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Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD
  1. P Montuschi1,
  2. F Macagno2,
  3. P Parente3,
  4. S Valente2,
  5. L Lauriola3,
  6. G Ciappi2,
  7. S A Kharitonov4,
  8. P J Barnes4,
  9. G Ciabattoni5
  1. 1Department of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy
  2. 2Department of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy
  3. 3Department of Pathology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy
  4. 4Department of Thoracic Medicine, Imperial College, School of Medicine, National Heart and Lung Institute, London, UK
  5. 5Department of Drug Sciences, School of Pharmacy, University “G D’Annunzio”, Italy
  1. Correspondence to:
    Professor P Montuschi
    Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F Vito 1, 00168 Rome, Italy; pmontuschirm.unicatt.it

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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Footnotes

  • 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.

  • 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.

  • 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.

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