Effects of selective COX-2 inhibition on allergen-induced bronchoconstriction and airway inflammation in asthma Kameran Daham, MD, PhD, Anna James, PhD,

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Presentation transcript:

Effects of selective COX-2 inhibition on allergen-induced bronchoconstriction and airway inflammation in asthma Kameran Daham, MD, PhD, Anna James, PhD, David Balgoma, PhD, Maciej Kupczyk, MD, PhD, Bo Billing, MD, PhD, Agneta Lindeberg, RN, Elisabeth Henriksson, BMA, Garret A. FitzGerald, MD, PhD, Craig E. Wheelock, PhD, Sven-Erik Dahlén, MD, PhD, Barbro Dahlén, MD, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 2, Pages 306-313 (August 2014) DOI: 10.1016/j.jaci.2013.12.002 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Study design: Two randomized periods with etoricoxib 90 mg once daily for 10 to 13 days vs control period with no treatment. MCh, Methacholine challenge; R, randomization; study day 1, baseline data before start of period; study day 2, effects of etoricoxib/no treatment baseline data; study day 3, effects of etoricoxib/no treatment on allergen-induced airway obstruction, urinary mediators, and inflammatory cells in induced sputum. *Cumulative allergen challenge. **Urine before and 1 and 2 hours after allergen challenge. ***Blood before allergen challenge. Journal of Allergy and Clinical Immunology 2014 134, 306-313DOI: (10.1016/j.jaci.2013.12.002) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Effects of etoricoxib on airway sensitivity to allergen (A) and methacholine (B), expressed as individual PD20 values. Filled circles represent the etoricoxib treatment period, and open circles represent the control period. Horizontal lines indicate geometric mean values. Study days 1 and 2 represent the first day (baseline) and the penultimate day of each period, respectively. Journal of Allergy and Clinical Immunology 2014 134, 306-313DOI: (10.1016/j.jaci.2013.12.002) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Effects of etoricoxib on the total cell counts (box and whisker plots showing median, 25th and 75th percentiles, and min/max) (A) and differential cell counts in induced sputum expressed as percentages of total (mean [SEM]) (B). Black bars represent the treated period, and open bars represent the control period. Study days 1, 2, and 3 represent the first (baseline), penultimate, and last day (after allergen provocation) of each period, respectively. *P < .05 compared with study day 1. Journal of Allergy and Clinical Immunology 2014 134, 306-313DOI: (10.1016/j.jaci.2013.12.002) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Effect of etoricoxib on Feno measurements (geometric mean [SEM]). Black bars represent etoricoxib treatment, and open bars represent the control period. Study days 1, 2, and 3 represent the first day (baseline), penultimate day, and last day (before allergen provocation) of each period, respectively. Journal of Allergy and Clinical Immunology 2014 134, 306-313DOI: (10.1016/j.jaci.2013.12.002) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Assessment of COX-2 activity (A) and COX-1 activity (B) in plasma and serum, respectively. COX-1 activity was assessed by TXB2 generation in clotted blood (1 hour, 37°C), and COX-2 activity was assessed by PGE2 levels in blood incubated with LPS (100 μg/mL; 24 hours, 37°C). Black bars represent etoricoxib treatment, and open bars represent the control period (mean [SEM]). Study days 1, 2, and 3 represent the first day (baseline), the penultimate day, and the last day (before allergen provocation) of treatment, respectively. Significant comparisons between etoricoxib and control arms are indicated, as well as comparison with study day 1 (*P ≤ .001) and comparison with study day 2 (#P < .05). Journal of Allergy and Clinical Immunology 2014 134, 306-313DOI: (10.1016/j.jaci.2013.12.002) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Effects of etoricoxib on metabolites in urine. A, Tetranor-PGDM. B, 2,3-DinorTXB2. C, Tetranor-PGEM. D, 2,3-Dinor-6-ketoPGF1α. E, LTE4. LTE4, Leukotriene; PGDM, prostaglandin D metabolite; PGEM, PGE metabolite. Patients were untreated (open bars) or treated with etoricoxib (black bars). Urine was collected before provocation (Pre) and 1 and 2 hours after allergen provocation (1 hour post and 2 hour post, respectively). Data are normalized per hour. Error bars represent SEM. *Indicates significantly different from value before provocation (P < .05). #Indicates significantly different (P < .05) from untreated. Journal of Allergy and Clinical Immunology 2014 134, 306-313DOI: (10.1016/j.jaci.2013.12.002) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions