Effects of selective COX-2 inhibition on allergen-induced bronchoconstriction and airway inflammation in asthma.
BACKGROUND
Prostaglandins that constrict and relax airways are synthesized in reactions catalyzed by either COX-1 or COX-2. It is not known whether selective inhibition of COX-2 makes asthmatic responses better or worse.


OBJECTIVE
To determine the effects of the selective COX-2 inhibitor, etoricoxib, on allergen-induced bronchoconstriction in asthmatic subjects.


METHODS
Sixteen subjects with mild atopic asthma underwent rising dose inhalation challenges with allergen or methacholine to determine PD20 FEV1 during a control study period or after 10 to 13 days of treatment with etoricoxib (90 mg once daily). The order of study periods was randomized with at least 2-week washout periods. Induced sputum cells and fractional exhaled nitric oxide levels were used to assess airway inflammation and blood assays for COX-1 and COX-2 activity to assess enzyme inhibition. Urinary excretion of lipids was used to assess prostaglandin biosynthesis.


RESULTS
Etoricoxib did not change baseline lung function, nor airway responsiveness to allergen or to methacholine. Neither were the allergen-induced increase in sputum eosinophils and fractional exhaled nitric oxide levels affected by treatment. The biochemical effectiveness of the treatment was established both in the blood assays and by the distinct inhibitory effect of etoricoxib on urinary excretion of tetranor-prostaglandin E2 (P < .001).


CONCLUSIONS
This first study of COX-2 inhibition in provoked asthma found no negative effects of etoricoxib on allergen-induced airflow obstruction and sputum eosinophils, basal lung function, or methacholine responsiveness. The study suggests that short-term use of COX-2 inhibitors is safe in subjects with asthma.
Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden. Electronic address: kameran.daham@ki.se.
Kameran
K
Daham
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Anna
A
James
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
David
D
Balgoma
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Maciej
M
Kupczyk
Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Bo
B
Billing
Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Agneta
A
Lindeberg
Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Elisabeth
E
Henriksson
University of Pennsylvania, Philadelphia, Pa.
Garret A
GA
FitzGerald
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Craig E
CE
Wheelock
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Sven-Erik
SE
Dahlén
Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Barbro
B
Dahlén
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D000077613:Etoricoxib; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D011453:Prostaglandins / Q000652:urine; D011725:Pyridines / Q000627:therapeutic use*; D013183:Sputum / Q000166:cytology; D013450:Sulfones / Q000627:therapeutic use*
D000485:Allergens; D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D011725:Pyridines; D013450:Sulfones; C532049:tetranor prostaglandin M; D016210:Methacholine Chloride; D009569:Nitric Oxide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D000077613:Etoricoxib
Asthma; COX; NSAIDs; airway hyperresponsiveness; eicosanoids; leukotrienes; mass spectrometry; prostaglandin; thromboxane; urinary metabolites