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ASTHMA: Hiroshi Kanazawa, Takahiro Yoshikawa, Kazuto Hirata, and Junichi Yoshikawa Effects of Pranlukast Administration on Vascular Endothelial Growth Factor Levels in Asthmatic Patients Chest 2004; 125: 1700-1705 [Abstract] [Full text] [PDF]

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Elevated Levels of VEGF in Acute Exacerbation of COPD are reduced after Treatment

Daya Upadhyay, Thomas C Corbridge, Leonard Buccellato, David McClintock, Manu Jain.   (4 July 2004)

Elevated Levels of VEGF in Acute Exacerbation of COPD are reduced after Treatment 4 July 2004
Daya Upadhyay, MD Stanford University Medical Center, Pulmonary and Critical Care, 300 Pasteur Drive, Stanford, CA, Thomas C Corbridge, Leonard Buccellato, David McClintock, Manu Jain. Send letter to journal: Re: Elevated Levels of VEGF in Acute Exacerbation of COPD are reduced after Treatment upadhyayd{at}pol.net Daya Upadhyay, et al.	Elevated Levels of Vascular Endothelial Growth Factor in Acute Exacerbation of Chronic Obstructive Pulmonary Disease are reduced after Treatment Letter to the Editor Daya Upadhyay, MD (a,b), Thomas C Corbridge, MD (b), Leonard Buccellato, MD (b), David McClintock, (b), Manu Jain, MD (b). Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center (a), 300 Pasteur Drive, Stanford, CA 95305 and Northwestern University Medical Center (b), McGaw 2nd Floor, 240 East Huron Street, Chicago, IL 60611 Corresponding Author: Daya Upadhyay, MD Division of Pulmonary and Critical Care Medicine Stanford University Medical Center 300 Pasteur Drive, Rm H3143 Stanford, CA 94305-5236 Tele: (650) 723-6381 Fax: (650) 725-5489 Email: upadhyayd@pol.net To The Editor: We read with great interest the article by Kanazawa and colleagues in the May issue of CHEST (1). Their finding of a correlation between sputum vascular endothelial growth factor (VEGF) levels pre and post pranlukast suggests that VEGF may be important in the pathogenesis of obstructive airway diseases (1,2). In light of this information, we report our findings in a prospective control study of chronic obstructive pulmonary disease (COPD) patients. Serum VEGF levels of 18 patients with COPD (9 stable and 9 with acute exacerbations) were compared with 20 normal controls. Serum VEGF levels were assessed by an enzyme-linked immunosorbent assay (ELISA) (R& D Systems Inc, MN, USA). The mean VEGF concentration of the stable COPD group was significantly higher (883.89 pg/ml) than normal controls (364.46 pg/ml) (p<0.05). Further, serum VEGF levels were significantly higher in patients with acute exacerbations of COPD (1368.48 pg /ml) and were decreased post treatment on the day of discharge (647.49 pg/ml) (p<0.05). These data may implicate a role of VEGF in the pathogenesis of COPD. Although, more investigative work is necessary to determine whether VEGF is involved in the pathogenesis of COPD, the relationship of VEGF with lung inflammation deserves comment. Kanazawa et al (1) demonstrated that higher levels of sputum VEGF in Asthma are reduced after pranlukst administration. McColley et al (3) has shown that serum VEGF concentrations are increased in patients in cystic fibrosis (CF), rise further during an acute exacerbation and decrease following treatment. Similarly, our findings of increased VEGF levels during acute exacerbations of COPD, and reduction post treatment suggest a coupling of VEGF and inflammation. Both CF and COPD are marked by significant inflammation of the airways, predominantly neutrophilic, which worsens during an acute exacerbation (4, 5). The role of hypoxia needs to be considered as well (6, 7). Sputum VEGF levels measured by Kanazawa et al (1, 2) were significantly higher in asthma and in COPD as compared to serum VEGF, supporting a model of local VEGF production in the airways. Simultaneous measure of serum and sputum VEGF levels may confirm this model and suggest utility of serum VEGF levels as biomarkers of COPD outcome studies. References: 1.Kanazawa H, Yoshikawa T, Hirata K, Yoshikawa J. Effects of pranlukast administration on vascular endothelial growth factor levels in asthmatic patients. Chest. 2004;125,1700-1705. 2.Kanazawa H, Asai K, Hirata K, Yoshikawa J. Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. Am J Med. 2003;114,354-358. 3.McColley SA, Stellmach V, Boas SR, Jain M, Crawford SE. Serum vascular endothelial growth factor is elevated in cystic fibrosis and decreases with treatment of acute pulmonary exacerbation. Am J Respir Crit Care Med. 2000;161,1877-1880. 4.Khan TZ, Wagener JS, Boat T, Martinez J, Accurso FJ, Riches DWH. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995;151,1075-1082. 5.Aaron SD, Angel JB, Lunau M, Wright K, Fex C, Le Saux N, Dales RE. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163,349-355. 6.Pfeifer M, Blumberg FC, Wolf K, Sandner P, Elsner D, Riegger GA, Kurtz A. Vascular remodeling and growth factor gene expression in the rat lung during hypoxia. Respir Physiol 1998;111,201-212. 7.Boussat S, Eddahibi S, Coste A, Fataccioli V, Gouge M, Housset B, Adnot S, Maitre B. Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2000;279,L371-378.