Efficacy of the novel phosphodiesterase-4 inhibitor BAY 19-8004 on lung function and airway inflammation in asthma and chronic obstructive pulmonary disease (COPD).
Selective inhibitors of phosphodiesterase-4 (PDE4) inhibit the hydrolysis of intracellular cAMP, which may result in bronchodilation and suppression of inflammation. We examined the effect of 1 week treatment with BAY 19-8004 (5 mg once daily), a novel orally administered PDE4 inhibitor, on trough FEV1 and markers of inflammation in induced sputum in patients with asthma or chronic obstructive pulmonary disease (COPD). Seven patients with asthma (mean [SD] FEV1 69.5 [9.3]% predicted; reversibility in FEV1 26.2 [10.1]%; all non-smokers) and 11 patients with COPD (FEV1 58.6 [8.3]% predicted; reversibility in FEV1 6.5 [4.7]%; median [range] 44 [21-90] pack years of smoking) were included in this randomized, double-blind, placebo-controlled trial. FEV1 was measured before and after 1 week of treatment; sputum was induced by 4.5% saline inhalation on the last day of treatment. FEV1 did not improve during either treatment in both patient groups (p>0.2). Sputum cell counts were not different following placebo and BAY 19-8004 treatment in asthma and COPD patients (p>0.2). However, only in patients with COPD, small but significant reductions in sputum levels of albumin and eosinophil cationic protein were observed (p<0.05). In conclusion, 1 week of treatment with the selective PDE4 inhibitor BAY 19-8004 does not affect FEV1 and sputum cell numbers in patients with asthma or COPD. However, such treatment does seem to reduce levels of albumin and eosinophil cationic protein in sputum samples obtained from patients with COPD.
Grootendorst
D C
DC
Department of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands. d.c.grootendorst@lumc.nl
Gauw
S A
SA
Benschop
N
N
Sterk
P J
PJ
Hiemstra
P S
PS
Rabe
K F
KF
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000378:metabolism; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D001798:Blood Proteins / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy*; D012260:Ribonucleases / Q000378:metabolism; D013183:Sputum / Q000166:cytology / Q000378:metabolism; D013451:Sulfonic Acids / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014508:Urea / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*
D000418:Albumins; C487213:BAY 19-8004; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D013451:Sulfonic Acids; D014409:Tumor Necrosis Factor-alpha; D014508:Urea; D012260:Ribonucleases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4