61 results on '"C Smaczny"'
Search Results
2. WS02.01 Abdominal symptoms significantly decline after 24 weeks of elexacaftor/tezacaftor/ivacaftor treatment: first results obtained with the cystic fibrosis-specific CFAbd-Score in Germany and the UK
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J.G. Mainz, C. Zagoya, L. Polte, L. Naehrlich, L. Sasse, O. Eickmeier, C. Smaczny, A. Barucha, L. Bechinger, F. Duckstein, P. Eschenhagen, L. Kurzidim, L. Caley, D. Peckham, and C. Schwarz
- Subjects
Pulmonary and Respiratory Medicine ,Pediatrics, Perinatology and Child Health - Published
- 2022
3. Im Spannungsfeld zwischen Anspruch und Wirklichkeit: intravenöse antibiotische Suppressionstherapien bei erwachsenen CF-Patienten an einem großen deutschen CF-Zentrum
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C. Smaczny, G. Rohde, and C. Hügel
- Published
- 2020
4. Intravenöse Antibiotikatherapie bei erwachsenen Mukoviszidose-Patienten: Leitlinien und der Alltag
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C Smaczny and C Kaiser
- Published
- 2019
5. Editorial
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C. Smaczny
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Pulmonary and Respiratory Medicine - Published
- 2021
6. [CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]
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C, Schwarz, B, Schulte-Hubbert, J, Bend, M, Abele-Horn, I, Baumann, W, Bremer, F, Brunsmann, D, Dieninghoff, O, Eickmeier, H, Ellemunter, R, Fischer, J, Grosse-Onnebrink, J, Hammermann, H, Hebestreit, M, Hogardt, C, Hügel, M, Hug, S, Illing, A, Jung, B, Kahl, A, Koitschev, R, Mahlberg, J G, Mainz, F, Mattner, A, Mehl, A, Möller, C, Muche-Borowski, T, Nüßlein, M, Puderbach, S, Renner, E, Rietschel, F C, Ringshausen, S, Schmidt, L, Sedlacek, H, Sitter, C, Smaczny, B, Tümmler, R, Vonberg, M O, Wielpütz, H, Wilkens, B, Wollschläger, J, Zerlik, U, Düesberg, and S, van Koningsbruggen-Rietschel
- Subjects
Cystic Fibrosis ,Germany ,Practice Guidelines as Topic ,Pseudomonas aeruginosa ,Cystic Fibrosis Transmembrane Conductance Regulator ,Humans ,Pseudomonas Infections - Abstract
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.Mukoviszidose (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
- Published
- 2018
7. MRT-basierte Flussmessungen im Truncus pulmonalis zur Detektion einer pulmonal-arteriellen Hypertonie in Patienten mit zystischer Fibrose
- Author
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Anjorin A, Posselt H, T. Wolf, C. Smaczny, Thomas J. Vogl, and N. D. Abolmaali
- Subjects
medicine.medical_specialty ,Cardiac output ,business.industry ,medicine.medical_treatment ,Significant difference ,Velocity encoding ,medicine.disease ,Cystic fibrosis ,Surgery ,Main Pulmonary Artery ,Internal medicine ,Heart rate ,medicine ,Cardiology ,Lung transplantation ,Radiology, Nuclear Medicine and imaging ,In patient ,business - Abstract
PURPOSE: Development of pulmonary arterial hypertension (PH) is a common problem in the course of patients suffering from cystic fibrosis (CF). This study was performed to evaluate MRI based flow measurements (MR venc ; Velocity ENCoding) to detect signs of an evolving PH in patients suffering from CF. MATERIALS AND METHODS: 48 patients (median age: 16 years, range: 10 - 40 years, 25 female) suffering from CF of different severity (mean FEV 1 : 74 % ± 23, mean Shwachman-score: 63 ± 10) were examined using MRI based flow measurements of the main pulmonary artery (MPA). Phase-contrast flash sequences (TR: 9.6 ms, TE: 2.5 ms, bandwidth: 1395 Hertz/Pixel) were utilized. Results were compared to an age- and sex-matched group of 48 healthy subjects. Analyzed flow data where: heart frequency (HF), cardiac output (HZV), acceleration time (AT), proportional acceleration time related to heart rate (ATr), mean systolic blood velocity (MFG), peak velocity (Peak), maximum fow (Fluss max ), mean flow (Fluss mitt ) and distensibility (Dist). RESULTS: The comparison of means revealed significant differences only for MFG, Fluss max and Dist, but overlap was marked. However, using a scatter-plot of AT versus MFG, it was possible to identify five CF-patients demonstrating definite signs of PH: AT = 81 ms ± 14, MFG = 46 ± 11 cm/s, Dist = 41 % ± 7. These CF-patients where the most severely affected in the investigated group, two of them were listed for complete heart and lung transplantation. The comparison of this subgroup and the remaining CF-patients revealed a highly significant difference for the AT (p = 0.000001) without overlap. CONCLUSION: Screening of CF-patients for the development of PH using MRvenc of the MPA is not possible. In later stages of disease, the quantification of AT, MFG and Dist in the MPA may be useful for the detection, follow-up and control of therapy of PH. MR venc of the MPA completes the MRI-based follow-up of lung parenchyma damage in patients suffering from CF.
- Published
- 2008
8. Mukoviszidose (Cystische Fibrose): Ernährung und exokrine Pankreasinsuffizienz
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M. STERN, H. ELLEMUNTER, B. PALM, H.-G. POSSELT, and C. SMACZNY
- Published
- 2015
9. Editorial
- Author
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C. Smaczny
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Pulmonary and Respiratory Medicine - Published
- 2017
10. [Emergencies in adult mucoviscidosis patients]
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C, Smaczny, T, Born, and T O F, Wagner
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Adult ,Male ,Critical Care ,Cystic Fibrosis ,Gastrointestinal Diseases ,Infertility ,Humans ,Female - Abstract
Cystic fibrosis is an inherited autosomal recessive metabolic disease caused by mutations on the CFTR gene. This leads to defective chloride channels on epithelial cell membranes and causes various disorders of the respiratory, gastrointestinal, and urogenital tracts.As a result, all exocrine glands produce a viscous secretion, leading to pulmonary symptoms such as chronic cough, secretion retention, recurring infections as well as bronchiectasis and obstructive lung emphysema. Gastrointestinal effects include exocrine and often also endocrine pancreatic insufficiency with chronic diarrhea and maldigestion syndrome as well as pancreoprivic diabetes mellitus; biliary cirrhosis occurs in 10% of cases. Additional effects include reduced fertility in women and infertility in men.Life-threatening complications include bleeding from the bronchial arteries, pneumothorax, and distal intestinal obstruction syndrome (DIOS), previously known as meconium ileus equivalent. Treatment requires rapid diagnosis and should be carried out in experienced centres, since the mortality rate can otherwise be up to 50%.
- Published
- 2012
11. Antibiotikainhalation in der Pneumologie, Erfahrungen aus der Mukoviszidosebehandlung
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C Smaczny
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Pulmonary and Respiratory Medicine - Published
- 2012
12. [Lung transplantation in cystic fibrosis--a position paper]
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J, Gottlieb, M, Ballmann, C, von Mallinckrodt, D, Staab, C, Smaczny, A, Simon, T, Welte, and T O, Wagner
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Cystic Fibrosis ,Germany ,Pulmonary Medicine ,Humans ,Lung Transplantation - Abstract
Lung transplantation in cystic fibrosis is an established therapy, due to the fact that vast majority of adult CF patients will develop respiratory failure. Even adolescents and children can be transplanted successfully today. Lung transplantation in cystic fibrosis requires special consideration concerning candidate selection, surgery and postoperative follow-up care. Due to a donor shortage and increasing waiting time, early referral to transplant centres of potential candidates is crucial. In the process of candidate selection, assumed improvements in quality of life and survival benefit should be weighed against contraindications. Centre-based follow-up and close cooperation with local physicians are key factors for success. During follow-up care, the transplantation team should be contacted immediately in the case of any problem or change in medication.
- Published
- 2009
13. [MRI-based flow measurements in the main pulmonary artery to detect pulmonary arterial hypertension in patients with cystic fibrosis]
- Author
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T, Wolf, A, Anjorin, H, Posselt, C, Smaczny, T J, Vogl, and N, Abolmaali
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Adult ,Male ,Adolescent ,Cystic Fibrosis ,Hypertension, Pulmonary ,Reproducibility of Results ,Pulmonary Artery ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,Young Adult ,Image Interpretation, Computer-Assisted ,Humans ,Female ,Rheology - Abstract
Development of pulmonary arterial hypertension (PH) is a common problem in the course of patients suffering from cystic fibrosis (CF). This study was performed to evaluate MRI based flow measurements (MR(venc); Velocity ENCoding) to detect signs of an evolving PH in patients suffering from CF.48 patients (median age: 16 years, range: 10 - 40 years, 25 female) suffering from CF of different severity (mean FEV (1): 74% +/- 23, mean Shwachman-score: 63 +/- 10) were examined using MRI based flow measurements of the main pulmonary artery (MPA). Phase-contrast flash sequences (TR: 9.6 ms, TE: 2.5 ms, bandwidth: 1395 Hertz/Pixel) were utilized. Results were compared to an age- and sex-matched group of 48 healthy subjects. Analyzed flow data where: heart frequency (HF), cardiac output (HZV), acceleration time (AT), proportional acceleration time related to heart rate (ATr), mean systolic blood velocity (MFG), peak velocity (Peak), maximum fow (Fluss(max)), mean flow (Fluss(mitt)) and distensibility (Dist).The comparison of means revealed significant differences only for MFG, Fluss(max) and Dist, but overlap was marked. However, using a scatter-plot of AT versus MFG, it was possible to identify five CF-patients demonstrating definite signs of PH: AT = 81 ms +/- 14, MFG = 46 +/- 11 cm/s, Dist = 41% +/- 7. These CF-patients where the most severely affected in the investigated group, two of them were listed for complete heart and lung transplantation. The comparison of this subgroup and the remaining CF-patients revealed a highly significant difference for the AT (p = 0.000001) without overlap.Screening of CF-patients for the development of PH using MRvenc of the MPA is not possible. In later stages of disease, the quantification of AT, MFG and Dist in the MPA may be useful for the detection, follow-up and control of therapy of PH. MR(venc) of the MPA completes the MRI-based follow-up of lung parenchyma damage in patients suffering from CF.
- Published
- 2008
14. Mukoviszidose (Zystische Fibrose): Ernährung und exokrine Pankreasinsuffizienz
- Author
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B. Palm, C. Smaczny, H. Ellemunter, M. Stern, and H.-G. Posselt
- Subjects
business.industry ,Medicine ,business - Published
- 2007
15. Autorenverzeichnis
- Author
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L. Graul-Neumann, D. Horn, C. Hübner, P. Huppke, R. König, F. Majewski, P. Meinecke, R. Pankau, T. Rosenbaum, D. Schnabel, M. Schuelke, J. Spranger, U. Theile, S. Tinschert, E. Wilichowski, H.A. Wollmann, M. Zenker, P. Bartmann, D. Bassler, C. Bührer, A.W. Flemmer, J. Forster, A. Franz, M. Gonser, L. Gortner, P. Groneck, R. Hentschel, E. Herting, U.B. Hoyme, H. Hummler, C. Jandeck, G. Jorch, R. Korinthenberg, J. Liese, R.F. Maier, J. Martius, A. Merkenschlager, C.F. Poets, F. Pohlandt, C. Roll, R. Roos, B. Roth, K.T.M. Schneider, Ch. Speer, H. Stopfkuchen, A. Teichmann, W. Thomas, K. Vetter, A. von der Wense, S. Zielen, B. Assmann, G.F. Hoffmann, S. Kölker, M. Lindner, E. Mönch, R. Santer, U. Spiekerkötter, J. Zschocke, K. Bauer, H.-J. Böhles, Jack Sinclair, K.W. Jauch, F. Jochum, Thomas Kauth, B. Koletzko, M. Krawinkel, K. Krohn, Walter Mihatsch, A. Moß, S. Mühlebach, S. Verwied-Jorky, M. Wabitsch, K.-P. Zimmer, N. Albers, D. L'Allemand, G. Binder, J.H. Brämswig, H.G. Dörr, A. Grüters-Kieslich, B.P. Hauffa, S. Heger, O. Hiort, R. Holl, P.M. Holterhus, B. Köhler, Eckhard Korsch, J. Kratzsch, H. Krude, K. Mohnike, A. Neu, R. Pfäffle, A. Richter-Unruh, F.G. Riepe, G. Simic-Schleicher, E. Schönau, G. Sinnecker, W. Sippell, H. Willgerodt, J. Wölfle, S.A. Wudy, E. Aygören-Pürsün, M. Bas, U. Baumann, T. Biedermann, J. Blume, B. Buchholz, G. Dückers, D. Dunsch, M. Edelhäuser, S. Ehl, C. Feiterna-Sperling, M. Funk, K. Hartmann, C. Königs, W. Kreuz, J. Krudewig, H.-J. Laws, R. Linde, I. Martinez-Saguer, M. Maurer, David Nadal, T. Niehues, G. Notheis, H. Ott, I. Schulze, B. Wedi, U. Wintergerst, G. Bürk, I. Foeldvari, M. Frosch, H. Girschick, K. Gerhold, N. Guellac, J.P. Haas, R. Häfner, W. Häuser, A. Heiligenhaus, T. Hospach, G. Horneff, H.-I. Huppertz, A. Illhardt, A.F. Jansson, T. Kallinich, H. Michels, K. Mönkemöller, U. Neudorf, M. Richter, E. Schnöbel-Müller, A. Thon, B. Zernikow, W. Behnisch, H. Cario, R. Dickerhoff, S. Eber, M. Führer, E. Kohne, A.E. Kulozik, J. Kunz, M. Muckenthaler, W. Eberl, G. Gaedicke, W. Muntean, W. Streif, J.D. Beck, F. Berthold, S. Bielack, G. Calaminus, A. Claviez, U. Creutzig, U. Dirksen, M. Dworzak, U. Göbel, N. Graf, B. Grießmeier, G. Henze, B. Hero, H. Jürgens, U. Kaiser, T. Klingebiel, E. Koscielniak, C. Kramm, T. Langer, B. Lawrenz, T. Lehrnbecher, U. Leiss, H.-J. Mentzel, M. Minkov, J. Peitz, R. Placzek, D. Reinhardt, A. Reiter, S. Rutkowski, P. Schmittenbecher, D.T. Schneider, B.M. Schreiber-Gollwitzer, M. Schrappe, H. Schroten, H.M. Schröder, V. Schuster, D. von Schweinitz, N. Sörensen, G. Tallen, B. Timmermann, M. Warmuth-Metz, M. Weckesser, L. Wessel, T. Wirth, J.E.A. Wolff, W. Wößmann, A. am Zehnhoff-Dinnesen, C. Apitz, R. Arnold, H. Baumgartner, G. Bennink, H. Bertram, M. Blankenburg, G. Bönner, J. von der Breek, J. Breuer, R. Buchhorn, J. Bürsch, R. Cesnjevar, I. Dähnert, I. Deisenhofer, G.-P. Diller, T. Doenst, K.-O. Dubowy, A. Eicken, P. Ewert, C. Fink, J. Franke, R. Gebauer, M. Gorenflo, null Grabitz, N.A. Haas, H.-J. Häusler, A. Hager, J. Hebebrand, W. Henschel, M. Hirt, M.M. Hoeper, J. Hörer, M. Hofbeck, A. Horke, V. Hraska, M. Hulpke-Wette, J. Janou šek, C. Jux, L. Kändler, R. Kandolf, R. Kaulitz, W. Kienast, S. Klaassen, W. Knirsch, H.H. Kramer, J.G. Kreuder, T. Kriebel, S. Läer, K.T. Laser, T.-P. Lê, M.A.G. Lewin, A. Lindinger, C.R. Mackenzie, S. Mebus, S.H. van der Mei, O. Miera, S. Ovroutski, T. Paul, J. Photiadis, R. Dalla Pozza, C. Rickers, W. Rosendahl, W. Ruschewski, J.S. Sachweh, H.-J. Schäfers, J. Scheewe, K.-R. Schirmer, C. Schlensak, M. Schlez, A.A. Schmaltz, K. Schmitt, H. Schneider, M.B. Schneider, D. Schranz, C. Schreiber, I. Schulze-Neick, L.F.J. Sieverding, H. Singer, J. Stieh, N. Sreeram, W.-R. Thies, J. Thul, R. Trauzeddel, C. Tschöpe, A. Uebing, H.E. Ulmer, M. Vogel, M. Vogt, J. Weil, A. Wessel, J.C. Will, E. Wühl, M. Ballmann, J. Barben, C.P. Bauer, J. Bend, D. Berdel, O. Blankenstein, W. Bremer, F. Brunsmann, T. Buchholz, A. Bufe, N. Derichs, E. Eber, F. Friedrichs, T. Frischer, U. Gembruch, U. Gieler, M. Götz, W.H. Haas, E. Hamelmann, J. Hammer, M. Hellermann, J. Jacobeit, A. Jung, V. Keim, R. Kitz, A. Kleinheinz, S. Koletzko, I. Kopp, M. Kopp, S. Lau, R. Lauener, null Loff, K. Magdorf, C. Muche-Borowski, F.-M. Müller, H. Müsken, L. Naehrlich, T. Nicolai, Th. Nüßlein, E. Paditz, Frau B. Palm, K. Paul, S. Pfeiffer-Auler, Frau D. Pfeiffer-Kascha, H.-G. Posselt, B. Przybilla, H.-C. Räwer, F. Ratjen, I. Reese, J. Riedler, E. Rietschel, M. Rose, R. Rossi, F. Ruëff, T. Schäfer, S. Schmidt, S. Schmitt-Grohé, J. Schulze, A. Schuster, J. Seidenberg, H. Sitter, C. Smaczny, T. Spindler, D. Staab, M. Stern, C.P. Strassburg, K. Strömer, M. Stuhrmann-Spangenberg, R. Szczepanski, A. Tacke, M. Tiedgen, M.S. Urschitz, J. Vagts, C. Vogelberg, U. Wahn, A. Walker, T. Werfel, J.H. Wildhaber, M. Zach, Th. Zimmermann, A. Ballauff, N. Bannert, I. Böhn, S. Buderus, P. Bufler, M. Burdelski, P. Gerner, K.-P. Grosse, J. Henker, P. Henneke, W. Huber, T. Lang, M.J. Lentze, M. Melter, T. Müller, E.-D. Pfister, B. Rodeck, A. Schmidt-Choudhury, H. Skopnik, S. Wirth, H. Witt, H. Bachmann, J. Dötsch, J.H. Ehrich, Arno Fuchshuber, B. Hoppe, P.F. Hoyer, M.J. Kemper, D. Michalk, D. Müller, D.E. Müller-Wiefel, M. Pohl, B. Tönshoff, K. Zerres, T. Bast, F.A.M. Baumeister, R. Berner, H. Bode, H.J. Christen, H. Collmann, F. Ebinger, H. Eiffert, S. Evers, R. Gold, S. Groß, F. Hanefeld, F. Heinen, H. Holthausen, A. Hübner, G. Jacobi, D. Karch, C. Kauschke, G. Kerkhoff, C. Kiese-Himmel, J. Klepper, A. Kohlschütter, E. Korn-Merker, I. Krägeloh-Mann, P. Kropp, G. Kurlemann, U. de Langen-Müller, H.G. Lenard, Th. Michael, A. von Moers, U. Felderhoff-Müser, R. Nau, B.A. Neubauer, G. Neuhäuser, K. Neumann, M. Noterdaeme, R. Pothmann, D. Rating, B. Reitter, E. Rickels, A.M. Ritz, H. Rosenkötter, B. Schmitt, U. Stephani, B. Stöver, D. Tibussek, R. Trollmann, G. Trommer, I. Tuxhorn, G. Wohlrab, K.P. Boergen, S. Brosch, W. Delb, R. Frank, B. Herrmann, N. von Hofacker, O. Kraus de Camargo, R.v. Kries, R. Michaelis, M. Papousek, H.G. Schlack, J. Schriever, K. Skrodzki, H.-M. Straßburg, U. Thyen, K. Becker, T. Fels, G. Fitze, S. Grasshoff-Derr, P. Göbel, P. Illing, J. Lieber, A. Schmidt, L.M. Wessel, L.D. Berthold, G. Hahn, W. Hirsch, J.D. Moritz, C. Schröder, R. Schumacher, J. Stegmann, M. Steinborn, R. Tietze, R. Wunsch, W. Deppe, T. Hermann, D. Kiosz, E. Leidig, H. Mayer, J. Oepen, R. Stachow, F. Ahrens, G. Frey, I. Huttegger, M.-L. Preil, P.P. Schmittenbecher, H. Traupe, O. Eberhardt, C. Hasler, R. Krauspe, N.M. Meenen, A. Meurer, R. Rödl, R. Stücker, and C. Zilkens
- Published
- 2007
16. [New concepts of pathophysiology and therapy in cystic fibrosis]
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T O, Hirche, S, Loitsch, C, Smaczny, and T O F, Wagner
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Adult ,Phenotype ,Cystic Fibrosis ,Germany ,Cystic Fibrosis Transmembrane Conductance Regulator ,Humans - Abstract
Today, the majority of cystic fibrosis (CF) patients treated in Germany have reached adulthood. However, with increasing age the morbidity and frequency of severe pulmonary complications continues to rise. Further optimization of conventional therapy alone will be insufficient to compensate for this development. In recent years, there has been impressive progress in our understanding of the molecular basis of the CF gene and its product, the cystic fibrosis transmembrane conductance regulator (CFTR). This knowledge can now be applied to develop new therapeutic strategies. However, important questions remain to be solved, i. e., little is known about the pathways that link the malfunctioning of the CFTR protein with the observed clinical phenotype. This review briefly touches on CF genetics as it applies to lung disease and will focus on the current hypotheses of CFTR (dys)function and its impact on pulmonary fluid homeostasis. New treatment options that target the molecular basis of the disease will be discussed.
- Published
- 2005
17. Die thorakale Lymphangiomatose – seltene Ursache eines Chylothorax einer jungen Frau post partum und Differenzialdiagnose zur Lymphangioleiomyomatose
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K. Firner, J. Achenbach, H. Watz, C. Smaczny, and Tof Wagner
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2005
18. Sex steroids and body composition in men with cystic fibrosis
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M Heilmann, M Friemert, N Puvogel, C Smaczny, E. Leifke, Georg Brabant, and A. von zur Mühlen
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Adult ,Male ,medicine.medical_specialty ,Bone density ,Cystic Fibrosis ,Endocrinology, Diabetes and Metabolism ,Endocrinology ,Sex hormone-binding globulin ,Absorptiometry, Photon ,Bone Density ,Internal medicine ,medicine ,Humans ,Testosterone ,Gonadal Steroid Hormones ,Bone mineral ,biology ,General Medicine ,Cross-Sectional Studies ,Concomitant ,biology.protein ,Lean body mass ,Body Composition ,Glucocorticoid ,medicine.drug ,Hormone - Abstract
OBJECTIVE: Delayed sexual maturation and low body weight is common in cystic fibrosis (CF). Concomitant data on sex hormones and concomitant body composition are lacking in men with CF. DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Serum levels of testosterone, 17beta-oestradiol (E(2)), 25-hydroxyvitamin D (25(OH)D), sex hormone-binding globulin (SHBG) and LH were measured by RIA and total and regional lean body mass (LBM), fat body mass (FBM), bone mineral content and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry, in men with CF (n=40; age 24.7+/-5.4 years) and age-matched healthy controls (n=28; age 25.7+/-3.7). Only men without acute disease exacerbation or systemic glucocorticoid treatment were included. RESULTS: Mean levels of hormonal serum parameters differed significantly between healthy controls (testosterone=20.2+/-5.5 nmol/l; E(2)=95.0+/-20.2 pmol/l; 25(OH)D=62.8+/-28.3 nmol/l) and patients (testosterone=15.9+/-4.1 nmol/l; E(2)=60.7+/-19.4 pmol/l; 25(OH)D=39.5+/-17.8 nmol/l; P
- Published
- 2003
19. Diabetes mellitus in patients with cystic fibrosis: the impact of diabetes mellitus on pulmonary function and clinical outcome
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J, Rosenecker, R, Höfler, G, Steinkamp, I, Eichler, C, Smaczny, M, Ballmann, H G, Posselt, J, Bargon, and H, von der Hardt
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Adult ,Liver Cirrhosis ,Male ,Cystic Fibrosis ,Comorbidity ,Diabetes Complications ,Diabetic Neuropathies ,Cholelithiasis ,Forced Expiratory Volume ,Germany ,Diabetes Mellitus ,Humans ,Insulin ,Diabetic Nephropathies ,Life Tables ,Prospective Studies ,Lung ,Respiratory Tract Infections ,Cholestasis ,Diabetic Retinopathy ,Survival Analysis ,Respiratory Function Tests ,Austria ,Case-Control Studies ,Disease Progression ,Female ,Intestinal Obstruction ,Lung Transplantation - Abstract
In this multicenter study, the impact of CF-related diabetes mellitus (CFRD) on pulmonary function and clinical outcome has been investigated. To better characterize the relationship between insulin deficiency and clinical outcome we prospectively followed a group of 56 CF patients, 28 with CFRD (group 1) and 28 without diabetes (group 2) for 5 years. The clinical course of the patients was registered at each center. Data included were mortality, pulmonary function, body mass index, in-patient treatment, and CF-typical and diabetes typical complications. At the end of the study nearly twice the number of patients had died in group 1 as compared to group 2, however due to the low patient number this did not reach statistical significance. In patients with diabetes FEV1 and FVC declined significantly over the five year study period, whereas patients without diabetes did not show a significant decline during the study period. Retinopathy, nephropathy, and neuropathy were only observed in diabetic patients. In conclusion, the data presented in this prospective, multicenter study give evidence that insulin deficiency leads to a direct decline in pulmonary function suggesting a cause and effect relationship between insulin deficiency and lung disease.
- Published
- 2001
20. [Cost comparison of hospital and ambulatory i.v. therapy in adult cystic fibrosis patients. Results of a controlled prospective study]
- Author
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C, Krauth, R, Busse, C, Smaczny, G, Ullrich, T O, Wagner, J, Weber, and T, Welte
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Adult ,Male ,Cystic Fibrosis ,Quality Assurance, Health Care ,Middle Aged ,Anti-Bacterial Agents ,Hospitalization ,Surveys and Questionnaires ,Injections, Intravenous ,Ambulatory Care ,Costs and Cost Analysis ,Humans ,Female ,Prospective Studies ,Aged - Abstract
The regular i.v.-therapy of adults with cystic fibrosis (CF) on an in-patient basis is regarded as expensive. Home treatment is supposed to be cheaper. During a prospective controlled study to compare in-patient treatment (SIT) with home i.v.-treatment (HIT) in regard to clinical, psychosocial and economic parameters, delivered health services and costs in the German setting were evaluated in a comparable manner.During the study period 4/95 to 9/96 45 patients with altogether 56 hospital and 40 home i.v.-courses of approximately 14 days were included in the study. Principal instruments to record the resource consumption were documentation sheets kept by the medical staff and the patients. In addition, pharmacy accounts in HIT and patient records and hospital controlling data in SIT were used.The average costs of a course were 14,038 DM for HIT and 18,702 DM for SIT. Striking are the large differences in medication costs. Two main reasons could be identified for the cost difference: 1, the use of a mobile infusion system in HIT and 2, the much higher prices of pharmaceuticals in the ambulatory care sector compared to the hospital sector, where extremely high profits of the home care service firms or the pharmacy can be supposed. The social costs of HIT (when antibiotics are valued to opportunity costs) are estimated at less than 10,500 DM. From a societal perspective HIT is preferable, from the perspective of the statutory health insurance funds hospital therapy is preferable.1. The widely accepted hypothesis that ambulatory care is cheaper than hospital care is--at least in the German setting--not a-priori true. 2. In the treatment of CF patients incentive failures exist which induce unnecessary and avoidable hospital stays if the perspective of the statutory sickness funds is dominant. 3. Changes in system conditions as e.g. the permission of mail-order pharmacies might help to implement a more rational allocation of resources.
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- 1999
21. ['Since when have you had mucoviscidosis?' Comment on as yet rarely recognized disease entity in internal medicine]
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C, Smaczny and M, Hamm
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Adult ,Health Knowledge, Attitudes, Practice ,Cystic Fibrosis ,Germany ,Internal Medicine ,Prevalence ,Humans ,Child - Abstract
In Germany, many adult patients with cystic fibrosis are still treated by pediatricians. There are still not enough specialists for internal medicine (and particularly pulmonologists) with sufficient knowledge about cystic fibrosis for the treatment of estimated 2000 adult CF-patients. The knowledge about the three basic principles of cystic fibrosis therapy--regular high-dose antibiotics, high-energy and high-fat nutritional support and specific physiotherapy--has to be transferred to adult medicine in order to assure competent care for this "new" group of patients. Cystic fibrosis is also becoming more and more and more important in the field of intensive care medicine and transplantation. Specific diagnostic procedures are important in adult respiratory medicine in order to confirm or exclude late manifestations of the disease. Understanding of the genetic basis of cystic fibrosis and the correlations between genotype and phenotype is beginning to emerge.
- Published
- 1999
22. [Why do adults with mucoviscidosis refuse a medically recommended course of intravenous antibiotic therapy?]
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G, Ullrich, C, Smaczny, G, Steinkamp, J, Weber, T, Welte, R, Busse, and T O, Wagner
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Adult ,Treatment Refusal ,Health Knowledge, Attitudes, Practice ,Cystic Fibrosis ,Chronic Disease ,Pneumonia, Bacterial ,Humans ,Pseudomonas Infections ,Antibiotic Prophylaxis ,Opportunistic Infections ,Infusions, Intravenous ,Drug Administration Schedule ,Home Infusion Therapy - Abstract
Regular courses of intravenous antibiotics are recommended for the treatment of chronic Pseudomonas aeruglnosa (PA) infection in patients with cystic fibrosis. We report the results of interviews performed to evaluate why a subgroup of patients vote against regular intravenous (i.v.) antibiotic treatment.Structured interviews covering a) the individual's perception of chronic PA infection, b) the patient's expectations regarding the effectiveness of i.v. treatment, c) the patient's personal reasons for refusal of i.v. treatment. STUDY COHORT: 16 out of 18 adult patients treated in the adult CF outpatient clinic at Hannover Medical School who had voted against the physician's recommendation to receive regular i.v. therapy twice a year.More than one half of the patients did not regard chronic PA infection as important due to the lack of specific symptoms. A subgroup of patients had no idea of what their clinical status should be if i.v. antibiotics would be necessary; these patients reported prior experience of treatment courses which had been ineffective and had been instituted after talking into the patients. The most frequent reasons against IV treatment were not being sick enough and fear of adverse drug effects.The results are being discussed considering the physician-patient relationship. The reasons why patients refuse help should be extensively explored rather than simply addressing this attitude as "non-compliance". Patients, too, come to reasonable decisions, and it is important to know their thoughts and reasoning if one intends to influence them.
- Published
- 1997
23. [Antibiotic treatment strategies in cystic fibrosis]
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C, Smaczny
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Cystic Fibrosis ,Dose-Response Relationship, Drug ,Administration, Inhalation ,Administration, Oral ,Humans ,Infusions, Intravenous ,Long-Term Care ,Respiratory Tract Infections ,Drug Administration Schedule ,Anti-Bacterial Agents - Published
- 1996
24. Sex steroids and body composition in men with cystic fibrosis.
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E Leifke, M Friemert, M Heilmann, N Puvogel, C Smaczny, A von zur Muhlen, and G Brabant
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- 2003
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25. Every CFTR variant counts - Target-capture based next-generation-sequencing for molecular diagnosis in the German CF Registry.
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Ahting S, Nährlich L, Held I, Henn C, Krill A, Landwehr K, Meister J, Nährig S, Nolde A, Remke K, Ruppel R, Sauer-Heilborn A, Schebek M, Schopper G, Schulte-Hubbert B, Schwarz C, Smaczny C, Wege S, and Hentschel J
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- Humans, Germany, Genetic Testing methods, Female, Male, Genotype, Mutation, Cystic Fibrosis genetics, Cystic Fibrosis diagnosis, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Registries, High-Throughput Nucleotide Sequencing methods
- Abstract
Background: In times of genotype guided therapy options, a total of 3.2 % of people with CF (pwCF) in the German CF Registry[1] only have one or no CFTR-variant detected after genetic analysis. Additionally, genetic data in the Registry can be documented as free text and can therefore be prone to error. In order to allow the greatest possible amount of pwCF access to modern therapies, we conducted a re-evaluation of free text entries and established a custom-whole-CFTR-locus NGS-approach for all pwCF who remained without genetic confirmation afterwards., Methods: To this end, we assembled 731 free text variants of 655 pwCF in the German CF Registry. All variants were evaluated using ClinVar, HGMD and CFTR1/2, corrected in the Registries' database and uploaded to ClinVar. PwCF whose diagnosis remained uncertain as well as additional pwCF or pwCFTR-RD that were assembled through a nationwide call for testing of unclear cases were offered genetic analysis. Samples were analysed using a target-capture based NGS-custom-design-panel covering the entire CFTR-locus., Results: Evaluation of free text variants led to the discovery of 43 variants not formerly reported in the context of CF. The Registries' dropdown list was extended by 497 variants and over 500 pwCF were provided with their most up-to-date genotype. Samples of 47 pwCF/pwCFTR-RD were sequenced via NGS with an overall success rate of 61.7 %, resulting in implementation of entire CFTR-genotyping into routine diagnostics., Conclusion: Entire CFTR-genotyping can greatly increase the genetic diagnostic rate of pwCF/pwCFTR-RD and should be considered after inconspicuous CFTR screening panels in CFTR-diagnostics., Competing Interests: Declaration of Competing Interest The following authors declare a conflict of interest in preparing this article: SN has received grants from the CTN-ECFS, DZL and a Speaker’s fee from Vertex pharmaceuticals. LN has received institutional fees from the German Center for Lung Research, Vertex Pharmaceuticals and the Mukoviszidose Institute. He participated in the Trial Steering Committee for CF STORM and is the Medical lead of the German CF-registry and the Pharmacovigilance study manager of the ECFSPR. CS has received a Speaker’s fee from Vertex, TFF Pharma, Chiesi and Viatris and is an ECFS Board Member.All other author’s declare no conflicts of interest., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)
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- 2024
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26. [CF Lung Disease - a German S3 Guideline: Pseudomonas aeruginosa].
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Schwarz C, Bend J, Hebestreit H, Hogardt M, Hügel C, Illing S, Mainz JG, Rietschel E, Schmidt S, Schulte-Hubbert B, Sitter H, Wielpütz MO, Hammermann J, Baumann I, Brunsmann F, Dieninghoff D, Eber E, Ellemunter H, Eschenhagen P, Evers C, Gruber S, Koitschev A, Ley-Zaporozhan J, Düesberg U, Mentzel HJ, Nüßlein T, Ringshausen FC, Sedlacek L, Smaczny C, Sommerburg O, Sutharsan S, Vonberg RP, Weber AK, and Zerlik J
- Abstract
Competing Interests: Disclosure The authors report no conflicts of interest in this work.
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- 2024
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27. Genomic diversity and clinical relevance of Mycobacterium simiae .
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Wetzstein N, Diricks M, Andres S, Kuhns M, Marschall L, Biciusca T, Smaczny C, Friesen I, Niemann S, and Wichelhaus TA
- Abstract
Introduction: Mycobacterium simiae is a slow-growing non-tuberculous mycobacterium that can cause non-tuberculous mycobacterium (NTM) pulmonary disease and extrapulmonary infections. Until now, detailed genomic and clinical characteristics, as well as possible transmission routes of this rare pathogen remain largely unknown., Methods: We conducted whole genome sequencing of available M. simiae isolates collected at a tertiary care centre in Central Germany from 2006 to 2020 and set them into context with publicly available M. simiae complex sequences through phylogenetic analysis. Resistance, virulence and stress genes, as well as known Mycobacteriaceae plasmid sequences were detected in whole genome raw reads. Clinical data and course were retrieved and correlated with genomic data., Results: We included 33 M. simiae sensu stricto isolates from seven patients. M. simiae showed low clinical relevance with only two patients fulfilling American Thoracic Society (ATS) criteria in our cohort and three receiving NTM-effective therapy. The bacterial populations were highly stable over time periods of up to 14 years, and no instances of mixed or re-infections with other strains of M. simiae were observed. Clustering with <12 single nucleotide polymorphisms distance was evident among isolates from different patients; however, proof for human-to-human transmission could not be established from epidemiological data., Conclusion: Overall, the available sequence data for M. simiae complex was significantly extended and new insights into its pathogenomic traits were obtained. We demonstrate high longitudinal genomic stability within single patients. Although we cannot exclude human-to-human transmission, we consider it unlikely in the light of available epidemiological data., Competing Interests: Conflict of interest: N. Wetzstein, M. Diricks, S. Andres, M. Kuhns, L. Marschall, T. Biciusca, C. Smaczny, I. Friesen and S. Niemann have nothing to disclose. Conflict of interest: T.A. Wichelhaus reports research grants from BMBF, JPIAMR, Deutsche Krebshilfe and MSD, and speaker fees and consulting honoraria from Insmed and Osartis, all outside the submitted work., (Copyright ©The authors 2024.)
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- 2024
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28. Impact of elexacaftor/tezacaftor/ivacaftor on lung function, nutritional status, pulmonary exacerbation frequency and sweat chloride in people with cystic fibrosis: real-world evidence from the German CF Registry.
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Sutharsan S, Dillenhoefer S, Welsner M, Stehling F, Brinkmann F, Burkhart M, Ellemunter H, Dittrich AM, Smaczny C, Eickmeier O, Kappler M, Schwarz C, Sieber S, Naehrig S, and Naehrlich L
- Abstract
Background: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF., Methods: This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months., Findings: The study included 2645 pwCF from 67 centres in Germany (mean age 28.0 ± 11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1 s (ppFEV
1 ) increased by 11.3% (95% confidence interval [CI] 10.8-11.8, p < 0.0001), body mass index (BMI) z -score increased by 0.3 (95% CI 0.3-0.4, p < 0.0001) in individuals aged 12 to <18 years and BMI in adults increased by 1.4 kg/m2 (95% CI 1.3-1.4, p < 0.0001), pulmonary exacerbations decreased by 75.9% (p < 0.0001) and mean sweat chloride concentration decreased by 50.9 mmol/L (95% CI -52.6, -49.3, p < 0.0001). Improvements in ppFEV1 over the first year of therapy were greater in pwCF who had not previously received cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (12.6% [95% CI 11.9-13.4] vs. 9.7% [95% CI 9.0-10.5] in those with prior CFTR modulator treatment., Interpretation: These real-world data are consistent with the findings of randomised clinical trials, and support the use of ETI as a highly effective treatment option for pwCF who have at least one F508del allele., Funding: None., Competing Interests: SS received personal fees or grants from Galapagos, Proteostasis Therapeutics, Celtaxsys, Vertex Pharmaceuticals, Boehringer Ingelheim, Corbus Pharmaceuticals, Insmed Germany GmbH and Ionis Pharmaceuticals outside the submitted work. SD participated in the Advance program, financially supported by Vertex Pharmaceuticals. MW received personal fees from Vertex Pharmaceuticals, Chiesi, CSL Behring, and Grifols outside of the submitted work. CSm received personal fees from Vertex Pharmaceuticals outside the submitted work. FS has no conflict of interest. FB has no conflict of interest. MB receives payments from Mukoviszidose Institut gGmbH. AMD received personal fees from Vertex outside of the submitted work and institutional payments from Vertex for the conduct of clinical studies. HE received personal fees Vertex Pharmaceuticals and Insmed Germany GmbH outside the submitted work. CS received personal fees or grants from Chiesi, GlaxoSmithKline, Boehringer Ingelheim, Vertex Pharmaceuticals and GILEAD outside the submitted work. OE received personal fees or grants from Boerhringer Ingelheim, Chiesi, Corbus Pharmaceuticals, GILEAD, Novartis, Vertex Pharmaceuticals outside the submitted work. MK has no conflict of interest. SaS receives payments for statistical analysis of data that were made to STAT-UP Statistical Consulting & Data Science GmbH. SN received institutional payments from Vertex for the conduct of clinical studies. LN received institutional payments from The German Center of Lung research and Vertex Pharmaceuticals for the conduct of clinical studies, was the medical lead of the German CF Registry and the Pharmacovigilance Study manager of the European Cystic Fibrosis Society Patient Registry and received Medial Writing support from Articulate Science., (© 2023 The Author(s).)- Published
- 2023
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29. Transforming Growth Factor ß1 and Gap Junction Protein Alpha 4 Gene Heterogeneity in Relation to the Severity of Clinical Disease in Cystic Fibrosis.
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Laubach JP, Ludwig M, Horn T, Eickmeier O, Smaczny C, Schubert R, Zielen S, Majoor C, Aydin M, Schnell A, and Schmitt-Grohé S
- Abstract
Background: High TGFβ1-producing variants cause severe clinical disease in F508del homozygous patients. Lately, we showed that a single nucleotide polymorphism (SNP), rs41266431, in the GJA4 gene modifies the disease severity of cystic fibrosis (CF). Our aim was to investigate whether the clinical phenotype associated with GJA4 variants was independent of TGFβ1 variants., Methods: Homozygous F508del patients (n = 115, mean age 27.2 years, m/f (65/50)) were included in this study. A deep sequence analysis was performed for GJA4 and TGBβ1, and disease severity was assessed over 3 years using lung function tests (LFTs), body mass index, diabetes mellitus, colonization with Pseudomonas aeruginosa, survival to end-stage lung disease (ESLD), as well as distinct inflammatory biomarkers., Results: The analyses revealed that one SNP (rs41266431) in GJA4 may be clinically relevant. Carriers homozygous for the G variant (n = 84; 73%) presented with worse LFTs (forced vital capacity (FVC) % predicted: mean 80/86.6, p < 0.035) and a lower survival to ESLD ( p < 0.029). For the TGBβ1 variant: 509 carriers of the C variant ( CT + CC genotype, n = 105, 91.3%) had better LFTs (Forced expiratory flow at 75% of the FVC (FEF75% predicted: median 40/29.5, p < 0.015), although a similar outcome to ESLD. A gene-gene interaction was not observed between TGBβ1 and GJA4 variants for any clinical measure., Conclusions: GJA4 variants are independent of TGBβ1 variants. Both variants had an impact on the LFTs, although only GJA4 variants were associated with an improved outcome for ESLD., Clinical Trial Registration: The study was registered with ClinicalTrials.gov, number NCT04242420, retrospectively on January 24th, 2020., Competing Interests: Dr. Sabina Schmitt-Grohé is on the advisory committee of Vertex and has received a travel grant from Vertex (for ECFS 2019) and ERS (ERS Research Seminars). Moreover, she gave a talk to Vertex, participated in studies for the same, received a fee for a congress report (ECFS conference Liverpool 2019), and attended a vertex-sponsored conference (1.CF-Akademie, Schloss Hohenkammer). In addition, she got financial reimbursement for a talk for Deutsche CF Hilfe and received a personal fee for an expert opinion for the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. Dr. Stefan Zielen reports grants and personal fees from Bene-Arzneimittel GmbH, grants and personal fees from Biotest GmbH, grants from Vifor Pharma Deutschland GmbHÐ, grants from ALK Arzneimittel, personal fees from Novartis GmbH, personal fees from Böhringer Ingelheim, personal fees from Lofarma GmbH, personal fees from IMS HEALTH GmbH and Co., personal fees from GSK, Stallergen, Procter and Gamble, and Allergopharma GmbH, grants and Allergy Therapeutics, Engelhard Arzneimittel, Sanofi-Pasteur, AstraZeneca, Erydel, and Bionorica GmbH, outside the submitted work., (© 2023 The Author(s). Published by IMR Press.)
- Published
- 2023
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30. Corrigendum: Elexacaftor-Tezacaftor-Ivacaftor treatment reduces abdominal symptoms in cystic fibrosis-early results obtained with the CF-specific CFAbd-Score.
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Mainz JG, Zagoya C, Polte L, Naehrlich L, Sasse L, Eickmeier O, Smaczny C, Barucha A, Bechinger L, Duckstein F, Kurzidim L, Eschenhagen P, Caley L, Peckham D, and Schwarz C
- Abstract
[This corrects the article DOI: 10.3389/fphar.2022.877118.]., (Copyright © 2023 Mainz, Zagoya, Polte, Naehrlich, Sasse, Eickmeier, Smaczny, Barucha, Bechinger, Duckstein, Kurzidim, Eschenhagen, Caley, Peckham and Schwarz.)
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- 2023
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31. Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients.
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Wetzstein N, Diricks M, Kohl TA, Wichelhaus TA, Andres S, Paulowski L, Schwarz C, Lewin A, Kehrmann J, Kahl BC, Dichtl K, Hügel C, Eickmeier O, Smaczny C, Schmidt A, Zimmermann S, Nährlich L, Hafkemeyer S, Niemann S, Maurer FP, and Hogardt M
- Subjects
- Anti-Bacterial Agents therapeutic use, Humans, Molecular Epidemiology, Phylogeny, Cystic Fibrosis complications, Cystic Fibrosis drug therapy, Cystic Fibrosis epidemiology, Mycobacterium Infections, Nontuberculous epidemiology, Mycobacterium Infections, Nontuberculous microbiology, Mycobacterium abscessus genetics
- Abstract
Infections due to Mycobacterium abscessus are a major cause of mortality and morbidity in cystic fibrosis (CF) patients. Furthermore, M. abscessus has been suspected to be involved in person-to-person transmissions. In 2016, dominant global clonal complexes (DCCs) that occur worldwide among CF patients have been described. To elucidate the epidemiological situation of M. abscessus among CF patients in Germany and to put these data into a global context, we performed whole-genome sequencing of a set of 154 M. abscessus isolates from 123 German patients treated in 14 CF centers. We used MTBseq pipeline to identify clusters of closely related isolates and correlate those with global findings. Genotypic drug susceptibility for macrolides and aminoglycosides was assessed by characterization of the erm (41), rrl, and rrs genes. By this approach, we could identify representatives of all major DCCs (Absc 1, Absc 2, and Mass 1) in our cohort. Intrapersonal isolates showed higher genetic relatedness than interpersonal isolates (median 3 SNPs versus 16 SNPs; P < 0.001). We further identified four clusters with German patients from same centers clustering with less than 25 SNPs distance (range 3 to 18 SNPs) but did not find any hint for in-hospital person-to-person transmission. This is the largest study investigating phylogenetic relations of M. abscessus isolates in Germany. We identified representatives of all reported DCCs but evidence for nosocomial transmission remained inconclusive. Thus, the occurrence of genetically closely related isolates of M. abscessus has to be interpreted with care, as a direct interhuman transmission cannot be directly deduced. IMPORTANCE Mycobacterium abscessus is a major respiratory pathogen in cystic fibrosis (CF) patients. Recently it has been shown that dominant global clonal complexes (DCCs) have spread worldwide among CF patients. This study investigated the epidemiological situation of M. abscessus among CF patients in Germany by performing whole-genome sequencing (WGS) of a set of 154 M. abscessus from 123 German patients treated in 14 CF centers. This is the largest study investigating the phylogenetic relationship of M. abscessus CF isolates in Germany.
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- 2022
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32. Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score.
- Author
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Mainz JG, Zagoya C, Polte L, Naehrlich L, Sasse L, Eickmeier O, Smaczny C, Barucha A, Bechinger L, Duckstein F, Kurzidim L, Eschenhagen P, Caley L, Peckham D, and Schwarz C
- Abstract
Background: The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families. The aim of this study was to assess effects of ETI on GI symptoms using the CFAbd-Score. Methods: Gastrointestinal symptoms were prospectively assessed in pwCF using the CFAbd-Score before and up to 26 weeks during therapy. The CFAbd-Score was also administered to a healthy control (HC) group. The one-sided questionnaire includes 28 items grouped in five domains. Data analysis included calculation of scores with a weighting tool, developed according to FDA recommendations. Results: A total of 107 pwCF attended in four CF centres in Germany and four centres in the UK completed the CFAbd-Score on at least two occasions. Results were compared to those obtained from the questionnaire of 45 HCs. Despite differences in demographics, age and proportion of pancreatic insufficiency between German and UK patients, analyses based on linear mixed-effects models at week 24 of ETI therapy revealed that estimated marginal means (EMMs) of total CFAbd-Scores significantly reduced (mean ± SE: 14.9 ± 1.2→10.6 ± 1.4; p < 0.01). Also EMMs of all five domains significantly declined ("pain" 16.3 ± 1.6→10.2 ± 2.3, "GERD" 15.8 ± 1.8→8.2 ± 1.9, "disorders of bowel movement" 20.9 ± 1.5→16.0 ± 1.7, "disorders of appetite" 7.9 ± 1.1→2.6 ± 1.1 and "quality of life impairment" 10.1 ± 1.92→3.9 ± 1.9). However, during 24 weeks, CF participants' symptoms mostly still did not reach the reference levels of HCs. Discussion: Using the CFAbd-Score, the first PROM specifically developed for assessment of CF-related abdominal symptoms, we demonstrate comprehensive improvements in GI symptoms after initiation of the highly effective modulator therapy ETI., Competing Interests: JGM, OE, CSM, and CSC report independent grants and speaker/board honoraria from Vertex, outside submitted work. LN reports institutional fees for study participating from Vertex Pharmaceuticals, German Center for Lung research and Boehringer Ingelheim, outside the submitted work. DP received for advisory board and speaker fees from Vertex Pharmaceuticals, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mainz, Zagoya, Polte, Naehrlich, Sasse, Eickmeier, Smaczny, Barucha, Bechinger, Duckstein, Kurzidim, Eschenhagen, Caley, Peckham and Schwarz.)
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- 2022
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33. Mannose-Binding Lectin (MBL) and Gap Junction Protein Alpha 4 (GJA4) Gene Heterogeneity in Relation to Severity of Clinical Disease in Cystic Fibrosis.
- Author
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Laubach JP, Ludwig M, Horn T, Eickmeier O, Smaczny C, Schubert R, Zielen S, Majoor C, Aydin M, and Schmitt-Grohé S
- Subjects
- Connexins genetics, Genotype, Humans, Respiratory Function Tests, Cystic Fibrosis genetics, Pseudomonas Infections complications, Pseudomonas Infections genetics
- Abstract
Background: Recently, we provided evidence that a single nucleotide polymorphism (SNP), rs41266431, on the gap junction protein alpha 4 (GJA4) gene, acts as a modifier for clinical disease severity in patients with cystic fibrosis (CF). These features are very similar to those of variants of the mannose-binding lectin (MBL). This study aimed to clarify whether the clinical disease phenotype associated with GJA4 variants is independent of MBL variants., Methods: One hundred and twelve patients with homozygous F508del (mean age, 27.6 years; m/f, 61/51) were recruited from the CF centers of Bonn, Frankfurt, and Amsterdam. A sequence analysis was performed for GJA4 and MBL. The clinical phenotype was assessed over three years using pulmonary function tests, body mass index, Pseudomonas aeruginosa colonization, diabetes mellitus, survival to end-stage lung disease, and inflammatory markers., Results: A clinically relevant SNP of GJA4 was identified by sequence analysis. Pulmonary function (FVC% pred, mean 78/85; p < 0.055) and survival to end-stage lung disease were lower ( p < 0.043) for this variant (rs41266431) in carriers homozygous for the G variant (n = 82/112; 73%) than in other carriers. Serum MBL (820/372 ng/mL, p < 0.001) was significantly higher in "MBL-sufficient" genotypes (n = 79/112; 71%) than in "MBL-insufficient" genotypes, and a trend for a significant difference in BMI percentiles (35.2/23.8; p < 0.059) was observed. For the MBL-sufficient genotype (median age at death, 38/26 years), there was a trend for better survival ( p < 0.076). There was no augmentation by gene-gene interaction between MBL and GJA4 variants for any outcome parameter., Conclusions: The clinical disease phenotype associated with GJA4 variants is independent of MBL variants. MBL-sufficient variants were associated with superior BMI and a trend for better survival than MBL insufficient variants., Competing Interests: (1) Sabina Schmitt-Grohé is on the advisory committee of Vertex and has received a travel grant from Vertex (for ECFS 2019) and ERS (ERS Research Seminars). Moreover, she gave a talk to Vertex, participated in studies for the same, received a fee for a congress report (ECFS conference Liverpool 2019), and attended a vertex-sponsored conference (1.CF-Akademie, Schloss Hohenkammer). In addition, she got financial reimbursement for a talk for Deutsche CF Hilfe and received a personal fee for an expert opinion for the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen., (© 2022 The Author(s). Published by IMR Press.)
- Published
- 2022
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34. Impact of a Gap Junction Protein Alpha 4 Variant on Clinical Disease Phenotype in F508del Homozygous Patients With Cystic Fibrosis.
- Author
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Horn T, Ludwig M, Eickmeier O, Neerinex AH, Maitland-van der Zee AH, Smaczny C, Wagner TOF, Schubert R, Zielen S, Majoor C, Bos LD, and Schmitt-Grohé S
- Abstract
Background: Lung disease phenotype varies widely even in the F508del (homozygous) genotype. Leukocyte-driven inflammation is important for pulmonary disease pathogenesis in cystic fibrosis (CF). Blood cytokines correlate negatively with pulmonary function in F508del homozygous patients, and gap junction proteins (GJA) might be related to the influx of blood cells into the lung and influence disease course. We aimed to assess the relationship between GJA1/GJA4 genotypes and the clinical disease phenotype., Methods: One-hundred-and-sixteen homozygous F508del patients (mean age 27 years, m/f 66/50) were recruited from the CF centers of Bonn, Frankfurt, and Amsterdam. Sequence analysis was performed for GJA1 and GJA4 . The clinical disease course was assessed over 3 years using pulmonary function tests, body mass index, Pseudomonas aeruginosa colonization, diabetes mellitus, survival to end-stage lung disease, blood and sputum inflammatory markers., Results: Sequence analysis revealed one clinically relevant single nucleotide polymorphism. In this GJA4 variant (rs41266431), homozygous G variant carriers ( n = 84/116; 72.4%) had poorer pulmonary function (FVC% pred: mean 78/86, p < 0.040) and survival to end-stage lung disease was lower ( p < 0.029). The frequency of P. aeruginosa colonization was not influenced by the genotype, but in those chronically colonized, those with the G/G genotype had reduced pulmonary function (FVC% pred: mean 67/80, p < 0.049). Serum interleukin-8 (median: 12.4/6.7 pg/ml, p < 0.052) and sputum leukocytes (2305/437.5 pg/ml, p < 0.025) were higher for the G/G genotype., Conclusions: In carriers of the A allele (27.6%) the GJA4 variant is associated with significantly better protection against end-stage lung disease and superior pulmonary function test results in F508del homozygous patients. This SNP has the potential of a modifier gene for phenotyping severity of CF lung disease, in addition to the CFTR genotype., Clinical Trial Registration: The study was registered with ClinicalTrials.gov, number NCT04242420, retrospectively on January 24th, 2020., (Copyright © 2020 Horn, Ludwig, Eickmeier, Neerinex, Maitland-van der Zee, Smaczny, Wagner, Schubert, Zielen, Majoor, Bos and Schmitt-Grohé.)
- Published
- 2020
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35. A Case of Lymphangioleiomyomatosis (LAM) of the Lung in a Patient with a History of Breast Cancer.
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Koc-Günel S, Tekeli N, Smaczny C, Vogl T, and Rohde G
- Subjects
- Female, Humans, Middle Aged, Tomography, X-Ray Computed, Breast Neoplasms complications, Lung Neoplasms complications, Lung Neoplasms diagnosis, Lymphangioleiomyomatosis complications, Lymphangioleiomyomatosis diagnosis
- Abstract
BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare progressive cystic and nodular disease of the lung characterized by smooth muscle cell proliferation. LAM predominantly affects young premenopausal women. This report is of a case of LAM presenting in a 47-year-old woman with a past history of breast cancer and discusses the possibility of an association between the two conditions. CASE REPORT A 47-year-old woman presented as an emergency with an exacerbation of a four-month history of shortness of breath and dry cough. Her symptoms began following the start of anti-hormonal treatment with letrozole and goserelin acetate for a moderately differentiated (grade 2) invasive ductal carcinoma of the breast (pT2, pN0, M0) which was positive for expression of estrogen receptor (ER+), progesterone receptor (PR+), and human epidermal growth factor receptor 2 (HER2+). Until the previous four months, she had breast-conserving treatment with radiotherapy and tamoxifen therapy. Following hospital admission, she was found to be in type I respiratory failure. Chest X-ray, lung computed tomography (CT), and positron-emission tomography (PET) showed diffuse cystic and nodular lung lesions, consistent with a diagnosis of LAM, and antihormonal therapy was discontinued. She developed pericarditis that was treated with the anti-inflammatory agent, colchicine. Treatment with letrozole and sirolimus improved her respiratory symptoms. CONCLUSIONS A rare case of LAM is presented in a woman with a recent history of breast cancer. Because both tumors were hormone-dependent, this may support common underlying gene associations and signaling pathways between the two types of tumor.
- Published
- 2019
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36. [CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa].
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Schwarz C, Schulte-Hubbert B, Bend J, Abele-Horn M, Baumann I, Bremer W, Brunsmann F, Dieninghoff D, Eickmeier O, Ellemunter H, Fischer R, Grosse-Onnebrink J, Hammermann J, Hebestreit H, Hogardt M, Hügel C, Hug M, Illing S, Jung A, Kahl B, Koitschev A, Mahlberg R, Mainz JG, Mattner F, Mehl A, Möller A, Muche-Borowski C, Nüßlein T, Puderbach M, Renner S, Rietschel E, Ringshausen FC, Schmidt S, Sedlacek L, Sitter H, Smaczny C, Tümmler B, Vonberg R, Wielpütz MO, Wilkens H, Wollschläger B, Zerlik J, Düesberg U, and van Koningsbruggen-Rietschel S
- Subjects
- Cystic Fibrosis complications, Cystic Fibrosis microbiology, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Germany, Humans, Pseudomonas Infections diagnosis, Cystic Fibrosis diagnosis, Cystic Fibrosis therapy, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Practice Guidelines as Topic, Pseudomonas aeruginosa isolation & purification
- Abstract
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., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-018., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2018
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37. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis.
- Author
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Eickmeier O, Fussbroich D, Mueller K, Serve F, Smaczny C, Zielen S, and Schubert R
- Subjects
- Adolescent, Adult, Biomarkers, Case-Control Studies, Child, Cystic Fibrosis complications, Cystic Fibrosis genetics, Cystic Fibrosis physiopathology, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cytokines metabolism, Docosahexaenoic Acids blood, Female, Humans, Inflammation Mediators metabolism, Lung pathology, Lung physiopathology, Male, Middle Aged, Respiratory Function Tests, Sputum metabolism, Young Adult, Cystic Fibrosis metabolism, Docosahexaenoic Acids metabolism, Lung metabolism
- Abstract
Background: Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF., Methods: In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach., Results: DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05)., Conclusions: SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients and may serve as a representative peripheral biomarker of the lung resolution program for CF patients., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2017
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38. Airway inflammation in mild cystic fibrosis.
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Eckrich J, Zissler UM, Serve F, Leutz P, Smaczny C, Schmitt-Grohé S, Fussbroich D, Schubert R, Zielen S, and Eickmeier O
- Subjects
- Adolescent, Biomarkers analysis, Cell Count methods, Child, Female, Humans, Male, Patient Acuity, Respiratory Function Tests methods, Sputum immunology, Statistics as Topic, Cystic Fibrosis complications, Cystic Fibrosis diagnosis, Inflammation diagnosis, Inflammation etiology, Inflammation immunology, Interleukins analysis, Respiratory System immunology, Respiratory System physiopathology, Respiratory Tract Infections diagnosis, Respiratory Tract Infections etiology, Respiratory Tract Infections immunology, Tumor Necrosis Factor-alpha analysis
- Abstract
Background: Airway infection and inflammation play major roles in the progression of cystic fibrosis (CF) lung disease. In patients with mild disease, airway inflammation is a clinically relevant and often underdiagnosed feature. Lung function, sputum cell counts, and cytokine profiles in CF with mild disease might be different in patients with and without involvement of small airway disease (SAD)., Methods: Patients with mild CF (n=32) and 22 healthy controls were enrolled in this study. Patients with CF were assigned to two groups: (1) patients without SAD (n=19, median age 12.3years, MEF
25 >50% predicted), and (2) patients with SAD (n=13 median age, 13.2years, MEF25 <50% predicted). Lung function parameters were measured, cells in induced sputum were counted, and cytokines/chemokines (IL-1β, IL-6, IL-8, TNF-α) were analyzed by real-time quantitative PCR (qRT-PCR) and cytometric bead array (CBA)., Results: Patients with CF had significant elevated levels of pro-inflammatory genes in qRT-PCR and secreted gene products in CBA compared to controls. Patients with CF and SAD had significantly increased trapped air (RV/TLC) and pronounced airway inflammation compared to controls as indicated by elevated levels of sputum biomarkers like total cells, neutrophils, and IL6., Conclusions: Our study demonstrated that patients with CF with mild disease defined by lung function might be further endotyped according to their involvement of SAD. In patients with CF and SAD, airway neutrophilic inflammation is more pronounced and is in part distinct from that seen in patients without SAD., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)- Published
- 2017
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39. Sequential Inhalational Tobramycin-Colistin-Combination in CF-Patients with Chronic P. Aeruginosa Colonization - an Observational Study.
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Riethmüller J, Herrmann G, Graepler-Mainka U, Hellwig D, Heuer HE, Heyder S, Köster H, Kinder B, Kröger K, Paul K, Poplawska K, Melichar VO, Smaczny C, and Mellies U
- Subjects
- Administration, Inhalation, Adolescent, Adult, Chronic Disease, Cystic Fibrosis microbiology, Cystic Fibrosis pathology, Drug Administration Schedule, Drug Combinations, Female, Forced Expiratory Volume drug effects, Humans, Male, Prospective Studies, Pseudomonas Infections microbiology, Pseudomonas Infections pathology, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa growth & development, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Colistin therapeutic use, Cystic Fibrosis drug therapy, Pseudomonas Infections drug therapy, Tobramycin therapeutic use
- Abstract
Background/aims: In cystic fibrosis (CF), chronic microbial lung infections are difficult to treat and cause morbidity and increased mortality., Methods: In a multicentre, open-label, exploratory, non-interventional study, inhaled tobramycin (300 mg twice daily) and colistin (1 million I.U. twice daily) were sequentially combined with the aim to investigate the effect on 41 CF patients with chronic P. aeruginosa infections for six months (mean age 24 ± 10.8y)., Results: Six patients had adverse events that were assessed as being related to treatment. Mucus production and coughing both decreased in 39%, whereas FEV1 absolute and relative to baseline increased by 4.9% and 9.1%, respectively (p = 0.004) in 29 patients, who were definitely treated sequentially. Efficacy of the therapy was rated 'excellent' or 'good' by the physicians in 80.5% of the patients., Conclusions: The results indicate that treatment with inhaled antibiotics, sequentially combined, was very well tolerated by most patients and may have a beneficial effect, even if transitory on lung function and respiratory symptoms., (© 2016 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2016
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40. High variability in oral glucose tolerance among 1,128 patients with cystic fibrosis: a multicenter screening study.
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Scheuing N, Holl RW, Dockter G, Hermann JM, Junge S, Koerner-Rettberg C, Naehrlich L, Smaczny C, Staab D, Thalhammer G, van Koningsbruggen-Rietschel S, and Ballmann M
- Subjects
- Adolescent, Analysis of Variance, Child, Cystic Fibrosis complications, Cystic Fibrosis physiopathology, Diabetes Complications, Diabetes Mellitus physiopathology, Fasting, Female, Glucose Intolerance complications, Glucose Intolerance physiopathology, Glucose Tolerance Test, Humans, Male, Young Adult, Blood Glucose metabolism, Cystic Fibrosis blood, Diabetes Mellitus blood, Glucose Intolerance blood
- Abstract
Background: In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate within-patient variability of oral glucose tolerance., Methods: In total, 4,643 standardized oral glucose tolerance tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 [11.5; 21.5] years, 48.8% females) were studied. Patients included were clinically stable, non-pregnant, and had at least two oral glucose tolerance tests, with no prior lung transplantation or systemic steroid therapy. Transition frequency from any one test to the subsequent test was analyzed and within-patient coefficients of variation were calculated for fasting and two hour blood glucose values. All statistical analysis was implemented with SAS 9.4., Results: A diabetic glucose tolerance was confirmed in 41.2% by the subsequent test. A regression to normal glucose tolerance at the subsequent test was observed in 21.7% and to impaired fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The average within-patient coefficient of variation for fasting blood glucose was 11.1% and for two hour blood glucose 25.3%., Conclusion: In the cystic fibrosis patients studied, a highly variable glucose tolerance was observed. Compared to the general population, variability of two hour blood glucose was 1.5 to 1.8-fold higher.
- Published
- 2014
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41. BIIL 284 reduces neutrophil numbers but increases P. aeruginosa bacteremia and inflammation in mouse lungs.
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Döring G, Bragonzi A, Paroni M, Aktürk FF, Cigana C, Schmidt A, Gilpin D, Heyder S, Born T, Smaczny C, Kohlhäufl M, Wagner TO, Loebinger MR, Bilton D, Tunney MM, Elborn JS, Pier GB, Konstan MW, and Ulrich M
- Subjects
- Adult, Animals, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents adverse effects, Disease Models, Animal, Female, Humans, Inflammation metabolism, Inflammation physiopathology, Leukocyte Count, Lung microbiology, Lung pathology, Male, Mice, Pseudomonas Infections blood, Pseudomonas Infections complications, Pseudomonas Infections physiopathology, Receptors, Leukotriene B4 antagonists & inhibitors, Treatment Outcome, Amidines administration & dosage, Amidines adverse effects, Bacteremia etiology, Carbamates administration & dosage, Carbamates adverse effects, Cystic Fibrosis blood, Cystic Fibrosis complications, Cystic Fibrosis physiopathology, Inflammation drug therapy, Neutrophils drug effects, Neutrophils metabolism, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa isolation & purification
- Abstract
Background: A clinical study to investigate the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients., Methods: P. aeruginosa DNA in the blood of CF patients during and after acute pulmonary exacerbations and in stable patients with non-CF bronchiectasis (NCFB) and healthy individuals was assessed by PCR. The effect of BIIL 284 treatment was tested in an agar bead murine model of P. aeruginosa lung infection. Bacterial count and inflammation were evaluated in lung and other organs., Results: Most CF patients (98%) and all patients with NCFB and healthy individuals had negative P. aeruginosa DNA in their blood. Similarly, the P. aeruginosa-infected mice showed bacterial counts in the lung but not in the blood or spleen. BIIL 284 treatment decreased pulmonary neutrophils and increased P. aeruginosa numbers in mouse lungs leading to significantly higher bacteremia rates and lung inflammation compared to placebo treated animals., Conclusions: Decreased airway neutrophils induced lung proliferation and severe bacteremia in a murine model of P. aeruginosa lung infection. These data suggest that caution should be taken when administering anti-inflammatory compounds to patients with bacterial infections., (© 2013.)
- Published
- 2014
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42. Diabetes in cystic fibrosis: multicenter screening results based on current guidelines.
- Author
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Scheuing N, Holl RW, Dockter G, Fink K, Junge S, Naehrlich L, Smaczny C, Staab D, Thalhammer G, van Koningsbruggen-Rietschel S, and Ballmann M
- Subjects
- Adolescent, Blood Glucose metabolism, Child, Demography, Female, Glucose Tolerance Test, Humans, Kaplan-Meier Estimate, Male, Proportional Hazards Models, Risk Factors, Sex Characteristics, Young Adult, Cystic Fibrosis complications, Cystic Fibrosis diagnosis, Diabetes Complications diagnosis, Mass Screening, Practice Guidelines as Topic
- Abstract
Background: Published estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations. Therefore, we evaluated age-dependent occurrence of glucose abnormalities and associated risk factors in CF patients who participated in a multicenter screening program using oral glucose tolerance tests (OGTT)., Methods: Between 2001 and 2010, 43 specialized CF centers from Germany and Austria serially performed 5,179 standardized OGTTs in 1,658 clinically stable, non-pregnant CF patients with no prior steroid medication or lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD) diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards models were created to elucidate the influence of sex or underweight., Results: At baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI 1.23-10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22-3.98] times higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11-1.71]) and IFG+IGT (1.43 [1.11-1.83]), and in males also for DGT (1.49 [1.09-2.04])., Conclusions/significance: If confirmation of diabetes by a second test is required, as recommended in current guidelines, age at CFRD diagnosis was higher compared to most previous studies. However, known risk factors for glucose abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test is important for a consistent diagnosis of CFRD.
- Published
- 2013
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43. Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis.
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Friedrich-Rust M, Schlueter N, Smaczny C, Eickmeier O, Rosewich M, Feifel K, Herrmann E, Poynard T, Gleiber W, Lais C, Zielen S, Wagner TO, Zeuzem S, and Bojunga J
- Subjects
- Adolescent, Adult, Child, Female, Fibrosis diagnostic imaging, Fibrosis epidemiology, Fibrosis etiology, Humans, Liver Cirrhosis etiology, Male, Middle Aged, Prevalence, Prospective Studies, Young Adult, Cystic Fibrosis complications, Elasticity Imaging Techniques methods, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis epidemiology, Pancreas diagnostic imaging, Pancreas pathology
- Abstract
Background: Patients with cystic fibrosis (CF) have a relevant morbidity and mortality caused by CF-related liver-disease. While transient elastography (TE) is an established elastography method in hepatology centers, Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is a novel ultrasound-based elastography method which is integrated in a conventional ultrasound-system. The aim of the present study was to evaluate the prevalence of liver-fibrosis in patients with CF using TE, ARFI-imaging and fibrosis blood tests., Methods: 106 patients with CF were prospectively included in the present study and received ARFI-imaging of the left and right liver-lobe, ARFI of the pancreas TE of the liver and laboratory evaluation., Results: The prevalence of liver-fibrosis according to recently published best practice guidelines for CFLD was 22.6%. Prevalence of significant liver-fibrosis assessed by TE, ARFI-right-liver-lobe, ARFI-left-liver-lobe, Fibrotest, Fibrotest-corrected-by-haptoglobin was 17%, 24%, 40%, 7%, and 16%, respectively. The best agreement was found for TE, ARFI-right-liver-lobe and Fibrotest-corrected-by-haptoglobin. Patients with pancreatic-insufficiency had significantly lower pancreas-ARFI-values as compared to patients without., Conclusions: ARFI-imaging and TE seem to be promising non-invasive methods for detection of liver-fibrosis in patients with CF., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2013
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44. [Emergencies in adult mucoviscidosis patients].
- Author
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Smaczny C, Born T, and Wagner TO
- Subjects
- Adult, Cystic Fibrosis complications, Female, Gastrointestinal Diseases etiology, Humans, Infertility etiology, Male, Critical Care methods, Cystic Fibrosis diagnosis, Cystic Fibrosis therapy, Gastrointestinal Diseases diagnosis, Gastrointestinal Diseases therapy, Infertility diagnosis, Infertility therapy
- Abstract
Cystic fibrosis is an inherited autosomal recessive metabolic disease caused by mutations on the CFTR gene. This leads to defective chloride channels on epithelial cell membranes and causes various disorders of the respiratory, gastrointestinal, and urogenital tracts.As a result, all exocrine glands produce a viscous secretion, leading to pulmonary symptoms such as chronic cough, secretion retention, recurring infections as well as bronchiectasis and obstructive lung emphysema. Gastrointestinal effects include exocrine and often also endocrine pancreatic insufficiency with chronic diarrhea and maldigestion syndrome as well as pancreoprivic diabetes mellitus; biliary cirrhosis occurs in 10% of cases. Additional effects include reduced fertility in women and infertility in men.Life-threatening complications include bleeding from the bronchial arteries, pneumothorax, and distal intestinal obstruction syndrome (DIOS), previously known as meconium ileus equivalent. Treatment requires rapid diagnosis and should be carried out in experienced centres, since the mortality rate can otherwise be up to 50%.
- Published
- 2012
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45. [Drug treatment of cystic fibrosis - cost patterns and savings potential for outpatient treatment].
- Author
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Baltin CT, Smaczny C, and Wagner TO
- Subjects
- Adult, Cost Savings statistics & numerical data, Female, Germany, Health Expenditures statistics & numerical data, Hospitals, University statistics & numerical data, Humans, Long-Term Care economics, Male, Middle Aged, Retrospective Studies, Young Adult, Ambulatory Care economics, Cystic Fibrosis drug therapy, Cystic Fibrosis economics, Drug Costs statistics & numerical data, Drugs, Generic economics, Drugs, Generic therapeutic use, National Health Programs economics
- Abstract
Background and Purpose: Drug treatment of cystic fibrosis (CF) is associated with significant costs. To help ensure sustainable care, this study assesses the costs associated with outpatient treatment of adult CF patients in Germany. It identifies main cost drivers, evaluates the potential for cost savings from "aut idem" substitution and presents a projection of lifelong medication costs., Methods: The analysis is based on a complete set of prescriptions for adult CF patients from the outpatient clinic of the university hospital of Frankfurt am Main during 2007 (n = 124 patients). Annual treatment costs were calculated on the basis of the "Rote Liste", while the potential for cost savings from "aut idem" drug substitution was obtained through ABDATA Pharma Data Service., Results: The annual outpatient drug costs for an adult patient with CF averages € 17,219 (n = 124), which increases to € 21,782 if i.v. therapies are included. With an average life expectancy at birth of 39.7 years, total lifetime drug treatment costs amount to € 824,159 (reference year 2007, inflation rate 2.7%, 3% discount rate). "Aut idem" substitution with cheaper drugs could reduce pharmaceutical expenditures by 4.1%., Conclusion: Our results confirm the costly nature of drug treatment for CF patients, both on an annual and in particular on a lifelong basis. At the same time, the potential for cost savings through "aut idem" substitution with cheaper drugs remains limited. The added transparency around a small set of costdriving drugs, which is offered in this study, represents a solid contribution to assess treatment choices and financing options to help secure adequate yet sustainable care for CF patients.
- Published
- 2010
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46. [Lung transplantation in cystic fibrosis--a position paper].
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Gottlieb J, Ballmann M, von Mallinckrodt C, Staab D, Smaczny C, Simon A, Welte T, and Wagner TO
- Subjects
- Germany, Humans, Cystic Fibrosis surgery, Lung Transplantation methods, Lung Transplantation trends, Pulmonary Medicine trends
- Abstract
Lung transplantation in cystic fibrosis is an established therapy, due to the fact that vast majority of adult CF patients will develop respiratory failure. Even adolescents and children can be transplanted successfully today. Lung transplantation in cystic fibrosis requires special consideration concerning candidate selection, surgery and postoperative follow-up care. Due to a donor shortage and increasing waiting time, early referral to transplant centres of potential candidates is crucial. In the process of candidate selection, assumed improvements in quality of life and survival benefit should be weighed against contraindications. Centre-based follow-up and close cooperation with local physicians are key factors for success. During follow-up care, the transplantation team should be contacted immediately in the case of any problem or change in medication., ((c) Georg Thieme Verlag KG Stuttgart-New York.)
- Published
- 2009
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47. [MRI-based flow measurements in the main pulmonary artery to detect pulmonary arterial hypertension in patients with cystic fibrosis].
- Author
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Wolf T, Anjorin A, Posselt H, Smaczny C, Vogl TJ, and Abolmaali N
- Subjects
- Adolescent, Adult, Cystic Fibrosis complications, Female, Humans, Male, Reproducibility of Results, Sensitivity and Specificity, Young Adult, Cystic Fibrosis diagnosis, Hypertension, Pulmonary diagnosis, Image Interpretation, Computer-Assisted methods, Magnetic Resonance Imaging methods, Pulmonary Artery pathology, Rheology methods
- Abstract
Purpose: Development of pulmonary arterial hypertension (PH) is a common problem in the course of patients suffering from cystic fibrosis (CF). This study was performed to evaluate MRI based flow measurements (MR(venc); Velocity ENCoding) to detect signs of an evolving PH in patients suffering from CF., Materials and Methods: 48 patients (median age: 16 years, range: 10 - 40 years, 25 female) suffering from CF of different severity (mean FEV (1): 74% +/- 23, mean Shwachman-score: 63 +/- 10) were examined using MRI based flow measurements of the main pulmonary artery (MPA). Phase-contrast flash sequences (TR: 9.6 ms, TE: 2.5 ms, bandwidth: 1395 Hertz/Pixel) were utilized. Results were compared to an age- and sex-matched group of 48 healthy subjects. Analyzed flow data where: heart frequency (HF), cardiac output (HZV), acceleration time (AT), proportional acceleration time related to heart rate (ATr), mean systolic blood velocity (MFG), peak velocity (Peak), maximum fow (Fluss(max)), mean flow (Fluss(mitt)) and distensibility (Dist)., Results: The comparison of means revealed significant differences only for MFG, Fluss(max) and Dist, but overlap was marked. However, using a scatter-plot of AT versus MFG, it was possible to identify five CF-patients demonstrating definite signs of PH: AT = 81 ms +/- 14, MFG = 46 +/- 11 cm/s, Dist = 41% +/- 7. These CF-patients where the most severely affected in the investigated group, two of them were listed for complete heart and lung transplantation. The comparison of this subgroup and the remaining CF-patients revealed a highly significant difference for the AT (p = 0.000001) without overlap., Conclusion: Screening of CF-patients for the development of PH using MRvenc of the MPA is not possible. In later stages of disease, the quantification of AT, MFG and Dist in the MPA may be useful for the detection, follow-up and control of therapy of PH. MR(venc) of the MPA completes the MRI-based follow-up of lung parenchyma damage in patients suffering from CF.
- Published
- 2009
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48. Comparative evaluation of chest radiography, low-field MRI, the Shwachman-Kulczycki score and pulmonary function tests in patients with cystic fibrosis.
- Author
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Anjorin A, Schmidt H, Posselt HG, Smaczny C, Ackermann H, Deimling M, Vogl TJ, and Abolmaali N
- Subjects
- Adolescent, Adult, Child, Cystic Fibrosis diagnostic imaging, Female, Humans, Male, Respiratory Function Tests methods, Statistics, Nonparametric, Cystic Fibrosis physiopathology, Magnetic Resonance Imaging methods, Radiography, Thoracic
- Abstract
The aim of this study was to investigate whether the parenchymal lung damage in patients suffering from cystic fibrosis (CF) can be equivalently quantified by the Chrispin-Norman (CN) scores determined with low-field magnetic resonance imaging (MRI) and conventional chest radiography (CXR). Both scores were correlated with pulmonary function tests (PFT) and the Shwachman-Kulczycki method (SKM). To evaluate the comparability of MRI and CXR for different states of the disease, all scores were applied to patients divided into three age groups. Seventy-three CF patients (mean SKM score: 62 +/- 8) with a median age (range) of 14 years (7-32) were included. The mean CN scores determined with both imaging methods were comparable (CXR: 12.1 +/- 4.7; MRI: 12.0 +/- 4.5) and showed high correlation (P < 0.05, R = 0.97). Only weak correlations were found between imaging, PFT, and SKM. Both imaging modalities revealed significantly more severe disease expression with age, while PFT and SKM failed to detect early signs of disease. We conclude that imaging of the lung in CF patients is capable of detecting subtle and early parenchymal destruction before lung function or clinical scoring is affected. Furthermore, low-field MRI revealed high consistency with chest radiography and may be used for a thorough follow-up while avoiding radiation exposure.
- Published
- 2008
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49. Prevalence and clinical significance of Staphylococcus aureus small-colony variants in cystic fibrosis lung disease.
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Besier S, Smaczny C, von Mallinckrodt C, Krahl A, Ackermann H, Brade V, and Wichelhaus TA
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Chronic Disease, Cystic Fibrosis epidemiology, Cystic Fibrosis microbiology, Cystic Fibrosis physiopathology, Drug Resistance, Bacterial, Female, Forced Expiratory Volume, Humans, Infant, Infant, Newborn, Male, Middle Aged, Phenotype, Prevalence, Respiratory System microbiology, Risk Factors, Staphylococcal Infections epidemiology, Staphylococcal Infections physiopathology, Staphylococcus aureus genetics, Staphylococcus aureus growth & development, Staphylococcal Infections microbiology, Staphylococcus aureus classification, Staphylococcus aureus isolation & purification
- Abstract
Small-colony variants (SCVs) of Staphylococcus aureus can be isolated from the chronically infected airways of patients suffering from cystic fibrosis (CF). These slow-growing morphological variants have been associated with persistent and antibiotic-resistant infections, such as osteomyelitis and device-related infections, but no information is available to date regarding the clinical significance of this special phenotype in CF lung disease. We therefore investigated the prevalence of S. aureus SCVs in CF lung disease in a 12-month prospective study and correlated the microbiological culture results with the patients' clinical data. A total of 252 patients were screened for the presence of SCVs. The prevalence rate was determined to be 17% (95% confidence interval, 10 to 25%) among S. aureus carriers. S. aureus isolates with the SCV phenotype showed significantly higher antibiotic resistance rates than those with the normal phenotype. Patients positive for SCVs were significantly older (P = 0.0099), more commonly cocolonized with Pseudomonas aeruginosa (P = 0.0454), and showed signs of more advanced disease, such as lower forced expiratory volume in 1 s (P = 0.0148) than patients harboring S. aureus with a solely normal phenotype. The logistic regression model determined lower weight (P = 0.016), advanced age (P = 0.000), and prior use of trimethoprim-sulfamethoxazole (P = 0.002) as independent risk factors for S. aureus SCV positivity. The clinical status of CF patients is known to be affected by multiple parameters. Nonetheless, the independent risk factors determined here point to the impact of S. aureus SCVs on chronic and persistent infections in advanced CF lung disease.
- Published
- 2007
- Full Text
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50. Serum leptin and cytokines in whole blood in relation to clinical and nutritional status in cystic fibrosis.
- Author
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Schmitt-Grohé S, Hippe V, Igel M, von Bergmann K, Posselt HG, Krahl A, Smaczny C, Wagner TO, Nikolaizik W, Lentze MJ, and Zielen S
- Subjects
- Adolescent, Adult, Anorexia etiology, Case-Control Studies, Child, Child, Preschool, Cytokines biosynthesis, Enzyme-Linked Immunosorbent Assay methods, Female, Humans, Infant, Interleukin-8 blood, Leptin physiology, Lipopolysaccharides pharmacology, Luminescence, Male, Severity of Illness Index, Tumor Necrosis Factor-alpha, Body Mass Index, Cystic Fibrosis blood, Cytokines blood, Leptin blood, Nutritional Status
- Abstract
Objectives: Leptin plays an important role in the energy balance and may be affected by hormonal and metabolic derangement associated with chronic disease. The aim of this study was to assess the correlation between leptin, proinflammatory cytokines and nutritional status with regard to clinical status in homozygous delta F 508 cystic fibrosis patients., Methods: Patients with mild (Shwachman score 71-100 points, group A) disease were compared with those with moderate disease (Shwachman score 41-55 points, group B) and age-matched controls (group C, n = 22). Leptin was assessed by enzyme-linked immunosorbent assay and cytokines (interleukin-8, tumor necrosis factor alpha) before and after stimulation with 5 ng lipopolysaccharide by a chemiluminescent immunometric assay., Results: Twenty-two patients were recruited for each group (median A/B/C forced expiratory volume in 1 second 80%/59%/-; median age 12/13.5/12.5 years). Leptin (median 3.25/2.65/3.3 pg/mL; P = 0.083) and body mass index were lower (group A/B/C 18.55/16.75/20.5 kg/m(2); P = 0.023), but dietary intake was significantly higher (group A/B/C 50.5/68/43 kcal/kg body weight; P = 0.026) in moderate disease. Cytokines before stimulation with lipopolysaccharide were highest in moderate disease, but there was no significant difference after stimulation (interleukin-8 median A/B/C before--15/25.1/8.0 pg/mL, P < 0.005; after--570.5/573.5/415.5 pg/mL, not significant; tumor necrosis factor alpha median A/B/C 43/56/30 pg/mL, P < 0.0001; 580/427/720.5 pg/mL, not significant.)., Conclusions: There is a physiological regulation of leptin even in more advanced states of disease with significantly lower body mass index than controls. However, our data do not support the idea of elevated cytokine levels inducing anorexia in homozygous delta F 508 cystic fibrosis patients.
- Published
- 2006
- Full Text
- View/download PDF
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