Background: Several clinical guidelines recommend chronic inhaled therapy for pwCF (people with cystic fibrosis) and chronic Pseudomonas aeruginosa infection of the lungs.Methods: To demonstrate what kind of therapy regimens are used in Germany, we retrospectively analysed chronic inhaled antibiotic therapy within the cohort of the German CF Registry in 2020. For comparison we also analysed the use of inhaled antibiotics in pwCF with intermittent Pseudomonas or without Pseudomonas infection. Results: A total of 1960 pwCF had chronic P. aeruginosa infection and were retrospectively evaluated. Almost 90% (n = 1751) received at least one inhaled antibiotic. The most commonly used inhaled antibiotic was colistin solution for inhalation (55.2%), followed by aztreonam solution for inhalation (32.6%) and tobramycin solution for Inhalation (30%). Almost 56% of adults and 44% of children alternated two antibiotics for inhalation. In children, alternating colistin + tobramycin was the most often used regimen. In adults, only 23% used colistin + tobramycin; there was a wide range of treatment regimens among adults using two inhaled antibiotics alter-nately. 2456 pwCF had no Pseudomonas infection, but almost 24% had a chronic inhaled antibiotic therapy, while 56% of 361 pwCF and intermittent chronic Pseudomonas infection had a chronic inhaled antibiotic therapy.Conclusion: In all three groups the most commonly used inhaled antibiotic was colistin solution for inhalation. Almost 56% of adults and 44% of children with chronic Pseudomonas infection alternated two antibiotics for inhalation. It will be interesting to see how the introduction of the highly effective modulator elexacaftor/ tezacaftor/ivacaftor will change the use of inhaled antibiotics.

Einleitung suPAR als lösliche Form des zellmembrangebundenen uPAR entsteht durch Spaltung während einer Entzündung oder Immunaktivierung.

Zusammenfassung Einleitung Die Implantation eines pleuralen getunnelten Dauerkatheters (indwelling pleural catheter = IPC) stellt bei symptomatischen rezidivierenden benignen und malignen Pleuraergüssen (BPE und MPE) neben einer Pleurodese eine weitere etablierte Therapiemethode dar.Zur Sicherheit des IPC, insbesondere zu Pneumothorax und Katheterinfektionen, existierten wenige Studien.Ziel unserer Untersuchung war, die Komplikationshäufigkeit nach IPC-Anlage und deren prädiktive Faktoren bei Patienten mit BPE vs. MPE zu ermitteln. Methoden Retrospektive Analyse aller IPC-Implantationen im Bereich Pneumologie am Universitätsklinikum Dresden im Zeitraum von 2015 – 2018. Ergebnisse Bei 86 Patienten (je 43 m/f; Alter 66,9 ± 13,3 Jahre) wurde bei symptomatischem BPE und MPE ein IPC implantiert. Ein BPE bzw. MPE bestand bei 12,8 % (11/86) bzw. 87,2 % (75/86) der Erkrankten.Als Sofortkomplikation nach IPC-Anlage war bei 43/86 (50 %) Patienten ein meist kleiner, asymptomatischer Pneumothorax nachweisbar. 34/43 (79 %) Patienten bedurften diesbezüglich keiner spezifischen Therapie. Bei 9/43 war ein IPC-Sog im Median über 3 Tage erforderlich. 8/43 Patienten wiesen einen großen Pneumothorax mit partieller/kompletter Regredienz im Median nach 2 Tagen auf.Bei 15,1 % (13/86) der Gesamtgruppe und 36,4 % (4/11) der BPE vs. 12 % (9/75) der MPE kam es im Median nach 87 (BPE/MPE 116/87) Tagen zu einer Katheterinfektion. Diese war bei BPE (p = 0,035), großem Pneumothorax (4/8 Patienten; p = 0,015) und längerer Katheterverweildauer (124 ± 112 vs. 71 ± 112 Tage; p = 0,07) häufiger. Schlussfolgerung Kleine Pneumothoraces sind häufig nach IPC-Implantation, bedürfen aber meist keiner spezifischen Therapie. Bei 15,1 % aller Patienten war im Median nach 87 Tagen eine Katheterinfektion nachweisbar. Diese trat häufiger bei BPE, längerer Katheterverweildauer und großen Pneumothoraces auf.

Einleitung Daten Verlaufs der Vitalparameter innerhalb der ersten 24 h auf die Prädiktion des CRB-65 bei CAP existieren bisher nicht. Ziel dieser Studie war eine Evaluation des CRB-65 unter Verwendung des niedrigsten Blutdruckwertes (RR) innerhalb der ersten 24 Stunden nach Krankenhausaufnahme.

Background Implant of indwelling pleural catheters (IPC) represents an established therapy method in addition to pleurodesis for symptomatic recurrent benign and malignant pleural effusions (BPE and MPE). There are only few studies on IPC safety during follow-up, especially with regard to infection and pneumothorax rates. The aim of our investigation was to determine the complication frequency after IPC implant and its predictive factors in patients with BPE vs. MPE. Methods Retrospective analysis of all IPC implantations in the pneumology department at the University Hospital Dresden during 2015-2018. Results An IPC was implanted in 86 patients (43m/f each; age 66.9 +/- 13.3 years) with symptomatic BPE and MPE. BPE and MPE was present in 12.8% (11/86) and 87.2% (75/86) of the patients, respectively. A predominantly small and asymptomatic pneumothorax was detectable as an immediate complication in 43/86 (50%) of patients; 34/43 (79%) of patients did not require any specific therapy. For 9/43 patients, IPC suction was required for a median period of three days; 8/43 patients had a large pneumothorax with partial or complete regression after a median period of two days. Catheter infection developed in 15.1% (13/86) of the total group and 36.4% (4/11) of the BPE vs. 12% (9/75) of the MPE after a median period of 87 (BPE/MPE 116/87) days. This was more common in BPE (p=0.035), large pneumothorax (4/8 patients; p=0.015) and longer catheter dwell times (124 +/- 112 vs. 71 +/- 112 days; p=0.07). Conclusion Small pneumothoraxes are frequent after IPC implantation, but usually do not require specific therapy. IPC infection was detected in 15.1% of all patients after a median period of 87 days. This was more common in patients with BPE, longer catheter dwell times and large pneumothorax.

Einleitung Ein erheblicher Anteil von Patienten mit ambulant erworbener Pneumonie (CAP) leidet an einer schweren Immunsuppression. Empfohlene Scores zur Risikoprädiktion sind bei dieser Patientengruppe bisher nicht validiert.

Einleitung Der IPC stellt bei symptomatischen rezidivierenden BPE/MPE neben einer Pleurodese eine weitere etablierte Therapiemethode dar.

ZusammenfassungMukoviszidose (Cystic Fibrosis, CF) ist die häufigste, autosomal-rezessiv vererbte Multisystemerkrankung. In Deutschland sind ca. 8000 Menschen betroffen. Die Erkrankung wird durch Mutationen im Cystic Fibrosis Transmembrane Conductance Regulator (CFTR-) Gen verursacht; diese führen zu einer Fehlfunktion des Chloridkanals CFTR. Dadurch kommt es in den Atemwegen zu einer unzureichenden Hydrierung des epithelialen Flüssigkeitsfilms und somit zu einer chronischen Inflammation. Rezidivierende Infektionen der Atemwege sowie pulmonale Exazerbationen der Lunge führen im Verlauf zu zunehmender Inflammation, pulmonaler Fibrose und fortschreitender Lungendestruktion bis hin zur respiratorischen Globalinsuffizienz, die für über 90 % der Mortalität verantwortlich ist. Das Ziel der medikamentösen Therapie ist die pulmonale Inflammation und v. a. die Infektion der Atemwege zu reduzieren. Der Kolonisation und chronischen Infektion mit Pseudomonas aeruginosa (Pa) kommt die größte Bedeutung zu. Diese führt zu weiterem Verlust an Lungenfunktion. Für die medikamentöse Therapie der chronischen Pa-Infektion stehen viele unterschiedliche Therapieoptionen zur Verfügung.Mit dieser S3-Leitlinie wird eine einheitliche Definition für die chronische Pa-Infektion implementiert sowie eine evidenzbasierte Diagnostik und Therapie dargelegt, um eine Orientierung bei der individuellen Therapieentscheidung zu geben.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90% of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa ( Pa ) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa -infection. This is a S3-clinical guideline which implements a definition for chronic Pa -infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa -infection in order to give guidance for individual treatment options.

Mukoviszidose (zystische Fibrose, CF) ist eine der häufigsten autosomal-rezessiv vererbten Erkrankungen der kaukasischen Bevölkerung. Der genetische Defekt im CFTR-Gen führt zu einer Verringerung des Chloridionentransports an der Zellmembran. Die resultierende Dehydrierung des epithelialen Flüssigkeitsfilms bedingt ihrerseits eine Reduktion der Sekret-Clearance. Die Folge ist eine Multiorganerkrankung. Die pulmonale Manifestation mit chronischen Infektionen und der Inflammation ist hierbei die dominierende Todesursache. Akute und chronische Infektion mit Pseudomonas aeruginosa (PA) können zu einem Abfall in der Lungenfunktion führen und sich direkt negativ auf die Überlebenswahrscheinlichkeit auswirken.

Das durchschnittliche Lebensalter von Patienten mit Cystischer Fibrose hat in den letzten Jahren deutlich zugenommen und liegt aktuell bei über 40 Jahren. Die stabileren klinischen Verläufe und das höhere Lebensalter bedingen in der CF-Betreuung vermehrt Aspekte der Lebens- und Familienplanung.

Einleitung: Die optimale Risikoprädiktion eines kurzfristigen ungünstigen Verlaufs bei Patienten mit ambulant erworbener Pneumonie (CAP) mit klinischen Scores und Biomarkern ist nicht zufriedenstellend gelöst. Die neuen kardiovaskulären Marker Copeptin und Proadrenomedullin (MR-proADM) sind vielversprechend zur Evaluation der mittel- und längerfristigen Prognose bei CAP. Diese prospektive Studie evaluiert beide Marker erstmals hinsichtlich ihrer prognostischen Wertigkeit zur Vorhersage kurzfristiger klinischer Hochrisikoendpunkte.

printing supported by . Visit Chiesi at Stand B2.10 MONDAY, SEPTEMBER 3RD 2012 P2516 Effect of Cryptococcus neoformans on the immune system of immunocompetent patients Jinlin Wang, Yongfeng Luo, Xiaoqun Wei, Yanping Zai, Shiyue Li. The State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, Guangdong, China On one hand the host immune system regulates the susceptibility and resistance to cryptococcal infection, on the other Cn can also affect T-cell activation and polarization during infection. Cn may potentially interfere with the differentiation of Th1 cells, which may be an escape mechanism of evade host defence and contribute to the cryptococcal infection in immunocompetent paients. However, most of these effects on T-cell biology were only found in cell and animal studies so far. Objectives: To determine the effect of Cn on the immune system of immunocompetent patients. Methods: Twenty immunocompetent patients with pulmonary cryptococcal infection were enrolled. Blood plasma concentrations of IFN-γ, IL-4 and IL-12 were measured using Elisa. PBMC were then isolated and incubated with or without IL-12 for 48 hours, followed by the assay of IFN-γ and IL-4 concentration in the supernatant. Results: Plasma IFN-γ was greatly decreased in the patients when compared to the healthy controls. No significant differences in plasma IL-4 and IL-12 were observed. Although IL-12 treatment can both increase IFN-γ level in PBMC culture supernatant from the two groups, the increment for cryptococcal infection patients was much lower(3.1-fold) compared with that from healthy control(7.4-fold). IL-12 treatment had no observed effect on the IL-4 production of PBMC. Conclusions: Cryptococcal infection can damage the host immune system, leading to a deficient response to the IL-12 stimulation and an impaired Th1 polarization. This may explain the persistence of Cn in the immunocompetent patients. P2517 Exhaled breath biomarkers in patients with ventilator associated pneumonia (VAP) Ulrike Grigat, Phillip Trefz, Patricia Fucs, Jochen Schubert, Wolfram Miekisch. Anesthesiology and Intensive Care Theraphy, University of Rostock, Germany Volatile organic compounds (VOC) in breath have been described as biomarkers of metabolism, oxidative stress and cancer. This pilot study was intended to find out whether VAP related breath biomarkers could be recognized by means of a smart and rapid combination of VOC sample preparation and analysis. 20 mechanically ventilated patients (10 with pneumonia, 10 controls) were investigated. 15 mL of alveolar gas were withdrawn from the respiratory circuit. VOCs were pre-concentrated by means of needle trap micro extraction (NTME) at the bedside and identified/quantified by means of gas chromatographymass spectrometry (GC/MS). Results were analysed using ANOVA on ranks. Expired concentrations of VOC’s ranged from (400 pptV to 3000 ppbV (0.02 to 14.2 nmol/L). Exhaled acetone concentrations were higher in control patients (median 2895 ppbV vs. 187 ppbV, p=0.037). VAP patients exhaled lower concentrations of C8 aldehydes (median 2.061 ppbV vs. 19.683 ppbV, p=0.013) than control patients. Exhaled pentane showed a tendency to higher concentrations in VAP patients (median 9.907 ppbV vs. 6.040 ppbV). The NTMEGC/MS assay enabled reliable detection of volatile substances from ventilated patients in trace amounts. Elevated pentane concentrations indicate oxidative stress in VAP, reduced aldehyde concentrations may be due to chemical quenching through ROS or ONOOpresent in the alveoli of pneumonia patients. Analysis of exhaled oxygenated compounds bears the potential of non invasive monitoring and recognition of pathological pulmonary processes. P2518 Copeptin predicts early clinical deterioration and persistent instability in community-acquired pneumonia Martin Kolditz1, Michael Halank1, Bernhard Schulte-Hubbert1 , Sybille Bergmann2, Steffen Albrecht3, Gert Höffken1. 1Division of Pulmonology, Medical Department 1, University Hospital Carl Gustav Carus, Dresden, Germany; 2Institute of the Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Dresden, Germany; 3Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Dresden, Germany Optimal risk prediction of early clinical deterioration in CAP remains unresolved. We prospectively examined the predictive value of the new biomarkers copeptin and proadrenomedullin (MR-proADM) in comparison to clinical scores and inflammatory markers to predict early high risk prognosis in CAP. Methods: 51 consecutive hospitalised adult patients were enrolled. We measured CRB-65and PSI-scores, the ATS/IDSA 2007 minor criteria to predict ICUadmission and the biomarkers CRP, procalcitonin, copeptin and MR-proADM on admission. Predefined outcome parameters were combined mortality or ICUadmission after 7 days and clinical instability after 72 hours. Results: Copeptin was the only biomarker significantly elevated in patients with either adverse short term outcome (p=0.003). In ROC-curve analysis copeptin predicted ICU admission or death within 7 days (AUC 0.81, cut-off 35 pmol/l: sensitivity 78%, specificity 79%) and persistent clinical instability after 72 h (AUC 0.74). In Kaplan-Meier-analysis patients with high copeptin showed lower ICUfree survival within 7 days (p=0.001). The diagnostic accuracy of copeptin was superior to the CRB-65 score and comparable to the PSI-score and the ATS/IDSA minor criteria. If copeptin was included as additional minor criterion for combined 7-day mortality/ICU-admission, the diagnostic accuracy of the criteria was significantly improved (AUC 0.85, p=0.045). Conclusion: Copeptin predicts early deterioration and persistent clinical instability in hospitalised CAP and improves the predictive properties of existing clinical scores. It should be evaluated within a biomarker guided strategy for early identification of high risk CAP patients. P2519 Correlation of Mycobacterium tuberculosis-specific and non-specific quantitative T cell IFN-γ responses with mycobacillary load in a HIV-prevalent high burden setting Grant Theron, Jonny Peter, Laura Lenders, Richard van-Zyl Smit, Richard Meldua, Ureshnie Govender, Keertan Dheda. Medicine, University of Cape Town, Western Cape, South Africa Background: Measures of bacillary load in patients with tuberculosis (TB) may be useful for predicting and monitoring response to treatment. The relationship between quantitative T-cell responses and mycobacterial load is poorly studied. We hypothesised that, in a high burden setting, the magnitude of mycobacterial antigen-specific and non-specific T-cell IFN-γ responses would correlate with (a) bacterial load and (b) culture conversion in patients undergoing treatment. Methods: We compared the magnitude of purified-protein-derivative (PPD) and RD1-specific (TSPOT.TB and QFT-GIT) peripheral blood IFN-γ T-cell responses with associates of sputum bacillary load [liquid culture time-to-positivity, smearmicroscopy grade, Xpert-MTB/RIF Ct values, and the presence of cavities on a chest radiograph] in 513 individuals with suspected TB in Cape Town, South Africa. Serial IGRA responses were evaluated at 2 (n=35) and 6 months (n=13) post-treatment initiation. Results: PPD and RD1-specific IFN-γ responses were not associated with culture TTP (p-values for TSPOT.TB, QFT-GIT and PPD of 0.11, 0.07 and 0.09), smeargrade (0.42, 0.09, and 0.85), Ct values (0.70, 0.91, and 0.49) or the presence of cavities on the chest radiograph (0.12, >0.05, and 0.08). 2-month IGRA conversion rates (positive to negative) were negligible [<10% for TSPOT.TB (3/28) and QFT-GIT (1/29)] and lower compared to culture [60% (21/35); p<0.01]. Conclusions: In a high-burden setting M. tuberculosis-specific and non-specific antigen-driven IFN-γ responses do not correlate with bacillary load and are not useful for prognostication or treatment monitoring. P2520 LL-37 is produced intrapleurally in infectious pleural effusion Carlos Antonio Amado1, Javier Villuela1, Mayte García-Unzueta2, Juan José Ruiz-Cubillan1, Alejandro Daly1, Beatriz Abascal1, Diego Ferrer1, Francisca Santos2, David Iturbe1, Ramón Agüero1. 1Neumology, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain; 2Biochemistry, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain LL-37 is an antimicrobial peptide produced by neutrophils, respiratory epithelial and mesothelial cells that has been studied for its broad spectrum activity against microorganisms. It also recruits inflammatory cells and promotes immune responses. It has never been measured in pleural fluid. Aims and objectives: The objective of our study is to measure the pleural and serum levels of LL-37 in pleural effusion patients, and to compare these levels and the pleural-to-serum LL-37 ratio among pleural fluids of three frequent etiologies: infectious, malignant and congestive heart failure(CHF). Methods: We obtained 42 pleural effusions and divided them into 3 diagnostic categories. LL-37 was measured in the pleural fluid and serum of 23 infectious effusions, 10 malignant effusions and 9 CHF effusions by ELISA. Statistical analyses were performed using software SPSS 17.0. Results: Results are presented: mean ± Std. Deviation(median, minimunmaximun). Pleural Fluid LL-37 levels: Infectious 3.77±4.81 ng/ml (1.64, 0.38-19.4) malignant 2.58±4.17 (0.87, 0.09-135), CHF 1.59±1.02 (0.99, 0.47-3.3) (p= 0.4). Serum LL-37 levels: Infectious 2.09±3.42 ng/ml(0.98, 0.06-16.35) malignant 3.44±4.3(1.19, 0.17-12.6), CHF 3.44±3.02(2.6, 0.71-10.3) (p=0.13) Pleural fluid-to-Serum LL-37 ratio levels: Infectious 1.33±1.88(1.29, 100-0.43) malignant 0.60±0.92(0.72, 1.11-0.21), CHF 0.46±0.93(0.44, 1.12-0.24) (p< 0.001. Infectious vs malignant p=0.002, infectious vs CHF p<0.001, malignant vs CHF not significant). Conclusions: Pleural fluid-to-Serum LL-37 ratios are significantly elevat