Anticholinergika in der Therapie der chronisch-obstruktiven Lungenerkrankung (COPD)

Die chronisch-obstruktive Lungenerkrankung (COPD) stellt weltweit einen der wichtigsten Morbiditats- und Mortalitatsfaktoren dar. Der Erkrankung liegt in der uberwiegenden Mehrzahl der Falle ein jahrelanger Nikotinabusus zugrunde. Anders als beim Asthma bronchiale ist bei den Patienten mit COPD neben der Hypersekretion submuskuloser Drusen insbesondere die Erhohung des Bronchialmuskeltonus durch cholinerge Mechanismen eine dominierende Komponente der Bronchialobstruktion. Anticholinergika sind daher Mittel der ersten Wahl fur die Therapie der Bronchialobstruktion bei COPD. Anticholinergika verbessern neben der Lungenfunktion gleichermasen die Belastungstoleranz sowie Lebens- und Schlafquali…

Wirksamkeit und Verträglichkeit einer festen Kombination von Salmeterol (50 μg)/Fluticason (250 μg) in einem einzigen Inhalationssystem (Diskus®) bei Patienten mit leicht- bis mittelgradigem Asthma bronchiale

BACKGROUND Inhaled corticosteroids and long-acting beta-agonists are first-line agents for the treatment of patients with persisting bronchial asthma. Several lines of evidence have shown, that inhaled corticosteroids and long-acting beta-agonist have multiple synergisms both in vivo and in vitro, leading to improved clinical asthma control. METHODS A prospective, open, multi-centre study was performed to evaluate the efficacy and safety of a fixed combination of inhaled Fluticasone (250 microgram BID) and Salmeterol (50 microgram BID) in a single inhaler device (Diskus). 3345 patients (48 % male, mean age 52 years, range 17 - 90 years) with mild to moderate asthma were treated over a perio…

Tiotropium - ein langwirksames, inhalatives Anticholinergikum zur Therapie der chronisch-obstruktiven Lungenerkrankung (COPD)

Anticholinergics are agents of first choice for the symptomatic treatment of patients with COPD. Tiotropium (Ba 679 BR, Spiriva) is a long-acting inhaled anticholinergic designed for once-daily bronchodilator treatment of COPD. Tiotropium is a selective antagonist of pulmonary M1 and M3 muscarinic receptor subtypes, that produces a long-lasting (24 hours), dose-dependent bronchodilation and bronchoprotection against constrictive stimuli, e. g. methacholine, following inhalation of single doses. Clinical trials with tiotropium in COPD patients over a maximum treatment duration of one year have confirmed a persisting bronchodilator effect of tiotropium compared with placebo and ipratropium, a…

Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: The BRIGHT study

Summary Introduction QVA149 is a novel, inhaled, once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β 2 -agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the effects of QVA149 on exercise tolerance, hyperinflation, lung function and lung volumes versus placebo and tiotropium. Methods Patients with moderate-to-severe COPD were randomized to QVA149 110/50 μg, placebo or tiotropium 18 μg once daily in a blinded, 3-period crossover study for 3 weeks. The primary endpoint was exercise endurance time at Day 21 for QVA149 versus placebo. R…

Oberer und unterer Respirationstrakt (V 39–V 44)

Cigarette Smoking, But Not Sensitization toAlternaria, Is Associated with Severe Asthma in Urban Patients

Hereditary susceptibility and allergen exposure have been identified as general risk factors for asthma. However, risk factors for severe asthma still remain to be identified. To further assess and quantify risk factors associated with severe asthma in adult patients apart from clinical exacerbations, 306 randomly selected subjects (mean age 40+/-17 years, 46% males) presenting to an inner city pulmonary practice between 1995 and 1996 were retrospectively investigated. Of these, 117 patients were atopic, 112 had current asthma, and 22 asthmatics had severe asthma. Risk factors associated with atopy were family history of atopy and any domestic pet ownership (OR: 3.1, 95% CI: 1.64-6.1). Asth…

Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals.

Elevated serum immunoglobulin (Ig)E is the hallmark of atopy, and contributes to asthma and bronchial hyperresponsiveness in atopic individuals. In contrast, the significance of IgE in nonallergic subjects is less clear. The aim of the present study is to clarify a potential association of IgE and asthma in absence of clinical allergy. To this purpose 1,219 consecutive patients of a pulmonary practice were evaluated. Nonallergic patients were defined by negative skin prick test, history of atopy and specific IgE, 509 subjects (42%) were nonallergic. Among these, 80 patients (16%) had elevated total IgE levels (150 U x mL(-1)). Prevalence and severity of asthma in nonallergic subjects with I…

Bodyplethysmographischer Wirkeintritt von Formoterol bei Patienten mit mittel- bis schwergradiger partiell reversibler Atemwegsobstruktion

BACKGROUND Formoterol is a long acting beta2-agonist used for the treatment of obstructive airway diseases. Compared with Salmeterol, Formoterol has a rapid onset of bronchodilation. There are only scant data regarding the comparative onset of action using bodyplethysmography in moderate to severely obstructive patients. METHODS In a mono-center, single-blinded parallel group study 60 patients (age: 61.9 +/- 12.8 years, 65 % male) with moderate to severe (mean FEV(1) 40.6 +/- 15.3 % of predicted), partially reversible (FEV(1) post bronchodilator > 15 % from baseline) airway obstruction were treated with either formoterol 12 microg bid or salmeterol 50 microg bid over a period of two weeks. …

Improvement in quality of life with omalizumab in patients with severe allergic asthma.

Patients with severe persistent asthma experience daily symptoms and frequent serious exacerbations that contribute to a significant impairment of health-related quality of life (QoL).A pooled analysis was completed of six controlled clinical trials that evaluated the effect of add-on omalizumab on asthma-related QoL in patients with severe persistent allergic (IgE-mediated) asthma. Asthma-related QoL was assessed at baseline and treatment endpoint using the well-validated Juniper Asthma Quality of Life Questionnaire (AQLQ). Change from baseline in AQLQ total score was compared between treatments using analysis of covariance methods. The percentage of patients who achieved a clinically mean…

Photobiologie und klinische Immunologie (V 66–V 70)

Baseline Characteristics According To Gender In A Large Exacerbations Trial

P191 QVA149 once daily improves exercise tolerance and lung function in patients with moderate to severe COPD: the BRIGHT study: Abstract P191 Table 1

Introduction QVA149 is a novel once-daily fixed-dose combination of the long-acting β 2 -agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237) in development for the treatment of chronic obstructive pulmonary disease (COPD). The BRIGHT study evaluated the effects of QVA149 versus placebo and tiotropium on exercise tolerance and lung function in patients with moderate-to-severe COPD. Methods In a double-blind, double-dummy, 3-period crossover study, patients with moderate-to-severe COPD were randomised to QVA149 110/50 µg, placebo or tiotropium 18 µg once daily for 3 weeks. The primary endpoint was exercise endurance time for QVA149 versus placebo during a sub…

Glutathione deficiency of the lower respiratory tract in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology. Increased oxidant burden and antioxidant, e.g. glutathione (GSH), deficiency in the lower respiratory tract have been thought to play a role in the progression of IPF. Sputum induction is a safe noninvasive tool to study inflammation in the respiratory tract. The aim of the present study was to evaluate the direct measurement of GSH in induced sputum supernatant. Sixteen IPF patients and 15 healthy, nonsmoking subjects underwent sputum induction. Total GSH in sputum, saliva and plasma was measured spectrophotometrically. Sputum GSH was decreased more then four-fold in IPF patients when compared to healthy subjects (mean …

24-h efficacy and pharmacokinetics of tiotropium Respimat® 5 μg in patients with asthma

Background: Once-daily tiotropium Respimat® (tioR) add-on therapy has demonstrated efficacy in patients with moderate symptomatic asthma. Aim and Objectives: To investigate whether dosing regimen (QD vs BID) affected 24-h bronchodilator efficacy and exposure of tioR. Methods: 2 randomised, double-blind, crossover trials (trial 1, NCT01152450 [placebo-controlled]; trial 2, NCT01696071); 4-week treatments of tioR 5 µg QD, 2.5 µg BID and placebo Respimat® (pboR) added to medium-dose ICS (400-800 µg budesonide or equivalent). Primary end point (Week 4): area under the curve response for FEV1 (FEV1 AUC(0-24h)) (trial 1, tioR vs pboR; trial 2, QD vs BID). Pharmacokinetic end points (steady state)…

Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?

Small cell lung cancer (SCLC) is usually classified into a two-stage system, limited (LD) and extensive disease (ED). However, the criteria for these two categories remain controversial. The widely used Veterans Administration Lung Study Group (VALG) definition of LD includes patients with primary tumor and nodal involvement limited to one hemithorax. In contrast, the International Association for the Study of Lung Cancer (IASLC) recommends that LD should additionally include all patients without distant metastasis. As a consequence, since treatment modalities for LD and ED could be different, individual clinical outcome of SCLC patients may be influenced by the staging system chosen. Among…

Tiotropium Respimat® in asthma: a double-blind, randomised, dose-ranging study in adult patients with moderate asthma

Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat® SoftMist™ inhaler (tiotropium Respimat®) significantly reduces the risk of severe exacerbations and improves lung function in patients with severe persistent asthma that is not fully controlled despite using inhaled corticosteroids (ICS) and long-acting β2-agonists. To further explore the dose–response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat® as add-on to ICS in symptomatic patients with moderate persistent asthma. In this randomised, double-blind, placebo-controlled, four-way crossover study, patients were randomised to tiotro…