Pneumologie 2009; 63(8): 439-450
DOI: 10.1055/s-0029-1214799
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Biomarker bei infektiösen und nicht infektiösen Lungenerkrankungen außer Malignome

Biomarker in Pulmonary DiseasesA.  Gillissen1 , V.  Wiechmann2 , U.  R.  Jürgens3
  • 1Robert-Koch-Klinik, Thoraxzentrum des Klinikums St. Georg, Leipzig
  • 2Institut für Pathologie und Tumordiagnostik des Klinikums St. Georg, Leipzig
  • 3Schwerpunkt Pneumologie, Allergologie, Schlafmedizin, Medizinische Klinik und Poliklinik II, Universitätsklinik Bonn
Weitere Informationen

Publikationsverlauf

eingereicht 29. 1. 2009

akzeptiert nach Revision 15. 5. 2009

Publikationsdatum:
07. August 2009 (online)

Zusammenfassung

Biomarker haben einen festen Stellenwert in der Medizin und unterstützen in der Diagnosestellung, sie weisen eine für bestimmte Erkrankungen prädiktive Wertigkeit auf, helfen u. U. besser die eingeleitete Therapie zu steuern und den klinischen Verlauf der betroffenen Patienten zu überwachen. Allerdings ist nur ein kleiner Teil der Vielzahl an untersuchten Markern für die Betreuung pneumologischer Patienten von verlässlichem Wert, wie z. B. Procalcitonin in der Therapiesteuerung von Patienten mit einer Pneumonie oder einer Sepsis, der Alpha-1-Antitrypsin-Serumspiegel bei Alpha-1-Antitrypsin-Mangelpatienten, die D-Dimere in der Diagnostik einer Lungenembolie oder einer Venenthrombose, Stickstoffmonoxid beim Asthma oder die Keimisolation im Sputum zur antibiogrammgerechten Antibiotikatherapie bei der chronisch-obstruktiven Lungenerkrankung oder der Pneumonie. Der qualitative Nachweis und die Quantifizierung von Markern im Atemkondensat oder der Nachweis von Molekülen in der Ausatemluft sind neue, noch nicht etablierte Verfahren, die möglicherweise in der Zukunft helfen werden, bestimmte Erkrankungen besser zu diagnostizieren oder zu therapieren. Grundsätzlich haben Biomarker, zusammen mit den übrigen uns zur Verfügung stehenden Verfahren, nur einen unterstützenden, nichtsdestotrotz aber einen wichtigen praktischen Wert. In dieser Übersicht wird anhand von neueren Studienergebnissen die Wertigkeit von Biomarkern bei nicht malignen Erkrankungen der Atemwege und der Lungen beleuchtet.

Abstract

Biological markers in various compartments of the human body have demonstrated potential value in diagnosis, prediction, guidance of therapy as well as in monitoring the clinical course of diseases of the airways and the lung. But only certain surrogate parameters are from clinical value, such as procalcitonin in pneumonia and sepsis, alpha-1-antitrypsin to diagnose alpha-1-antitrypsin deficiency, D-Dimere to detect emboli, nitric oxide in exhaled air in asthma, or isolation of germs from sputum to guide antibiotic treatment. Quantification of numerous markers in exhaled breath condensate or the detection of compounds in exhaled air are more recent attempts to further elucidate those biomarkers for clinical use. In general, biomarkers have an important supportive value in addition to routine diagnostic methods. The article reviews recent data regarding the usefulness of markers in non-malignant pulmonary diseases.

Literatur

  • 1 Cazzola M, MacNee W, Martinez F J. et al . Outcomes for COPD pharmacological trials: from lung function to biomarkers.  Eur Respir J. 2008;  31 416-469
  • 2 Gillissen A, Bartling A, Rasche K. Bronchoalveoläre Lavage.  Klinikarzt. 1997;  26 50-56
  • 3 Stanescu D, Sanna A, Veriter C. et al . Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils.  Thorax. 1996;  51 267-271
  • 4 Brightling C E, Monteiro W, Ward R. et al . Sputum eosinophilia and short-therm response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial.  Lancet. 2008;  356 1480-1485
  • 5 Perng D-W, Huang H-Y, Chen H-M. et al . Characteristics of airway inflammation and bronchodilator reversibility in COPD: a potential guide to treatment.  Chest. 2004;  126 375-381
  • 6 Gompertz S, O'Brien C, Bayley D L. et al . Changes in bronchial inflammation during acute exacerbations of chronic bronchitis.  Eur Respir J. 2001;  17 1112-1119
  • 7 Stolz D, Christ-Crain M, Morgenthaler N G. et al . Copeptin, C-reactive protein and proclacitonin as prognostic biomarkers in acute exacerbation of COPD.  Chest. 2007;  131 1058-1067
  • 8 Magnussen H. COPD: eine entzündliche Erkrankung der Atemwege?.  Pneumologie. 2004;  58 320-324
  • 9 Stockley R A, O'Brien C, Pye A, Hill S L. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD.  Chest. 2000;  117 1638-1645
  • 10 Papi A, Ballettato M, Braccioni F. et al . Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations.  Am J Respir Crit Care Med. 2006;  173 1114-1121
  • 11 Saetta M, Di Stefano A, Maestrelli P. et al . Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis.  Am Rev Respir Dis. 1993;  147 301-306
  • 12 Saetta M, Di Stefano A, Turato G. et al . CD8 T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1998;  157 822-826
  • 13 Schäfer H, Ewig S. Acute exacerbations in chronic obstructive pulmonary disease (COPD) - microbial patterns and risk factors.  Monaldi Arch Chest Dis. 2000;  55 415-419
  • 14 Eller J, Ede A, Schaberg T. et al . Infective exazerbations of chronic obstructive pulmonary disease. Relation between bacteriologic etiology and lung function.  Chest. 1998;  113 1542-1548
  • 15 Höffken G, Lorenz J, Kern W. et al . S3-Leitlinie zu Epidemiologie, Diagnostik, antimikrobieller Therapie und Management von erwachsenen Patienten mit ambulant erworbenen tiefen Atemwegsinfektion.  Pneumologie. 2005;  59 612-664
  • 16 GOLD Executive Committee .Global initiative for chronic obstructive lung disease. http://www.goldcopd.com; Stand: 2008
  • 17 Vogelmeier C, Buhl R, Criee C-P. et al . Leitlinie der Deutschen Atemwegsliga und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD).  Pneumologie. 2007;  61 e1-e40
  • 18 Hogg J C, Chu F, Utokaparch S. et al . The nature of small-airway obstruction in chronic obstructive pulmonary disease.  N Engl J Med. 2004;  350 2645-2653
  • 19 Saetta M. Airway inflammation in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1999;  160 17-20
  • 20 Yoshikawa T, Dent G, Ward J. et al . Impaired neutrophil chemotaxis in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2007;  175 473-479
  • 21 Borrill Z L, Roy K, Singh D. Exhaled breath condensate biomarkers in COPD.  Eur Respir J. 2008;  32 472-486
  • 22 Dalaveris E, Kerenidi T, Katsabeki-Katsafli A. et al . VEGF, TNF-a and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer.  Lung Cancer. 2008;  64 219-225
  • 23 Kharitonov S A, Barnes P J. Exhaled biomarker.  Chest. 2006;  130 1541-1546
  • 24 Nowak D, Kasielski M, Antczak A. et al . Increased content of thiobarbituric acid-reactive substances and hydrogen peroxide in the expired breath condensate of patients with stable chronic obstructive pulmonary disease: no significant effect of cigarette smoking.  Respir Med. 1999;  93 389-396
  • 25 Rahman I. Reproducibility of oxidative stress biomarkers in breath condensate: are they reliable?.  Eur Respir J. 2004;  23 183-184
  • 26 Hoydonck van P GA, Wuyts W A, Vanaudenaerde B M. et al . Quantitative analysis of 8-isoprostane and hydrogen peroxide in exhaled breath condensate.  Eur Respir J. 2004;  23 189-192
  • 27 Silkoff P E, Erzurum S C, Lundberg J O. et al . Amercian Thoracic Society. ATS workshop proceedings: exhaled nitric oxide and nitric oxide oxidative metabolism in exhaled breath condensate.  Proc Am Thorac Soc. 2006;  3 131-145
  • 28 American Thoracic Society, European Respiratory Society . ATS/ERS recommendations of standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005.  Am J Respir Crit Care Med. 2005;  171 912-930
  • 29 Kharitonov S A, Barnes P J. Clincial aspects of exhaled nitric oxide.  Eur Respir J. 2000;  16 781-792
  • 30 Holz O, Jörres R. Nichtinvasive Verfahren zum Nachweis der Atemwegesentzündung im Vergleich. Kosten-Nutzen-Wertigkeit.  Pneumologie. 2004;  58 510-515
  • 31 Jörres R. Modelling the production of nitric oxide within the human airways.  Eur Respir J. 2000;  16 555-560
  • 32 Barceló B, Pons J, Ferrer J M. et al . Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4 + CD25 + regulatory T-lymphocyte response to tobacco smoking.  Eur Respir J. 2008;  31 555-562
  • 33 Smyth L J, Starkey C, Vestbo J. et al . CD4-regulatory cells in COPD patients.  Chest. 2007;  132 156-163
  • 34 Vassilakopoulos T, Hussain S N. Ventilatory muscle activation and inflammation: cytokines, reactive oxygen species, and nitric oxide.  J Appl Physiol. 2007;  102 1687-1695
  • 35 Walter R E, Wilk J B, Larson M G. et al . Systemic inflammation and COPD. The Framingham Heart Study.  Chest. 2008;  133 19-25
  • 36 Bozinovski S, Hutchinson A, Thompson M. et al . Serum amyloid A is a biomarker of acute exacerbations of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2008;  177 269-278
  • 37 Karadog F, Karul A B, Cilag O. et al . Biomarkers of systemic inflammation in stable and exacerbation phases of COPD.  Lung. 2008;  186 403-409
  • 38 Daubin C, Parienti J-J, Vabret A. et al . Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study.  BMC Infect Dis. 2008;  8 145-1471[ – 2334 – 8 – I45]
  • 39 Stolz D, Breidthardt T, Christ-Crain M. et al . Use of B-type natriuretic peptide in the risk stratification of acute exacerbations of COPD.  Chest. 2008;  133 1088-1094
  • 40 Man S FP, Xing L, Connett J E. et al . Circulating fibronectin to C-reactive protein ratio and mortality: a biomarker in COPD?.  Eur Respir J. 2008;  32 1451-1457
  • 41 Cote C, Zilberberg M D, Mody S H. et al . Haemoglobin level and its clinical impact in a cohort of patients with COPD.  Eur Respir J. 2007;  29 923-929
  • 42 Blankenberg S, McQueen M J, Smieja M. et al . Comparative impact of multiple biomarkers and N-terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the heart outcomes prevention evaluation (HOPE) study.  Circulation. 2006;  114 201-208
  • 43 Shlipak M G, Ix J H, Bibbins-Domingo K. et al . Biomarkers to predict recurrent cardiovascular disease: the heart and soul study.  Am J Med. 2008;  121 50-57
  • 44 Pfisterer M, Buser P, Rickli H. et al . BNP-guided vs symptom-guided heart failure therapy: the trials of intensified vs standard medical therapy in elderly patients with congestive heart failure (TIME-CHF) randomized trial.  JAMA. 2009;  301 383-391
  • 45 Myers G L, Christenson R H, Cushman M. et al . National academy of clinical biochemistry laboratory medicine practice guidelines: emerging biomarkers for primary prevention of cardiovascular disease.  Clin Chem. 2009;  55 378-384
  • 46 Maisel A, Müller C, Adams Jr. K. et al . State of the art: using natriuretic peptide levels in clinical practice.  Eur J Heart Fail. 2008;  10 824-839
  • 47 Rutten F H, Cramer M J, Zuithoff N P. et al . Comparison of B-type natriuretic peptide assays for identifying heart failure in stable elderly patients with a clinical dignosis of chronic obstructive pulmonary disease.  Eur J Heart Fail. 2007;  9 651-659
  • 48 Arnold J MO, Howlett J G, Dorian P. et al . Canadian Cardiovascular Society consensus conference recommendations on heart failure update 2007: prevention, management during intercurrent illness or acute cecompensation, and use of biomarkers.  Can J Cardiol. 2007;  23 21-45
  • 49 Ishii J, Nomura M, Ito M. et al . Plasma concentration of brain natriuretic peptide as a biochemical marker for the evaluation of right ventricular overload and mortality in chronic respiratory disease.  Clin Chim Acta. 2000;  301 19-30
  • 50 Müller C, Laule-Kilian K, Frana B. et al . Use of B-type natriuretic peptide in the management of acute dyspnea in patients with pulmonary disease.  Am Heart J. 2006;  151 471-477
  • 51 Morrison L K, Harrison A, Krishnaswamy P. et al . Utility of a rapid B-natriuretic peptide assays in differentiating congestive heart failure from lung diseases in patients presenting with dyspnea.  J Am Coll Cardiol. 2002;  39 202-209
  • 52 Snell N, Newbold P. The clinical utility of biomarkers in asthma and COPD.  Curr Opin Pharmacol. 2008;  8 222-235
  • 53 American Thoracic Society, European Respiratory Society . American Thoracic Society/European Respiratory Society statement: Standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency.  Am J Respir Crit Care Med. 2003;  168 818-900
  • 54 Gillissen A, Schmidt E W, Rasche B. et al . The biochemical behaviour of alpha1-antitrypsin under substitution therapy at homozygote (PI-ZZ) patients.  Klin Wschr. 1989;  67 328-335
  • 55 Köhnlein T, Welte T. Alpha-1 Antitrypsin-Mangel. 1. Ausg. Bremen, London, Boston; Uni-Med 2003
  • 56 Biedermann A, Köhnlein T. Alpha-1-Antitrypsin-Mangel - eine versteckte Ursache der COPD. Überblick über Pathogenese, Diagnostik, Klinik und Therapie.  Dt Ärztebl. 2006;  103 A1828-A1832
  • 57 Wencker M, Banik N, Buhl R. et al . Long-term treatment of alpha-1 antitrypsin deficiency-related pulmonary emphysema with human alpha-1 antitrypsin.  Eur Respir J. 1998;  11 428-433
  • 58 Adachi T, Motojima S, Hirata A. et al . Eosinophil viability-enhancing activity in sputum from patients with bronchial asthma. Contribution of interleukin-5 and granulocyte/macrophage colony-stimulating factor.  Am J Respir Crit Care Med. 1995;  151 618-623
  • 59 Green R H, Brightling C E, McKenna S. et al . Asthma exacerbations and sputum eosinophil counts: a randomized controlled trial.  Lancet. 2002;  360 1715-1721
  • 60 Jatakanon A, Lalloo U G, Lim S. et al . Increased neutrophils and cytokines, TNF-alpha and IL-8, in induced sputum of non-asthmatic patients with chronic dry cough.  Thorax. 1999;  54 234-237
  • 61 Maneechotesuwan K, Essilfie-Quaye S, Kharitonov S A. et al . Loss of control of asthma following inhaled corticosteroid withdrawal is associated with increased sputum interleukin-8 and neutrophils.  Chest. 2007;  132 98-105
  • 62 Gibson P G, Fujimura M, Niimi A. Eosinophilic bronchitis: clinical manifestations and implications for treatment.  Thorax. 2002;  57 178-182
  • 63 Pizzichini E, Pizzichini M MM, Gibson P. et al . Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis.  Am J Respir Crit Care Med. 1998;  158 1511-1517
  • 64 Julius P, Hochheim D, Boser K. et al . Interleukin-5 receptors on human lung eosinophiles after segmental allergen challenge.  Clin Exp Allergy. 2004;  34 1064-1070
  • 65 Ohnishi T, Sur S, Collins D S. et al . Eosinophil survival activity identified as interleukin-5 is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge.  J Allergy Clin Immunol. 1993;  92 607-615
  • 66 Julius P, Lommatzsch M, Küpper M. et al . Safety of segmental allergen challenge in human allergic asthma.  J Allergy Clin Immunol. 2008;  121 712-717
  • 67 Lommatzsch M, Virchow Jr J C. Die allergische Entzündung der oberen und unteren Atemwege.  Allergologie. 2002;  25 96-107
  • 68 Laitinen L A, Laitinen A, Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial.  J Allergy Clin Immunol. 1992;  90 32-42
  • 69 Khor Y H, Feltis B N, Reid D W. et al . Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction.  Clin Exp Allergy. 2007;  37 1189-1198
  • 70 Boman G, Ludviksdottir D, Janson C. et al . Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma.  Respir Med. 2008;  93 552-556
  • 71 Leuppi J D, Downs S H, Downie S R. et al . Exhaled nitric oxide levels in atopic children: relation to specific allergic sensitisation, AHR, and respiratory symptoms.  Thorax. 2002;  57 518-523
  • 72 Henriksen A H, Lingaas-Holmen T, Sue-Chu M. et al . Combined use of exhaled nitric oxide and airway hyperresponsiveness in characterizing asthma in a large population survey.  Eur Respir J. 2000;  15 849-855
  • 73 Smith A D, Cowan J O, Brasset K P. et al . Use of exhaled nitric oxide measurements to guide treatment in chronic asthma.  N Engl J Med. 2005;  352 2163-2173
  • 74 Shaw D E, Berry M A, Thomas M. et al . The use of exhaled nitric oxide to guide asthma management.  Am J Respir Crit Care Med. 2007;  176 231-237
  • 75 Szefler S, Mitchell H, Sorkness C A. et al . Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial.  Lancet. 2008;  372 1065-1072
  • 76 Baur X, Barbinova L. Messung von exhaliertem Stickstoffmonoxid. Klinischer Einsatz bei Atemwegserkrankungen.  Dt Ärztebl. 2009;  104 A790-A796
  • 77 Dressel H, de la Motte D, Reichert J. et al . Exhaled nitric oxide: independent effects of atopy, smoking, respiratory tract infection, gender and height.  Respir Med. 2008;  102 962-969
  • 78 Olin A-C, Rosengren A, Thelle D S. et al . Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample.  Chest. 2006;  130 1319-1325
  • 79 Olin A-C, Bake B, Torén K. Fraction of exhaled nitric oxide at 50 ml/s.  Chest. 2007;  131 1852-1856
  • 80 Kaiser K B. Risk factors in allergy/asthma.  Allergy Asthma Proc. 2004;  25 7-10
  • 81 Wenzel S E. Mechnisms of severe asthma.  Clin Exp Allergy. 2003;  33 1622-1628
  • 82 Hashimoto T, Akiyama K, Kawaguchi H. et al . Correlation of allergen-induced IL-5 and IL-13 production by peripheral blood T cells of asthma patients.  Int Arch Allergy Appl Immunol. 2004;  134 7-11
  • 83 Zhu Y, Chen L, Huang Z. et al . Cutting edge: IL-5 primes the Th2 cytokine-producing capacity in eosinophils through a STAT5-dependent mechanism.  J Immunol. 2004;  173 2918-2922
  • 84 Kardos P, Brutschke M, Buhl R. et al . Kombination von Asthma und COPD: Häuftiger als erwartet?.  Pneumologie. 2006;  60 366-372
  • 85 Mandell L A, Wunderink R G, Anzueto A. et al . Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.  Clin Infect Dis. 2007;  44 27-72
  • 86 Ruiz M, Ewig S, Marcos M A. et al . Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity.  Am J Respir Crit Care Med. 1999;  160 397-405
  • 87 Ruiz M, Ewig S, Torres A. et al . Severe community-acquired pneumonia. Risk factors and follow-up epidemiology.  Am J Respir Crit Care Med. 1999;  160 923-929
  • 88 Hoheisel G B, Winkler J, Gessner C. et al . Klinik und Diagnose bronchopulmonaler Infektionen im Alter.  Pneumologie. 2008;  62 297-304
  • 89 Kothe H, Bauer T, Marre R. et al . Outcome of community-acquired pneumonia: influence of age, residence status and antimicrobial treatment.  Eur Respir J. 2008;  32 139-146
  • 90 Krüger S, Ewig S, Marre R. et al . Procalcitonin-predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes.  Eur Respir J. 2008;  31 349-355
  • 91 Frank J A, Polly E, Parsons E. et al . Pathogenetic significance of biological markers of ventilator-associated lung injury in experimental and clinical studies.  Chest. 2006;  130 1906-1914
  • 92 Gibot S, Cravoisy A, Kolopp-Sarda M N. et al . Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis.  Crit Care Med. 2005;  33 792-796
  • 93 Christ-Crain M, Breidthardt T, Stolz D. et al . Use of B-type natriuretic peptide in the risk stratification of community-acquired pneumonia.  J Intern Med. 2008;  264 166-176
  • 94 Fraunberger P, Walli A K. Biomarker bei Sepsis und Entzündung.  J Lab Med. 2008;  31 294-309
  • 95 Póvoa P. Serum markers in community-acquired pneumonia and ventilator-associated pneumonia.  Curr Opin Infect Dis. 2008;  21 157-162
  • 96 Schütz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers for the assessment of disease severity and guidance of treatment in bacterial infections.  Adv Sepsis. 2008;  6 82-89
  • 97 Müller B, Schütz P, Trampuz A. Circulating biomarkers as surrogates for bloodstream infections.  Int J Antimicro Agents. 2007;  30 16-23
  • 98 Briel M, Schütz P, Müller B, Christ-Crain M. et al . Procalcitonin-guided antibiotic use vs a standard approcach for acute respiratory tract infections in primary care.  Arch Intern Med. 2008;  168 2000-2007
  • 99 Christ-Crain M, Jaccard-Stolz D, Bingisser R. et al . Effect of a procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial.  Lancet. 2004;  363 600-607
  • 100 Müller B, Schütz P, Christ-Crain M. Procalcitonin.  Schweiz Med Forum. 2008;  8 388-390
  • 101 Kofoed K, Andersen O, Kronborg G. et al . Use of plasma C-reactive protein, procalcitonin, neutrohils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study.  Critical care. 2007;  11 R38 DOI: (doi:10.1186/cc5723)
  • 102 Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update.  Ann Intern Med. 2008;  149 177-184
  • 103 Wagner D, Hörster R, Lange B. et al . Stellenwert der T-Zell-Interferon-gamma-Sekretionstests in der Tuberkulosediagnostik.  Dtsch Med Wschr. 2008;  133 354-357
  • 104 Storla D G, Kristiansesn I, Oftung F. et al . Use of interferon gamma-based assay to diagnose tuberculosis infection in health care workers after short term exposure.  BMC Infect Dis. 2009;  9 60 DOI: (doi: 10.1186/1471-2334-9-60)
  • 105 Mack U, Migliori G B, Sester M. et al . LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement.  Eur Respir J. 2009;  33 956-973
  • 106 Arend S M, Engelhard A C, Groot G. et al . Tuberculin skin testing compared with T-cell responses to Mycobacterium tuberculosis-specific and nonspecific antigens for detection of latent infection in persons with recent tuberculosis contact.  Clin Diagn Lab Immunol. 2001;  8 1089-1096
  • 107 Vier H, Gillissen A. Tuberkulosediagnostik: So wird der Verdacht zur Gewissheit.  PneumoNews. 2008;  2 39
  • 108 Lange C, Schaberg T, Diel R. et al . Aktueller Stand der Tuberkulosediagnostik.  Dtsch Med Wschr. 2006;  131 341-347
  • 109 Lalvani A. Diagnosing tuberculosis infection in the 21st century: new tools to tackle an old enemy.  Chest. 2007;  131 1898-1906
  • 110 Dosanjh D P, Hinks T S, Innes J A. et al . Improved diagnostic evaluation of suspected tuberculosis.  Ann Intern Med. 2008;  148 325-336
  • 111 Saltini C, Amicosante M. Beryllium disease.  Am J Med Sci. 2001;  321 89-98
  • 112 Lynch III J P, Toews G B. Idiopathic pulmonary fibrosis. In: Fishman AP, Elias JA, Fishman JA et al., Hrsg Fishman's pulmonary diseases and disorders. New York; McGraw Hill 1998: 1069-1084
  • 113 Perez T, Remy-Jardin M, Cortet B. Airways involvements in rheumatoid arthritis.  Am J Respir Crit Care Med. 1998;  157 1658-1665
  • 114 Misumi S, Lynch D A. Idiopathic pulmonary fibrosis/usual interstitialpneumonia. Imaging diagnosis, specturm of abnormalities, and temporal progression.  Proc Am Thorac Soc. 2006;  3 307-314
  • 115 Ryu J H, Myers J L, Capizzi S A. et al . Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease.  Chest. 2005;  127 178-184
  • 116 Martinez F J. Idiopathic interstitial pneumonias. Usual interstitital pneumonia versus nonspecific pneumonia.  Proc Am Thorac Soc. 2006;  3 81-95
  • 117 American Thoracic Society, European Respiratory Society . American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias.  Am J Respir Crit Care Med. 2002;  165 277-304
  • 118 Katzenstein A L, Myers J L. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.  Am J Respir Crit Care Med. 1998;  157 1301-1351
  • 119 Lacasse Y, Selman M, Costabel U. et al . Clincial diagnosis of hypersensitivity pneumonitis.  Am J Respir Crit Care Med. 2003;  168 952-958
  • 120 Ziegenhagen M W, Rothe M, Schlaak M. et al . Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis.  Eur Respir J. 2003;  21 407-413
  • 121 Lammi L, Kinnula V L, Lähde S. et al . Propeptide levels of type III and type I procollagen in the serum and bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis.  Eur Respir J. 1997;  10 2725-2730
  • 122 Li X, Molina-Molina M, Abdul-Hafez A. et al . Angiotensin converting enzyme-2 is protective but downregulated in human and experimental lung fibrosis.  Am J Physiol Lung Cell Mol Physiol. 2008;  295 L178-L185
  • 123 Suga M, Iyonaga K, Ichiyasu H. et al . Clinical significance of MCP-1 levels in BALF and serum in patients with interstitital lung diseases.  Eur Respir J. 1999;  14 376-382
  • 124 Agostini C, Gurrieri C. Chemokine/cytokine cocktail in idiopathic pulmonary fibrosis.  Proc Am Thorac Soc. 2006;  3 357-363
  • 125 Guo X, Lin H-M, Lin Z. et al . Surfactant protein A and B genetic variants predispose to idiopathic pulmonary fibrosis.  Eur Respir J. 2001;  18 482-490
  • 126 Pardo A, Selman M. Idiopathic pulmonary fibrosis: new insights in its pathogenesis.  Int J Biochem Cell Biol. 2002;  34 1534-1538
  • 127 Hyzy R, Huang S, Myers J. et al . Acute exacerbation of idiopathic pulmonary fibrosis.  Chest. 2007;  132 1652-1658
  • 128 Nagai S, Handa T, Ito Y. et al . Bronchoalveolar lavage in idiopathic interstitital lung diseases.  Semin Respir Crit Care Med. 2007;  28 496-503
  • 129 Ryu Y J, Chung M P, Han J. et al . Bronchoalveolar lavage in fibrotic idiopathic interstitital pneumonias.  Respir Med. 2007;  101 655-660
  • 130 Govender P, Baugh J A, Pennington S R. et al . Role of proteomics in the investigation of pulmonary fibrosis.  Expert Rev Proteomics. 2007;  4 379-388
  • 131 Kriegova E, Melle C, Kolek V. et al . Protein profilces of bronchoalveolar lavage fluids from patients with pulmonary sarcoidosis.  Am J Respir Crit Care Med. 2006;  173 1145-1154
  • 132 Meyer G, Planquette B, Sanchez O. Long-term outcome of pulmonary embolism.  Curr Opin Hematol. 2008;  15 499-503
  • 133 DeMonaco N A, Dang Q, Kapoor W N. et al . Pulmonary embolism incidence is increasing with use of spiral computed tomography.  Am J Med. 2008;  121 611-617
  • 134 British Thoracic Society . British Thoracic Society guidelines for the management of suspected acute pulmonary embolism.  Thorax. 2003;  58 470-484
  • 135 Kline J A, Hernandez-Nino J, Rose G A. et al . Surrogate markers for adverse outcomes in normotensive patients with pulmonary embolism.  Crit Care Med. 2006;  34 2773-2780
  • 136 Aksay E, Yanturali S, Kiyan S. Can elevated tropinin I levels predict complicated clinical course and inhospital mortality in patients with acute pulmonary embolism?.  Am J Emerg Med. 2007;  25 138-143
  • 137 Pruszczyk P, Kostrubiec M, Bochowicz A. et al . N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism.  Eur Respir J. 2003;  22 649-653
  • 138 Stolba R, Lenglinger F, Rezenka E. et al . Wertigkeit eines neuen, quantitativen D-Dimer-Test für die Ausschlußdiagnostik von Pulmonalembolien bei symptomatischen Patienten.  J Lab Med. 2000;  24 153-157
  • 139 Michiels J J, Gadisseur A, Planken M v d. et al . A critical appraisal of non-invasive diagnosis and exlusion of deep vein thrombosis and pulmonary embolism in outpatients with suspected deep vein thrombosis or pulmonary embolism: how many tests to we need?.  Int Angiol. 2005;  24 27-39
  • 140 Nordenholz K E, Mitchel A M, Kline J A. Direct comparison of the diagnostic accuracy of fifty protein biological markers of pulmonary embolism for use in the emergency department.  Acad Emerg Med. 2008;  15 795-799
  • 141 Christopher Study Investigators . Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography.  JAMA. 2006;  295 179
  • 142 Mitchell A M, Nordenholz K E, Kline J A. Tandem measurment of D-dimer and myeloperoxidase or C-reactive protein to effectively screen for pulmonary embolism in the emergency department.  Acad Emerg Med. 2008;  15 800-805
  • 143 Horvath I, Hunt J F, Barnes P J. Exhaled breath condensate: methodological recommendations and unresolved questions.  Eur Respir J. 2005;  26 523-548
  • 144 Chan H P, Lewis C, Thomas P S. Exhaled breath analysis: Novel approaches for early detection of lung cancer.  Lung Cancer. 2008;  63 164-168
  • 145 Conrad D H, Goyette J, Thomas P S. Proteomics as a method for early detection of cancer: a review of proteomics, exhaled breath condensate, and lung cancer screening.  J Gen Intern Med. 2007;  23 78-84
  • 146 Gray R D, MacGregor G, Noble D. et al . Sputum proteomics in inflammatory and suppurative respiratory diseases.  Am J Respir Crit Care Med. 2008;  178 444-452
  • 147 Merkel D, Rist W, Seither P. et al . Proteomic studyof human bronchoalveolar lavage fluids from smokers with chronic obstructive pulmonary disease by combining surface-enhanced laser desorption/ionization-mass spectrometry profiling with mass spectrometric protein identification.  Proteomics. 2005;  5 2972-2980
  • 148 Martin P, Makepeace K, Hille S A. et al . Microsatellite instability regulates transcription factor binding and gene expression.  Proc Natl Acad Sci USA. 2005;  102 3800-3804
  • 149 Carpagnano G E, Foschino-Barbaro M P, Spanevello A. et al . 3p microsatellite signature in exhaled breath condensate and tumor tissue of patients with lung cancer.  Am J Respir Crit Care Med. 2008;  177 337-341
  • 150 Zervou M I, Tzortzaki E G, Makris D. et al . Differences in microsatellite DNA level between asthma and chronic obstructive pulmonary disease.  Eur Respir J. 2006;  28 472-478
  • 151 Makris D, Tzanakis N, Damianaki A. et al . Microsatelite DNA instability and COPD exacerbations.  Eur Respir J. 2008;  32 612-618
  • 152 Mazzone P J, Hammel J, Dweik D. et al . Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetic sensor array.  Thorax. 2007;  62 565-568
  • 153 Dragoneri S, Schot R, Mertens B J. et al . An electronic nose in the discrimination of patients with asthma and controls.  J Allergy Clin Immunol. 2007;  120 856-862
  • 154 Belda-Iniesta C, de Castro Carpeno J, Carrasco J A. et al . New screeing method of lung cancer by detecting volatile organic compounds in breath.  Clin Transl Oncol. 2007;  9 364-368
  • 155 Dragonieri S, Annema J T, Schot R. et al . An electronic nose in the discrimination of patients wiht non-small cell lung cancer and COPD.  Lung Cancer. 2008;  64 166-170
  • 156 Machado R F, Laskowski D, Deffenderfer O. et al . Detection of lung cancer by sensory array analyses of exhaled breath.  Am J Respir Crit Care Med. 2005;  17 1286-1291
  • 157 Moorhead K T, Lee D, Chase J G, Moot A R. et al . Classifying algorithmus for SIFT-MS technology and medical diagnosis.  Comput Methods Programs Biomed. 2008;  89 226-238
  • 158 Gaspar E M, Lucena A F, Duro da Costa J. et al . Organic metabolites in exhaled human breath: a multivariate approach for identification of biomarkers in lung disorders.  J Chromatogr A . 2008;  1216 2749-2756
  • 159 Buszewski B, Ulanowska A, Ligor T. et al . Analysis of exhaled breath from smokers, passive smokers and non-smokers by solid-phase microextraction gas chromatographie/mass spectrometry.  Biomed Chromatogr. 2008;  23 551-556

Prof. Dr. A. Gillissen

Robert-Koch-Klinik,
Thoraxzentrum des Klinikums St. Georg

Nikolai-Rumjanzew-Str. 100
04207 Leipzig

URL: http://www.rkk-leipzig.de