronchiolitis in the Pediatric Department, Wilhelminen-Hospital, Vienna. RSV infection was confirmed with nasopharyngeal swab and RSV enzyme-immuno-assay and urinary Cotinine levels (measured by chromatography tandem mass spectography) were assessed as an indicator for SHS. Main outcome assessing clinical severity of bronchiolitis was oxygen (O2)-saturation (%) at rest on admission. Secondary outcomes were “Clinical severity score at admission” (CSSA) and “Disease severity score” (DSS) combining different respiratory parameters. Results: Preliminary results of two RSV seasons are presented. Between 3/2015 and 3/2016 eighty-one patients with a mean age of 106 days (SD: ± 80; range: 10–348) with a male:female ratio of 43:38 were included. Mean birth-weight was 3373 g (SD: ± 550; range: 2051–5000). Number of patients with (urinary cotinine ≥ 7 ng/dl) and without SHS exposure was 13 (16 %) and 68 (84 %), respectively. Mean O2-saturation for patients with and without SHS exposure was 95.1 % and 96,6 %, respectively (pU-test) = 0.045). Mean CSSA and DSS for patients with and without SHS exposure was 3.1 versus 2.5, (p = 0.014) and 1.6 versus 2.4 (n. s.). Conclusions:  Preliminary data show that children hospitalized for RSV bronchiolitis with SHS exposure have significantly lower O2 saturation and higher symptom levels compared to children without SHS exposure.

P46 A double-blind, randomized, placebo-controlled multi-center, multinational study evaluating the efficacy and safety of Tavipec capsules in acute bronchitis Gabriele Zacke1*, Christian Kähler2, Tadeusz Derezinski3, Joanna Bocian-Sobkowska4, Andrea Keckeis5 Montavit, Absam, Austria Pneumology Lung Centre S-W, Wangen im Allgäu, Germany 3 Medical Center ESCULAP, Gniewkowo, Poland 4 Medical Center BONUS, Skorzewo, Poland 5 Medical Center for Pneumology, Bludenz, Austria 1 2

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Background:  Spikeoil (Tavipec®) is a phytomedicine obtained by steam distillation of the flowering tops of Lavandula latifolia. The trial was designed to evaluate the efficacy and safety of Tavipec® in patients suffering from acute bronchitis. Methods:  Patients with acute bronchitis without any confounding respiratory disease were randomly assigned to treatment with Tavipec® 150 mg 2 capsules 3 times daily or placebo in a double-blind, parallel-group design. No additional treatment (antibiotics, corticosteroids etc.) was admitted. The primary endpoint, the bronchitis severity score (BSS) ≥ 5 score points was evaluated by the investigator at baseline and after 7 days of treatment. Secondary endpoints included the BSS at day 10, additional signs and symptoms of bronchitis, Quality of life (QoL) and safety evaluated at day 7 and day 10. Results:  269 patients were enrolled and 245 (Tavipec®: 125; placebo: 120) patients remained for statistical analysis. The mean decrease in BSS from baseline to day 7 was 4.54 (SD 2.34) and 2.92 (SD 2.64) for treatment with Tavipec® and placebo. The difference of the BSS between Tavipec® and placebo is significant (p = 0.00014). The improvement of BSS from baseline to day 10 was higher 6.48 (SD 2.17) versus 4.33 (SD 2.96) under the treatment of Tavipec® (p = 0.00003). The QoL of the patients was significantly improved under the treatment of spikeoil compared to placebo at day 7 and day 10. The treatment with Tavipec® was safe and well tolerated. Conclusions:  These results show that the treatment of acute bronchitis with spikeoil (Tavipec®) is statistically superior to placebo and is well tolerated.

P47 Effects of a 3-week inpatient pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis – a randomized, controlled trial Tessa Schneeberger1,6*, Rainer Glöckl1,2, Inga Jarosch1, Jürgen Behr3, Claus Neurohr3, Marion Frankenberger3, Antje Prasse4, Michael Kreuter5, Klaus Kenn1,6 Department of Respiratory Medicine, Schoen Klinik Berchtesgadener Land, Schönau Am Königssee, Germany 2 Department of Prevention, Rehabilitation and Sports Medicine, Klinikum rechts der Isar, Technische Universität München (TUM), Munich, Germany 3 Department of Internal Medicine V, University of Munich and Asklepios Clinic München-Gauting, Comprehensive Pneumology Center Munich, Munich, Germany 4 Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany 5 Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, and Translational Lung Research Center Heidelberg (TLRCH), Heidelberg, Germany 6 Department of Pulmonary Rehabilitation, Philipps-University of Marburg, Marburg, Germany 1

Background:  There is growing evidence that patients with idiopathic pulmonary fibrosis (IPF) benefit from pulmonary rehabilitation (PR) regarding exercise capacity and health related quality of life (HRQL). However, effects of PR on mental issues of HRQL are still unknown. Aim of this study was to investigate the effects of an inpatient PR for IPF patients in comparison to a control group (CG) with usual care.

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abstracts Methods:  33 IPF patients were included in this randomized controlled trial. Patients were randomized into an active PRgroup (PRG; n = 18; 68 ± 9y; FVC:73 ± 17 %/pred.), which took part in a 3-week inpatient PR and into a CG (n = 15; 65 ± 10y; FVC:72 ± 21 %/pred.) without PR. Data of 6-minute walking distance (6MWD), physical activity in familiar environment (steps via SenseWear™), HRQL (CRQ; SF-36), anxiety and depression (HADS) was collected at the beginning of the study and after following PR (PRG), or 6 weeks of usual care (CG). Results: PRG increased significantly (each p < 0.05) in 6MWD (+60 ± 94 m), HRQL (CRQ: fatigue +0.9 ± 1.5 pts., emotional function +0.9 ± 1.1 pts., mastery +0.7 ± 1.2 pts.; SF36-mental score:+6.1 ± 7.9pts.) including anxiety (HADS-A: -2 ± 3 pts.) and depression (HADS-D: -2 ± 2 pts.) symptoms. CRQ category of dyspnea (+0.7 ± 1.4 pts.; p = 0.63) and number of steps/day (p = 0.160) didn’t change statistically significant. For the CG no statistically significant changes were found with one exception in CRQ (6MWD: –21 ± 56 m; CRQ: fatigue +0.04  ±  0.7 pts., emotional function –0.2  ±  0.5 pts., mastery +0.0 ± 0.6 pts.; SF36-mental score: –1.0 ± 9.9; HADS-anxiety: +0.3 ± 3 pts.; HADS-depression: +0.5 ± 2 pts.; number steps/day:142 ± 1032). The CRQ category of dyspnea even worsened significantly (-0.5 ± 0.7 pts.; p = 0.034). Significant group differences were shown for increases in 6MWD, CRQ categories (expect mastery, p = 0.057) and HADS-Depression (each p ≤ 0.05). Conclusions: In comparison to the CG with usual care, patients of the PRG were able to improve exercise capacity (∆6MWD  =  +81 m) and especially HRQL, including mental aspects to a significant and clinically relevant extend. Relevant effects on physical activity weren’t found within the observed period.

P48 Bacterial colonization in a group of 240 consecutive patients with lung diseases in an inpatient rehabilitation centre in Austria Alfred Lichtenschopf, Hannes Selle, Kathrin Schaupp, Kinga Hohenwarter SKA Weyer/Enns, Waidhofen/Ybbs, Austria Background:  In the first half of 2016 we started an inpatient rehabilitation program for patients with Cystic Fibrosis in Weyer/Enns, a rehabilitation centre for inpatient rehabilitation. To optimize hygiene strategies, we analysed the bacteriological colonization spectrum of our patients. Sputum cultures were taken from all lung patients excluding only those with Asthma. Infection control was adjusted to these findings. Methods: Sputum cultures were taken from all patients with lung diseases (all chronic conditions, COPD GOLD II to IV, postoperative patients with lung cancer, idiopathic fibrosis, etc.) and were immediately cultivated by cystic fibrosis standard (MIQ24/2006). They were also read using this standard. Results:  From March 1st to June 23rd the following hygienically relevant bacteria were cultivated: 16 instances of Pseudomonas aeruginosa, two of these with multi-resistance (not MRGN3/4); 6 instances of Stenotrophomonas maltophilia; One instance of both Acinetobacter junii and Acinetobacter johnsonii; 33 instances of Staphylococcus aureus, two of these MRSA; 4 instances of Haemophilus influenza; 18 instances of Klebsiella pneumonia; 7 instances of Enterobacter cloacae und aerogenes. From all patients with hygienically relevant bacteria, only one had been diagnosed before rehabilitation.

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Conclusions:  There were patients with undiagnosed hygienically relevant bacteria in our rehabilitation centre at every patient rotation. Therefore patients should be screened at the beginning of their stay and it is essential to better organize the hygienic requirements, such as single rooms, further training and therapy in an individual therapy setting.

P49 Pulmonary rehabilitation: a tool to improve walking distance and subjective feeling of illness Petra Prager1*, Martin Skoumal2, Andreas Spary1 1 2

Pensionsversicherungsanstalt ZAR Graz, Graz, Austria Pensionsversicherungsanstalt Chefarzt, Vienna, Austria

Background:  Pulmonary rehabilitation is recommended in patients with COPD in order to reduce dyspnoe, improve physical activity, cope with the needs of daily living, maintain working ability and stop or diminish progression of chronic pulmonary disease. To study the effects of pulmonary rehabilitation we included 14 patients with COPD stage II-III in our investigation. Methods: In the year 2015 14 patients with COPD II-III underwent an ambulant pulmonary rehabilitation program for six weeks in our rehabilitation center. This program consisted of endurance training, weight training, breathing physiotherapy and psychological as well as dietary support. As parameter for verifying the subjective and objective improvement of patients health status, six minute walk test (6MWT) and chronic respiratory questionnaire (CRQ) was used. This CRQ consists of several categories: dyspnoe, mood, exhaustion and coping with disease. Due to different reasons only 10 of these 14 patients absolved a 6MWT at the beginning and at the end of the rehabilitation program, therefore we present the results of these 10 patients. Results:  There was an average improvement of 34.81 m in the 6 MWT, the CRQ showed an improvement of 4.4 points concerning dyspnoe, in mood, there was an improvement of 3.83 points, in exhaustion an improvement of 4.25 points and in coping with disease there was an improvement of 4.75 points. Conclusions: For patients with COPD, pulmonary rehabilitation is an important tool in addition to drug therapy to improve physical activity, fulfill daily routine and improve quality of life. This has been proved by extention of walking distance and better subjective feeling of illness.

P50 Health economic aspects of obstructive sleep apnea. Evidence from 4 European countries S. M. Cheilari1, L. F. M. Oschmann2, A. L. Espeland2, P. van Meijel3, L. M. Schrettl1, M. Matlak1, A. Giovanni4, O. Flikweert3, Christoph Puelacher5* International Health and Social Management, Management Center Innsbruck, Innsbruck, Austria 2 Health Economics Policy and Management, University of Oslo, Oslo, Norway 3 European Master in Health Economics and Management, Erasmus University Rotterdam, Rotterdam, Netherlands, 4 Health Economics and Management, University of Bologna, Bologna, Italy 5 PKA Schlaflabor Telfs, Telfs, Austria 1

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Background: This paper is aiming to highlight the discrepancies in the management of care for the diagnosis and treatment of obstructive sleep apnea (OSA) and the economic inefficiencies that occur through the example of 4  European countries; Austria, Germany, Italy, Netherlands. The authors focused on the reimbursement policies that each country follows and the economic consequences for the stakeholders involved. Simultaneously, opportunities for cross-border healthcare were examined. Methods:  A systematic review has been conducted through data, statistics, or information gathered from books, publications, institutions on the economic aspects of OSA including direct and indirect medical and non-medical costs of the disease. Particularly for Austria, due to scarce literature resources, the reimbursement policies of selected Social Insurance Institutions, covering 93 % of the population were investigated through qualitative research (e-mails sent to Institutions with specific questions) and insights from our project partner. Results: Diagnosis and treatment regarding OSA is of a high standard in the Netherlands while in Germany is heavily dependent on the relevant insurance.A high potential for healthcare crossborder collaboration exists between the North of Italy and Austria, asjustified by recent passive and active mobility data. Conclusions:  To conclude, cost-effectiveness approaches in healthcare services and value-based reimbursement schemes are a mandate that will lead to the decrease of the healthcare costs and likewise make the system more functional and transparent. Applicability of the current legislation for cross border health and raise of awareness of physicians and patients about the disease is required.

So waren das im Jahr 2012 16 Patienten:11 davon mit einer respiratorischen Globalinsuffizienz bei zugrundeliegender COPD IV, 3 Patienten mit Erkrankungen aus dem neuromuskulären Formenkreis, sowie 2 schwer einstellbare Formen einer OSAS. Von den 11 COPD Erkrankten stellten wir 10 Betroffene auf einen BiPAP („bilevel positive airway pressure“) ST-Modus ein – bei einem Patienten war die Beatmung im AVAPS-Modus notwendig. Im Schnitt benötigten wir einen IPAP von mind. 12 mbar bis max. 22 mbar und einen PEEP von mind. 6 mbar – max. 12 mbar Beatmungsdruck, um an therapeutisch wirksame Ergebnisse zu erzielen. Bei Auswertung der Compliancedaten (2 Patienten verstarben innerhalb eines halben Jahres, 1 Patient wird auswertig kontrolliert) zeigten sich eine durchschnittliche tägliche Nutzung von 4,8 h. Damit konnten pCO2 Senkungen von min. 5 mmHg bis max. 25 mmHg erreicht werden (bei einem gemessenen max. pCO2 von 99,5 mmHg). Den durch mehrere Studien belegten Nutzen der außerklinischen Beatmung bei chronisch stabiler COPD wollen wir durch die Auswertung der gesammelten Daten unserer auf eine NIV-Heimbeatmung eingestellten Patienten von den Jahren 2012 bis Mitte 2016 hiermit weiter bzw. deutlicher hervorheben.

P52 Bone marrow biopsy in granulomatous disorders: when and why? Mihails Bratkovskis1* State Centre of Tuberculosis and Lung Diseases, Riga, Latvia

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P51 Erfolgskonzept Nichtinvasive (NIV) Heimbeatmung bei Patienten mit stabiler chronisch osbtruktiver Atemwegserkrankung Elisabeth Haselwanter1*, Markus Stein1, Herbert Jamnig1 Abteilung für Pneumologie, LKH Hochzirl-Natters, Natters, Österreich

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Bei Patienten der COPD im fortgeschrittenen Stadium kann es zu einem respiratorischem Versagen durch Überbelastung der Atempumpe einerseits sowie der verminderten Atemmuskelkapazität durch veränderte Längen- und Spannungsbeziehung andererseits kommen. Hier kann die maschinell gegebene Unterstützung der Atmung in Form der Nichtinvasiven Heimbeatmung von großem Nutzen sein kann. Um zu den gewünschten Therapieerfolgen zu gelangen ist vor allem auch die Motivation und Mitarbeit des Patienten gefordert – eine optimale Anpassung der Maske und der Beatmungseinstellungen durch geschultes Personal in ausgewiesenen Zentren sind Grundvoraussetzungen für ein langfristiges Anwenden der NIV. Bezüglich der Beatmungseinstellungen gilt es einen Kompromiss zwischen „idealen“ Blutgasen und erreichbaren Drücken zu finden. Im Schnitt stellen wir im LKH Hochzirl-Natters auf der Abteilung für Pneumologie (RCU) im Jahr 20 Patienten auf ein Heimbeatmungsgerät ein. Ca. 90 % davon sind Patienten mit chronisch obstruktiver Atemwegserkrankung (die restlichen 10 % vorwiegend aus dem Kreis der neuromuskulären Erkrankungen).

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Background:  Bone marrow biopsy to a rare kind of biopsies used in diagnostics of granulomatous disorders. 269 biopsies were done at our Center as routine method of analysis when diffusive pathology in lungs was detected. Methods:  57 analytical investigations were done among 269 bone marrow biopsies in connecton with Granulomatous: 28 biopsies (or 49.1 %) were positive. We made bone marrow biopsies as last non-operational kind of biopsies in diagnostic algorithm of our investigations for patients with Granulomatous. Conclusions:  In our opinion, the usage of bone marrow biopsy in diagnostics of granulomatous disorders has typical evidence. Bone marrow biosies: When? 1. Tuberculosis miliary or sarcoidosis generalisation? 2. Metastases in marrow – or granulomatous? 3. Unknown aneamia in granulomatous inflammation. 4. Sarcoidosis in marrow – indication by hormone therapy. Bone marrow biosies: Why? Bone marrow biosy is positive – simple techniques biopsy and absence of complication. Bone marrow biosy is negative – rare granulomatous disorders localisation in marrow (~5 %).

P53 Analysis of Dear-Doctor-Letters and Information-Letters for medicinal products published by the BfArM 2008–2014 Rüdiger Siekmeier1*, Jürgen Hannig1 Drug Regulatory Affairs, Pharmaceutical Institute, University Bonn, Bonn, Germany

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abstracts Background: The German Medicines Law regulates marketing and post market surveillance of medicines. In cases of incidents and other important issues, e. g. security advices, counterfeits, recalls, distribution stop, and supply shortages manufacturers have to inform the responsible Authority (D: BfArM and PEI, AU: AGES) and public by Dear-Doctor-Letters (DDL, Rote-Hand-Briefe) and Information-Letters (IL). These should be clearly identifiable, provide information on drug, batch, underlying issue and measures to be performed as well as contact data whereas advertising or ameliorating text should be avoided. Here we analysed DDL and IL for medicinal products published by the BfArM. Methods: DDL and IL published by BfArM 2008–2014 (https://www.bfarm.de/DE/Arzneimittel/Pharmakovigilanz/ Risikoinformationen/RI_rhb/_functions/RI_rhb_Filtersuche_ Formular.html?gtp=3494768_list%253D19&queryResultId=null &pageNo=0) were analysed. Results:  Totally, 233 publications were analyzed of which 158 and 75 were DDL and IL, respectively. Document title and type of action were clearly described in titles of all DDL and IL (100 %, both). Identifiers, e. g. date and reference number as well as contact data (phone number, contact person) were more frequent in DDL vs. IL (92 % vs. 85 % and 96 % vs. 89 %, respectively). Product characteristics for further identification, e. g. lot-No, article No., and product identification number (PZN) were provided in 13 % of both. Ameliorating statements were found in 2 % and 5 % of DDL and IL, respectively. Typical issues for DDL and IL were supply shortages, affecting mainly systemic antiinfectives, antineoplastics/immune modulators, cardiovascular drugs and nervous drugs, as well as security advices. Reasons for publications of security advices were very different, e. g. recommendations, adverse effects interferences and contaminations. Conclusions:  The quality of DDL and IL underlines their important role for information in cases of product problems. DDL tend to be of higher quality than IL. Information regarding supply shortages plays an important role in DDL and IL.

P54 Product problems and fulfillment of MEDDEV criteria in products for gas supply and humidifiers – analysis of field safety notes published by the BfArM 2005–2013 Jürgen Hannig1, Rüdiger Siekmeier1* Drug Regulatory Affairs, Pharmaceutical Institute, University Bonn, Bonn, Germany

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Background:  The European Directive 93/42/EEC regulates marketing and post market surveillance of medical devices in the European Economic Area. In cases of incidents and field safety corrective actions (FSCA) manufacturers have to inform responsible Competent Authority (D: BfArM, AU: BASG) and public by field safety notices (FSN). Here FSN for products for gas supply and humidifiers (both, apparatuses and consumables) were studied in respect to the MEDDEV 2.12-1 rev 8. Methods: FSCA and FSN published by BfArM 2005–2013 (http://www.bfarm.de/DE/Medizinprodukte/riskinfo/ kundeninfo/functions/kundeninfo-node.html) were analyzed. Results:  In 22 published FSCA (13 products for gas supply, 9 humidifiers) we found 19/14 German and English FSN, respectively. FSN were clearly characterized as FSN in 15/10 cases and declaration of type of action was found in 10/10 cases. Product

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names and reason of the reportable incident were found in 19/14 and 18/14 FSN. Lot numbers or other information for product characterization were available in 5/5 and 12/10 cases. Information on product related risks with previous use of affected devices was provided in 12/11 cases and in 18/14 cases manufacturers provided information to mitigate product related risks. Request to pass the FSN to other persons who need to be aware and a contact person or phone number was found in 10/12 and 13/11 cases. Typical reasons of reportable incidents in apparatuses were manufacturing errors (e. g. failure of electrical components) resulting in risk for delay or stop of therapy or user risk (e. g. fire hazard) and production failure in consumables resulting in risk for inappropriate therapy. Dependent on type and failure of products reported measures for risk mitigation were e. g. additional recommendations for use, reconstruction by the manufacturer or change of components e.g inner tubes. Conclusions:  Most FSN fulfil MEDDEV criteria. However, type and content of FSN should be further improved.

P55 The most common detected bacteria in sputum of patients with CAP (community acquired pneumonia) treated in hospital Vesna Cukic* Clinic for Pulmonary Diseases and TB „Podhrastovi“, Clinical Centre of Sarajevo University, Sarajevo, Bosnia and Herzegovina Objective:  To show the most common bacteria in sputum of patients with CAP hospitalized in Clinic for pulmonary diseases and TB “Podhrastovi” in four-year period:from 2012 to 2015. Methods: This is the retrospective analysis. Each patient gave sputum 3 days in a row. Sputum was examined – bacterial culture with antibiotics sensitivity, Gram stain, Mycobacterium tuberculosis; in patients we had doubts about diagnosis bronchoscopy with BAL (bronchoalveolar lavage) was done. We show patients according to age, sex, whether they had pneumonia or bronchopneumonia, bacteria isolated in sputum and in BAL. Results:  There were 247 males and 113 females. 167 (43.39 %) had pneumonia (119 males and 48 females). Number of males was significantly bigger (χ2 = 30.186; p < 0.001). 193 (53.61 %) had bronchopneumonia (128 males and 65 females). Number of males was significantly bigger (χ2 = 20.556; p < 0.001). Number of patients with negative bacterial culture (131–78, 44 %) was bigger than ones with positive culture (36–21, 56 %) (χ2 = 50.042; p > 0.001) in pneumonia. Number of patients with negative bacterial culture (154–79, 79 %) was bigger than ones with positive culture (39–20, 21 %) (χ2 = 68.523; p < 0.001) in bronchopneumonia. Streptococcus pneumoniae was most common detected bacterium; in pneumonia (χ2 = 33.222; p < 0.001); in bronchopneumonia (χ2 = 51.231; p < 0.001). Conclusions: It is very important to detect the bacterial cause of CAP to administrate the targeted antibiotics.

40. Jahrestagung der Österreichischen Gesellschaft für Pneumologie

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Autorenverzeichnis abstracts

Autorenverzeichnis E

Absenger G. P 22 Aigner C. P 23 Ambrogi C. M. P 25 Ancochea J. P 40 Andrianopoulos V. P 12 Ankersmit J. H. P 13, P 41 Arns B. P 21, P 22 Augustin F. P 27, P 35 Avian A. P 14, P 16, P 18, P 19

Eber E. F 03 Eferl R. P 05 Einwallner E. P 41 Errhalt P. F 13, P 22 Espeland A. P 50

B Baumer H. F 01 Behr J. P 47 Bekos C. P 41 Benazzo A. P 10, P 37, P 39 Berger W. P 07, P 08 Bertoglio P. P 25 Biasin V. P 05, P 06 Bigenzahn W. P 38 Bloch W. P 01 Bocian-Sobkowska J. P 46 Bohanes T. P 34 Bratkovskis M. P 52 Brcic L. P 05, P 08 Breul B. P 32 Brguljan M. P. P 41 Brndiar M. P 34 Buist S. P 40 Bundalo T. P 21, P 22 Burghuber C. O. P 21, P 22, P 26 Burney P. P 40

C Caballero A. P 40 Chandran N. P 04 Cheilari S. P 50 Cikes N. P 05 Cima K. P 15 Crnkovic S. P 05, P 06 Cukic V. P 55

D Delgado G. P 42, P 44 Denk-Linnert D. P 38, P 39 Derezinski T. P 46 Deri M. P 15 Didcock J. P 13 Dome B. P 07, P 09, P 24 Dong Y. P 08, P 24, P 25 Douschan P. P 14, P 16, P 18, P 19 Dworan N. P 21 Döme B. P 08, P 23, P 25, P 28, P 31

13

F Fabian K. P 23 Fabikan H. P 26 Farkas J. P 41 Fediuk M. F 03, P 32, P 33, P 43 Filipits M. P 22 Fink-Neuboeck N. P 32 Fink-Neuböck N. P 20, P 33, P 43 Flick H. P 30 Flikweert O. P 50 Foris L. P 02 Foris V. P 14, P 16, P 18, P 19 Frankenberger M. P 47 Frauenfelder T. P 24 Frechinger R. P 11 Frischer T. P 45 Fuchs T. P 33 Funk C. G. P 26

G García-Rio F. P 40 Gerger A. P 30 Ghanim B. P 01, P 02, P 04, P 05 Giovanni A. P 50 Gloeckl R. P 12 Glueck M. O. P 41 Glöckl R. P 47 Glück O. P 10 Gnatiuc L. P 40 González-García M. P 40 Grammer T. P 44 Group R. C. B. t. f. P 40 Group S. P. t. a. P 40 Grusch M. P 07, P 08 Gungl A. P 05, P 06

H Hacker P. P 13 Hannig J. P 53, P 54 Haselwanter E. P 51 Haslbauer F. P 22 Hegedus B. P 07, P 23, P 24 Hochmair M. P 21, P 22, P 26 Hoda A. M. F 10, P 07, P 09, P 23, P 24, P 25, P 28, P 31 Hoda M. P 08

Hoetzenecker K. P 10, P 38 Hoffmann J. P 01 Hohenwarter K. P 48 Holzer S. P 21, P 22, P 26 Horner A. P 40 Hrdliczka E. P 10 Hubner M. F 11 Humenberger M. P 11 Hutarew G. F15 Hötzenecker K. P 39

ÖGP

A

J Jakob V. F 09 Jakopovic M. P 08 Jaksch P. P 13, P 37 Jamnig H. F 14, P 51 Jandl K. P 01 Janik S. P 13 Jarosch I. P 12, P 47

K Kainz K. P 45 Kaiser B. P 11, P 40 Kaltenbrunner M. F 06 Keckeis A. P 46 Kenessey I. P 23 Kenn K. P 12, P 47 Kirchbacher K. P 21 Kleber M. P 42, P 44 Klepetko W. F 10, F 11, P 01, P 02, P 04, P 05, P 07, P 08, P 09, P 10, P 13, P 23, P 24, P 25, P 28, P 31, P 36, P 37, P 38, P 39, P 41 Klikovits T. F 10, F 11, P 07, P 08, P 23, P 24, P 25, P 28, P 31 Kliman J. P 13 Kneussl M. F 11 Kocher F. P 27, P 35 Kolb R. P 22 Kollegger J. F 06 Kos A. F 13 Kovacs G. P 01, P 02, P 05, P 14, P 16, P 18 Kovalszky I. P 23 Kovács G. P 19 Kreczy A. F 14 Krenbek D. P 21 Kreuter M. P 47 Kwapiszewska G. P 01, P 02, P 05, P 06 Kähler C. P 46

L Labek A. P 11 Laimer G. P 27 Lainscak M. P 41

40. Jahrestagung der Österreichischen Gesellschaft für Pneumologie

783

ÖGP

abstracts Lambers C. P 37 Lamprecht B. F 09, P 11, P 40 Lang C. P 10 Lang E. P 07 Lang G. P 10, P 37 Laschitz M. F 01 Laszlo V. P 07, P 08, P 09, P 24, P 25, P 28, P 31 Leonhard M. P 38 Lernbass A. M. P 43 Lewik G. P 10 Lichtenberger P. F 09 Lichtenschopf A. P 48 Lindenmann J. F 03, P 20, P 30, P 32, P 33, P 43 Lohinai Z. P 23 Lovsin J. P 20 Lucciarini P. P 27, P 35 Löffler-Ragg J. P 03, P 15, P 17

M Maier A. F 03, P 20, P 32, P 33, P 43 Maier H. P 27, P 35 Mandl M. F 09 Mangge H. P 02 Marcun R. P 41 Marsh L. P 05 Marsh M. L. P 06 Matilla J. P 37 Matilla R. J. P 36 Matlak M. P 50 Maurer E. P 17 Meijel v. P. P 50 Meinitzer A. P 02 Menezes M. A. P 40 Mikes R. P 22 Miravitlles M. P 40 Modl M. F 03 Mohn-Staudner A. P 21, P 22 Moldvay J. P 23 Moser B. P 13, P 36 Murakozy G. P 37 Mussi A. P 25 Mädel C. P 45 März W. P 42, P 44

N Nagaraj C. P 02 Nagy B. P 02, P 04 Neuböck N. F 03 Neurohr C. P 47 Ng C. P 27, P 35 Nguyen M. P 09, P 28, P 31 Nguyen-Kim L. D. T. P 24

O Oca d. M. M. P 40 Odler B. P 05, P 14, P 19 Oehler R. P 24

784

Olschewski A. P 01, P 02, P 04, P 05, P06, P 14, P 16, P 18, P 19 Olschewski H. F 07, P 01, P 02, P 04, P 05, P 14, P 16, P 18, P 19, P 30 Opitz-Schmitz I. P 24 Oschmann L. P 50 Ostoros G. P 23 Ozsvar J. P 09

P Papp R. P 02, P 04 Patocka K. P 21, P 22 Perez-Padilla R. P 40 Pfeiffer S. F 07, P 14, P 19 Pfleger A. F 03 Pichler M. P 30 Pieber T. P 02 Pilz S. P 42, P 44 Polachova J. F 07 Prager P. P 49 Prasse A. P 47 Puelacher C. P 50 Puhan A. M. P 40

R Rainer B. F 14 Raso E. P 23 Reid G. P 08 Renyi-Vamos F. P 23 Rieger S. E. P 15 Roesner I. P 38, P 39 Roth N. F 02 Rozsas A. P 07 Rudzki J. P 22 Rumbold R. P 21

Smolle-Jüttner F. P 20, P 33, P 43 Sonnweber T. P 03, P 15 Soriano B. J. P 40 Spary A. P 49 Spruit A. M. P 12 Stacher-Priehse E. P 05 Stark B. F 11 Steger S. F 15 Stein M. P 51 Steindl A. P 28, P 31 Steringer-Mascherbauer R. P 17 Stockhammer P. P 08, P 24, P 25 Strießnig A. P 20 Stubenberger E. F 11, P 34 Studnicka M. F 15, P 40 Swatek P. F 03, P 29, P 32

T Taghavi S. P 37 Tahon S. P 28, P 31 Tancevski I. P 03 Team E. t. P 40 Team P. t. P 40 Tesik P. F 11 Timar J. P 23 Titze L. P 42, P 44 Tornyos A. P 14, P 19 Torres-Duque A. C. P 40 Traxler D. P 41 Trinker M. P 14 Tripsky J. P 34 Trobisch A. F 03

V Valipour A. P 26 Vanfleteren E. L. P 12 Vanfleteren L. P 40

S Sacher M. P 27 Sahu-Osen A. P 05 Schaupp K. P 48 Scheed A. P 36 Scheu I. V. P 16 Schmid T. F 14, P 27, P 35 Schneeberger T. P 47 Schneider F. P 05 Schneider-Stickler B. P 38 Schrettl L. P 50 Schumacher M. P 22 Schwarz C. F 06 Schwarz S. P 10, P 37, P 38, P 39 Schweiger T. P 10, P 36, P 38, P 39 Seebacher G. F 11, P 34 Selle H. P 48 Setinek U. P 21, P 22 Siekmeier R. P 42, P 44, P 53, P 54 Simader E. P 41 Skoumal M. P 49 Smolle A. M. P 30 Smolle-Juettner M. F. F 03, P 32

40. Jahrestagung der Österreichischen Gesellschaft für Pneumologie

W Wandschneider W. F 01 Watzinger K. P 03, P 1 Weippert C. F 15 Weiss G. P 15, P 17 Witsch-Baumgartner M. P 17 Wohlkoenig C. F 07 Wouters F. E. P 12 Wurzinger K. F 05

Z Zacharasiewicz A. P 45 Zacke G. P 46 Zelger B. F 14 Zettelbauer S. F 14 Zimmermann M. P 41 Zschocke J. P 17 Zöchbauer-Müller S. P 22

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