Biomedical subjects

Yamo Deniz

Publications and source records attributed to Yamo Deniz.

9 recordsLinked to original sources

PubMed2006

Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment.

An estimated 300 million people are affected by asthma worldwide and the burden is likely to rise substantially in the next few decades. Estimates of the prevalence of asthma range from 7% in France and Germany to 11% in the USA and 15-18% in the United Kingdom. Approximately 20% of these patients have severe asthma, of which 20% is inadequately controlled. Patients with inadequately controlled severe persistent asthma are at a particularly high risk of exacerbations, hospitalization and death, and often have severely impaired quality of life. Current management of asthma focuses on a stepwise approach tailored to disease severity. In addition to needing high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABAs), patients with severe persistent asthma often require additional controller medications, such as anti-leukotrienes, oral LABAs, oral corticosteroids and/or anti-IgE therapy. There is currently little evidence on which to base treatment decisions in patients with inadequately controlled severe persistent asthma already treated with ICS and LABAs. The anti-IgE monoclonal antibody omalizumab is the most recent addition to the list of treatment options for these patients and has been shown to reduce exacerbations and emergency visits and improve lung function, symptom scores and quality of life in patients with difficult-to-treat asthma whose symptoms remain inadequately controlled despite receiving ICS and LABAs. Comparative trials are needed to determine the merits of different treatments and strategies for patients with inadequately controlled severe persistent asthma and to identify patients likely to benefit from new treatment options.

Adrenergic beta-Agonists↗

PubMed2006

Asthma in older adults: observations from the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) study.

BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) was a 3-year, multicenter, observational study of 4,756 patients 6 years or older with severe or difficult-to-treat asthma by physician evaluation. More than 280 pulmonologist and allergist sites across the United States participated. OBJECTIVE: To compare health care utilization (HCU), medication use, asthma control, and quality of life (QoL) in older (> or =65 years; n = 566) and younger (18-64 years; n = 2,912) adult patients in TENOR. METHODS: Patients had to be under a physician's care for at least 1 year and have high medication use or HCU in the past year. Heavy smokers (> or =30 pack-years) and patients with cystic fibrosis were excluded. RESULTS: Although older patients in TENOR had worse lung function as measured by decreased percent predicted forced expiratory volume in 1 second (FEV1) (P < .001), they had significantly lower HCU compared with younger patients. They also had higher use of inhaled corticosteroids and better QoL than younger patients. Older patients reported fewer problems controlling their asthma (P < .001) but reported worse communication with their physicians (P = .02). CONCLUSIONS: Older patients in TENOR appeared to do better than younger patients, despite having worse lung function. Older patients in TENOR may have received more aggressive care than older asthmatic patients in other studies, based on a higher use of inhaled and oral corticosteroids. Whether differences in treatment or disease influenced other physiologic or inflammatory outcomes that contribute to the disconnect between HCU and FEV1 awaits further study.

Adolescent↗

PubMed2005

Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis.

BACKGROUND: Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis. OBJECTIVES: We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT. METHODS: Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 mug Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy. RESULTS: Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044). CONCLUSION: Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and allergen immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.

Adolescent↗

PubMed2005

Severity assessment in asthma: An evolving concept.

BACKGROUND: Guidelines for the clinical management of asthma base specific treatment recommendations on the assessment of disease severity. Thus, the accuracy of such assessments is essential for proper clinical management. The consistency of asthma severity assessment in patients with difficult-to-treat disease is unknown. OBJECTIVE: The objectives of this analysis were to compare the asthma severity assessment according to 3 methodologies in patients from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. METHODS: Asthma severity on the basis of the National Asthma Education and Prevention Program and the Global Initiative for Asthma guidelines was compared with physician assessment and benchmarked against asthma-related health care use. Guideline-based asthma severity symptom components were derived from patient-reported questionnaires. Lung function levels were determined by prebronchodilator FEV(1) measurements; asthma-related medication and recent health care use were reported by patients. RESULTS: There was a clear lack of agreement among the asthma severity assessment modalities. Asthma severity was associated with asthma-related health care use, and patients considered to have severe asthma according to both sets of guidelines and physicians' assessment had the highest health care and medication use. CONCLUSION: Classification of asthma severity on the basis of current asthma symptoms and lung function may be useful but not completely reflective of a patient's true asthma condition. Clinical assessment of asthma severity should consider a patient's medication use and consumption of health care resources for asthma exacerbations. Additional studies that apply criteria for asthma severity longitudinally are needed to support recommendations for optimal assessment of asthma severity.

Adolescent↗

PubMed2005

The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation.

Anti-IgE therapy with omalizumab reduces serum levels of free IgE and downregulates expression of IgE receptors (Fc epsilonRI) on mast cells and basophils. In the airways of patients with mild allergic asthma, omalizumab reduces Fc epsilonRI+ and IgE+ cells and causes a profound reduction in tissue eosinophilia, together with reductions in submucosal T-cell and B-cell numbers. In patients with seasonal allergic rhinitis, omalizumab inhibits the allergen-induced seasonal increases in circulating and tissue eosinophils. Omalizumab decreases Fc epsilonRI expression on circulating dendritic cells, which might lead to a reduction in allergen presentation, T(H)2 cell activation, and proliferation. As a systemic anti-IgE agent, omalizumab has demonstrated clinical efficacy in patients with moderate and severe allergic asthma and in those with seasonal and perennial allergic rhinitis, as well as in patients with concomitant allergic asthma and allergic rhinitis. The anti-inflammatory effects of omalizumab at different sites of allergic inflammation and the clinical benefits of anti-IgE therapy in patients with allergic asthma and allergic rhinitis emphasize the fundamental importance of IgE in allergic inflammation.

Anti-Allergic Agents↗

PubMed2005

Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma.

BACKGROUND: Limited data are available on levels of IgE in large cohorts of patients with severe or difficult-to-treat asthma. OBJECTIVE: To examine IgE levels and disease in patients from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. METHODS: From January 2001 to October 2001, 4,923 patients were screened for inclusion in the study. Of these, 4,756 patients 6 years or older with severe or difficult-to-treat asthma were enrolled and completed a baseline study visit. Total serum IgE levels were measured at the baseline visit and are summarized by geometric means. RESULTS: The mean total IgE level of the population is 106.6 IU/mL (95% confidence interval, 101.5-112.0 IU/mL). Children (6-12 years old) and adolescents (13-17 years old) have higher mean IgE levels than adults (> or =18 years old) (P < .001). Males have a higher mean IgE level than females (P < .001). IgE levels are higher among nonwhite patients than white patients (P < .001). Current smokers have higher IgE levels than past smokers or never smokers (P < .001). Among children, patients with severe asthma have a higher mean IgE level (280.2 IU/mL) than patients with moderate (145.8 IU/mL) or mild (137.8 IU/mL) asthma (P < .001). Among adults, patients with childhood-onset asthma have higher IgE levels (124.3 IU/mL [n = 1,348]) than patients with adult-onset asthma (65.7 IU/mL [n = 1,956]) (P < .001). CONCLUSION: In patients with severe or difficult-to-treat asthma from the TENOR study, higher total IgE levels were observed in males, children, smokers, nonwhite racial/ethnic groups, and adults with childhood-onset disease. In addition, IgE levels are associated with asthma severity among younger patients.

Adolescent↗

PubMed2004

Effects of omalizumab, a humanized monoclonal anti-IgE antibody, on nasal reactivity to allergen and local IgE synthesis.

BACKGROUND: Treatment with omalizumab has been shown to reduce serum free IgE concentrations and to have beneficial effects on allergic airway disease. However, its effect on IgE synthesis is unknown. OBJECTIVE: To determine whether omalizumab therapy affects nasal reactivity to allergen and local IgE production. METHODS: Nineteen patients with perennial allergic rhinitis were treated with intravenous omalizumab every 2 weeks for 26 weeks in an open-label study. Serum free and total IgE concentrations were measured at baseline and every 2 weeks throughout the study. Nasal challenge to dust mite allergen was performed at baseline and after 12 and 24 weeks of treatment. Nasal lavage fluid obtained before and after each nasal challenge was evaluated for mite-specific antibodies, plaque-forming cells, and productive epsilon messenger RNA (mRNA). RESULTS: During treatment, serum free IgE concentrations were decreased by 97% to 99%, and the nasal response to allergen challenge was significantly reduced on days 80 and 164. The postchallenge increase in nasal lavage mite specific IgE was significantly reduced by treatment with omalizumab on day 168. IgE plaque-forming cells and productive epsilon mRNA were not significantly affected by omalizumab treatment. CONCLUSIONS: Omalizumab treatment markedly reduced serum free IgE and the clinical response to nasal allergen challenge. However, the absence of an effect on IgE-secreting B cells and epsilon mRNA in nasal lavage fluid suggests that omalizumab treatment for 6 months does not significantly modulate synthesis of nasal IgE.

Adult↗

PubMed2003

Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma.

BACKGROUND: Prevention of serious asthma exacerbations is an important therapeutic goal in patients with asthma. OBJECTIVE: The purpose of this study was to investigate the effect of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody, on the rate of serious exacerbations during long-term therapy. METHODS: A pooled analysis was completed of 3 multicenter, randomized, double-blind, placebo-controlled phase III studies with omalizumab in adults/adolescents aged > or =12 years (n = 1071) and in children aged 6 to 12 years (n = 334) who required treatment with inhaled corticosteroids for allergic asthma. Rates of serious asthma exacerbations were computed and compared between omalizumab- and placebo-treated patients. Serious exacerbations were those leading to unscheduled outpatient visits, emergency room treatment, or hospitalization during 1 year of treatment. RESULTS: In all, 767 patients were treated with omalizumab (at least 0.016 mg/kg/IgE [IU/mL], administered subcutaneously every 4 weeks). Another 638 patients were treated with placebo. The rate of unscheduled, asthma-related outpatient visits was lower for the omalizumab-treated patients than for the placebo-treated patients (rate ratio [95% CI], 0.60 [0.44, 0.81]; P <.01), as were asthma-related emergency room visits (rate ratio [95% CI], 0.47 [0.24, 1.01]; P =.05). Importantly, hospitalizations for asthma were markedly reduced in patients receiving omalizumab (rate ratio [95% CI], 0.08 [0.00, 0.25]; P <.01). CONCLUSION: Omalizumab reduces the rate of serious asthma exacerbations and the need for unscheduled outpatient visits, emergency room treatment, and hospitalization in patients with moderate-to-severe allergic asthma.

Adolescent↗

PubMed2003

Pharmacodynamics of omalizumab: implications for optimised dosing strategies and clinical efficacy in the treatment of allergic asthma.

OBJECTIVE: Omalizumab (Xolair), is a recombinant humanised monoclonal anti-immunoglobulin E (IgE) antibody, for the treatment of allergic asthma. This review describes how the correlation between clinical outcomes and a suitable surrogate marker (free serum IgE) led to the development of an individualised dosing strategy for omalizumab. It also demonstrates how subsequent studies using this dosing strategy were able to achieve low levels of IgE and clinical benefit. DATA SOURCES: Published articles and data on file (Novartis Pharma AG, Genentech). RESULTS: Studies in patients with IgE-mediated diseases of the airways have shown that clinical benefit with omalizumab is observed when free IgE levels in serum are reduced to 50 ng/ml (20.8 IU/ml) or less (target 25 ng/ml (10.4 IU/ml)). The ability of omalizumab to reduce free IgE levels to such levels is dependent on dose, the patient's weight and baseline IgE level. To simplify dosing, and ensure that free IgE reduction is achieved, an individualised tiered dosing table was developed from which patients with asthma, depending on weight and starting IgE level, receive omalizumab 150-375 mg by subcutaneous injection every 2 or 4 weeks. This dosing strategy has proved clinically efficacious for improving disease control in patients with allergic asthma, as shown by significantly lower exacerbation rates and decreased dependence on treatment with inhaled corticosteroids, along with improvements in symptoms, lung function and usage of rescue bronchodilators. CONCLUSIONS: The clinical efficacy of omalizumab has been optimised through the development of an individualised dosing table that emerged from an understanding of the pharmacodynamics of this agent.

Antibodies, Anti-Idiotypic↗