Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD

• Published in: Thorax 2005-10, Vol.60 (10), p.827-833
• Main Authors: Montuschi, P, Macagno, F, Parente, P, Valente, S, Lauriola, L, Ciappi, G, Kharitonov, S A, Barnes, P J, Ciabattoni, G
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Gas Analysis - methods; Chronic Obstructive Pulmonary Disease; COPD; COX; Cross-Over Studies; cyclo-oxygenase; Cyclooxygenase Inhibitors - therapeutic use; Dinoprostone - metabolism; Double-Blind Method; EBC; Eicosanoids - metabolism; exhaled breath condensate; Female; FEV1; Forced Expiratory Volume - physiology; forced expiratory volume in 1 second; forced vital capacity; FVC; Humans; Ibuprofen - therapeutic use; Lactones - therapeutic use; leukotriene B4; Leukotriene B4 - metabolism; LTB4; Male; Medical sciences; Middle Aged; non-steroidal anti-inflammatory drug; Nonsteroidal anti-inflammatory drugs; NSAID; Outpatient care facilities; Patients; PGE2; Pneumology; prostaglandin E2; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - metabolism; Sputum - chemistry; Sulfones - therapeutic use; thromboxane B2; Thromboxane B2 - metabolism; TxB2; Vital Capacity - physiology
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thx.2004.035592

Background: Leukotriene (LT) B4 concentrations are increased and prostaglandin (PG) E2 concentrations are decreased in exhaled breath condensate (EBC) in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX) inhibition on exhaled LTB4 and PGE2 concentrations in patients with COPD and to identify the COX isoform responsible for exhaled PGE2 production. Methods: Two studies were performed. A double blind, crossover, randomised, placebo controlled study with ibuprofen (400 mg qid for 2 days), a non-selective COX inhibitor, was undertaken in 14 patients with stable COPD, and an open label study with oral rofecoxib (25 mg once a day for 5 days), a selective COX-2 inhibitor, was undertaken in a different group of 16 COPD patients. EBC was collected before and after drug treatment. Exhaled LTB4 and PGE2 concentrations were measured with specific immunoassays. Results: All patients complied with treatment as indicated by a reduction in ex vivo serum thromboxane B2 concentrations (ibuprofen) and a reduction in lipopolysaccharide induced increase in ex vivo plasma PGE2 values (rofecoxib) of more than 80%. Exhaled LTB4 was increased after ibuprofen (median 175.5 (interquartile range 128.8–231.5) pg/ml v 84.0 (70.0–98.5) pg/ml, p