Exhaled Breath Condensates as a Source for Biomarkers for Characterization of Inflammatory Lung Diseases — Oak Academic Publishing
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Exhaled Breath Condensates as a Source for Biomarkers for Characterization of Inflammatory Lung Diseases
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Section of Allergy and Immunology, Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, USA
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Department of Biochemistry and Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, USA
1 Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Section of Allergy and Immunology, Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, USA
2 Department of Biochemistry and Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, USA
Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the inflamed lung. The collection of lung secretions by traditional methods including bronchoalveolar lavage and induced sputum collection are limited by their invasive nature. Exhaled breath condensate (EBC) is a simple and non-invasive technique of collecting fluid samples, which are representative of airway lining fluid. Advances in collection methods and evolving molecular techniques have led to development of more sensitive assays for existing biomarkers and identification of new biomarkers, which can be potentially useful in monitoring lung inflammation. In this review, we present the current understanding of various biomarkers including small molecules (H 2 O 2 , pH and nitric oxide related biomarkers), lipid mediators (8-isprostane, leukotrienes and prostaglandins), small proteins (cytokines and chemokines) and nucleic acids (DNA and microRNAs). We also discuss the differential profile of biomarkers in recognizing different patterns of lung inflammation. As the sensitivity of methods of EBC improves, this biofluid will play an increasing role in diagnosis and monitoring of lung diseases.
Centers for Disease Control and Prevention, “Vital Signs: Asthma Prevalence, Disease Characteristics, and Self-Management Education—United States, 2001-2009,” 2011. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6017a4.htm
Centers for Disease Control and Prevention, “Chronic Obstructive Pulmonary Disease among Adults—United States, 2011,” 2012. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6146a2.htm
J. Hunt, “Exhaled Breath Condensate: An Evolving Tool for Noninvasive Evaluation of Lung Disease,” The Journal of Allergy and Clinical Immunology, Vol. 110, No. 1, 2002, pp. 28-34. doi:10.1067/mai.2002.124966
J. Liu, D. H. Conrad, S. Chow, V. H. Tran, D. H. Yates and P. S. Thomas, “Collection Devices Influence the Constituents of Exhaled Breath Condensate,” European Respiratory Journal, Vol. 30, No. 4, 2007, pp. 807-808. doi:10.1183/09031936.00080207
O. U. Soyer, E. A. Dizdar, O. Keskin, C. Lilly and O. Kalayci, “Comparison of Two Methods for Exhaled Breath Condensate Collection,” Allergy, Vol. 61, No. 8, 2006, pp. 1016-1018. doi:10.1111/j.1398-9995.2006.01064.x
I. Horváth, J. Hunt, P. J. Barnes, K. Alving, A. Antczak, E. Baraldi, G. Becher, W. J. C. van Beurden, M. Corradi, R. Dekhuijzen, R. A. Dweik, T. Dwyer, R. Effros, S. Erzurum, B. Gaston, C. Gessner, A. Greening, L. P. Ho, J. Hohlfeld, Q. Jobsis, D. Laskowski, S. Loukides, D. Marlin, P. Montuschi, A. C. Olin, A. E. Redington, P. Rein-hold, E. L. J. van Rensen, I. Rubinstein, P. Silkoff, K. Toren, G. Vass, C. Vogelberg and H. Wirtz, “Exhaled Breath Condensate: Methodological Recommendations and Unresolved Questions,” European Respiratory Journal, Vol. 26, No. 3, 2005, pp. 523-548. doi:10.1183/09031936.05.00029705
R. M. Effros, M. B. Dunning 3rd, J. Biller and R. Shaker, “The Promise and Perils of Exhaled Breath Condensates,” American Journal of Physiology Lung Cellular and Molecular Physiology, Vol. 287, No. 6, 2004, pp. L1073-L1080. doi:10.1152/ajplung.00069.2004
M. D. Davis, A. Montpetit and J. Hunt, “Exhaled Breath Condensate: An Overview,” Immunology and Allergy Clinics of North America, Vol. 32, No. 3, 2012, pp. 363-375. doi:10.1016/j.iac.2012.06.014
G. I. Sidorenko, E. I. Zborovskii and D. I. Levina, “Surface-Active Properties of the Exhaled Air Condensate (a New Method of Studying Lung Function),” Terapevticheskii Arkhiv, Vol. 52, No. 3, 1980, pp. 65-68.
R. M. Effros, B. Peterson, R. Casaburi, J. Su, M. Dunning, J. Torday, J. Biller and R. Shaker, “Epithelial Lining Fluid Solute Concentrations in Chronic Obstructive Lung Disease Patients and Normal Subjects,” Journal of Applied Physiology, Vol. 99, No. 4, 2005, pp. 1286-1292. doi:10.1152/japplphysiol.00362.2005
C. Caffarelli, E. Calcinai, L. Rinaldi, C. Povesi Dascola, L. Terracciano and M. Corradi, “Hydrogen peroxide in exhaled breath condensate in asthmatic children during acute exacerbation and after treatment,” Respiration, Vol. 84, No. 4, 2012, pp. 291-298. doi:10.1159/000341969
A. B. Tonnel and B. Wallaert, “Oxidants and Bronchial Inflammatory Processes,” The European Respiratory Journal, Vol. 3, No. 9, 1990, pp. 987-988.
D. Nowak, S. Kalucka, P. Bialasiewicz and M. Król, “Exhalation of H2O2 and Thiobarbituric Acid Reactive Substances (TBARs) by Healthy Subjects,” Free Radical Biology and Medicine, Vol. 30, No. 2, 2001, pp. 178-186. doi:10.1016/S0891-5849(00)00457-3
F. De Benedetto, A. Aceto, B. Dragani, A. Spacone, S. Formisano, R. Cocco and C. M. Sanguinetti, “Validation of a New Technique to Assess Exhaled Hydrogen Peroxide: Results from Normals and COPD Patients,” Monaldi Archives for Chest Disease, Vol. 55, No. 3, 2000, pp. 185-188.
Y. Hu, Z. Zhang and C. Yang, “A Sensitive Chemiluminescence Method for the Determination of H2O2 in Exhaled Breath Condensate,” Analytical Science, Vol. 24, No. 2, 2008, pp. 201-205. doi:10.2116/analsci.24.201
A. H. Al-Obaidy and A.-G. M. Al-Samarai, “Exhaled Breath Condensate pH and Hydrogen Peroxide as Non-Invasive Markers for Asthma,” Saudi Medical Journal, Vol. 28, No. 12, 2007, pp. 1860-1863.
A. Emelyanov, G. Fedoseev, A. Abulimity, K. Rudinski, A. Fedoulov, A. Karabanov and P. J. Barnes, “Elevated Concentrations of Exhaled Hydrogen Peroxide in Asthmatic Patients,” Chest, Vol. 120, No. 4, 2001, pp. 1136-1139. doi:10.1378/chest.120.4.1136
S. Loukides, I. Horvath, T. Wodehouse, P. J. Cole and P. J. Barnes, “Elevated Levels of Expired Breath Hydrogen Peroxide in Bronchiectasis,” American Journal of Respiratory and Critical Care Medicine, Vol. 158, No. 3, 1998, pp. 991-994.
D. Kietzmann, R. Kahl, M. Müller, H. Burchardi and D. Kettler, “Hydrogen Peroxide in Expired Breath Condensate of Patients with Acute Respiratory Failure and with ARDS,” Intensive Care Medicine, Vol. 19, No. 2, 1993, pp. 78-81. doi:10.1007/BF01708366
E.-J. D. Oudijk, W. B. M. Gerritsen, E. H. J. Nijhuis, D. Kanters, B. L. P. Maesen, J.-W. J. Lammers and L. Koenderman, “Expression of Priming-Associated Cellular Markers on Neutrophils during an Exacerbation of COPD,” Respiratory Medicine, Vol. 100, No. 10, 2006, pp. 1791-1799. doi:10.1016/j.rmed.2006.01.022
Q. Jobsis, H. C. Raatgeep, S. L. Schellekens, A. Kroesbergen, W. C. Hop and J. C. de Jongste, “Hydrogen Peroxide and Nitric Oxide in Exhaled Air of Children with Cystic Fibrosis during Antibiotic Treatment,” European Respiratory Journal, Vol. 16, No. 1, 2000, pp. 95-100. doi:10.1034/j.1399-3003.2000.16a17.x
Q. Jobsis, H. C. Raatgeep, S. L. Schellekens, W. C. Hop, P. W. Hermans and J. C. de Jongste, “Hydrogen Peroxide in Exhaled Air of Healthy Children: Reference Values,” European Respiratory Journal, Vol. 12, No. 2, 1998, pp. 483-485. doi:10.1183/09031936.98.12020483
M. B. Schleiss, O. Holz, M. Behnke, K. Richter, H. Magnussen and R. A. Jorres, “The Concentration of Hydrogen Peroxide in Exhaled Air Depends on Expiratory Flow Rate,” European Respiratory Journal, Vol. 16, No. 6, 2000, pp. 1115-1118. doi:10.1034/j.1399-3003.2000.16f16.x
M. D. Davis and J. Hunt, “Exhaled Breath Condensate pH Assays,” Immunology and Allergy Clinics of North America, Vol. 32, No. 3, 2012, pp. 377-386. doi:10.1016/j.iac.2012.06.003
J. Vaughan, L. Ngamtrakulpanit, T. N. Pajewski, R. Turner, T. A. Nguyen, A. Smith, P. Urban, S. Hom, B. Gaston and J. Hunt, “Exhaled Breath Condensate pH is a Robust and Reproducible Assay of Airway Acidity,” European Respiratory Journal, Vol. 22, No. 6, 2003, pp. 889-894. doi:10.1183/09031936.03.00038803
M. M. Tomasiak-Lozowska, Z. Zietkowski, K. Przeslaw, M. Tomasiak, R. Skiepko and A. Bodzenta-Lukaszyk, “Inflammatory Markers and Acid-Base Equilibrium in Exhaled Breath Condensate of Stable and Unstable Asthma Patients,” International Archives of Allergy and Immunology, Vol. 159, No. 2, 2012, pp. 121-129. doi:10.1159/000335674
A. I. Papaioannou, S. Loukides, M. Minas, K. Kontogianni, P. Bakakos, K. I. Gourgoulianis, M. Alchanatis, S. Papiris and K. Kostikas, “Exhaled Breath Condensate pH as a Biomarker of COPD Severity in Ex-Smokers,” Respiratory Research, Vol. 12, 2011, p. 67. doi:10.1186/1465-9921-12-67
J. Hunt, Y. Yu, J. Burns, B. Gaston, L. Ngamtrakulpanit, D. Bunyan, B. K. Walsh, A. Smith and S. Hom, “Identification of Acid Reflux Cough Using Serial Assays of Exhaled Breath Condensate pH,” Cough, Vol. 2, 2006, p. 3. doi:10.1186/1745-9974-2-3
B. K. Walsh, D. J. Mackey, T. Pajewski, Y. Yu, B. M. Gaston and J. F. Hunt, “Exhaled-Breath Condensate pH Can Be Safely and Continuously Monitored in Mechanically Ventilated Patients,” Respiratory Care, Vol. 51, No. 10, 2006, pp. 1125-1131.
J. P. Eiserich, R. P. Patel and V. B. O’Donnell, “Pathophysiology of Nitric Oxide and Related Species: Free Radical Reactions and Modification of Biomolecules,” Molecular Aspects of Medicine, Vol. 19, No. 4-5, 1998, pp. 221-357. doi:10.1016/S0098-2997(99)00002-3
R. C. Strunk, S. J. Szefler, B. R. Phillips, R. S. Zeiger, V. M. Chinchilli, G. Larsen, K. Hodgdon, W. Morgan, C. A. Sorkness and R. F. Lemanske Jr., “Relationship of Exhaled Nitric Oxide to Clinical and Inflammatory Markers of Persistent Asthma in Children,” The Journal of Allergy and Clinical Immunology, Vol. 112, No. 5, 2003, pp. 883-892. doi:10.1016/j.jaci.2003.08.014
J. Liu, A. Sandrini, M. C. Thurston, D. H. Yates and P. S. Thomas, “Nitric Oxide and Exhaled Breath Nitrite/Nitrates in Chronic Obstructive Pulmonary Disease Patients,” Respiration, Vol. 74, No. 6, 2007, pp. 617-623. doi:10.1159/000106379
A. van der Vliet, J. P. Eiserich, M. K. Shigenaga and C. E. Cross, “Reactive Nitrogen Species and Tyrosine Nitration in the Respiratory Tract: Epiphenomena or a Pathobiologic Mechanism of Disease?” American Journal of Respiratory and Critical Care Medicine, Vol. 160, No. 1, 1999, pp. 1-9.
M. Corradi, P. Montuschi, L. E. Donnelly, A. Pesci, S. A. Kharitonov and P. J. Barnes, “Increased Nitrosothiols in Exhaled Breath Condensate in Inflammatory Airway Diseases,” American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 4, 2001, pp. 854-858.
E. Baraldi, G. Giordano, M. F. Pasquale, S. Carraro, A. Mardegan, G. Bonetto, C. Bastardo, F. Zacchello and S. Zanconato, “3-Nitrotyrosine, a Marker of Nitrosative Stress, Is Increased in Breath Condensate of Allergic Asthmatic Children,” Allergy, Vol. 61, No. 1, 2006, pp. 90-96. doi:10.1111/j.1398-9995.2006.00996.x
B. Balint, S. A. Kharitonov, T. Hanazawa, L. E. Donnelly, P. L. Shah, M. E. Hodson and P. J. Barnes, “Increased Nitrotyrosine in Exhaled Breath Condensate in Cystic Fibrosis,” European Respiratory Journal, Vol. 17, No. 6, 2001, pp. 1201-1207. doi:10.1183/09031936.01.00072501
J. D. Morrow, K. E. Hill, R. F. Burk, T. M. Nammour, K. F. Badr and L. J. Roberts 2nd, “A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism,” Proceedings of the National Academy Sciences of the USA, Vol. 87, No. 23, 1990, pp. 9383-9387. doi:10.1073/pnas.87.23.9383
P. Montuschi, P. J. Barnes and L. J. Roberts 2nd, “Isoprostanes: Markers and Mediators of Oxidative Stress,” FASEB Journal, Vol. 18, No. 15, 2004, pp. 1791-1800. doi:10.1096/fj.04-2330rev
P. Montuschi, M. Corradi, G. Ciabattoni, J. Nightingale, S. A. Kharitonov, and P. J. Barnes, “Increased 8-Isoprostane, a Marker of Oxidative Stress, in Exhaled Condensate of Asthma Patients,” American Journal of Respiratory and Critical Care Medicine, Vol. 160, No. 1, 1999, pp. 216-220.
P. Montuschi, J. V. Collins, G. Ciabattoni, N. Lazzeri, M. Corradi, S. A. Kharitonov and P. J. Barnes, “Exhaled 8-Isoprostane as An in Vivo Biomarker of Lung Oxidative Stress in Patients with COPD and Healthy Smokers,” American Journal of Respiratory and Critical Care Medicine, Vol. 162, No. 3, 2000, pp. 1175-1177.
P. Montuschi, S. A. Kharitonov, G. Ciabattoni, M. Corradi, L. van Rensen, D. M. Geddes, M. E. Hodson and P. J. Barnes, “Exhaled 8-Isoprostane as a New Non-Invasive Biomarker of Oxidative Stress in Cystic Fibrosis,” Thorax, Vol. 55, No. 3, 2000, pp. 205-209. doi:10.1136/thorax.55.3.205
C. T. Carpenter, P. V. Price and B. W. Christman, “Exhaled Breath Condensate Isoprostanes Are Elevated in Patients with Acute Lung Injury or ARDS,” Chest, Vol. 114, No. 6, 1998, pp. 1653-1659. doi:10.1378/chest.114.6.1653
M. Barreto, M. P. Villa, C. Olita, S. Martella, G. Ciabattoni and P. Montuschi, “8-Isoprostane in Exhaled Breath Condensate and Exercise-Induced Bronchoconstriction in Asthmatic Children and Adolescents,” Chest, Vol. 135, No. 1, 2009, pp. 66-73. doi:10.1378/chest.08-0722
B. Samuelsson, “Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation,” Science, vol. 220, no. 4597, pp. 568–575, May 1983. doi:10.1126/science.6301011
P. Montuschi, S. A. Kharitonov, G. Ciabattoni and P. J. Barnes, “Exhaled Leukotrienes and Prostaglandins in COPD,” Thorax, Vol. 58, No. 7, 2003, pp. 585-588. doi:10.1136/thorax.58.7.585
A. Bodini, C. D’Orazio, D. Peroni, M. Corradi, G. Folesani, E. Baraldi, B. M. Assael, A. Boner and G. L. Piacentini, “Biomarkers of Neutrophilic Inflammation in Exhaled Air of Cystic Fibrosis Children with Bacterial Airway Infections,” Pediatric Pulmonology, Vol. 40, No. 6, 2005, pp. 494-499. doi:10.1002/ppul.20336
S. Caballero Balanzá, A. Martorell Aragonés, J. C. Cerdá Mir, J. Belda Ramírez, J. B. Ramírez, R. Navarro Ivánez, A. Navarro Soriano, R. Félix Toledo and A. Escribano Montaner, “Leukotriene B4 and 8-Isoprostane in Exhaled Breath Condensate of Children with Episodic and Persistent Asthma,” Journal of Investigational Allergology and Clinical Immunology, Vol. 20, No. 3, 2010, pp. 237-243.
G. E. Carpagnano, G. P. Palladino, D. Lacedonia, A. Koutelou, S. Orlando and M. P. Foschino-Barbaro, “Neutrophilic Airways Inflammation in Lung Cancer: The Role of Exhaled LTB-4 and IL-8,” BMC Cancer, Vol. 11, 2011, p. 226. doi:10.1186/1471-2407-11-226
E. Ono, H. Mita, M. Taniguchi, N. Higashi, T. Tsuburai, M. Hasegawa, E. Miyazaki, T. Kumamoto and K. Akiyama, “Increase in Inflammatory Mediator Concentrations in Exhaled Breath Condensate after Allergen Inhalation,” Journal of Allergy and Clinical Immunology, Vol. 122, No. 4, 2008, pp. 768-773.
S. Carraro, M. Corradi, S. Zanconato, R. Alinovi, M. F. Pasquale, F. Zacchello and E. Baraldi, “Exhaled Breath Condensate Cysteinyl Leukotrienes Are Increased in Children with Exercise-Induced Bronchoconstriction,” Journal of Allergy and Clinical Immunology, Vol. 115, No. 4, 2005, pp. 764-770. doi:10.1016/j.jaci.2004.10.043
L. Mastalerz, M. Sanak, J. Kumik, A. Gawlewicz-Mroczka, N. Celejewska-Wójcik, A. Cmiel and A. Szczeklik, “Exhaled Eicosanoids Following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study,” Journal of Allergy (Cairo), vol. 2012, 2012, Article ID: 696792. doi:10.1155/2012/696792
M. Sanak, A. Gielicz, G. Bochenek, M. Kaszuba, E. Nizankowska-Mogilnicka and A. Szczeklik, “Targeted Eicosanoid Lipidomics of Exhaled Breath Condensate Provide a Distinct Pattern in the Aspirin-Intolerant Asthma Phenotype,” Journal of Allergy and Clinical Immunology, Vol. 127, No. 5, 2011, pp. 1141-1147.
I. D. Pavord and A. E. Tattersfield, “Bronchoprotective Role for Endogenous Prostaglandin E2,” Lancet, Vol. 345, No. 8947, 1995, pp. 436-438. doi:10.1016/S0140-6736(95)90409-3
R. J. Church, L. A. Jania and B. H. Koller, “Prostaglandin E(2) Produced by the Lung Augments the Effector Phase of Allergic Inflammation,” Journal of Immunology, Vol. 188, No. 8, 2012, pp. 4093-4102. doi:10.4049/jimmunol.1101873
V. Lucidi, G. Ciabattoni, S. Bella, P. J. Barnes and P. Montuschi, “Exhaled 8-Isoprostane and Prostaglandin E2 in Patients with Stable and Unstable Cystic Fibrosis,” Free Radical Biology and Medicine, Vol. 45, No. 6, 2008, pp. 913-919. doi:10.1016/j.freeradbiomed.2008.06.026
E. Huszár, Z. Szabó, A. Jakab, I. Barta, I. Herjavecz and I. Horváth, “Comparative Measurement of Thromboxane A2 Metabolites in Exhaled Breath Condensate by Different Immunoassays,” Inflammation Research, Vol. 54, No. 8, 2005, pp. 350-355. doi:10.1007/s00011-005-1361-x
M. G. Kiehl, H. Ostermann, M. Thomas, C. Müller, U. Cassens and J. Kienast, “Inflammatory Mediators in Bronchoalveolar Lavage Fluid and Plasma in Leukocytopenic Patients with Septic Shock-Induced Acute Respiratory Distress Syndrome,” Critical Care Medicine, Vol. 26, No. 7, 1998, pp. 1194-1199. doi:10.1097/00003246-199807000-00019
H. Schütte, J. Lohmeyer, S. Rosseau, S. Ziegler, C. Siebert, H. Kielisch, H. Pralle, F. Grimminger, H. Morr and W. Seeger, “Bronchoalveolar and Systemic Cytokine Profiles in Patients with ARDS, Severe Pneumonia and Cardiogenic Pulmonary Oedema,” European Respiratory Journal, Vol. 9, No. 9, 1996, pp. 1858-1867. doi:10.1183/09031936.96.09091858
C. E. Brightling, F. A. Symon, S. S. Birring, P. Bradding, I. D. Pavord and A. J. Wardlaw, “TH2 Cytokine Expression in Bronchoalveolar Lavage fluid T Lymphocytes and Bronchial Submucosa Is a Feature of Asthma and Eosinophilic Bronchitis,” Journal of Allergy and Clinical Immunology, Vol. 110, No. 6, 2002, pp. 899-905. doi:10.1067/mai.2002.129698
B. Barceló, J. Pons, A. Fuster, J. Sauleda, A. Noguera, J. M. Ferrer and A. G. N. Agustí, “Intracellular Cytokine Profile of T Lymphocytes in Patients with Chronic Obstructive Pulmonary Disease,” Clinical & Experimental Immunology, Vol. 145, No. 3, 2006, pp. 474-479. doi:10.1111/j.1365-2249.2006.03167.x
T. L. Bonfield, J. R. Panuska, M. W. Konstan, K. A. Hilliard, J. B. Hilliard, H. Ghnaim and M. Berger, “Inflammatory Cytokines in Cystic Fibrosis Lungs,” American Journal of Respiratory and Critical Care Medicine, Vol. 152, No. 6, 1995, pp. 2111-2118.
S. S. Hacievliyagil, H. Gunen, L. C. Mutlu, A. B. Karabulut and I. Temel, “Association between Cytokines in Induced Sputum and Severity of Chronic Obstructive Pulmonary Disease,” Respiratory Medicine, Vol. 100, No. 5, 2006, pp. 846-854. doi:10.1016/j.rmed.2005.08.022
W. A. Neveu, J. L. Allard, D. M. Raymond, L. M. Bou-rassa, S. M. Burns, J. Y. Bunn, C. G. Irvin, D. A. Kaminsky and M. Rincon, “Elevation of IL-6 in the Allergic Asthmatic Airway Is Independent of Inflammation But Associates with Loss of Central Airway Function,” Respiratory Research, Vol. 11, No. 1, 2010, p. 28. doi:10.1186/1465-9921-11-28
S. K. Shahid, S. A. Kharitonov, N. M. Wilson, A. Bush and P. J. Barnes, “Increased Interleukin-4 and Decreased Interferon-γ in Exhaled Breath Condensate of Children with Asthma,” American Journal of Respiratory and Critical Care Medicine, Vol. 165, No. 9, 2002, pp. 1290-1293. doi:10.1164/rccm.2108082
P. P. R. Rosias, E. Dompeling, M. A. Dentener, H. J. Pennings, H. J. E. Hendriks, M. P. A. Van Iersel and Q. Jobsis, “Childhood Asthma: Exhaled Markers of Airway Inflammation, Asthma Control Score, and Lung Function Tests,” Pediatric Pulmonology, Vol. 38, No. 2, 2004, pp. 107-114. doi:10.1002/ppul.20056
C. M. H. H. T. Robroeks, Q. Jobsis, J. G. M. C. Damoiseaux, P. H. M. Heijmans, P. P. R. Rosias, H. J. E. Hendriks and E. Dompeling, “Cytokines in Exhaled Breath Condensate of Children with Asthma and Cystic Fibrosis,” Annals of Allergy, Asthma & Immunology, Vol. 96, No. 2, 2006, pp. 349-355. doi:10.1016/S1081-1206(10)61247-1
P. P. Rosias, C. M. Robroeks, A. Kester, G. J. den Hartog, W. K. Wodzig, G. T. Rijkers, L. J. Zimmermann, C. P. van Schayck, Q. Jobsis and E. Dompeling, “Biomarker Reproducibility in Exhaled Breath Condensate Collected with Different Condensers,” European Respiratory Journal, Vol. 31, No. 5, 2008, pp. 934-942. doi:10.1183/09031936.00073207
C. M. H. H. T. Robroeks, G. T. Rijkers, Q. Jobsis, H. J. E. Hendriks, J. G. M. C. Damoiseaux, L. J. I. Zimmermann, O. P. van Schayck and E. Dompeling, “Increased Cytokines, Chemokines and Soluble Adhesion Molecules in Exhaled Breath Condensate of Asthmatic Children,” Clinical & Experimental Allergy, Vol. 40, No. 1, 2010, pp. 77-84. doi:10.1111/j.1365-2222.2009.03397.x
C. Gessner, R. Scheibe, M. Wotzel, S. Hammerschmidt, H. Kuhn, L. Engelmann, G. Hoheisel, A. Gillissen, U. Sack and H. Wirtz, “Exhaled Breath Condensate Cytokine Patterns in Chronic Obstructive Pulmonary Disease,” Respiratory Medicine, Vol. 99, No. 10, 2005, pp. 1229-1240. doi:10.1016/j.rmed.2005.02.041
Z. Zietkowski, M. M. Tomasiak, R. Skiepko and A. Bodzenta-Lukaszyk, “RANTES in Exhaled Breath Condensate of Stable and Unstable Asthma Patients,” Respiratory Medicine, Vol. 102, No. 8, 2008, pp. 1198-1202. doi:10.1016/j.rmed.2008.03.010
Z. Zietkowski, R. Skiepko, M. M. Tomasiak-Lozowska, E. Zietkowska and A. Bodzenta-Lukaszyk, “Eotaxin in Exhaled Breath Condensate of Allergic Asthma Patients with Exercise-Induced Bronchoconstriction,” Respiration, Vol. 82, No. 2, 2011, pp. 169-176. doi:10.1159/000323180
K. D. G. van de Kant, E. M. M. Klaassen, Q. Jobsis, K. Koers, G. T. Rijkers, C. P. van der Grinten, O. C. P. van Schayck, V. L. Passos and E. Dompeling, “Wheezing in Preschool Children Is Associated with Increased Levels of Cytokines/Chemokines in Exhaled Breath Condensate,” The Journal of Allergy and Clinical Immunology, Vol. 126, No. 3, 2010, pp. 669-671. doi:10.1016/j.jaci.2010.07.013
T. Zakharkina, A.-R. Koczulla, O. Mardanova, A. Hattesohl and R. Bals, “Detection of Microorganisms in Exhaled Breath Condensate during Acute Exacerbations of COPD,” Respirology, Vol. 16, No. 6, 2011, pp. 932-938. doi:10.1111/j.1440-1843.2011.01977.x
Z. Xu, F. Shen, X. Li, Y. Wu, Q. Chen, X. Jie and M. Yao, “Molecular and Microscopic Analysis of Bacteria and Viruses in Exhaled Breath Collected Using a Simple Impaction and Condensing Method,” PLoS ONE, Vol. 7, No. 7, 2012, Article ID: e41137. doi:10.1371/journal.pone.0041137
G. E. Carpagnano, A. Koutelou, M. I. Natalicchio, D. Martinelli, C. Ruggieri, A. Di Taranto, R. Antonetti, F. Carpagnano and M. P. Foschino-Barbaro, “HPV in Exhaled Breath Condensate of Lung Cancer Patients,” British Journal of Cancer, Vol. 105, No. 8, 2011, pp. 1183-1190. doi:10.1038/bjc.2011.354
K. Chikasue, M. Kimura, K. Ikeda, T. Ohnishi, S. Kawanishi, T. Iio, M. Kataoka and Y. Arao, “Detection of Torque Teno Virus DNA in Exhaled Breath by Polymerase Chain Reaction,” Acta Medica Okayama, Vol. 66, No. 5, 2012, pp. 387-397.
E. Sonkoly, M. Stahle and A. Pivarcsi, “MicroRNAs and Immunity: Novel Players in the Regulation of Normal Immune Function and Inflammation,” Seminars in Cancer Biology, Vol. 18, No. 2, 2008, pp. 131-140. doi:10.1016/j.semcancer.2008.01.005
Y. Xie, N. W. Todd, Z. Liu, M. Zhan, H. Fang, H. Peng, M. Alattar, J. Deepak, S. A. Stass and F. Jiang, “Altered miRNA Expression in Sputum for Diagnosis of Non-Small Cell Lung Cancer,” Lung Cancer, Vol. 67, No. 2, 2010, pp. 170-176. doi:10.1016/j.lungcan.2009.04.004
L. Yu, N. W. Todd, L. Xing, Y. Xie, H. Zhang, Z. Liu, H. Fang, J. Zhang, R. L. Katz and F. Jiang, “Early Detection of Lung Adenocarcinoma in Sputum by a Panel of MicroRNA Markers,” International Journal of Cancer, Vol. 127, No. 12, 2010, pp. 2870-2878. doi:10.1002/ijc.25289
R. M. Effros, J. Biller, B. Foss, K. Hoagland, M. B. Dunning, D. Castillo, M. Bosbous, F. Sun and R. Shaker, “A Simple Method for Estimating Respiratory Solute Dilution in Exhaled Breath Condensates,” American Journal of Respiratory and Critical Care Medicine, Vol. 168, No. 12, 2003, pp. 1500-1505. doi:10.1164/rccm.200307-920OC
P. Montuschi, “LC/MS/MS Analysis of Leukotriene B4 and Other Eicosanoids in Exhaled Breath Condensate for Assessing Lung Inflammation,” Journal of Chromatography B, Vol. 877, No. 13, 2009, pp. 1272-1280. doi:10.1016/j.jchromb.2009.01.036
G. de Laurentiis, D. Paris, D. Melck, M. Maniscalco, S. Marsico, G. Corso, A. Motta and M. Sofia, “Metabonomic Analysis of Exhaled Breath Condensate in Adults by Nuclear Magnetic Resonance Spectroscopy,” European Respiratory Journal, Vol. 32, No. 5, 2008, pp. 1175-1183. doi:10.1183/09031936.00072408