Selective Inducible Nitric Oxide Synthase Inhibition Has No Effect on Allergen Challenge in Asthma
| Autor: | Brian J. O'Connor, Ashley Woodcock, Sheila Schwartz, Duncan Richards, Dave Singh, Richard G. Knowles, S. J. Langley |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Allergy Nitric Oxide Synthase Type II Sulfides Pharmacology Nitric Oxide Critical Care and Intensive Care Medicine Placebo Bronchial Provocation Tests Nitric oxide chemistry.chemical_compound Double-Blind Method Forced Expiratory Volume Intensive care Humans Medicine Montelukast Asthma Cross-Over Studies biology business.industry respiratory system medicine.disease Crossover study respiratory tract diseases Nitric oxide synthase Breath Tests chemistry Immunology biology.protein Female Bronchial Hyperreactivity business medicine.drug |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 176:988-993 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.200704-588oc |
| Popis: | Exhaled breath nitric oxide (Fe(NO)) is increased in asthma. NO is produced predominantly by inducible nitric oxide synthase (iNOS).We evaluated the selective and potent iNOS inhibitor GW274150 in asthma.Twenty-eight steroid-naive patients with asthma participated in a double-blind, randomized, double-dummy, placebo-controlled, three-period cross-over study. Subjects received GW274150 (90 mg), montelukast (10 mg), or placebo once daily for 14 days. Fe(NO) was assessed predose on Days 1, 7, 10, and 14. Adenosine 5'-monophosphate (AMP) challenge was performed on Day 10, allergen challenge on Day 14 followed by methacholine challenge (MCh) 24 hours later, and then bronchoscopy.GW274150 reduced predose Fe(NO) by 73, 75, and 71% on Days 7, 10, and 14, respectively, compared with placebo. Montelukast did not reduce Fe(NO). GW274150 did not inhibit AMP reactivity whereas for montelukast there was a trend toward inhibition: the mean doubling dose difference versus placebo was 0.64 (95% confidence interval [95% CI], 0 to 1.28). GW274150 did not inhibit early (EAR) and late (LAR) asthmatic responses to allergen, or MCh reactivity, despite reduced Fe(NO) levels. Montelukast inhibited EAR and LAR FEV1; the mean difference versus placebo for minimal FEV1 was 0.37 L (95% CI, 0.19 to 0.55) and 0.18 L (95% CI, 0.04 to 0.32), respectively. MCh reactivity was inhibited by montelukast (mean doubling dose difference vs. placebo, 0.51; 95% CI, 0.02 to 1.01). GW271540 also had no effect on inflammatory cell numbers in bronchoalveolar lavage fluid after allergen challenge.Selective iNOS inhibition effectively reduces Fe(NO) but does not affect airway hyperreactivity or airway inflammatory cell numbers after allergen challenge in subjects with asthma. Clinical trial registered with www.clinicaltrials.gov (NCT00273013). |
| Databáze: | OpenAIRE |
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