Effects of pranlukast administration on vascular endothelial growth factor levels in asthmatic patients.
OBJECTIVE
We have previously found that vascular endothelial growth factor (VEGF) levels in induced sputum were increased in asthmatic patients, and that its levels were closely associated with the degree of airway obstruction and microvascular permeability. Therefore, this study was designed to examine the effects of pranlukast, a selective leukotriene receptor antagonist, on VEGF levels in induced sputum from steroid-untreated or steroid-treated asthmatic patients.


METHODS
Double-blind, randomized, placebo-controlled, crossover study.


METHODS
University hospital.


METHODS
Twenty-three asthmatic patients (steroid-untreated, 13 patients; steroid-treated, 10 patients) and 10 healthy control subjects.


METHODS
All asthmatic patients received 4-weeks of therapy with pranlukast (225 mg bid), and sputum induction was performed before and after the 4-week treatment course.


RESULTS
In steroid-untreated asthmatic patients, the mean percentage of eosinophils (%EOS) and mean eosinophil cationic protein (ECP) levels in induced sputum were significantly decreased after 4 weeks of pranlukast administration (%EOS: before, 16.7% [SD, 7.1%]; after, 12.3% [SD, 4.0%]; p = 0.03; ECP levels: before, 774 ng/mL [SD, 258 ng/mL]; after, 564 ng/mL [SD, 204 ng/mL]; p = 0.034). Moreover, VEGF levels in the induced sputum and the airway vascular permeability index also were decreased after pranlukast administration (VEGF levels: before, 5,670 pg/mL [SD, 1,780 pg/mL]; after, 4,380 pg/mL [SD, 1,540 pg/mL]; p = 0.026; airway vascular permeability index: before, 0.032 [SD, 0.012]; after, 0.017 [SD, 0.006]; p = 0.01). In addition, the change in airway vascular permeability index from before to after pranlukast administration was significantly correlated with the change in VEGF levels (r = 0.782; p = 0.007). However, in steroid-treated asthmatic patients there was no significant difference in mean VEGF levels in induced sputum between placebo administration (before, 3,640 pg/mL [SD, 1,020 pg/mL]; after, 3,640 pg/mL [SD, 960 pg/mL] and pranlukast administration (before, 3,660 pg/mL [SD, 940 pg/mL]; after, 2,950 pg/mL [SD, 890 pg/mL]).


CONCLUSIONS
Pranlukast administration decreased airway microvascular permeability through, at least in part, a decrease in airway VEGF levels in steroid-untreated asthmatic patients. However, it is likely that pranlukast administration added little efficacy to inhaled corticosteroid therapy for reduction in airway VEGF levels.
Kanazawa
Hiroshi
H
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. kanazawa-h@med.osaka-cu.ac.jp
Yoshikawa
Takahiro
T
Hirata
Kazuto
K
Yoshikawa
Junichi
J
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000097:blood* / Q000188:drug therapy*; D001798:Blood Proteins / Q000032:analysis; D002867:Chromones / Q000494:pharmacology*; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D005260:Female; D006801:Humans; D008297:Male; D012260:Ribonucleases / Q000032:analysis; D013183:Sputum / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D018927:Anti-Asthmatic Agents; D001798:Blood Proteins; D002867:Chromones; D047091:Eosinophil Granule Proteins; D042461:Vascular Endothelial Growth Factor A; D012260:Ribonucleases; C047681:pranlukast