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9. Role of oxidants in influenza virus-induced gene expression

Author

Knobil, Katharine, Choi, Augustine M.K., Weigand, Gordon W., and Jacoby, David B.

Subjects
Oxidizing agents -- Physiological aspects, Gene expression -- Physiological aspects, Influenza viruses -- Genetic aspects, Epithelial cells -- Physiological aspects, Biological sciences
Abstract

Research was conducted to examine the role of reactive oxygen intermediates in the influenza virus-induced gene expression of antioxidant enzymes in the activation of nuclear factor-Kappa-Beta. Viral content was determined by exposing rhesus monkey kidney cell monolayers to serial 10-fold dilutions of virus stock while human influenza virus A/Port Chalmers/72 was harvested in embryonated chicken eggs. Results showed that the viral infection of cultured epithelial cells led to significant oxidant stresses.

Published
1998

11. Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation

Author

Choi, Augustine M.K., Knobil, Katharine, Otterbein, Sherrie L., Eastman, Deborah A., and Jacoby, David B.

Subjects
Active oxygen in the body -- Physiological aspects, Influenza -- Physiological aspects, Stress (Physiology) -- Research, Antioxidants -- Physiological aspects, Mice -- Physiological aspects, Biological sciences
Abstract

Previous studies have suggested that influenza infections induce the production of toxic oxygen radicals which may damage lung tissues. To combat this effect, it is necessary for the host to produce antioxidant enzymes to detoxify the superoxides. In a study of mice infected with the influenza virus, the production of antioxidant enzymes were induced by the expression of the genes encoding manganese superoxide dismutase (MnSOD), indoleamine-2,3-dioxygenase, heme oxygenase-1, and glutathione peroxidase in the lung. Except for MnSOD, gene expression of the antioxidants resulted in increased enzyme activity. There were also variations in the degree of enzyme production. These results suggest that oxidant stress response to the influenza virus is determined by the host's genetic background.

Published
1996

15. Continuous Intravenous Epoprostenol for Pulmonary Hypertension Due to the Scleroderma Spectrum of Disease: A Randomized, Controlled Trial

Author

Badesch, David B., Tapson, Victor F., McGoon, Michael D., Brundage, Bruce H., Rubin, Lewis J., Wigley, Fredrick M., Rich, Stuart, Barst, Robyn J., Barrett, Pamela S., Kral, Kenneth M., Jöbsis, Maria M., Loyd, James E., Murali, Srinivas, Frost, Adaani, Girgis, Reda, Bourge, Robert C., Ralph, David D., Elliott, C. Gregory, Hill, Nicholas S., Langleben, David, Schilz, Robert J., McLaughlin, Vallerie V., Robbins, Ivan M., Groves, Bertron M., Shapiro, Shelley, Medsger, Thomas A., Jr., Gaine, Sean P., Horn, Evelyn, Decker, James C., and Knobil, Katharine

Published
2000

17. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study.

Author

Celli, Bartolomé R, Thomas, Nicola E, Anderson, Julie A, Ferguson, Gary T, Jenkins, Christine R, Jones, Paul W, Vestbo, Jørgen, Knobil, Katharine, Yates, Julie C, Calverley, Peter M A, Celli, Bartolomé R, Thomas, Nicola E, Anderson, Julie A, Ferguson, Gary T, Jenkins, Christine R, Jones, Paul W, Vestbo, Jørgen, Knobil, Katharine, Yates, Julie C, and Calverley, Peter M A

Abstract

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function. No drug has been shown conclusively to reduce this decline. OBJECTIVES: In a post hoc analysis of the Toward a Revolution in COPD Health (TORCH) study, we investigated the effects of combined salmeterol 50 microg plus fluticasone propionate 500 microg, either component alone or placebo, on the rate of post-bronchodilator FEV(1) decline in patients with moderate or severe COPD. METHODS: A randomized, double-blind, placebo-controlled study was conducted from September 2000 to November 2005 in 42 countries. Of 6,112 patients from the efficacy population, 5,343 were included in this analysis. MEASUREMENTS AND MAIN RESULTS: Spirometry was measured every 24 weeks for 3 years. There were 26,539 on-treatment observations. The adjusted rate of decline in FEV(1) was 55 ml/year for placebo, 42 ml/year for salmeterol, 42 ml/year for fluticasone propionate, and 39 ml/year for salmeterol plus fluticasone propionate. Salmeterol plus fluticasone propionate reduced the rate of FEV(1) decline by 16 ml/year compared with placebo (95% confidence interval [CI], 7-25; P < 0.001). The difference was smaller for fluticasone propionate and salmeterol compared with placebo (13 ml/year; 95% CI, 5-22; P = 0.003). Rates of decline were similar among the active treatment arms. FEV(1) declined faster in current smokers and patients with a lower body mass index, and varied between world regions. Patients who exacerbated more frequently had a faster FEV(1) decline. CONCLUSIONS: Pharmacotherapy with salmeterol plus fluticasone propionate, or the components, reduces the rate of decline of FEV(1) in patients with moderate-to-severe COPD, thus slowing disease progression. Clinical trial (GSK Study Code SCO30003) registered with www.clinicaltrials.gov (NCT00268216) Udgivelsesdato: 2008/8/15, RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function. No drug has been shown conclusively to reduce this decline. OBJECTIVES: In a post hoc analysis of the Toward a Revolution in COPD Health (TORCH) study, we investigated the effects of combined salmeterol 50 microg plus fluticasone propionate 500 microg, either component alone or placebo, on the rate of post-bronchodilator FEV(1) decline in patients with moderate or severe COPD. METHODS: A randomized, double-blind, placebo-controlled study was conducted from September 2000 to November 2005 in 42 countries. Of 6,112 patients from the efficacy population, 5,343 were included in this analysis. MEASUREMENTS AND MAIN RESULTS: Spirometry was measured every 24 weeks for 3 years. There were 26,539 on-treatment observations. The adjusted rate of decline in FEV(1) was 55 ml/year for placebo, 42 ml/year for salmeterol, 42 ml/year for fluticasone propionate, and 39 ml/year for salmeterol plus fluticasone propionate. Salmeterol plus fluticasone propionate reduced the rate of FEV(1) decline by 16 ml/year compared with placebo (95% confidence interval [CI], 7-25; P < 0.001). The difference was smaller for fluticasone propionate and salmeterol compared with placebo (13 ml/year; 95% CI, 5-22; P = 0.003). Rates of decline were similar among the active treatment arms. FEV(1) declined faster in current smokers and patients with a lower body mass index, and varied between world regions. Patients who exacerbated more frequently had a faster FEV(1) decline. CONCLUSIONS: Pharmacotherapy with salmeterol plus fluticasone propionate, or the components, reduces the rate of decline of FEV(1) in patients with moderate-to-severe COPD, thus slowing disease progression. Clinical trial (GSK Study Code SCO30003) registered with www.clinicaltrials.gov (NCT00268216).

Published
2008

18. Combination of fluticasone and salmeterol (advair diskus®) improves cough in patients with chronic obstructive pulmonary disease. (COPD: 12:00pm-1:45pm)

Author

Knobil, Katharine, Yates, Julie, Horstman, Donald, Darken, Patrick, and Wire, Patrick

Subjects
Health
Abstract

PURPOSE: To evaluate a Chronic Bronchitis Symptoms Questionnaire (CBSQ) in assessing the improvement in chronic bronchitis related symptoms in patients with chronic obstructive pulmonary disease (COPD) when treated with the [...]

Published
2002

19. Fracture incidence from clinical trials of fluticasone propionate alone or in combination with salmeterol in the treatment of chronic obstructive pulmonary disease. (COPD: therapeutics and management: 12:30pm-2:00pm)

Author

Knobil, Katharine, Watkins, Michael, Yates, Julie, Darken, Patrick, and Wire, Patrick

Subjects
Health
Abstract

PURPOSE: To evaluate the incidence of fractures reported in clinical trials of fluticasone propionate 500mcg alone or in combination with salmeterol 50mcg (FSC 500/50) in the treatment of chronic obstructive [...]

Published
2002

31. Rapid onset of improvement in airflow with combination salmeterol and fluticasone propionate therapy administered by a single diskus in patients with COPD. (COPD: therapeutics and management: 12:30pm-2:00pm)

Author

Hanania, Nicola A., Knobil, Katharine, Watkins, Michael, Wire, Patrick, Yates, Julie, and Darken, Patrick

Subjects
Health
Abstract

PURPOSE: The early onset of improvement in airflow as measured by daily morning peak expiratory flow rate (PEF) was investigated with combined treatment of fluticasone propionate (250mcg or 500mcg) and [...]

Published
2002

32. Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations.

Author

Ferguson GT, Anzueto A, Fei R, Emmett A, Knobil K, and Kalberg C

Subjects
Adult, Aged, Albuterol adverse effects, Albuterol therapeutic use, Androstadienes adverse effects, Bronchodilator Agents adverse effects, Double-Blind Method, Drug Combinations, Female, Fluticasone, Forced Expiratory Volume drug effects, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive etiology, Pulmonary Disease, Chronic Obstructive physiopathology, Quality of Life, Salmeterol Xinafoate, Smoking adverse effects, Albuterol analogs & derivatives, Androstadienes therapeutic use, Bronchodilator Agents therapeutic use, Pulmonary Disease, Chronic Obstructive drug therapy
Abstract

Objectives: COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250/50 and salmeterol 50 microg twice daily on moderate to severe exacerbations., Methods: Patients received standardized treatment with fluticasone propionate/salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/salmeterol 250/50 or salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization., Results: In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with salmeterol (1.06 and 1.53 per subject per year, respectively, p<0.001), (2) the risk of time to first exacerbation by 25% (hazard ratio=0.750, p=0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% (p<0.001). Clinical improvements observed during run-in treatment with fluticasone propionate/salmeterol 250/50 were better maintained over 12 months with fluticasone propionate/salmeterol 250/50 than salmeterol. Adverse events were reported for a similar percentage of subjects across groups. A higher reporting of pneumonia was observed with fluticasone propionate/salmeterol 250/50 than salmeterol (7% vs. 4%)., Conclusions: We conclude that fluticasone propionate/salmeterol 250/50 is more effective than salmeterol at reducing the rate of moderate to severe exacerbations over 1 year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.

Published
2008
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