Abstract:
OBJECTIVES:Pharmacologically mediated bronchodilation is important in the management of asthma, and is primarily achieved with β₂-agonists. Novel compounds should preferably have a longer duration of action and a better systemic side effect profile than established alternatives at comparable peak bronchodilation. This single-dose crossover study was conducted to investigate and compare with formoterol the bronchodilatory and systemic effects, tolerability and safety of AZD3199, a novel ultra-long-acting β₂-agonist (uLABA). METHODS:Patients with asthma (n = 37) were randomized to receive AZD3199 (120, 480, 1920 µg), formoterol (9, 36 µg) or placebo inhaled via a Turbuhaler™. Bronchodilation was evaluated by maximum (E(max)) and average 22-26 h (E₂₂₋₂₆) forced expiratory volume in 1 second (FEV1). Serum potassium was evaluated by minimum (E(min)) and 0-4 h average (E(av)) determined from serial measurements. AZD3199 and formoterol were compared on the basis of relative dose potency. Adverse events, clinical laboratory tests and physical examinations were markers for safety and tolerability, with plasma AZD3199 as the indicator of drug exposure. RESULTS:All active treatments dose-dependently increased E(max) and AZD3199 (480 and 1920 µg) and formoterol (36 µg) significantly increased E(₂₂₋₂₆) versus placebo. Relative dose potency between AZD3199 and formoterol was 50-fold on the microgram scale with respect to E max and 11-fold with respect to E(₂₂₋₂₆). Small, dose-dependent effects on potassium, heart rate and QTc were seen after administration of AZD3199 compared with placebo. These well-known dose-related class effects of β₂-agonists were mild. Notably, serum potassium suppression was less pronounced after AZD3199 compared with formoterol at similar bronchodilation. Overall, AZD3199 was well tolerated. CONCLUSIONS:AZD3199 480 µg and 1920 µg produced 24-hour bronchodilation. At comparable peak bronchodilator effect, AZD3199 was associated with a lower level of systemic side effects than formoterol. AZD3199 was well tolerated, with no safety concerns identified to preclude further investigation. ClinicalTrials.gov study identifier: NCT00736489.
journal_name
Ther Adv Respir Disjournal_title
Therapeutic advances in respiratory diseaseauthors
Bjermer L,Rosenborg J,Bengtsson T,Lötvall Jdoi
10.1177/1753465813497527subject
Has Abstractpub_date
2013-10-01 00:00:00pages
264-71issue
5eissn
1753-4658issn
1753-4666pii
1753465813497527journal_volume
7pub_type
杂志文章,多中心研究,随机对照试验abstract::Immunotherapy has significantly altered the treatment landscape for many cancers, including non-small cell lung cancer (NSCLC). Currently approved immuno-oncology agents for lung cancer are aimed at the reversal of immune checkpoints, programmed death protein-1 (PD-1) and programmed death ligand-1 (PD-L1). Although re...
journal_title:Therapeutic advances in respiratory disease
pub_type: 杂志文章,评审
doi:10.1177/1753466618794133
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abstract::Pregnancy may be complicated by new onset or preexisting asthma. This article reviews the recognition and management of asthma during pregnancy, as well as general principles of asthma medication use during pregnancy. ...
journal_title:Therapeutic advances in respiratory disease
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abstract::Maintenance pharmacological treatment for stable chronic obstructive pulmonary disease (COPD) is based on inhaled drugs, including long-acting muscarinic receptor antagonists (LAMA), long-acting β2-adrenoceptor agonists (LABA) and inhaled corticosteroids (ICS). Inhaled pharmacological treatment can improve patients' d...
journal_title:Therapeutic advances in respiratory disease
pub_type: 杂志文章,评审
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abstract:OBJECTIVE:Severe exacerbations in alpha-1-antitrypsin (AAT)-deficient patients with chronic obstructive pulmonary disease (COPD) and/or emphysema are a major cause of hospitalization. A multicentre, observational, retrospective study was undertaken to evaluate the effect of continuous AAT augmentation therapy in reduci...
journal_title:Therapeutic advances in respiratory disease
pub_type: 杂志文章,多中心研究
doi:10.1177/1753465812438387
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abstract::Fluoroquinolones are commonly used to treat lung infections in patients with cystic fibrosis. These patients are susceptible to lung infection with common bacteria such as Staphylococcus aureus and Haemophilus influenzae, but are also prone to infection by opportunistic bacteria, including Pseudomonas aeruginosa. The ...
journal_title:Therapeutic advances in respiratory disease
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abstract::Angiogenesis is a driving force of a tumor's development. Targeting this process is an attractive option, as this is a feature shared by most of the solid tumors. A lot of antiangiogenic drugs have been developed following this path, including bevacizumab, sorafenib, sunitinib, vandetanib, ramucirumab, motesanib and m...
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abstract::The issue of electronic cigarettes is one of the most controversial topics in public health. There is intense debate and dividing opinions about their use patterns, health effects and association with smoking. This is expected since they were only recently introduced to the market and they refer to a harm-reduction ap...
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abstract:BACKGROUND:Proper adjustment of arterial oxygen saturation (SaO2) during daily activities in patients with interstitial lung disease (ILD) requiring long-term oxygen therapy is challenging. Given the multifactorial nature of the limited exercise tolerance in patients with ILDs, the isolated use of oxygen therapy may no...
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journal_title:Therapeutic advances in respiratory disease
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abstract:AIMS:The Cough Severity Diary (CSD) was developed in accordance with the FDA guidance for patient-reported outcome measures and is focused on capturing the patient's perception of cough in terms of frequency, intensity, and disruption due to their cough. The measure includes a series of seven items asking patients to r...
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abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease (ILD). Currently, two antifibrotic drugs are available for reducing forced vital capacity (FVC) decline in IPF. However, many pulmonologists wait before initiating treatment, especially when IPF patients have stable dise...
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abstract::A major impediment in the development of novel drugs for chronic obstructive pulmonary disease (COPD) has been the scarcity of a well-validated, robust, and easily obtainable intermediate end point such as serum biomarkers. To date the best serum biomarkers in COPD have been non-speci"c pro-in"ammatory molecules synth...
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pub_type: 杂志文章,评审
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abstract:BACKGROUND:Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) therapy has been approved for sepsis-associated acute respiratory distress syndrome, but its efficacy for other rapidly progressive interstitial pneumonias (RPIPs) is unclear. The purpose of this study was to examine the efficacy of PM...
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journal_title:Therapeutic advances in respiratory disease
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journal_title:Therapeutic advances in respiratory disease
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journal_title:Therapeutic advances in respiratory disease
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abstract:BACKGROUND:Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is well known as a life-threatening condition during its clinical course. However, the clinical features and prognosis in AE of unclassifiable idiopathic interstitial pneumonia (AE-UCIIP) remain to be elucidated. The aim of this study was to clarif...
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abstract:BACKGROUND:Endoscopic lung volume reduction coil (LVRC) treatment is a therapeutic option for selected patients with advanced emphysema. The effects and the safety of endoscopic lung volume reduction in patients with very low forced expired volume in one second (FEV1) remain to be determined. This study was conducted t...
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abstract:BACKGROUND:Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in patients with cystic fibrosis (CF). Tobramycin nebulization is used for the eradication of Pa infection. Nowadays, tobramycin dry powder inhalation (DPI) is available as well. This study reports the results of eradicating Pa with tobramycin...
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abstract::Avoidance of allergens in the treatment of asthma has hitherto not achieved significant benefit despite the strong evidence that allergy both increases severity and contributes to exacerbations of asthma. House dust mite, cat and dog allergens are the most common perennial allergic triggers and most avoidance strategi...
journal_title:Therapeutic advances in respiratory disease
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abstract:BACKGROUND:N-chlorotaurine (NCT), a long-lived oxidant produced by human leukocytes, can be synthesized chemically and used topically as a well-tolerated antiseptic to different body regions including sensitive ones. The aim of this study was to test the tolerability of inhaled 1% NCT in aqueous solution upon repeated ...
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abstract:OBJECTIVES:Both autofluorescence imaging bronchoscopy and narrow-band imaging have shown promise in the detection of premalignant airway lesions, each by utilizing different bandwidths of lights for better characterization of the mucosal and submucosal vascular grid. Since previously published meta-analyses have shown ...
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pub_type: 杂志文章,meta分析
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abstract:OBJECTIVES:To describe the health-related quality of life (HRQL) in a cohort of COPD patients recruited in primary care and identify the variables of the patients and the treatment associated with impaired HRQL. METHOD:Multicenter, observational study of patients with COPD recruited in Primary Care centers. Data regar...
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pub_type: 杂志文章,多中心研究
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更新日期:2007-12-01 00:00:00