Effects of celecoxib on major prostaglandins in asthma

• Published in: Clinical and experimental allergy Vol. 41; no. 1; pp. 36 - 45
• Main Authors: Daham, K., Song, W.- L., Lawson, J. A., Kupczyk, M., Gülich, A., Dahlén, S.-E., FitzGerald, G. A., Dahlén, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2011; Blackwell; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Asthma; Asthma - diagnosis; Asthma - drug therapy; Asthma - metabolism; Biological and medical sciences; Celecoxib; Chronic obstructive pulmonary disease, asthma; Cross-Over Studies; Drug Administration Schedule; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Indexing in process; Male; Medical sciences; Middle Aged; NSAIDs; Pneumology; Prostaglandins - biosynthesis; Prostaglandins - metabolism; Prostaglandins - urine; Pyrazoles - administration & dosage; Pyrazoles - therapeutic use; Respiratory Function Tests; salivary prostaglandin E2; Sulfonamides - administration & dosage; Sulfonamides - therapeutic use; urinary prostaglandin metabolites; Young Adult; Lung disease; Prostaglandin-endoperoxide synthase; Enzyme; Respiratory disease; Metabolite; Arachidonic acid derivatives; Enzyme inhibitor; Prostaglandin E2; Cyclooxygenase 2 inhibitor; Celecoxib; urinary prostaglandin metabolites; Asthma; salivary prostaglandin E; Non steroidal antiinflammatory agent; Immunology; Eicosanoid; NSAIDs; Bronchus disease; Obstructive pulmonary disease; Oxidoreductases; Saliva
• ISSN: 0954-7894; 1365-2222; 1365-2222
• DOI: 10.1111/j.1365-2222.2010.03617.x

Summary Background Prostaglandin (PG) D2 is a pro‐inflammatory and bronchoconstrictive mediator released from mast cells, and is currently evaluated as a new target for treatment of asthma and rhinitis. It is not known which cyclooxygenase (COX) isoenzyme catalyses its biosynthesis in subjects with asthma. Objectives Primarily, to assess whether treatment with the COX‐2 selective inhibitor celecoxib inhibited biosynthesis of PGD2, monitored as urinary excretion of its major tetranor metabolite (PGDM). Secondarily, to determine the effects of the treatment on biosynthesis of PGE2, thromboxane A2 and PGI2, also measured as major urinary metabolites. Methods Eighteen subjects with asthma participated in a cross‐over study where celecoxib 200 mg or placebo were given b.i.d. on 3 consecutive days following 2 untreated baseline days. Six healthy controls received active treatment with the same protocol. Urinary excretion of the eicosanoid metabolites was determined by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Lung function was followed as FEV1 and airway inflammation as fraction of exhaled nitric oxide (FENO). Results Celecoxib treatment inhibited urinary excretion of PGEM by 50% or more in subjects with asthma and healthy controls, whereas there was no significant change in the excretion of PGDM. In comparison with the healthy controls, the subjects with asthma had higher baseline levels of urinary PGDM but not of PGEM. The 3‐day treatment did not cause significant changes in FEV1 or FENO. Conclusion and Clinical Relevance Biosynthesis of PGD2 was increased in subjects with asthma and its formation is catalysed predominantly by COX‐1. By contrast, COX‐2 contributes substantially to the biosynthesis of PGE2. The asymmetric impact of celecoxib on prostanoid formation raises the possibility of long‐term adverse consequences of COX‐2 inhibition on airway homeostasis by the decreased formation of bronchodilator PGs and maintained production of increased levels of bronchoconstrictor PGs in asthmatics. Cite this as: K. Daham, W.‐ L. Song, J. A. Lawson, M. Kupczyk, A. Gülich, S.‐E. Dahlén, G. A. FitzGerald and B. Dahlén, Clinical & Experimental Allergy, 2011 (41) 36–45.