Analysis of Growth Factors and Inflammatory Cytokines in Exhaled Breath Condensate from Asthmatic ChildrenLeung T.-f.a · Wong G.W.K.a · Ko F.W.S.b · Li C.-y.a · Yung E.a · Lam C.W.K.c · Fok T.-f.a
Departments of aPaediatrics, bMedicine and Therapeutics, and cChemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Background: Vascular endothelial growth factor (VEGF), AA isoform of platelet-derived growth factor (PDGF-AA), and epidermal growth factor (EGF) are involved in the pathogenesis of airway inflammation in asthma. These molecules are closely associated with cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-4. This study investigates the relation between childhood asthma and levels of these mediators in exhaled breath condensate (EBC). Methods: EBC was collected from asthmatic children and controls using a disposable collection kit, and the concentrations of VEGF, PDGF-AA, EGF, TNF-α and IL-4 in EBC were measured using sandwich enzyme immunoassays. Exhaled nitric oxide concentration was measured by a chemiluminescence analyzer. Results: Thirty-five asthmatic patients aged between 7 and 18 years and 11 controls were recruited. Sixteen patients had intermittent asthma (IA) whereas 19 of them suffered from persistent asthma (PA). A significant correlation was found between IL-4 and TNF-α in EBC (ρ = 0.374, p = 0.010). PDGF-AA levels in EBC were higher in subjects with diminished FEV1 (p = 0.023) whereas IL-4 concentrations were increased in asthmatics (p = 0.007) as well as subjects with increased plasma total IgE (p = 0.033). Patients with PA receiving high-dose inhaled corticosteroid (ICS) had higher EBC IL-4 concentration than those on low-dose ICS (p = 0.007). Linear regression revealed that PDGF-AA levels in EBC were negatively associated with FEV1 percentage (β = –0.459, p = 0.006) among the asthmatic patients. Conclusions: IL-4 in EBC is increased in childhood asthma, and growth factors are detectable in a significant proportion of these children. Increased PDGF-AA is found in asthmatics with more severe airflow limitation.
© 2005 S. Karger AG, Basel
- Romagnani S: The role of lymphocytes in allergic disease. J Allergy Clin Immunol 2000;105:399–408.
- Holgate ST: Asthma: More than an inflammatory disease. Curr Opin Allergy Clin Immunol 2002;2:27–29.
- Montefort S, Roberts JA, Beasley R, Holgate ST, Roche WR: The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects. Thorax 1992;47:499–503.
- Laitinen LA, Heino M, Laitinen A, Kava T, Haahtela T: Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 1985;131:599–606.
- Puddicombe SM, Polosa R, Richter A, Krishna MT, Howarth PH, Holgate ST, Davies DE: The involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J 2000;14:1362–1374.
- Polosa R, Puddicombe SM, Krishna MT, Tuck AB, Howarth PH, Holgate ST, Davies DE: Expression of c-erbB receptors and ligands in the bronchial epithelium of asthmatic subjects. J Allergy Clin Immunol 2002;109:75–81.
- Munakata M, Nasuhara Y, Sato A, Takahashi T, Homma Y, Kawakami Y: Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway. Am J Respir Crit Care Med 1998;157:1907–1912.
- Tiedemann K, Malmström A, Westergren-Thorsson G: Cytokine regulation of proteoglycan production in fibroblasts: Separate and synergistic effects. Matrix Biol 1997;15:469–478.
- Holgate ST, Davies DE, Lackie PM, Wilson SJ, Puddicombe SM, Lordan JL: Epithelial-mesenchymal interactions in the pathogenesis of asthma. J Allergy Clin Immunol 2000;105:193–204.
- Bornfeldt KE, Raines EW, Graves LE, Skinner MP, Krebs EG, Ross R: Platelet-derived growth factor: Distinct signal transduction pathways associated with migration versus proliferation. Ann NY Acad Sci 1995;766:416–430.
- Heldin CH, Westermark B: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999;79:1283–1316.
- Li X, Wilson JW: Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 1997;156:229–233.
- Kuwano K, Bosken CH, Pare PD, Bai TR, Wiggs BR, Hogg JC: Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993;148:1220–1225.
- Dvorak HF, Brown LF, Detmar M, Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995;146:1029–1039.
- Hoshino M, Takahashi M, Aoike N: Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis. J Allergy Clin Immunol 2001;107:295–301.
- Yong CL, Hern KL: Vascular endothelial growth factor in patients with acute asthma. J Allergy Clin Immunol 2001;107:1106–1107.
Kharitonov SA, Barnes PJ: Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001;163:1692–1722.
- Csoma Z, Kharitonov SA, Balint B, Bush A, Wilson NM, Barnes PJ: Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med 2002;166:1345–1349.
- Shahid SK, Kharitonov SA, Wilson NM, Bush A, Barnes PJ: Increased interleukin-4 and decreased interferon-γ in exhaled breath condensate of children with asthma. Am J Respir Crit Care Med 2002;165:1290–1293.
- Hunt J: Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease. J Allergy Clin Immunol 2002;110:28–34.
British Thoracic Society, Scottish Intercollegiate Guidelines Network (SIGN): British guideline on the management of asthma. Thorax 2003;58(suppl 1):1–94.
National Institutes of Health, National Heart Lung and Blood Institute: Global initiative for asthma. NIH Publ 02-3659. Bethesda, NHLBI, 2002.
- ISAAC Steering Committee: Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998;351:1225–1232.
- Baraldi E, de Jongste JC, on behalf of the ERS/ATS Task Force: Measurement of exhaled nitric oxide in children, 2001. Eur Respir J 2002;20:223–237.
- Ip MS, Karlberg EM, Karlberg JP, Luk KD, Leong JC: Lung function reference values in Chinese children and adolescents in Hong Kong. I. Spirometric values and comparison with other populations. Am J Respir Crit Care Med 2000;162:424–429.
- Leung TF, Li CY, Lam CW, Au CS, Yung E, Chan IH, Wong GW, Fok TF: The relation between obesity and asthmatic airway inflammation. Pediatr Allergy Immunol 2004;15:344–350.
- Effros RM, Hoagland KW, Bosbous M, Castillo D, Foss B, Dunning M, Gare M, Lin W, Sun F: Dilution of respiratory solutes in exhaled condensates. Am J Respir Crit Care Med 2002;165:663–669.
- Batra V, Musani AI, Hastie AT, Khurana S, Carpenter KA, Zangrilli JG, Peters SP: Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin (IL)-4 and IL-13 after segmental allergen challenge and their effects on alpha-smooth muscle actin and collagen III synthesis by primary human lung fibroblasts. Clin Exp Allergy 2004;34:437–444.
- Bostrom H, Willetts K, Pekny M, Leveen P, Lindahl P, Hedstrand H, Pekna M, Hellstrom M, Gebre-Medhin S, Schalling M, Nilsson M, Kurland S, Tornell J, Heath JK, Betsholtz C: PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis. Cell 1996;85:863–873.
- Leung TF, Wong GW, Ko FW, Lam CW, Fok TF: Increased macrophage-derived chemokine in exhaled breath condensate and plasma from children with asthma. Clin Exp Allergy 2004;34:786–791.
- van Hoydonck PG, Wuyts WA, Vanaudenaerde BM, Schouten EG, Dupont LJ, Temme EH: Quantitative analysis of 8-isoprostane and hydrogen peroxide in exhaled breath condensate. Eur Respir J 2004;23:189–192.
- Effros RM, Biller J, Foss B, Hoagland K, Dunning MB, Castillo D, Bosbous M, Sun F, Shaker R: A simple method for estimating respiratory solute dilution in exhaled breath condensates. Am J Respir Crit Care Med 2003;168:1500–1505.
- McCafferty JB, Bradshaw TA, Tate S, Greening AP, Innes JA: Effects of breathing pattern and inspired air conditions on breath condensate volume, pH, nitrite, and protein concentrations. Thorax 2004;59:694–698.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.