Activity of aclidinium bromide, a new long-acting muscarinic antagonist: a phase I study.

Aim: Aclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine-induced bronchoconstriction.

Methods: This double-blind, partial-crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 microg) or placebo.

The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma.

Background: The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study enrolled 7241 patients aged 5 to 66 years with recent-onset, mild persistent asthma to assess early intervention with the inhaled corticosteroid budesonide on long-term asthma control.

Objective: The open-label phase of the START study was included to determine the effect on lung function and asthma control of adding budesonide to the reference group patients who had not initially received inhaled corticosteroids.

Methods: Patients were randomized to double-blind treatment with budesonide, 200 mug (those aged < 11 years) or 400 mug once daily, or placebo plus the usual asthma therapy for 3 years, after which all patients received 2 years of open-label treatment with budesonide once daily.

The severity of airways obstruction as a determinant of treatment response in COPD.

Guidelines recommend that patients with COPD are stratified arbitrarily by baseline severity (FEV1) to decide when to initiate combination treatment with a long-acting beta2-agonist and an inhaled corticosteroid. Assessment of baseline FEV1 as a continuous variable may provide a more reliable prediction of treatment effects. Patients from a 1-year, parallel-group, randomized controlled trial comparing 50 microg salmeterol (Sal), 500 microg fluticasone propionate (FP), the combination (Sal/FP) and placebo, (bid), were categorized post hoc into FEV1 < 50% and FEV1 > or = 50% predicted subgroups (n = 949/513 respectively).

Clinical trial design considerations in assessing long-term functional impacts of tiotropium in COPD: the UPLIFT trial.

An accelerated loss of lung function is one of the defining characteristics of chronic obstructive pulmonary disease (COPD). To date, the only successful intervention shown to conclusively attenuate the loss of lung function over time is smoking cessation. Pharmacological interventions including inhaled corticosteroids and ipratropium bromide have not altered the rate of decline of lung function.

Effectiveness of early budesonide intervention in Caucasian versus Asian patients with asthma: 3-year results of the START study.

Objective And Background: Few studies have assessed the effectiveness of inhaled corticosteroid therapy exclusively in Asian patients with asthma. The present analysis compared the efficacy of early intervention with inhaled budesonide in Caucasian and Asian patients over the first 3 years of the inhaled Steroid Treatment As Regular Therapy in early asthma study.

Methods: Patients aged 5-66 years with mild persistent asthma of View Article and Find Full Text PDF

Murine TLR4 is implicated in cigarette smoke-induced pulmonary inflammation.

Background: Chronic obstructive pulmonary disease (COPD) is associated with an abnormal inflammatory response of the lungs to noxious particles or gases. We investigated whether Toll-like receptor 4 (TLR4) is implicated in cigarette smoke (CS)-induced pulmonary inflammation in a murine model of COPD.

Methods: C3H/HeOuJ (Tlr4(WT)) and C3H/HeJ (Tlr4(defective)) mice were exposed to air or CS for 5 weeks (subacute) and 26 weeks (chronic), and pulmonary inflammation was evaluated.

Role of the tachykinin NK(1) receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea.

Neuroimmune interactions are important in airway diseases such as asthma. We evaluated the role of the tachykinin NK(1) receptor in the contractile response of isolated trachea from tachykinin NK(1) receptor wild type (WT) and knockout (KO) mice, to the antigen ovalbumin and the contractile agonist serotonin (5-hydroxytryptamine). One percent ovalbumin induced contractions of tracheas obtained from ovalbumin-immunized and exposed mice.

Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma.

Study Objectives: Asthmatic patients lose lung function faster than normal subjects. The effectiveness of early intervention with inhaled corticosteroids on this decline in lung function is not established in recent-onset disease.

Design: The Inhaled Steroid Treatment as Regular Therapy in Early Asthma study was a randomized, double-blind study in 7,165 patients (5 to 66 years old), with persistent asthma for < 2 years to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events and the decline in lung function.

Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide.

Background: Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking.

Objective: To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo.

Matrix metalloproteinase-12 and cathepsin D expression in pulmonary macrophages and dendritic cells of cigarette smoke-exposed mice.

An imbalance between proteinases and their inhibitors is believed to play an essential role in the development of chronic obstructive pulmonary disease (COPD) and pulmonary emphysema. COPD is mainly caused by cigarette smoking, and is characterized by an increase in inflammatory cells in small airways and lung parenchyma. We examined the mRNA expression of several proteinases in lungs of mice exposed to cigarette smoke or control air.

Similarities and differences in asthma and chronic obstructive pulmonary disease exacerbations.

There is no generally accepted definition of an exacerbation either for asthma or for chronic obstructive pulmonary disease. There is little consistency among the symptomatic or functional criteria used in different studies. The most consistent criterion is the introduction of systemic corticosteroids for the acute worsening of the disease.

Positioning of glucocorticosteroids in asthma and allergic rhinitis guidelines (versus other therapies).

Asthma and allergic rhinitis are both characterized by airway inflammation, and glucocorticosteroids form the cornerstone of their pharmacologic treatment. All patients with asthma should be prescribed rapid-acting inhaled beta2-agonists as needed to use as rescue therapy in case of symptoms. As soon as patients experience symptoms at least once a week, controller medications should be started on a daily basis to achieve and maintain control of their asthma.

Pharmacokinetic and pharmacodynamic properties of inhaled beclometasone dipropionate delivered via hydrofluoroalkane-containing devices.

Inhaled corticosteroids have a key role in the treatment of asthma and chronic obstructive pulmonary disease. In recent times, beclometasone dipropionate has been reformulated in pressurised metered dose inhalers (pMDIs), using hydrofluoroalkanes (HFAs) as a propellant. Extensive toxicological testing has shown that HFA-propellants are well tolerated.

Short-term cigarette smoke exposure enhances allergic airway inflammation in mice.

Rationale: Epidemiologic studies suggest that tobacco smoke contributes to the prevalence and occurrence of exacerbations in asthma. The effect of active smoking in adolescents with atopy is poorly understood.

Objectives: We developed an experimental model to investigate the influence of smoking on antigen-induced airway inflammation and airway responsiveness in mice that were previously sensitized.

Identification and characterization of human pulmonary dendritic cells.

Dendritic cells (DC) are specialized antigen-presenting cells, linking innate and adaptive immune responses, and thus play an important role in immunologically mediated diseases, including pulmonary diseases such as asthma and respiratory viral infections. Although much is known about the characteristics of lung DC in animal models, very few data concerning human lung DC are available. The goal of our study was to identify and characterize dendritic cells in human lung by preparing single-cell suspensions from surgical resection specimens and subsequent labeling with the recently developed blood dendritic cell antigen (BDCA) markers.

Burden and clinical features of chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality and represents a substantial economic and social burden throughout the world. It is the fifth leading cause of death worldwide and further increases in its prevalence and mortality are expected in the coming decades. The substantial morbidity associated with COPD is often underestimated by health-care providers and patients; likewise, COPD is frequently underdiagnosed and undertreated.

Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.

For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day).

Efficacy of flow- vs impedance-guided autoadjustable continuous positive airway pressure: a randomized cross-over trial.

Study Objectives: Autoadjustable continuous positive airway pressure (CPAP) devices are increasingly used in the treatment of obstructive sleep apnea (OSA). Since different measurements of upper airway obstruction are applied, it is uncertain whether these devices are equally effective in controlling sleep-disordered breathing. Hypothesizing that differences in therapeutic efficacy were to come out, we compared the performance of the AutoSet device (ResMed; Sydney, Australia), which features autoadjustable positive airway pressure (APAP) guided by detection of flow limitation (APAPfl), with the SOMNOsmart device (Weinmann; Hamburg, Germany), which features APAP guided by the forced oscillation technique (APAPfot).

The role of the tachykinin NK1 receptor in airway changes in a mouse model of allergic asthma.

Background: Tachykinins are present in sensory nerves and in nonneuronal cells like macrophages. Human data suggest a role for these peptides in asthma, but the exact role of tachykinins and their receptors in allergic airway inflammation is still a matter of debate.

Objective: The aim of this study was to determine the role of the tachykinin NK1 receptor in allergic airway responses in a mouse model.

Cost-effectiveness analysis of early intervention with budesonide in mild persistent asthma.

Background: The Inhaled Steroid as Regular Therapy in Early Asthma (START) study reported that early intervention with budesonide in mild persistent asthma reduces severe asthmatic events and improves symptom outcomes and lung function in adults and children.

Objective: We sought to estimate the incremental cost-effectiveness of early intervention with budesonide, as observed within the START study.

Methods: START was a randomized, 3-year controlled trial of budesonide in early onset mild asthma among 7165 subjects ages 5 to 66 years.

Comfort and pressure profiles of two auto-adjustable positive airway pressure devices: a technical report.

Study Objectives: The purpose of this study was to compare comfort parameters and pressure profiles of the AutoSet (Resmed) and the SOMNOsmart (Weinmann), two auto-adjustable positive airway pressure (APAP) devices.

Setting: The sleep disorders center of a university hospital.

Design: A single-blind randomized trial protocol was applied.

The role of neural inflammation in asthma and chronic obstructive pulmonary disease.

The tachykinins substance P and neurokinin A are found within airway nerves and immune cells. They have various effects on the airways that can contribute to the changes observed in asthma and chronic obstructive pulmonary disease. Both tachykinin NK(1) and NK(2) receptors have been involved in the bronchoconstriction and the proinflammatory changes induced by substance P and neurokinin A.

Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial.

Background: Although inhaled glucocorticosteroids are recommended for persistent asthma, their long-term effect on recent onset, mild, persistent asthma has yet to be established.

Methods: We did a randomised, double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids. Patients aged 5-66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications.