Biomarker in der Diagnostik, Therapie und Prognose infektiöser Lungenerkrankungen

Zusammenfassung

Biomarker spielen eine bedeutende Rolle im Management infektiöser Lungenerkrankungen, wenngleich bisher nur ansatzweise gezeigt werden konnte, dass biomarkergestützte Therapien klinischen Strategien überlegen sind.

Etablierte Indikationen für die Verwendung von Biomarkern sind die Steuerung der antibiotischen Therapiedauer der ambulant erworbenen Pneumonie (CAP) über PCT, die Entscheidung gegen Antibiotika im ambulanten Bereich über CRP oder PCT sowie die Verlaufsevaluation der CAP aus der Kinetik von CRP oder PCT.

Für die Prognosebeurteilung der CAP stehen die Standard-Biomarker der akuten Organdysfunktion wie z. B. Leukozyten- und Thrombozytenzahl, Kreatinin/Harnstoff sowie Laktat in Zusammenschau mit der Klinik im Vordergrund.

Das MR-pro-ADM könnte die Diagnostik in Zukunft weiter bereichern. Ein völlig neuartiges und zukünftig vielsprechendes Konzept ist die genetische Transkriptomanalyse.

Abstract

Biomarkers play an important role in the management of infectious pulmonary diseases, even though there is only limited evidence that biomarker-guided therapies are superior to clinical strategies.

Well-established indications for the use of biomarkers are the guidance of the duration of antibiotic therapy in community-acquired pneumonia (CAP) by PCT, the decision against the use of antibiotics by CRP or PCT in ambulatory settings, and the evaluation of CAP treatment by CRP or PCT kinetics.

In the prognostic assessment of CAP, the standard biomarkers of acute organ dysfunction should be given priority, e. g. leukocyte and platelet counts, creatinine/urea and lactate, in combination with clinical signs and symptoms.

MR-pro-ADM could enrich diagnostics in the future. Genetic transcriptome analysis is a completely new and promising concept.

• Literatur

• 1 van der Meer V, Neven AK, van den Broek PJ. et al. Diagnostic value of C reactive protein in infections of the lower respiratory tract: systematic review. BMJ 2005; 331: 26 doi:0.1136/bmj.38483.478183.EB
• 2 Holm A, Pedersen SS, Nexoe J. et al. Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care. Br J Gen Pract J R Coll Gen Pract 2007; 57: 555-560
• 3 Engel MF, Paling FP, Hoepelman AIM. et al. Evaluating the evidence for the implementation of C-reactive protein measurement in adult patients with suspected lower respiratory tract infection in primary care: a systematic review. Fam Pract 2012; 29: 383-393 doi:10.1093/fampra/cmr119
• 4 van Vugt SF, Broekhuizen BDL, Lammens C. et al. Use of serum C reactive protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough: diagnostic study. BMJ 2013; 346: f2450
• 5 Le Bel J, Hausfater P, Chenevier-Gobeaux C. et al. Diagnostic accuracy of C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting emergency department and having a systematic thoracic CT scan. Crit Care Lond Engl 2015; 19: 366 doi:10.1186/s13054-015-1083-6
• 6 Almirall J, Bolíbar I, Toran P. et al. Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia. Chest 2004; 125: 1335-1342
• 7 Huang Y, Chen R, Wu T. et al. Association between point-of-care CRP testing and antibiotic prescribing in respiratory tract infections: a systematic review and meta-analysis of primary care studies. Br J Gen Pract J R Coll Gen Pract 2013; 63: e787-794 doi:10.3399/bjgp13X674477
• 8 Aabenhus R, Jensen J-US, Jørgensen KJ. et al. Biomarkers as point-of-care tests to guide prescription of antibiotics in patients with acute respiratory infections in primary care. Cochrane Database Syst Rev 2014; CD010130
• 9 Ewig S, Höffken G, Kern WV. et al. [Management of Adult Community-acquired Pneumonia and Prevention – Update 2016]. Pneumologie 2016; 70: 151-200 doi:10.1055/s-0042-101873
• 10 Ruiz-González A, Falguera M, Porcel JM. et al. C-reactive protein for discriminating treatment failure from slow responding pneumonia. Eur J Intern Med 2010; 21: 548-552 doi:10.1016/j.ejim.2010.09.006
• 11 Coelho L, Póvoa P, Almeida E. et al. Usefulness of C-reactive protein in monitoring the severe community-acquired pneumonia clinical course. Crit Care Lond Engl 2007; 11: R92 doi:10.1186/cc6105
• 12 Coelho LM, Salluh JIF, Soares M. et al. Patterns of c-reactive protein RATIO response in severe community-acquired pneumonia: a cohort study. Crit Care Lond Engl 2012; 16: R53 doi:10.1186/cc11291
• 13 Eisenhut M. A persistently elevated C-reactive protein level in pneumonia may indicate empyema. Crit Care Lond Engl 2008; 12: 409 author reply 409 doi:10.1186/cc6204
• 14 Chen SC, Chen W, Hsu WH. et al. Role of pleural fluid C-reactive protein concentration in discriminating uncomplicated parapneumonic pleural effusions from complicated parapneumonic effusion and empyema. Lung 2006; 184: 141-145 doi:10.1007/s00408-005-2573-0
• 15 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 doi:10.1183/09031936.00054507
• 16 Müller F, Christ-Crain M, Bregenzer T. et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest 2010; 138: 121-129 doi:10.1378/chest.09-2920
• 17 Krüger S, Ewig S, Papassotiriou J. et al. Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP: results from the German competence network CAPNETZ. Respir Res 2009; 10: 65 doi:10.1186/1465-9921-10-65
• 18 Viasus D, Del Rio-Pertuz G , Simonetti AF. et al. Biomarkers for predicting short-term mortality in community-acquired pneumonia: A systematic review and meta-analysis. J Infect 2016; 72: 273-282 doi:10.1016/j.jinf.2016.01.002
• 19 Liu D, Su L-X, Guan W. et al. Prognostic value of procalcitonin in pneumonia: A systematic review and meta-analysis. Respirol Carlton Vic 2016; 21: 280-288 doi:10.1111/resp.12704
• 20 Burkhardt O, Ewig S, Haagen U. et al. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J 2010; 36: 601-607 doi:10.1183/09031936.00163309
• 21 Schuetz P, Müller B, Christ-Crain M. et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev 2012; CD007498.
• 22 Long W, Deng X, Zhang Y. et al. Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia. Respirol Carlton Vic 2011; 16: 819-824 doi:10.1111/j.1440-1843.2011.01978.x
• 23 Christ-Crain M, Stolz D, Bingisser R. et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006; 174: 84-93 doi:10.1164/rccm.200512-1922OC
• 24 Bouadma L, Luyt C-E, Tubach F. et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010; 375: 463-474 doi:10.1016/S0140-6736(09)61879-1
• 25 de Jong E, van Oers JA, Beishuizen A. et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016; 16: 819-827 doi:10.1016/S1473-3099(16)00053-0
• 26 Uranga A, España PP, Bilbao A. et al. Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial. JAMA Intern Med 2016; 176: 1257-1265 doi:10.1001/jamainternmed.2016.3633
• 27 Boussekey N, Leroy O, Alfandari S. et al. Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia. Intensive Care Med 2006; 32: 469-472 doi:10.1007/s00134-005-0047-8
• 28 Martin-Loeches I, Valles X, Menendez R. et al. Predicting treatment failure in patients with community acquired pneumonia: a case-control study. Respir Res 2014; 15: 75 doi:10.1186/1465-9921-15-75
• 29 Zhydkov A, Christ-Crain M, Thomann R. et al. Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia. Clin Chem Lab Med 2015; 53: 559-566 doi:10.1515/cclm-2014-0456
• 30 Valenzuela-Sánchez F, Valenzuela-Méndez B, Rodríguez-Gutiérrez JF. et al. New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure. Ann Transl Med 2016; 4: 329 doi:10.21037/atm.2016.08.65
• 31 Krüger S, Ewig S, Giersdorf S. et al. Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: Results from the German Competence Network, CAPNETZ. Am J Respir Crit Care Med 2010; 182: 1426-1434 doi:10.1164/rccm.201003-0415OC
• 32 Cavallazzi R, El-Kersh K, Abu-Atherah E. et al. Midregional proadrenomedullin for prognosis in community-acquired pneumonia: a systematic review. Respir Med 2014; 108: 1569-1580 doi:10.1016/j.rmed.2014.09.018
• 33 España PP, Capelastegui A, Mar C. et al. Performance of pro-adrenomedullin for identifying adverse outcomes in community-acquired pneumonia. J Infect 2015; 70: 457-466 doi:10.1016/j.jinf.2014.12.003
• 34 Albrich WC, Rüegger K, Dusemund F. et al. Biomarker-enhanced triage in respiratory infections: a proof-of-concept feasibility trial. Eur Respir J 2013; 42: 1064-1075 doi:10.1183/09031936.00113612
• 35 Salih W, Schembri S, Chalmers JD. Simplification of the IDSA/ATS criteria for severe CAP using meta-analysis and observational data. Eur Respir J 2014; 43: 842-851 doi:10.1183/09031936.00089513
• 36 Pletz MW, Rohde GG, Welte T. et al. Advances in the prevention, management, and treatment of community-acquired pneumonia. F1000Research 2016; 5
• 37 Krüger S, Pletz MW, Rohde GGU. Biomarker bei ambulant erworbener Pneumonie – was haben wir aus CAPNETZ gelernt?. Pneumologie 2011; 65: 110-113
• 38 Krüger S, Ewig S, Giersdorf S. et al. Dysnatremia, vasopressin, atrial natriuretic peptide and mortality in patients with community-acquired pneumonia: results from the german competence network CAPNETZ. Respir Med 2014; 108: 1696-1705 doi:10.1016/j.rmed.2014.09.014
• 39 Gamble J-M, Eurich DT, Marrie TJ. et al. Admission hypoglycemia and increased mortality in patients hospitalized with pneumonia. Am J Med 2010; 123: 556.e11-16 doi:10.1016/j.amjmed.2009.11.021
• 40 Lepper PM, Ott S, Nüesch E. et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ 2012; 344: e3397
• 41 Kolditz M, Höffken G, Martus P. et al. Serum cortisol predicts death and critical disease independently of CRB-65 score in community-acquired pneumonia: a prospective observational cohort study. BMC Infect Dis 2012; 12: 90 doi:10.1186/1471-2334-12-90
• 42 Singer M, Deutschman CS, Seymour CW. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 801-810 doi:10.1001/jama.2016.0287
• 43 Gwak MH, Jo S, Jeong T. et al. Initial serum lactate level is associated with inpatient mortality in patients with community-acquired pneumonia. Am J Emerg Med 2015; 33: 685-690 doi:10.1016/j.ajem.2015.03.002
• 44 Chen Y-X, Li C-S. Lactate on emergency department arrival as a predictor of mortality and site-of-care in pneumonia patients: a cohort study. Thorax 2015; 70: 404-410 doi:10.1136/thoraxjnl-2014-206461
• 45 Jo S, Jeong T, Lee JB. et al. Validation of modified early warning score using serum lactate level in community-acquired pneumonia patients. The National Early Warning Score-Lactate score. Am J Emerg Med 2016; 34: 536-541 doi:10.1016/j.ajem.2015.12.067
• 46 Vestjens SMT, Spoorenberg SMC, Rijkers GT. et al. High-sensitivity cardiac troponin T predicts mortality after hospitalization for community-acquired pneumonia. Respirol Carlton Vic 02/2017;
• 47 Davenport EE, Burnham KL, Radhakrishnan J. et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med 2016; 4: 259-271 doi:10.1016/S2213-2600(16)00046-1
• 48 Tsalik EL, Henao R, Nichols M. et al. Host gene expression classifiers diagnose acute respiratory illness etiology. Sci Transl Med 2016; 322ra11 8
• 49 Was bringt der Procalcitonin-Test in der hausärztlichen Praxis?. arznei-telegramm®; 2011 Jg. 42, Nr. 2 http://www.arznei-telegramm.de/html/2011_02/1102021_01.html [Accessed January 23, 2017]