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Paper of the Month

Hier finden Sie aktuelle Publikationen aus peer review Journalen mit Autorenschaften von Mitgliedern der DGP (Namen mit * gekennzeichnet).

Engel M […] Müller-Quernheim J*, Prasse A*, Welte T*, Hohlfeld J*, Subramanian D, Parr D, Gut IG, Greulich T*, Koczulla AR* et al.

PLoS One. 2017 Jul 13;12(7)

BACKGROUND: Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited.

METHODS: Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons.

RESULTS: We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype.

CONCLUSION: Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.


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Engel M […] Müller-Quernheim J*, Prasse A*, Welte T*, Hohlfeld J*, Subramanian D, Parr D, Gut IG, Greulich T*, Koczulla AR* et al.

PLoS One. 2017 Jul 13;12(7)

Kneidinger N*, Milger K, Janitza S, Ceelen F, Leuschner G*, Dinkel J, Königshoff M, Weig T, Schramm R, Winter H, Behr J*, Neurohr C.*

Eur Respir J. 2017 Apr 12;49(4).

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration.


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Kneidinger N*, Milger K, Janitza S, Ceelen F, Leuschner G*, Dinkel J, Königshoff M, Weig T, Schramm R, Winter H, Behr J*, Neurohr C.*

Eur Respir J. 2017 Apr 12;49(4).

El Agha E, Moiseenko A, Kheirollahi V, De Langhe S, Crnkovic S, Kwapiszewska G, Szibor M, Kosanovic D, Schwind F, Schermuly RT, Henneke I, MacKenzie B, Quantius J, Herold S, Ntokou A, Ahlbrecht K, Braun T, Morty RE, GĂĽnther A, Seeger W*, Bellusci S.

Cell Stem Cell. 2017 Apr 6;20(4):571.

Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung disease with unknown etiology. Due to a lack of effective treatment, IPF is associated with a high mortality rate. The hallmark feature of this disease is the accumulation of activated myofibroblasts that excessively deposit extracellular matrix proteins, thus compromising lung architecture and function and hindering gas exchange. Here we investigated the origin of activated myofibroblasts and the molecular mechanisms governing fibrosis formation and resolution. Genetic engineering in mice enables the time-controlled labeling and monitoring of lipogenic or myogenic populations of lung fibroblasts during fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic switch in fibroblastic phenotype during fibrosis formation. Conversely, we observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of human lung tissues and primary human lung fibroblasts indicates that this fate switching is involved in IPF pathogenesis, opening potential therapeutic avenues to treat patients.


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El Agha E, Moiseenko A, Kheirollahi V, De Langhe S, Crnkovic S, Kwapiszewska G, Szibor M, Kosanovic D, Schwind F, Schermuly RT, Henneke I, MacKenzie B, Quantius J, Herold S, Ntokou A, Ahlbrecht K, Braun T, Morty RE, GĂĽnther A, Seeger W*, Bellusci S.

Cell Stem Cell. 2017 Apr 6;20(4):571.

Martin Reck*, M.D., Ph.D., Delvys Rodríguez-Abreu, M.D., Andrew G. Robinson, M.D., Rina Hui, M.B., B.S., Ph.D., Tibor Csőszi, M.D., Andrea Fülöp, M.D., Maya Gottfried, M.D., Nir Peled, M.D., Ph.D., Ali Tafreshi, M.D., Sinead Cuffe, M.D., Mary O’Brien, M.D., Suman Rao, M.D., Katsuyuki Hotta, M.D., Ph.D., Melanie A. Leiby, Ph.D., Gregory M. Lubiniecki, M.D., Yue Shentu, Ph.D., Reshma Rangwala, M.D., Ph.D., and Julie R. Brahmer, M.D., for the KEYNOTE-024 Investigators

N Engl J Med 2016; 375:1823-1833November 10, 2016

Background Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). Methods In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. Results Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%). Conclusions In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy.


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Martin Reck*, M.D., Ph.D., Delvys Rodríguez-Abreu, M.D., Andrew G. Robinson, M.D., Rina Hui, M.B., B.S., Ph.D., Tibor Csőszi, M.D., Andrea Fülöp, M.D., Maya Gottfried, M.D., Nir Peled, M.D., Ph.D., Ali Tafreshi, M.D., Sinead Cuffe, M.D., Mary O’Brien, M.D., Suman Rao, M.D., Katsuyuki Hotta, M.D., Ph.D., Melanie A. Leiby, Ph.D., Gregory M. Lubiniecki, M.D., Yue Shentu, Ph.D., Reshma Rangwala, M.D., Ph.D., and Julie R. Brahmer, M.D., for the KEYNOTE-024 Investigators

N Engl J Med 2016; 375:1823-1833November 10, 2016

B. Schönhofer* et al. für die WeanNet Study Group

Dtsch Med Wochenschr 2016; 141: e166–e172

Hintergrund: Bei 40 % aller beatmungspflichtigen Patienten gibt es Probleme bei der Respiratorentwöhnung (Weaning). Ein prolongiertes Weaning geht mit einer erhöhten Mortalität einher. Methodik: In dieser Studie werden erstmals Daten zur Epidemiologie und zum Outcome von 6899 Patienten mit prolongiertem Weaning aus dem Register der Weaningzentren (WZ) im WeanNet veröffentlicht. Ergebnisse: Die Mehrzahl der Patienten (62,2%) konnte erfolgreich vom Respirator entwöhnt werden und verließ das Weaningzentrum ohne invasive Beatmung nach median 33 Tagen. Die Patienten mit prolongiertem Weaning litten an einer ausgeprägten Komorbidität (im Median 5 relevante Begleiterkrankungen). Nach prolongiertem Weaning war bei 19,4% der Patienten eine nicht-invasive Beatmung (NIV), verursacht durch eine chronisch ventilatorische Insuffizienz, erforderlich. Die Patienten, die mit NIV entlassen wurden, waren signifikant jünger als der Durchschnitt (68 vs. 71 Jahre). Bei 22,9 % war das Weaning nicht erfolgreich mit nachfolgender, dauerhafter invasiver Beatmung. Patienten mit chronisch obstruktiver Lungenerkrankung (COPD) als führender Ursache für die mechanische Beatmung wurden im Vergleich zu anderen Ursachen seltener vollständig vom Respirator entwöhnt und häufiger mit NIV zur außerklinischen Beatmung versorgt. Insgesamt 1027 der 6899 Patienten verstarben während der Behandlung im Weaningzentrum (14,9 %). Schlussfolgerungen: WeanNet kommt in der Versorgung von Patienten mit prolongiertem Weaning ein hoher Stellenwert zu.


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B. Schönhofer* et al. für die WeanNet Study Group

Dtsch Med Wochenschr 2016; 141: e166–e172