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DOI: 10.1055/s-2004-818411
Gehauchte Diagnosen? Zum Potenzial von Atemkondensatuntersuchungen
Expired Diagnosis?-The Potential of Exhaled Breath Analysis Herrn Prof. Dr. med. Joachim Schauer zum 65. Geburtstag gewidmet.Publication History
Eingereicht: 5. Februar 2004
Nach Revision angenommen: 8. März 2004
Publication Date:
20 April 2004 (online)
Nicht-invasive Diagnostik in der Pneumologie
Zu den neueren Entwicklungen in der Pneumologie gehören nicht-invasive Methoden der Informationsgewinnung aus den Atemwegen und dem Lungenparenchym. Zu diesen Methoden zählen das induzierte Sputum und das Atemkondensat sowie die Online-Messung von flüchtigen Substanzen in der Expirationsluft [1]. Diese Methoden stellen den Beginn einer Entwicklung dar, deren Ziel es ist, auf einfache Weise weitergehende Informationen über die Lunge zu erhalten und damit invasivere Diagnostik sparsam, ökonomisch und zielgerichtet einzusetzen. Gleichzeitig soll damit aber auch eine Screeningdiagnostik ermöglicht werden, die auf einen wesentlich größeren Kreis von potenziell Erkrankten ausgedehnt werden kann, als dies bisher für Erkrankungen der Lunge möglich war, von der rein funktionellen Möglichkeit der Atemflussanalyse einmal abgesehen.
Technisch einfacher noch als die Gewinnung von Sputum nach vorheriger Inhalation von 3 %iger Kochsalzlösung ist die Messung von Substanzen, die entweder gasförmig oder eingeschlossen in aerosolisierte Tröpfchen in der Ausatemluft enthalten sind. Dabei entstehen keinerlei Auswirkungen auf das Bronchialsystem, zumal diese Messungen am ruhig atmenden Patienten stattfinden können.
Zu den Mediatoren, die online (also ohne vorherige Sammlung und spätere Messung) bestimmbar sind, gehören Stickstoffmonoxid (NO) und Kohlenmonoxid (CO). Gegenwärtig gibt es vor allem Daten zum Stickstoffmonoxid [2] [3]. In verschiedenen Untersuchungen wurde ein Zusammenhang zwischen der NO-Konzentration in der Ausatemluft und dem Asthma bronchiale gefunden [4] [5] [6] [7] [8]. Mehrere Arbeiten haben sich mit der Standardisierung der Methode befasst [9] und festgelegt, dass die Ausatmung bei der Online-NO-Messung gegen einen fixen Widerstand stattfinden muss, wodurch sich das Gaumensegel verschließt und eine Kontamination des aus der Lunge stammenden Gases durch Nasenluft mit hoher Stickstoffmonoxid-Konzentration vermieden wird.
Das Exhalat enthält neben gasförmigen Bestandteilen auch eine Aerosolfraktion und vor allem Wasserdampf. Anteile dieser letzten beiden Bestandteile der Ausatemluft stellen den Hauptanteil des so genannten Atemkondensates (AK entspricht exhaled breath condensate: EBC) dar. In der Aerosolfraktion sind auch größere Moleküle wie Protein und DNA enthalten. Diesem Umstand verdankt das Atemkondensat seine potenzielle Bedeutung als Methode für Screening und Diagnostik von Lungenkrankheiten. Nachfolgende Übersicht soll darstellen, welche Möglichkeiten und Grenzen der Methode derzeit gegeben sind.
Literatur
- 1 Kharitonov S A, Barnes P J. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med. 2001; 163 (7) 1693-1722
- 2 Ricciardolo F L. Multiple roles of nitric oxide in the airways. Thorax. 2003; 58 (2) 175-182
- 3 Paredi P, Kharitonov S A, Barnes P J. Analysis of expired air for oxidation products. Am J Respir Crit Care Med. 2002; 166 (12 Pt 2) S31-37
- 4 Silkoff P E, Martin D, Pak J. et al . Exhaled nitric oxide correlated with induced sputum findings in COPD. Chest. 2001; 119 (4) 1049-1055
- 5 Blease K, Kunkel S L, Hogaboam C M. Acute inhibition of nitric oxide exacerbates airway hyperresponsiveness, eosinophilia and C-C chemokine generation in a murine model of fungal asthma. Inflamm Res. 2000; 49 (6) 297-304
- 6 Feder L S, Stelts D, Chapman R W. et al . Role of nitric oxide on eosinophilic lung inflammation in allergic mice. Am J Respir Cell Mol Biol. 1997; 17 (4) 436-442
- 7 Strunk R C, Szefler S J, Phillips B R. et al . Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol. 2003; 112 (5) 883-892
- 8 Nogami H, Shoji S, Nishima S. Exhaled nitric oxide as a simple assessment of airway hyperresponsiveness in bronchial asthma and chronic cough patients. J Asthma. 2003; 40 (6) 653-659
- 9 Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 1999; 160 (6) 2104-2117
- 10 Fairchild C I, Stampfer J F. Particle concentration in exhaled breath. Am Ind Hyg Assoc J. 1987; 48 (11) 948-949
- 11 Jorres R A, Holz O. [Non-invasive inflammation monitoring]. Pneumologie. 2001; 55 (9) 406-408
- 12 Becher G, Beck E, Rothe M. et al . Sammlung von nichtgasförmigen Bestandteilen des Ausatemluft durch Ausfrieren. Medizintechnik. 1997; 117 89-95
- 13 Griese M, Noss J, Bredow C von. Protein pattern of exhaled breath condensate and saliva. Proteomics. 2002; 2 (6) 690-696
- 14 Effros R M, Hoagland K W, Bosbous M. et al . Dilution of respiratory solutes in exhaled condensates. Am J Respir Crit Care Med. 2002; 165 (5) 663-669
- 15 Gessner C, Kuhn H, Seyfarth H J. et al . Factors influencing breath condensate volume. Pneumologie. 2001; 55 (9) 414-419
- 16 Vass G, Huszar E, Barat E. et al . Comparison of nasal and oral inhalation during exhaled breath condensate collection. Am J Respir Crit Care Med. 2003; 167 (6) 850-855
- 17 Huszar E, Vass G, Vizi E. et al . Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma. Eur Respir J. 2002; 20 (6) 1393-1398
- 18 Begin R, Drapeau G, Boileau R. et al . Enzyme activities of lung lavage in asbestosis. Clin Biochem. 1986; 19 (4) 240-243
- 19 Rao S. Amylase in bronchial washings as an aid to early diagnosis of bronchogenic carcinoma. J Assoc Physicians India. 1995; 43 (6) 400
- 20 Kietzmann D, Kahl R, Muller M. et al . Hydrogen peroxide in expired breath condensate of patients with acute respiratory failure and with ARDS. Intensive Care Med. 1993; 19 (2) 78-81
- 21 Corradi M, Rubinstein I, Andreoli R. et al . Aldehydes in exhaled breath condensate of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003; 167 (10) 1380-1386
- 22 Corradi M, Folesani G, Andreoli R. et al . Aldehydes and glutathione in exhaled breath condensate of children with asthma exacerbation. Am J Respir Crit Care Med. 2003; 167 (3) 395-399
- 23 Montuschi P, Ragazzoni E, Valente S. et al . Ciabattoni. Validation of leukotriene B4 measurements in exhaled breath condensate. Inflamm Res. 2003; 52 (2) 69-73
- 24 Gessner C, Hammerschmidt S, Kuhn H. et al . Exhaled breath condensate acidification in acute lung injury. Respir Med. 2003; 97 (11) 1188-1194
- 25 Montuschi P, Ragazzoni E, Valente S. et al . Validation of 8-isoprostane and prostaglandin E2 measurements in exhaled breath condensate. Inflamm Res. 2003; 52 (12) 502-507
- 26 Bucchioni E, Kharitonov S A, Allegra L. et al . High levels of interleukin-6 in the exhaled breath condensate of patients with COPD. Respir Med. 2003; 97 (12) 1299-1302
- 27 Carpagnano G E, Resta O, Foschino-Barbaro M P. et al . Interleukin-6 is increased in breath condensate of patients with non-small cell lung cancer. Int J Biol Markers. 2002; 17 (2) 141-145
- 28 Carpagnano G E, Barnes P J, Geddes D M. et al . Increased leukotriene B4 and interleukin-6 in exhaled breath condensate in cystic fibrosis. Am J Respir Crit Care Med. 2003; 167 (8) 1109-1112
- 29 Carpagnano G E, Kharitonov S A, Foschino-Barbaro M P. et al . Increased inflammatory markers in the exhaled breath condensate of cigarette smokers. Eur Respir J. 2003; 21 (4) 589-593
- 30 Shahid S K, Kharitonov S A, Wilson N M. et al . Increased interleukin-4 and decreased interferon-γ in exhaled breath condensate of children with asthma. Am J Respir Crit Care Med. 2002; 165 (9) 1290-1293
- 31 Scheideler L, Manke H G, Schwulera U. et al . Detection of nonvolatile macromolecules in breath. A possible diagnostic tool?. Am Rev Respir Dis. 1993; 148 (3) 778-784
- 32 Effros R M, Biller J, Foss B. et al . A simple method for estimating respiratory solute dilution in exhaled breath condensates. Am J Respir Crit Care Med. 2003; 168 (12) 1500-1505
- 33 Gessner C, Hammerschmidt S, Kuhn H. et al . Exhaled breath condensate nitrite and its relation to tidal volume in acute lung injury. Chest. 2003; 124 (3) 1046-1052
- 34 Conner G E, Salathe M, Forteza R. Lactoperoxidase and hydrogen peroxide metabolism in the airway. Am J Respir Crit Care Med. 2002; 166 (12 Pt 2) S57-61
- 35 Horvath I, MacNee W, Kelly F J. et al . “Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases”, summary of the ERS Research Seminar in Budapest, Hungary, September, 1999. Eur Respir J. 2001; 18 (2) 420-430
- 36 Schleiss M B, Holz O, Behnke M. et al . The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate. Eur Respir J. 2000; 16 (6) 1115-1118
- 37 Beurden W J van, Dekhuijzen P N, Harff G A. et al . Variability of exhaled hydrogen peroxide in stable COPD patients and matched healthy controls. Respiration. 2002; 69 (3) 211-216
- 38 Lehmann C, Rothe M, Becher B. A new method for rapid measurement of hydrogen peroxide in exhaled breath condensate. Am J Respir Crit Care Med. 2002; 165 53 (Abstract)
- 39 Dohlman A W, Black H R, Royall J A. Expired breath hydrogen peroxide is a marker of acute airway inflammation in pediatric patients with asthma. Am Rev Respir Dis. 1993; 148 (4 Pt 1) 955-960
- 40 Antczak A, Nowak D, Shariati B. et al . Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients. Eur Respir J. 1997; 10 (6) 1235-1241
- 41 Antczak A, Kurmanowska Z, Kasielski M. et al . Inhaled glucocorticosteroids decrease hydrogen peroxide level in expired air condensate in asthmatic patients. Respir Med. 2000; 94 (5) 416-421
- 42 Horvath I, Donnelly L E, Kiss A. et al . Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma. Am J Respir Crit Care Med. 1998; 158 (4) 1042-1046
- 43 Nowak D, Antczak A, Krol M. et al . Increased content of hydrogen peroxide in the expired breath of cigarette smokers. Eur Respir J. 1996; 9 (4) 652-657
- 44 Dekhuijzen P N, Aben K K, Dekker I. et al . Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996; 154 (3 Pt 1) 813-816
- 45 Nowak D, Kasielski M, Pietras T. et al . Cigarette smoking does not increase hydrogen peroxide levels in expired breath condensate of patients with stable COPD. Monaldi Arch Chest Dis. 1998; 53 (3) 268-273
- 46 Kasielski M, Nowak D. Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir Med. 2001; 95 (6) 448-456
- 47 De Benedetto F, Aceto A, Dragani B. et al . Validation of a new technique to assess exhaled hydrogen peroxide: results from normals and COPD patients. Monaldi Arch Chest Dis. 2000; 55 (3) 185-188
- 48 Loukides S, Horvath I, Wodehouse T. et al . Elevated levels of expired breath hydrogen peroxide in bronchiectasis. Am J Respir Crit Care Med. 1998; 158 (3) 991-994
- 49 Loukides S, Bouros D, Papatheodorou G. et al . Exhaled H(2)O(2) in steady-state bronchiectasis: relationship with cellular composition in induced sputum, spirometry, and extent and severity of disease. Chest. 2002; 121 (1) 81-87
- 50 Worlitzsch D, Herberth G, Ulrich M. et al . Catalase, myeloperoxidase and hydrogen peroxide in cystic fibrosis. Eur Respir J. 1998; 11 (2) 377-383
- 51 Jobsis Q, Raatgeep H C, Schellekens S L. et al . Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment. Eur Respir J. 2000; 16 (1) 95-100
- 52 Baldwin S R, Simon R H, Grum C M. et al . Oxidant activity in expired breath of patients with adult respiratory distress syndrome. Lancet. 1986; 1 (8471) 11-14
- 53 Heard S O, Longtine K, Toth I. et al . The influence of liposome-encapsulated prostaglandin E1 on hydrogen peroxide concentrations in the exhaled breath of patients with the acute respiratory distress syndrome. Anesth Analg. 1999; 89 (2) 353-357
- 54 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 (6) 389-396
- 55 Ferreira I M, Hazari M S, Gutierrez C. Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled beclomethasone. Am J Respir Crit Care Med. 2001; 164 (6) 1012-1015
- 56 Beurden W J van, Harff G A, Dekhuijzen P N. et al . An efficient and reproducible method for measuring hydrogen peroxide in exhaled breath condensate. Respir Med. 2002; 96 (3) 197-203
- 57 Zappacosta B, Persichilli S, Mormile F. et al . A fast chemiluminescent method for H(2)O(2) measurement in exhaled breath condensate. Clin Chim Acta. 2001; 310 (2) 187-191
- 58 Ho L P, Innes J A, Greening A P. Nitrite levels in breath condensate of patients with cystic fibrosis is elevated in contrast to exhaled nitric oxide. Thorax. 1998; 53 (8) 680-684
- 59 Kostikas K, Papatheodorou G, Ganas K. et al . pH in Expired Breath Condensate of Patients with Inflammatory Airway Diseases. Am J Respir Crit Care Med. 2002; 165 (10) 1364-1370
- 60 Corradi M, Pesci A, Casana R. et al . Nitrate in exhaled breath condensate of patients with different airway diseases. Nitric Oxide. 2003; 8 (1) 26-30
- 61 Cunningham S, McColm J R, Ho L P. et al . Measurement of inflammatory markers in the breath condensate of children with cystic fibrosis. Eur Respir J. 2000; 15 (5) 955-957
- 62 Formanek W, Inci D, Lauener R P. et al . Elevated nitrite in breath condensates of children with respiratory disease. Eur Respir J. 2002; 19 (3) 487-491
- 63 Kharitonov S A, Donnelly L E, Montuschi P. et al . Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma. Thorax. 2002; 57 (10) 889-896
- 64 Hunt J, Byrns R E, Ignarro L J. et al . Condensed expirate nitrite as a home marker for acute asthma [letter]. Lancet. 1995; 346 (8984) 1235-1236
- 65 Ganas K, Loukides S, Papatheodorou G. et al . Total nitrite/nitrate in expired breath condensate of patients with asthma. Respir Med. 2001; 95 (8) 649-654
- 66 Hanazawa T, Kharitonov S A, Barnes P J. Increased nitrotyrosine in exhaled breath condensate of patients with asthma. Am J Respir Crit Care Med. 2000; 162 (4 Pt 1) 1273-1276
- 67 Balint B, Kharitonov S A, Hanazawa T. et al . Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis. Eur Respir J. 2001; 17 (6) 1201-1207
- 68 Rothe M, Becher G, Kragl U. et al . Bestimmung von Tyrosin und Nitrotyrosin im Atemkondensat von CF-Patienten. Pneumologie. 2003; 57 S52 (Abstract)
- 69 Corradi M, Montuschi P, Donnelly L E. et al . Increased nitrosothiols in exhaled breath condensate in inflammatory airway diseases. Am J Respir Crit Care Med. 2001; 163 (4) 854-858
- 70 Driver A G, Kukoly C A, Ali S. et al . Adenosine in bronchoalveolar lavage fluid in asthma. Am Rev Respir Dis. 1993; 148 (1) 91-97
- 71 Mann J S, Holgate S T, Renwick A G. et al . Airway effects of purine nucleosides and nucleotides and release with bronchial provocation in asthma. J Appl Physiol. 1986; 61 (5) 1667-1676
- 72 Vizi E, Huszar E, Csoma Z. et al . Plasma adenosine concentration increases during exercise: a possible contributing factor in exercise-induced bronchoconstriction in asthma. J Allergy Clin Immunol. 2002; 109 (3) 446-448
- 73 Antczak A, Montuschi P, Kharitonov S. et al . Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma. Am J Respir Crit Care Med. 2002; 166 (3) 301-306
- 74 Montuschi P, Kharitonov S A, Ciabattoni G. et al . Exhaled leukotrienes and prostaglandins in COPD. Thorax. 2003; 58 (7) 585-588
- 75 Reinhold P, Becher G, Rothe M. Evaluation of the measurement of leukotriene B4 concentrations in exhaled condensate as a noninvasive method for assessing mediators of inflammation in the lungs of calves. Am J Vet Res. 2000; 61 (7) 742-749
- 76 Csoma Z, Kharitonov S A, Balint B. et al . Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med. 2002; 166 (10) 1345-1349
- 77 Neubauer B, Struck N, Mutzbauer T S. et al . Leukotriene-B4 concentrations in exhaled breath condensate and lung function after thirty minutes of breathing technically dried compressed air. Int Marit Health. 2002; 53 (1 - 4) 93-101
- 78 Montuschi P, Barnes P J. Exhaled leukotrienes and prostaglandins in asthma. J Allergy Clin Immunol. 2002; 109 (4) 615-620
- 79 Becher G, Winsel K, Beck E. et al . Leukotriene B4 in breathing condensate of patients with bronchopulmonary diseases and of normal patients. Appl Cardiopulmon Pathophysiol. 1995; 5 215-219
- 80 Baraldi E, Carraio S, Alinovi R. et al . Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations. Thorax. 2003; 58 (6) 505-509
- 81 Cap P, Pehal F, Petru V. et al . Leukotrienes in breath condensate in patients with asthma and COPD. Alergie. 2002; 1 15-20
- 82 Janssen L J. Isoprostanes: an overview and putative roles in pulmonary pathophysiology. Am J Physiol Lung Cell Mol Physiol. 2001; 280 (6) L1067-1082
- 83 Baraldi E, Ghiro L, Piovan V. et al . Increased exhaled 8-isoprostane in childhood asthma. Chest. 2003; 124 (1) 25-31
- 84 Montuschi P, Collins J V, Ciabattoni G. et al . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000; 162 (3 Pt 1) 1175-1177
- 85 Montuschi P, Ciabattoni G, Paredi P. et al . 8-Isoprostane as a biomarker of oxidative stress in interstitial lung diseases. Am J Respir Crit Care Med. 1998; 158 (5 Pt 1) 1524-1527
- 86 Montuschi P, Kharitonov S A, Ciabattoni G. et al . Exhaled 8-isoprostane as a new non-invasive biomarker of oxidative stress in cystic fibrosis. Thorax. 2000; 55 (3) 205-209 [Record as supplied by publisher]
- 87 Carpenter C T, Price P V, Christman B W. Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS. Chest. 1998; 114 (6) 1653-1659
- 88 Carpagnano G E, Kharitonov S A, Resta O. et al . Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients. Chest. 2002; 122 (4) 1162-1167
- 89 Nowak D, Kalucka S, Bialasiewicz P. et al . Exhalation of H2O2 and thiobarbituric acid reactive substances (TBARs) by healthy subjects. Free Radic Biol Med. 2001; 30 (2) 178-186
- 90 Larstad M, Ljungkvist G, Olin A C. et al . Determination of malondialdehyde in breath condensate by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 766 (1) 107-114
- 91 Mates M. Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology. 2000; 153 (1 - 3) 83-104
- 92 Hunt J F, Fang K, Malik R. et al . Endogenous airway acidification. Implications for asthma pathophysiology [see comments]. Am J Respir Crit Care Med. 2000; 161 (3 Pt 1) 694-699
- 93 Tate S, MacGregor G, Davis M. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax. 2002; 57 (11) 926-929
- 94 Vaughan J, Ngamtrakulpanit L, Pajewski T. et al . Exhaled breath condensate pH is a robust and reproducible assay of airway chemistry. Eur Respir J. 2003; in press
- 95 Hunt J F, Erwin E, Palmer L. et al . Expression and activity of pH-regulatory glutaminase in the human airway epithelium. Am J Respir Crit Care Med. 2002; 165 (1) 101-107
- 96 Ho L P, Faccenda J, Innes J A. et al . Expired hydrogen peroxide in breath condensate of cystic fibrosis patients. Eur Respir J. 1999; 13 (1) 103-106
- 97 McRae K, De Perrot M, Fischer S. et al . Detection of IL-10 in the exhaled breath condensate, plasma and tissue during ischemia-reperfusion injury in experimental lung transplantation. J Heart Lung Transplant. 2001; 20 (2) 184
- 98 Carpagnano G E, Kharitonov S A, Wells A U. et al . Increased vitronectin and endothelin-1 in the breath condensate of patients with fibrosing lung disease. Respiration. 2003; 70 (2) 154-160
- 99 Nayeri F, Millinger E, Nilsson I. et al . Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia. Respir Med. 2002; 96 (2) 115-119
Dr. Christian Gessner
Medizinische Klinik und Poliklinik I · Universitätsklinikum Leipzig
Johannisallee 32
04103 Leipzig
Email: gesc@medizin.uni-leipzig.de