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Vol. 137, No. 1, 2005
Issue release date: May 2005
Int Arch Allergy Immunol 2005;137:66–72

Analysis of Growth Factors and Inflammatory Cytokines in Exhaled Breath Condensate from Asthmatic Children

Leung T.-f. · Wong G.W.K. · Ko F.W.S. · Li C.-y. · Yung E. · Lam C.W.K. · Fok T.-f.
Departments of aPaediatrics, bMedicine and Therapeutics, and cChemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China

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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.

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  1. Romagnani S: The role of lymphocytes in allergic disease. J Allergy Clin Immunol 2000;105:399–408.
  2. Holgate ST: Asthma: More than an inflammatory disease. Curr Opin Allergy Clin Immunol 2002;2:27–29.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Tiedemann K, Malmström A, Westergren-Thorsson G: Cytokine regulation of proteoglycan production in fibroblasts: Separate and synergistic effects. Matrix Biol 1997;15:469–478.
  9. 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.
  10. 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.
  11. Heldin CH, Westermark B: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999;79:1283–1316.
  12. Li X, Wilson JW: Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 1997;156:229–233.
  13. 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.
  14. 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.
  15. 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.
  16. Yong CL, Hern KL: Vascular endothelial growth factor in patients with acute asthma. J Allergy Clin Immunol 2001;107:1106–1107.
  17. Kharitonov SA, Barnes PJ: Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001;163:1692–1722.
  18. 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.
  19. 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.
  20. Hunt J: Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease. J Allergy Clin Immunol 2002;110:28–34.
  21. British Thoracic Society, Scottish Intercollegiate Guidelines Network (SIGN): British guideline on the management of asthma. Thorax 2003;58(suppl 1):1–94.
  22. National Institutes of Health, National Heart Lung and Blood Institute: Global initiative for asthma. NIH Publ 02-3659. Bethesda, NHLBI, 2002.
  23. ISAAC Steering Committee: Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998;351:1225–1232.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.

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