Article Text
Abstract
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<0.001) and exhaled PGE2 was reduced (93.5 (84.0–105–5) pg/ml v 22.0 (15.0–25.5) pg/ml, p<0.0001). Rofecoxib had no effect on exhaled LTB4 (p = 0.53) or PGE2 (p = 0.23).
Conclusions: Non-selective COX inhibition decreases PGE2 and increases LTB4 in EBC, whereas selective COX-2 inhibition has no effect on these eicosanoids. PGE2 in EBC is primarily derived from COX-1 activity, and COX inhibition may redirect arachidonic acid metabolism towards the 5-lipoxygenase pathway.
- COPD, chronic obstructive pulmonary disease
- COX, cyclo-oxygenase
- EBC, exhaled breath condensate
- FEV1, forced expiratory volume in 1 second
- FVC, forced vital capacity
- LTB4, leukotriene B4
- NSAID, non-steroidal anti-inflammatory drug
- PGE2, prostaglandin E2
- TxB2, thromboxane B2
- cyclo-oxygenase
- exhaled breath condensate
- chronic obstructive pulmonary disease
- leukotriene B4
- prostaglandin E2
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Supplementary materials
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Footnotes
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The ibuprofen study was funded by Imperial College, School of Medicine at the National Heart and Lung Institute, London, UK. The rofecoxib study was funded by Merck, Sharp & Dohme.
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PM, FM, PP, SV, LL, GC, PJB, and GC have no competing interests. They have no financial and/or personal relationships with other people or organisations that could inappropriately influence this work.
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This work was performed at Imperial College, School of Medicine, National Heart and Lung Institute, London, UK and at the Catholic University of the Sacred Heart, Rome, Italy.