Efficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial.

Background: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). This double-blind, placebo-controlled randomized study evaluated the efficacy and safety of FF 200 mcg or 400 mcg once daily, either in the morning or in the evening, and FF 200 mcg twice daily (morning and evening), for 8 weeks in patients with persistent asthma.

Methods: Asthma patients maintained on ICS for ≥ 3 months with baseline morning forced expiratory volume in one second (FEV(1)) 50-80% of predicted normal value and FEV(1) reversibility of ≥ 12% and ≥ 200 ml were eligible.

Asthma diagnosis and treatment: filling in the information gaps.

Current approaches to the diagnosis and management of asthma are based on guideline recommendations, which have provided a framework for the efforts. Asthma, however, is emerging as a heterogeneous disease, and these features need to be considered in both the diagnosis and management of this disease in individual patients. These diverse or phenotypic features add complexity to the diagnosis of asthma, as well as attempts to achieve control with treatment.

Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial.

Background: Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24 h activity. FF is being developed as a once-daily treatment in combination with the long-acting β(2) agonist vilanterol trifenatate for asthma and chronic obstructive pulmonary disease.

Objectives: To determine the optimal dose(s) of FF for treating patients with asthma.

What effect does asthma treatment have on airway remodeling? Current perspectives.

Airway remodeling, or structural changes of the airway wall arising from injury and repair, plays an important role in the pathophysiology of asthma. Remodeling is characterized as structural changes involving the composition, content, and organization of many of the cellular and molecular constituents of the bronchial wall. These structural changes can include epithelial injury, subepithelial thickening/fibrosis, airway smooth muscle hyperplasia, goblet cell hypertrophy and hyperplasia, and angiogenesis.

Obesity and asthma: an association modified by age of asthma onset.

Background: Studies of asthma phenotypes have identified obesity as a component of a group characterized by a high proportion of subjects with adult-onset asthma. However, whether age of asthma onset modifies the association between obesity and asthma is unknown.

Objectives: We sought to compare the associations between body mass index (BMI) categories with physiological, inflammatory, and clinical parameters across age of asthma onset phenotypes; and to compare the rate of BMI change in relation to asthma duration, by age of onset asthma phenotypes.

Detrimental effects of environmental tobacco smoke in relation to asthma severity.

Background: Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown.

Methods: In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity.

Findings: From 2002-2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels.

Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial.

Background: Inhaled corticosteroids (ICS) and long-acting β(2)-agonists (LABAs) are recommended in patients with asthma that is not well-controlled; however, many patients continue to have inadequately controlled asthma despite this therapy.

Objective: To evaluate the efficacy and safety of omalizumab in patients with inadequately controlled severe asthma who are receiving high-dose ICS and LABAs, with or without additional controller therapy.

Design: Prospective, multicenter, randomized, parallel-group, double-blind, placebo-controlled trial.

Safety of investigative bronchoscopy in the Severe Asthma Research Program.

Background: Investigative bronchoscopy was performed in a subset of participants in the Severe Asthma Research Program to gain insights into the pathobiology of severe disease. We evaluated the safety aspects of this procedure in this cohort with specific focus on patients with severe asthma.

Objective: To evaluate prospectively changes in lung function and the frequency of adverse events related to investigative bronchoscopy.

Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children.

Background: Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control.

Methods: We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy.

Importance of hedgehog interacting protein and other lung function genes in asthma.

Background: Two recent large meta-analyses of genome-wide association studies of lung function in general populations of European descent identified 11 candidate genes/regions. The importance of these genes in lung function in white and African American subjects with asthma is unknown.

Objectives: To determine whether genes that regulate lung function in general populations are associated with lung function abnormalities in subjects with asthma from different racial groups.

House dust mite sublingual immunotherapy: results of a US trial.

Background: Few trials of sublingual immunotherapy (SLIT) in the United States have been reported.

Objective: This randomized, placebo-controlled feasibility SLIT study compared the safety and physiologic effects of high- versus low-dose Dermatophagoides farinae vaccine.

Methods: Thirty-one D farinae-sensitive adults with allergic rhinitis with or without mild intermittent asthma were eligible for randomization to high-dose maintenance vaccine (n = 10, 4200 allergen units [approximately 70 μg of Der f 1/d]), low-dose maintenance vaccine (n = 10; 60 allergen units [approximately 1 μg of Der f 1/d]), or placebo (n = 11) over 12 to 18 months.

Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine.

Background: Asthma was the most common comorbidity of patients hospitalized with 2009 H1N1 influenza.

Objective: We sought to assess the immunogenicity and safety of an unadjuvanted, inactivated 2009 H1N1 vaccine in patients with severe versus mild-to-moderate asthma.

Methods: We conducted an open-label study involving 390 participants (age, 12-79 years) enrolled in October-November 2009.

Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.

Background: Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial.

Objective: To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation.

Methods: This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma.

Racial differences in biologic predictors of severe asthma: Data from the Severe Asthma Research Program.

Background: Biologic factors are known to contribute to asthma severity. It is unknown whether these factors differentially contribute to asthma severity in black compared with white subjects.

Objective: We sought to assess the extent to which racial disparities between black and white subjects with severe asthma are attributable to physiologic, immunoinflammatory, and sociodemographic variables.

Determinants of exhaled breath condensate pH in a large population with asthma.

Background: Exhaled breath condensate (EBC) pH is 2 log orders below normal during acute asthma exacerbations and returns to normal with antiinflammatory therapy. However, the determinants of EBC pH, particularly in stable asthma, are poorly understood. We hypothesized that patients with severe asthma would have low EBC pH and that there would be an asthma subpopulation of patients with characteristically low values.

Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma.

Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably.

Role of viral respiratory infections in asthma and asthma exacerbations.

Viral respiratory tract infections are common and usually selflimited illnesses. For patients at risk of asthma, or with existing asthma, viral respiratory tract infections can have a profound effect on the expression of disease or loss of control. New evidence has shown that wheezing episodes early in life due to human rhinoviruses are a major risk factor for the later diagnosis of asthma at age 6 years.

Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program.

Rationale: Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity.

Objectives: To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant parameters between normal subjects and subjects with asthma to clarify their pathobiologic importance.

Predicting intermediate phenotypes in asthma using bronchoalveolar lavage-derived cytokines.

An important problem in realizing personalized medicine is the development of methods for identifying disease subtypes using quantitative proteomics. Recently we found that bronchoalveolar lavage (BAL) cytokine patterns contain information about dynamic lung responsiveness. In this study, we examined physiological data from 1,048 subjects enrolled in the US Severe Asthma Research Program (SARP) to identify four largely separable, quantitative intermediate phenotypes.

The relationship of airway hyperresponsiveness and airway inflammation: Airway hyperresponsiveness in asthma: its measurement and clinical significance.

Airway hyperresponsiveness (AHR) is a clinical feature of asthma and is often in proportion to the underlying severity of the disease. To understand AHR and the mechanisms that contribute to these processes, it is helpful to divide the airway components that affect this feature of asthma into "persistent" and "variable" categories. The persistent component of AHR represents structural changes in the airway, whereas the variable feature relates to inflammatory events.

Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma.

Background: Increased eosinophil levels have been linked to airway inflammation and asthma exacerbations. IL-5 is responsible for eosinophil differentiation, proliferation, and activation; IL-5 receptors are expressed on eosinophils and their progenitors, and targeting such receptors induces eosinophil apoptosis.

Objective: To evaluate the safety profile, pharmacokinetics, and pharmacodynamics of MEDI-563, a humanized mAb targeting the IL-5 receptor alpha chain.