Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma.

The Global Initiative for Asthma (GINA) guidelines aim at improving asthma control and preventing future risk. For patients with moderate to severe asthma an inhaled corticosteroid (ICS) or an ICS/long-acting beta2-agonist (LABA) combination with a short-acting beta2-agonist (SABA) as reliever is recommended. Despite the availability of effective maintenance therapies, a large proportion of patients still fail to achieve guideline-defined asthma control, and overuse of SABA reliever medication at the expense of ICS is commonly observed. New simplified treatment approaches may offer a solution and assist physicians to achieve overall asthma control. One such treatment approach, which is reco…

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…

Triple therapy de-escalation to dual bronchodilation in COPD patients: Baseline data from the DACCORD cohort

Background: GOLD recommends triple therapy only in COPD patients with frequent exacerbations despite long-acting bronchodilators who exhibit a high blood eosinophil level (≥300/μL). Indication for ICS containing therapy should be reassessed regularly. Methods: The German real life study DACCORD included COPD patients who had received free triple therapy for ≥ 6 months prior to study entry. At baseline, patients were switched to LABA+LAMA fixed-dose combination (FDC) or maintained triple therapy upon discretion of the treating physician. Here, we compare baseline data of the 2 groups. Results: 1182 patients were recruited into DACCORD of which 30.7% were moved to LABA+LAMA FDC. Patients in t…

Free Serum IgE In Patients With Severe Allergic Asthma Treated With Omalizumab

Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies. This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines. Pooled data from duplicate, Phase III, reslizumab versus placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL−1) were stratified by baseline therapy. Efficacy assessments were exacerbation rates and changes from baseline forced expiratory volume in …

Viral Components Enhance Antigen Presentation And Induce Sensitization Towards Harmless Inhaled Antigens

GOLD 2017 treatment pathways in ‘real life’: An analysis of the DACCORD observational study

Abstract Introduction The 2017 update to the Global Initiative for Obstructive Lung Disease (GOLD) strategy document includes recommendations for treatment intensification or step-down in chronic obstructive pulmonary disease (COPD), although recognises that limited supporting information is available. DACCORD is an ongoing observational, non-interventional study, recruiting patients following COPD maintenance treatment change or initiation, a subset of whom were receiving a long-acting β2-agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) on entry. Since there were no requirements in terms of prior medication (and no washout before commencing LABA/L…

β-Blockers in COPD

Background Cardiovascular disease is a frequent comorbidity in patients with COPD. Many physicians, particularly pulmonologists, are reluctant to use β-adrenoceptor blocking agents (β-blockers) in patients with COPD, despite their proven effectiveness in preventing cardiovascular events. Methods The large (5,162 patients) phase III TONADO 1 and 2 studies assessed lung function and patient-reported outcomes in patients with moderate to very severe COPD receiving long-acting bronchodilator treatment across 1 year. This post hoc analysis characterized lung-function changes, patient-reported outcomes, and safety in the subgroup of patients receiving β-blockers in the studies. Results In total, …

THE INHIBITORY EFFECT OF THE PLANT KALANCHOE PINNATA AND ITS FLAVONOID QUERCETIN ON AIRWAY HYPERRESPOSIVENESS

Monitoring free serum IgE in severe asthma patients treated with omalizumab

SummaryBackgroundBenefit of treatment with the monoclonal anti-IgE-antibody omalizumab in severe IgE-dependent asthma requires a significant reduction of serum free IgE concentrations. It is unclear if monitoring free serum IgE is clinically meaningful once omalizumab treatment is initiated.MethodsFree IgE and omalizumab serum concentrations were quantified in 22 patients with severe asthma (68% female, 47 ± 11 yrs, mean (±SD) pre-bronchodilator FEV1 62 ± 13%, baseline mean (±SEM) free serum IgE 652 ± 136 ng/ml) treated with omalizumab for 4 months using a Recovery-ELISA.ResultsOmalizumab treatment reduced free serum IgE prior to the second omalizumab injection by 73%, after 16 weeks by 81%…

Treatment Initiation in Therapy-Naive COPD Patients: An Analysis of the German Real-Life Daccord Register

Lithium Chloride Affects The Development Of Allergic Airway Disease

Omalizumab reduces oral corticosteroid use in patients with severe allergic asthma: Real-life data

SummaryBackgroundLong-term oral corticosteroid (OCS) therapy is associated with significant burden on patients and healthcare resources; treatments that may help reduce their use are important to improve asthma management.MethodsFrench and German clinicians prescribing omalizumab for >16 weeks to patients with severe persistent allergic asthma collected OCS use data. OCS use was recorded at baseline and at a non-specific time point beyond 16 weeks from initiation of omalizumab. The number of asthma exacerbations (FEV1 16 weeks. Of these, 166 (48.0%) were receiving maintenance OCS (France, n = 64; Germany, n = 102). Following omalizumab therapy, 84 (50.6%) patients on OCS at baseline reduced…

Disease-Modifikation und Dauer einer Omalizumab-Therapie bei Patienten mit schwerem allergischen Asthma

Hintergrund und Methodik: Omalizumab ist ein monoklonaler Anti-IgE-Antikorper zur Behandlung des schweren allergischen Asthma bronchiale. Ziel dieser Arbeit war die Bewertung der vorhandenen Evidenz durch ein Expertengremium und die Formulierung daraus resultierender Empfehlungen zu moglichen krankheitsmodifizierenden Effekten und der Dauer der Behandlung mit Omalizumab. Ergebnisse: Eine direkte oder indirekte Interaktion zwischen Omalizumab und der IgE-Produktion ist wahrscheinlich. Die aufgrund eines pharmakokinetisch-pharmakodynamischen Modells erwarteten IgE-modulierenden Eigenschaften von Omalizumab werden derzeit in der klinischen Anwendung uberpruft. Therapieentscheidungen auf Grundl…

Inhaled steroids and prevalence of osteoporosis in chronic obstructive pulmonary disease: Data from the DACCORD cohort

Introduction: Osteoporosis is a frequent COPD comorbidity with age, female gender, smoking, immobility and the use of oral steroids (OCS) as common risk factors. The role of inhaled steroids (ICS) is still under debate. Methods: Baseline data from the real life cohort DACCORD were analyzed. The diagnosis of osteoporosis was based on patients’ reports of physician-based diagnoses. Associations of ICS exposure at time of inclusion and osteoporosis were examined by group comparisons and multivariable logistic regression analyses with age, gender, smoking, exacerbation history (EH) and FEV1% as covariates. To avoid interactions with other steroid containing medications, exposure to any corticos…

Dual bronchodilation vs triple therapy in the “real-life” COPD DACCORD study

Roland Buhl,1 Carl-Peter Criée,2 Peter Kardos,3 Claus F Vogelmeier,4 Konstantinos Kostikas,5 Nadine S Lossi,6 Heinrich Worth7 1Pulmonary Department, Mainz University Hospital, Mainz, 2Department of Sleep and Respiratory Medicine, Evangelical Hospital Goettingen-Weende, Bovenden, 3Group Practice and Centre for Allergy, Respiratory and Sleep Medicine, Red Cross Maingau Hospital, Frankfurt am Main, 4Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany; 5WorldWide Medical Affairs Respiratory, Novartis Pharma AG, Basel, Switzerland;…

Cytokine Production Profile Of T-lymphocytes In Patients With Allergic Asthma Receiving Anti-IgE Therapy

Reslizumab (RES) in asthma patients (pts) with severe eosinophilic asthma stratified by GINA asthma steps 4 and 5: Analysis of two phase 3, placebo (PBO)-controlled trials

Background: RES reduced exacerbation frequency and improved lung function and asthma control in pts with inadequately controlled asthma and elevated blood eosinophils (EOS) in two PBO-controlled, phase 3 trials (Castro et al. Lancet Resp Med 2015). Aims/objectives: To determine the efficacy of RES in asthma pts stratified by GINA Step 4 (G4) and Step 5 (G5) categories of asthma severity. Methods: Pooled data from two 52-week, PBO-controlled trials of RES (3mg/kg IV Q4W) in pts with inadequately controlled asthma and blood EOS ≥400/µL on inhaled corticosteroid (ICS) ± another controller; primary results have been reported. Current analysis includes pts stratified by G4 (medium/high-dose ICS …

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…

Once-daily QVA149 improves dyspnoea and health status compared with tiotropium plus formoterol in patients without ICS use: A post-hoc analysis of the QUANTIFY study

Rationale: The QUANTIFY study compared the approved dual bronchodilator QVA149 with the free-dose combination of tiotropium plus formoterol (TIO+FOR) regarding lung function, dyspnoea and health status in patients with moderate-to-severe COPD. This post-hoc analysis reported on the subgroup of pts without ICS background therapy. Methods: This blinded, triple-dummy 26-week study randomised patients to QVA149 110/50 µg OD or TIO 18 µg OD plus FOR 12 µg b.i.d. (1:1). ICS was allowed as background therapy. Endpoints included lung function (trough FEV1), dyspnoea (TDI) and health status (COPD Assessment Test, CAT). Results: Of the 934 pts randomised (QVA149 [N=476] or TIO+FOR [N=458]); 87.9% com…

Local oropharyngeal side effects of inhaled corticosteroids in patients with asthma.

The widespread use of inhaled corticosteroids (ICS) for the treatment of persistent asthma, although highly effective, may be associated with both systemic and local side effects. Systemic side effects of ICS have been extensively studied. In contrast, relatively few studies have been performed to specifically evaluate local side effects of ICS. These local side effects--including oropharyngeal candidiasis, dysphonia, pharyngitis, and cough--are generally viewed as minor complications of therapy. However, they can be clinically significant, affect patient quality of life, hinder compliance with therapy, and mask symptoms of more serious disease. Local side effects result from deposition of …

Prospective evaluation of current asthma control using ACQ and ACT compared with GINA criteria

Background The goal of asthma treatment is to achieve and maintain current best control and reduce future risk of exacerbations and long-term morbidity. Objective To prospectively compare current asthma control as defined by ACQ (asthma control questionnaire) and ACT (asthma control test) criteria with the GINA (Global Initiative for Asthma) classification in treated patients in a real-life setting. Methods In 150 adult patients (48% male, age 46.3 ± 14.4 years., forced expiratory volume in 1 second [FEV 1 ], 2.3 ± 0.9 L or 78.5 ± 21.8% pred.), asthma control was evaluated using the GINA classification as the "true" and ACQ-7, ACQ-5, and ACT as "predictor" criteria. The relationship between…

European Real-Life Experience Of Omalizumab (Xolair) And Maintenance Oral Corticosteroid Use In Patients With Severe Persistent Allergic Asthma

Th1-induced Allergic Airway Disease Is More Susceptible To NTreg-mediated Suppression In Contrast ToTh2 Responses

Efficacy and safety of indacaterol and tiotropium in COPD patients according to dyspnoea severity.

Background Guidelines for chronic obstructive pulmonary disease (COPD) recommend that treatment choices be based partly on symptoms. Methods A post-hoc analysis of pooled data from clinical studies compared the efficacy and safety of once-daily inhaled bronchodilators indacaterol (150 and 300 μg) and open-label tiotropium (18 μg) according to baseline dyspnoea severity on the modified Medical Research Council (mMRC) scale in patients with COPD (mMRC scores <2 = ‘less dyspnoea’; scores ≥2 = ‘more dyspnoea’). Outcomes were assessed after 26 weeks. Results The analysis included 3177 patients. In patients with less dyspnoea: indacaterol (both doses) improved 24-h post-dose (‘trough’) forced exp…

Regulatory T Cells More Effectively Suppress Th1-Induced Airway Inflammation Compared with Th2

Abstract Asthma is a syndrome with different inflammatory phenotypes. Animal models have shown that, after sensitization and allergen challenge, Th2 and Th1 cells contribute to the development of allergic airway disease. We have previously demonstrated that naturally occurring regulatory T cells (nTregs) can only marginally suppress Th2-induced airway inflammation and airway hyperresponsiveness. In this study, we investigated nTreg-mediated suppression of Th2-induced and Th1-induced acute allergic airway disease. We demonstrate in vivo that nTregs exert their suppressive potency via cAMP transfer on Th2- and Th1-induced airway disease. A comparison of both phenotypes revealed that, despite …

The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update.

SummarySevere persistent asthma causes a substantial morbidity and mortality burden and is frequently inadequately controlled despite intensive guideline-based therapy. Targeting allergic inflammatory processes that underlie the pathogenesis of severe persistent asthma improves asthma control in a significant proportion of patients. Omalizumab, a humanized monoclonal anti-immunoglobulin E (IgE) antibody, has been developed to target IgE, which is central to triggering and maintaining allergic airway inflammation. In a comprehensive program of clinical trials, omalizumab has been shown to reduce asthma exacerbation and emergency visit rates, and to improve quality of life in patients with se…

Individual and Synergistic Effects of IL-5 and IL-13 on Trans-Compartmental Activation and Migration of Eosinophils and Murine Asthma Features

GINA 2019: a fundamental change in asthma management

GINA no longer recommends treating adults/adolescents with asthma with short-acting bronchodilators alone. Instead, they should receive symptom-driven (in mild asthma) or a daily corticosteroid-containing inhaler, to reduce risk of severe exacerbations.http://bit.ly/310LLzE

Effect of long-acting β2-agonists olodaterol and formoterol on heart rate and blood pressure in chronic obstructive pulmonary disease patients

Abstract Background Cardiovascular comorbidities are common in chronic obstructive pulmonary disease (COPD), and elevated heart rate reflects increased cardiovascular risk over time, which is associated with unfavourable neurohumoral activation. Long-acting β 2 -agonists (LABAs) are established treatments in COPD, but potentially increase heart rate. We report a post hoc pooled analysis of the effect of olodaterol (5 or 10 μg) or formoterol (12 μg) on heart rate and blood pressure (BP) in Global Initiative for Chronic Obstructive Lung Disease Stage 2–4 COPD patients. Methods Four randomised, double-blind, placebo-controlled, Phase III studies were analysed. Changes in heart rate and systoli…

Change of COPD maintenance medication over two years in a large real life cohort: The DACCORD study

Introduction Database studies suggest a steady intensification of COPD maintenance medication, with the majority of patients eventually receiving a LABA/LAMA/ICS combination. However, such studies include generally only data on medication use. Here, we analysed data from the ongoing, non-interventional, observational DACCORD study to determine whether there was a correlation between baseline GOLD 2011 category and change in medication use over 2 years. Methods This abstract presents data on medication use at baseline and at 1 and 2 years, by baseline GOLD 2011 category (A,B,C and D with symptoms evaluated using the COPD Assessment Test). Results 3315 patients with COPD have completed the 2 …

Indacaterol Once-Daily Reduces COPD Exacerbations over 52 Weeks of Treatment.

Disease Progression in COPD Patients Classified as Gold D According to Gold 2011 or Gold 2017 in the Real-Life Daccord Study

Prospective, Single-Arm, Longitudinal Study of Biomarkers in Real-World Patients with Severe Asthma.

ARIETTA was a prospective, single-arm, noninterventional, multicenter study in patients with severe asthma.To examine the predictive and prognostic abilities of type 2 biomarkers for severe asthma outcomes.Adult patients with severe asthma receiving daily inhaled corticosteroids (fluticasone propionate ≥500 μg or equivalent) and ≥1 second controller medication were enrolled. Biomarker, clinical, and safety data were collected over 52 weeks. The primary endpoint was the asthma exacerbation rate over 52 weeks in serum periostin-high (≥50 ng/mL at baseline) versus periostin-low subgroups (50 ng/mL). Correlations between biomarker levels (periostin, blood eosinophils, IgE, and fractional exhale…

Response to mepolizumab treatment is sustained across 4-weekly dosing periods

Background Mepolizumab (100 mg delivered s.c. every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. However, data on the durability of the response to mepolizumab during dosing periods are limited. The aim of this study was to investigate the efficacy profile in patients with severe eosinophilic asthma over the 4-weekly dosing period for various fixed mepolizumab doses. Methods This was a post hoc analysis of data from the phase IIb/III DREAM study. Patients ≥12 years of age with severe eosinophil…

P254 Once-daily Tiotropium And Olodaterol Fixed-dose Combination Via The Respimat(R) Improves Outcomes Versus Mono-components In Copd In Two 1-year Studies

Introduction Tiotropium (T), a once-daily long-acting muscarinic antagonist, is a well-established first-line maintenance treatment in chronic obstructive pulmonary disease (COPD); olodaterol (O) is a once-daily long-acting β 2 -agonist that has recently gained approval in several countries. Two Phase III replicate pivotal studies assessed the efficacy and safety of fixed-dose combinations of T and O (T+O) delivered via Respimat ® Soft Mist™ inhaler in patients with GOLD 2–4 COPD. Methods Two 52-week, double-blind, parallel-group studies randomised 5162 patients to O 5 µg, T 2.5 µg, T 5 µg, T+O 2.5/5 µg or T+O 5/5 µg. Primary efficacy end points were trough forced expiratory volume in 1 sec…

Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma.

The ability of omalizumab, an anti-immnoglobulin-E agent, to maintain long-term disease control in patients with moderate-to-severe allergic asthma was investigated in a 24-week double-blind extension to a 28-week core trial. During the extension, 483 of the initial 546 patients were maintained on randomised treatment and the lowest sustainable dose of beclomethasone dipropionate (BDP) as established during the steroid-reduction phase of the core trial. The use of concomitant asthma medication was permitted and investigators were allowed to adjust the BDP dose or switch patients from BDP to other asthma medications if deemed necessary. More omalizumab-treated patients (33.5%) than placebo-t…

New horizons in early stage COPD--improving knowledge, detection and treatment.

SummaryEarly stage COPD carries a significant healthcare burden that is currently underrecognised, underdiagnosed and undertreated. Furthermore, patients at this stage can rapidly decline to advanced disease, especially if they continue to smoke. The natural history of the disease in early stages remains largely unknown, and emerging evidence indicates that we are able to reduce lung function decline and exacerbations, and improve quality of life, in early stage COPD, mainly through smoking cessation. But new evidence from randomised clinical trials also suggests an impact of pharmacotherapy on clinical outcomes in early disease. Guidelines need to be updated to reflect this greater underst…

GARP inhibits allergic airway inflammation in a humanized mouse model

Background Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. Methods To analyze the therapeutic effects of sGARP, adult NOD/Scidγc−/− (NSG) mice received peripheral blood mononuclear cells (PBMC) …

Patients with allergic and eosinophilic asthma in the German severe asthma registry

Targeted treatment strategies for asthma require a precise diagnosis of phenotypes. 308 adult patients (age mean±SD: 50.3±13.5yrs) with severe asthma from the German Severe Asthma Registry (www.german-asthma-net.de) were evaluated based on history of allergy symptoms, results of skin prick tests, total/specific IgE, and blood cell differentials. 121 patients (39%) showed typical signs of allergic asthma including allergic symptoms and a positive skin prick test and/or specific IgE with no elevated blood eosinophils (median total IgE: 222 (range 4-4023) IU/ml, eosinophils: 128 (0-295)/µl, FeNO: 23 (7-300) ppb). 53 (43.8%) of these patients were treated with omalizumab. 50 patients (16%) had …

P120 Real life distribution of COPD severity in the German DACCORD registry: Lung function is the main driver of classification in GOLD group C and D

Introduction Currently there is limited real-life data available regarding the distribution of COPD patients using the GOLD 2011 criteria. The German DACCORD registry that collects data from a large ‘real life’ population sample was used to categorise COPD patients according to GOLD 2011. Methods To be eligible for entry into DACCORD, all patients had to have a diagnosis of COPD (consistent with the German Disease Management Programme definition), and, prior to entry, had to have either newly initiated bronchodilator maintenance medication, or to have a bronchodilator added to their maintenance regimen. No other inclusion criteria were applied, and the only exclusion criterion was a diagnos…

New developments in optimizing bronchodilator treatment of COPD: a focus on glycopyrrolate/formoterol combination formulated by co-suspension delivery technology

COPD causes considerable health and economic burden worldwide, with incidence of the disease expected to continue to rise. Inhaled bronchodilators, such as long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs), are central to the maintenance treatment of patients with COPD. Clinical studies have demonstrated that combined LAMA + LABA therapies improve efficacy while retaining a safety profile similar to LAMA or LABA alone. This has led to the development of several LAMA/LABA fixed-dose combination (FDC) therapies, which provide patients with the convenience of two active compounds in a single inhaler. GFF MDI (Bevespi Aerosphere®) is an FDC of glycopyrrolate/formote…

A Guideline-based Survey Of COPD Management Of Pneumologists In Germany

Effectiveness of omalizumab in patients 50 years and older with severe persistent allergic asthma.

Omalizumab is approved for the treatment of severe allergic asthma.To compare the efficacy of omalizumab therapy in patients 50 years or older with patients younger than 50 years.Between November 2005 and November 2007 a total of 174 asthma patients 50 years or older (40.7% male, 51.1% taking oral corticosteroids, and mean [SD] serum IgE level of 315 [353] U/L) and 297 asthma patients younger than 50 years (40.0% male, 50.5% taking oral corticosteroids, and mean [SD] serum IgE level of 363 [431] U/L) who met the European Union criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab for 4 months as part of 2 postmarketing surveillance trials.Compared with the pre…

Indoor air pollutants stimulate interleukin-8-specific mRNA expression and protein secretion of alveolar macrophages.

Indoor air pollutants may cause inflammatory changes of the airways and adjacent pulmonary tissue. After phagocytosis of inhaled particles alveolar macrophages (AM) release chemotactic mediators capable of attracting inflammatory cells into the lung tissue. To evaluate these mechanisms further peripheral blood mononuclear cells (PBMNC) and human AM (freshly recovered from the lower respiratory tract) were exposed to the indoor particles Soot FR 101 and Printex 90, the asbestos fiber Chrysotile B, and titanium dioxide (TiO2) at concentrations of 10 or 50 microg/10(6) cells for up to 8 h. The migration of granulocytes into the conditioned supernatants of AM and PBMNC was quantified by chemota…

Long-Term Safety of Tiotropium/Olodaterol Respimat in Patients with Moderate-to-Very Severe COPD and Renal Impairment in the TONADO Studies

Development of the International Severe Asthma Registry (ISAR): A Modified Delphi Study

BACKGROUND: The lack of centralised data on severe asthma has resulted in a scarcity of information about the disease and its management. The development of a common data collection tool for the International Severe Asthma Registry (ISAR) will enable standardised data collection, subsequently enabling data interoperability.OBJECTIVES: To create a standardised list of variables for the first international registry for severe asthma via expert consensus.METHODS: A modified Delphi process was used to reach consensus on a minimum set of variables to capture in ISAR: the core variables. The Delphi panel brought together 27 international experts in the field of severe asthma research. The process…

Overall asthma control: the relationship between current control and future risk.

Background Asthma guidelines emphasize both maintaining current control and reducing future risk, but the relationship between these 2 targets is not well understood. Objective This retrospective analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler ∗ ∗Symbicort SMART and Turbuhaler are trademarks owned by AstraZeneca. Neither the Symbicort SMART posology nor the dry powder formulation Turbuhaler are currently approved in the United States.) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations. Methods The perc…

Initiation of Mono vs. Dual Bronchodilation in the Therapy-Naive COPD Patient in the German Daccord Cohort

Coincident airway exposure to low-potency allergen and cytomegalovirus sensitizes for allergic airway disease by viral activation of migratory dendritic cells

Despite a broad cell-type tropism, cytomegalovirus (CMV) is an evidentially pulmonary pathogen. Predilection for the lungs is of medical relevance in immunocompromised recipients of hematopoietic cell transplantation, in whom interstitial CMV pneumonia is a frequent and, if left untreated, fatal clinical manifestation of human CMV infection. A conceivable contribution of CMV to airway diseases of other etiology is an issue that so far attracted little medical attention. As the route of primary CMV infection upon host-to-host transmission in early childhood involves airway mucosa, coincidence of CMV airway infection and exposure to airborne environmental antigens is almost unavoidable. For i…

Reduction Of Pulmonary Inflammation Through HIV-1 Envelope Protein GP120 In A Humanized Mouse Model Of Allergic Asthma Depends On Regulatory T Cells

P296 Effect of tiotropium/olodaterol therapy on copd exacerbations in the tonado® studies

Rationale The lung-function efficacy, symptomatic benefits and safety of combined tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, for the treatment of COPD, was established in the year-long TONADO ® studies (NCT01431274; NCT01431287). It is unknown if these benefits of T/O translate into a reduction in COPD exacerbation rate. Methods Two replicate, randomised, double-blind, parallel-group trials assessed T/O 2.5/5 μg and T/O 5/5 μg compared to the monocomponents T 5 μg, T 2.5 μg and O 5 µg (all delivered via Respimat ® inhaler) in patients with moderate to very severe COPD. Primary end points included lung function (forced expiratory volu…

Safety of tiotropium/olodaterol in chronic obstructive pulmonary disease: pooled analysis of three large, 52-week, randomized clinical trials.

Abstract Background An extensive clinical trial program supports the efficacy and safety of tiotropium/olodaterol in chronic obstructive pulmonary disease (COPD). We examined the safety of tiotropium/olodaterol compared with tiotropium in a large population of patients, focusing on cardiovascular and respiratory events. Methods Patients (n = 9942) who received once-daily tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (via Respimat®) in TONADO 1 & 2 and DYNAGITO were included. The number of patients and exposure-adjusted rate of events are presented for adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and cardiovascular and respiratory events. Findings Fewer patient…

Oberer und unterer Respirationstrakt (V 39–V 44)

WITHDRAWN: Scaling up strategies of the Chronic Respiratory Disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 – Area 5)

Development and validation of a novel risk score for asthma exacerbations: The risk score for exacerbations.

BACKGROUND: Identifying patients at risk of future severe asthma exacerbations, those whose asthma might be less treatment responsive, or both might guide treatment selection. OBJECTIVE: We sought to investigate predictors for failure to achieve Global Initiative for Asthma (GINA)-defined good current asthma control and severe exacerbations on treatment and to develop a simple risk score for exacerbations (RSE) for clinical use. METHODS: A large data set from 3 studies comparing budesonide/formoterol maintenance and reliever therapy with fixed-dose inhaled corticosteroid/long-acting ?2-agonist therapy was analyzed. Baseline patient characteristics were investigated to determine dominant pre…

A randomized, double-blind study to compare the efficacy and safety of two doses of mometasone furoate delivered via Breezhaler® or Twisthaler® in patients with asthma

Abstract Introduction Mometasone furoate (MF) is the inhaled corticosteroid (ICS) component in the long-acting β2-agonist (LABA)/ICS fixed-dose combination of indacaterol/MF, delivered via Breezhaler®, in development for asthma. MF at low (80 μg) and high (320 μg) doses delivered via Breezhaler® is expected to be comparable to MF at low (200 μg) and high (800 μg) doses respectively, delivered via Twisthaler®. Methods This was a randomized, double-blind, double-dummy, four-week, parallel-group study of 739 adolescents and adults with persistent asthma. Eligible patients were receiving ICS treatment up to the maximum dose per day on a stable regimen for at least four weeks before screening. T…

Guideline-based survey of outpatient COPD management by pulmonary specialists in Germany

Thomas Glaab1,2, Claus Vogelmeier3, Andreas Hellmann4, Roland Buhl11Department of Respiratory Diseases III, Medical Center of the Johannes Gutenberg-University, Mainz, 2Medical Affairs Germany, Respiratory Medicine, Boehringer Ingelheim Pharma GmbH and Co, KG, Ingelheim, 3Department of Respiratory Diseases, University Hospitals of Giessen and Marburg, Marburg, 4Federal Association of Pneumologists, Augsburg, GermanyBackground: Little is known about the role of guidelines for the practical management of chronic obstructive pulmonary disease (COPD) by office-based pulmonary specialists. The aim of this study was to assess their outpatient management in relation to current guideline recommenda…

Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4).

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0–3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patien…

Mast Cells Induce Migration of Dendritic Cells in a Murine Model of Acute Allergic Airway Disease

&lt;i&gt;Background: &lt;/i&gt;The migration of dendritic cells (DCs) from the lungs to the regional lymph nodes is necessary for the development of allergic airway disease. Following activation, mast cells release a variety of stored or de novo-produced inflammatory mediators, several of them being capable of activating DCs. In this study, the role of mast cells on DC migration from the lungs to the thoracic lymph nodes was investigated in sensitized mice. &lt;i&gt;Methods:&lt;/i&gt; Mast cell-deficient mice (Kit&lt;sup&gt;W-sh/W-sh&lt;/sup&gt;) and their wild-type counterparts were sensitized intraperitoneally with ovalbumine (OVA) in saline and challenged by a single intranasal administr…

Humoral immune responses of lung cancer patients against the Transmembrane Phosphatase with TEnsin homology (TPTE).

Abstract Objective The cancer/testis (C/T) antigen Transmembrane Phosphatase with TEnsin homology (TPTE) is aberrantly expressed in many tumors including lung cancer. In the present study, we analyzed TPTE-auto-antibodies in lung cancer patients. Methods Using a crude-lysate ELISA, we analyzed a large cohort of 307 sera from lung cancer patients and 47 healthy donors for TPTE-specific autoantibodies. Sero-reactivity was correlated with clinical parameters and patients’ survival. Results TPTE-specific antibodies were detected in 41 of 307 (13.4%) sera from lung cancer patients. Based on an optimal cut-off value calculated by ROC curve analysis sensitivity for diagnosing lung cancer was 52% a…

The ‘real-life’ COPD patient in Germany: The DACCORD study

Abstract Introduction DACCORD is an ongoing, longitudinal, non-interventional study within the German COPD National Prospective Registry. This manuscript describes the baseline characteristics of the first 5924 participants, recruited between November 2012 and November 2013. Methods The main inclusion criteria are a physician diagnosis of COPD, age ≥40 years, and initiating or changing COPD maintenance medication. Data collected included: Demographic and disease characteristics; prescribed medication; symptoms; COPD Assessment Test (CAT); modified Medical Research Council dyspnoea score (mMRC); exacerbations; comorbidities; and forced expiratory volume in 1 s (FEV 1 ). Results Approximately…

Staphylococcus aureusand its IgE-inducing enterotoxins in asthma: current knowledge

While immunoglobulin (Ig) E is a prominent biomarker for early-onset, its levels are often elevated in non-allergic late-onset asthma. However, the pattern of IgE expression in the latter is mostly polyclonal, with specific IgEs low or below detection level albeit with an increased total IgE. In late-onset severe asthma patients, specific IgE to Staphylococcal enterotoxins (se-IgE) can frequently be detected in serum, and has been associated with asthma, with severe asthma defined by hospitalisations, oral steroid use and decrease in lung function. Recently,se-IgE was demonstrated to even predict the development into severe asthma with exacerbations over the next decade.Staphylococcus aureu…

Efficacy of Tiotropium/Olodaterol Compared with Tiotropium in Patients Naïve to LAMA, LABA and ICS: Pooled Analysis of Four Clinical Trials

The prognostic impact of blood group-related antigen Lewis Y and the ABH blood groups in resected non-small cell lung cancer.

The blood group antigen Lewis Y is expressed on epithelial tumors of the respiratory, digestive and reproductive system. Despite being regarded as an attractive target for immunotherapy, its function is still not well defined and its prognostic value remains a subject of discussion. Eighty-three paraffin-embedded tissue sections of non-small cell lung cancer (NSCLC) patients in stage I-IIIa, who underwent surgical resection of the primary tumor (73% male; 43% adenocarcinoma), were stained with a new, highly specific monoclonal antibody against Lewis Y (clone A70-C/C8). A positive Lewis Y expression was observed in 51% of patients; adenocarcinomas were favorably stained (67%). Multivariate a…

Die Th2 Zytokine IL5 und IL13 wirken synergistisch auf die Aktivierung und Transmigration von Eosinophilen

Impact of grouping patients by 2017 GOLD strategy assessment criteria: a post hoc analysis of the TONADO and OTEMTO trials

Introduction: Compared to the 2014 scheme, the 2017 GOLD COPD strategy uses only symptoms and exacerbation history to group patients, and no longer gives reference to the severity of airflow limitation. Aims: This post hoc analysis of TONADO and OTEMTO data aims to determine the impact of updated assessment criteria on patient classification and characteristics within these groups. Methods: TONADO (NCT01431274/NCT01431287; N=5162) and OTEMTO (NCT01964352/NCT02006732; N=1621) Phase III trials investigated efficacy and safety of tiotropium+olodatorol fixed-dose combination in COPD patients. In this analysis, patients were classed as GOLD A–D by the 2017 or 2014 criteria. In TONADO the mMRC Dy…

The Severe Asthma Registry – German data

Patients with severe persistent asthma represent the highest unmet medical need among the asthmatic population. To improve the understanding of underlying mechanisms and disease progression the German Asthma Net (GAN, www.german-asthma-net.de) launched a Severe Asthma Registry in December 2011. Enrolled patients undergo detailed clinical and physiologic evaluations, including patients’ medical history, allergy and lung function tests, blood analyses as well as past and concomitant medication and comorbidities. Patients are followed up every year. As of February 2018, 1097 subjects were recruited in Germany, Austria, and Slovenia. The mean age±SEM of the 839 German adult patients is 50.6±0.5…

Bcl-2, Bcl-xl, and pp32/PHAPI in resected non-small-cell lung cancer patients

Einleitung: Fur viele Tumorarten ist der Einfluss des Apoptosesignalweges auf die Prognose der Tumorerkrankung beschrieben worden. So konnte fur die antiapoptotischen Proteine wie Bcl-2 und Bcl-xL gezeigt werden, dass sie den mitochondrialen Selbstzerstorungsmechanismus der Zellen herunterregulieren konnen. Fur nicht-kleinzellige Lungenkarzinomen (NSCLC) hingegen existieren widerspruchliche Angaben in der wissenschaftlichen Literatur in Bezug auf die prognostische Wertigkeit apoptotischer und insbesondere antiapoptotischer Faktoren. Ein weiterer wichtiger Faktor im genannten Mechanismus, welches NSCLC fur apoptotische Stimuli sensibilisieren soll, ist das Protein pp32/PHAPI. Fur bereits che…

S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma

ZusammenfassungDie vorliegende Leitlinie ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma, welche die bisher für den deutschen Sprachraum gültige Version aus dem Jahr 2006 ablöst. Die Fülle an neuen Erkenntnissen zur Pathophysiologie und zu den Phänotypen von Asthma und das erweiterte Spektrum an diagnostischen und therapeutischen Möglichkeiten bei dieser Erkrankung machte eine Neufassung und Aktualisierung notwendig. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

Roflumilast for asthma: Weighing the evidence

Eligibility for treatment with omalizumab in Italy and Germany.

Summary Omalizumab is an add-on therapy for patients with uncontrolled severe allergic asthma. In Europe, patients must fulfil a number of additional criteria to become eligible for omalizumab therapy, creating a challenge for epidemiology studies to quantify the potential patient pool. Thus, and in the absence of robust data, the number of omalizumab-eligible patients has remained unclear. To assess eligible patient numbers, a chart-audit design approach was employed to measure epidemiology variables based on patient-level data. 770 patient charts were reviewed in designated towns in Germany and Italy, in collaboration with >200 primary care physicians (PCPs) and respiratory specialists (R…

Patients in clinical trials on COPD triple therapy compared to real world populations

Age- and sex-dependent differences in patients with severe asthma included in the German Asthma Net cohort.

Severe asthma affects less than 5% of asthmatics, but is associated with high costs and increased mortality. The aim of this study was to assess age- and sex-dependent differences in this patient group.Retrospective analysis of 1317 children and adults with severe asthma who are included in the German Asthma Net registry.There were more adults than children in the registry and patients' mean age was 52. Apart from children18 years, there were more women (57%) than men. The age of first diagnosis ranged from 0 to 76 years. 38% of patients had a positive bronchial reversibility after short acting bronchodilators. Quality of life, FEV1 and MEF 25 decreased with older age whereas treatment with…

Körperliche Funktionsfähigkeit, Allgemeinbefinden und Zufriedenheit mit Tiotropium/Olodaterol im Behandlungsalltag von COPD-Patienten in Deutschland

The impact of grouping patients by the 2017 GOLD COPD strategy on response to therapy: post hoc results from the TONADO tiotropium+olodaterol trials

Introduction: In the 2017 GOLD COPD strategy the classification of patients by assessment of symptoms and history of exacerbation is used to guide treatment choices. The previous strategy also included lung function. Aims and objectives: To investigate the effect of the 2017 classification on an analysis of the efficacy of tiotropium+olodaterol (T+O) in GOLD stage A/B patients with COPD. Methods: Patients from the Phase III, replicate 52-week TONADO studies (NCT01431274, NCT01431287), who received T+O or the mono-components, were classed as GOLD A/B or C/D by the 2017 strategy (using exacerbation history) or 2014 strategy (using lung function and exacerbation history). Since mMRC Dyspnoea S…

Comparing asthma treatment in elderly versus younger patients

SummaryA randomised 6-month study compared two maintenance doses of budesonide/formoterol (Symbicort® Turbuhaler®)hhNeither the Symbicort SMART posology nor the dry powder formulation, Turbuhaler, is currently approved in the US. maintenance and reliever therapy (Symbicort SMART®), 160/4.5 μg 1 × 2 and 2 × 2, in 8053 asthmatics with symptoms despite treatment with inhaled corticosteroids ± inhaled long-acting β2-agonists. This analysis compared response to the two treatments in elderly patients, ≥65 years, with that in younger patients. Elderly patients with early- or late-onset asthma were also compared.Elderly patients had lower post-bronchodilator FEV1 percentage predicted normal at base…

Budesonide/Formoterol Maintenance And Reliever Therapy At Two Different Maintenance Doses

Soot-exposed mononuclear cells increase inflammatory cytokine mRNA expression and protein secretion in cocultured bronchial epithelial cells.

&lt;i&gt;Background:&lt;/i&gt; Soot particles are air pollutants capable of inducing airway and lung parenchymal injury. Mononuclear and bronchial epithelial cells are central to the maintenance of homeostasis and inflammation in the airways. &lt;i&gt;Objectives:&lt;/i&gt; The aim of this study was to evaluate the contribution of mononuclear cells to the release of inflammatory mediators by bronchial epithelial cells. &lt;i&gt;Methods:&lt;/i&gt; To model the in vivo situation, an in vitro system of cocultured blood monocytes and BEAS-2B cells was established in a transwell system. Blood monocytes were exposed to soot particles (FR 101) at concentrations of up to 100 μg/10&lt;sup&gt;6&lt;/su…

Global Initiative for Asthma (GINA) Strategy 2021 - Executive summary and rationale for key changes

Funder: Global Initiative for Asthma

The Fevipiprant Phase IIIb Systemic Corticosteroid Avoidance Study: SHIELD

Allergen-Immuntherapie in der aktuellen COVID-19-Pandemie – ein Positionspapier von ARIA, EAACI, AeDA, GPA und DGAKI (Kurzversion) – Positionspapier der deutschen ARIA-GruppeA in Kooperation mit der österreichischen ARIA-GruppeB, der schweizerischen ARIA-GruppeC, dem Ärzteverband Deutscher Allergologen (AeDA)D, der Deutschen Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)E und der Gesellschaft für Pädiatrische Allergologie (GPA)F in Kooperation mit der AG Klinische Immunologie, Allergologie und Umweltmedizin der DGHNO-KHCG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H

Quality of Life in NSCLC Survivors - A Multicenter Cross-Sectional Study.

The objective was to assess quality of life (QoL) in lung cancer survivors, compare it to the general population, and identify factors associated with global QoL, physical functioning, emotional functioning, fatigue, pain, and dyspnea.Data from NSCLC patients who had survived 1 year or longer after diagnosis were collected cross-sectionally in a multicenter study. QoL was assessed with the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the lung cancer module QLQ-LC13 across different clinical subgroups and compared to age- and sex-standardized general population reference values. Multivariable linear regression analyses wer…

Outcomes of Donor-Recipient Gender Mismatched Lung Transplantation in the Eurotransplant Area

Purpose An effect of donor-recipient gender mismatching on long-term survival outcomes following organ transplantation has been postulated but remains controversial. We aimed to investigate the influence of gender mismatches on long-term survival after lung transplantation in the Eurotransplant area. Methods In this retrospective, multicentre study in the Eurotransplant area, all lung transplants performed from DBD lungs in the period from 01.01.2000 until 31.12.2015 were included. A total of 7688 lung transplant recipients (≥ 14 years old) for long-term survival and the effect of gender mismatches (Kaplan-Meier, multivariate regression). Results More men (4079; 52 %) were transplanted comp…

The canonical but not the noncanonical wnt pathway inhibits the development of allergic airway disease

Abstract Asthma is a syndrome with multifactorial causes, resulting in a variety of different phenotypes. Current treatment options are not curative and are sometimes ineffective in certain disease phenotypes. Therefore, novel therapeutic approaches are required. Recent findings have shown that activation of the canonical Wnt signaling pathway suppresses the development of allergic airway disease. In contrast, the effect of the noncanonical Wnt signaling pathway activation on allergic airway disease is not well described. The aim of this study was to validate the therapeutic effectiveness of Wnt-1–driven canonical Wnt signaling compared with Wnt-5a–driven noncanonical signaling in murine mo…

Lung function and long-term safety of tiotropium/olodaterol in East Asian patients with chronic obstructive pulmonary disease

Background and purpose While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials. Materials and methods In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tio…

&lt;p&gt;Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO&lt;sup&gt;&amp;reg;&lt;/sup&gt; and OTEMTO&lt;sup&gt;&amp;reg;&lt;/sup&gt; studies: a subgroup analysis by age&lt;/p&gt;

BACKGROUND Increasing age is associated with poor prognosis in patients with COPD. OBJECTIVE This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years. METHODS In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO onl…

Mast cell-derived tumour necrosis factor is essential for allergic airway disease

Mast cells are thought to contribute to allergic airway disease. However, the role of mast cell-produced mediators, such as tumour necrosis factor (TNF), for the development of allergic airway disease is unclear. In order to define the role of mast cells in acute allergic airway disease two strains of mast cell-deficient mice (Kit W/Wv and Kit W-sh/W-sh ) were studied. Compared with their wild-type littermates, Kit W/Wv and Kit W-sh/W-sh mice developed significantly lower airway responsiveness to methacholine and less airway inflammation and goblet cell metaplasia, following sensitisation in the absence of adjuvant and airway challenge. Transfer of bone marrow-derived mast cells (BMMCs) fro…

A Non-Interventional Study of Tiotropium/Olodaterol versus Any Triple Combination Therapy for Chronic Obstructive Pulmonary Disease: The EVELUT® Study Protocol

Roland Buhl,1 Michael Dreher,2 Stephanie Korn,1 Christian Taube,3 Christian Stock,4 Christoph M Zehendner,5 Anke Kondla,5 Claus F Vogelmeier6 1Pulmonary Department, Johannes Gutenberg University Mainz, Mainz, Germany; 2Clinic of Cardiology, Pneumology, Angiology and Internal Medicine Intensive Care, University Hospital RWTH Aachen, Aachen, Germany; 3Clinic for Pneumonology, University Medicine Essen &amp;ndash; Ruhrlandklinik, Essen, Germany; 4Biostatistics + Data Sciences Corp, Boehringer Ingelheim Pharma GmbH &amp;amp; Co. KG, Ingelheim am Rhein, Germany; 5HP Country Medical Affairs, Boehringer Ingelheim Pharma GmbH &amp;amp; Co. KG, Ingelheim am Rhein, Germany; 6Department of Pneumology,…

Use of a portable device to record maximum inspiratory flow in relation to dyspnoea in patients with COPD

SummaryForced inspiratory measures have been described to reflect the reduction in dyspnoea upon bronchodilation in severe COPD. Based on this we evaluated the applicability and usefulness of a portable device for the assessment of forced inspiration. In 37 patients with COPD (GOLD II/II/IV n = 16/15/6, mean ± SD FEV1 46.2 ± 15.4%pred) lung function was recorded prior to inhalation of 24 μg formoterol and 30 min later. Assessments comprised spirometry including forced inspiration, body plethysmography, maximum inspiratory flow (InCheck, Clement Clarke), and changes in dyspnoea via visual analogue scale (VAS). The sequence was repeated on a second day to assess reproducibility. Bronchodilati…

S61 Analysis of the efficacy and safety of the combination of tiotropium + olodaterol in patients with COPD by previous usage of inhaled corticosteroids: Abstract S61 Table 1

Rationale Tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist (both administered once daily), have been studied as a once-daily combination. Two Phase III studies have demonstrated that T+O significantly improved lung function and symptoms over T and O monotherapy treatments in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). 1 During these studies, patients were allowed to continue existing treatment with inhaled corticosteroids (ICS); this analysis was conducted to determine the effects of study treatment in patients receiving or not receiving ICS as reported at baseline. Methods A total of 5162 patients we…

Budesonide/Formoterol Maintenance And Reliever Therapy At Two Different Maintenance Doses: Effect On Fractional Excretion Of Nitric Oxide (FENO)

Protective Effect Of Disodium Cromoglycate In Exercise-induced Asthma In Adults And Its Synergistic Effect In A Fixed Drug Combination With Reproterol

Tiotropium Respimat® Add-On To Inhaled Corticosteroids Improves Lung Function In Patients With Symptomatic Mild Asthma: Results From A Phase III Trial

Real-World Multicenter Experience with Mepolizumab and Benralizumab in the Treatment of Uncontrolled Severe Eosinophilic Asthma Over 12 Months

Moritz Z Kayser,1 Nora Drick,1 Katrin Milger,2,3 Jan Fuge,1,4 Nikolaus Kneidinger,2,3 Stephanie Korn,5 Roland Buhl,6 Jürgen Behr,2,3 Tobias Welte,1,4 Hendrik Suhling1 1Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 2Department of Medicine V, University Hospital, LMU, Munich, Germany; 3Comprehensive Pneumology Center-Munich (CPC‐M), Member of the German Center for Lung Research (DZL), Munich, Germany; 4Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; 5Clinical Research Centre for Respiratory Medicine, Mainz, Germany; 6Pulmonary Department, Mainz Universit…

Corresponding doses of mometasone furoate (MF) in once-daily inhaled fixed-dose combination (FDC) of indacaterol/mometasone furoate (IND/MF) and indacaterol/glycopyrronium/mometasone furoate (IND/GLY/MF): results from randomized clinical studies

Omalizumab as alternative to chronic use of oral corticosteroids in severe asthma.

Systemic/oral corticosteroids (OCS) have been used for decades in the management of acute asthma exacerbations and chronically in patients with uncontrolled severe asthma. However, while OCS are effective at treating acute exacerbations, there is only empirical evidence regarding the efficacy of OCS at reducing the rate of exacerbations. Evidence, although scarce, is suggestive of high exacerbation rates in severe asthma patients even when receiving maintenance treatment with OCS. In addition, use of OCS is associated with undesirable effects. Despite all this, physicians have continued to use OCS for managing severe asthma and acute exacerbation due to the lack of availability of effective…

Long-term safety of tiotropium/olodaterol Respimat&lt;sup&gt;&amp;reg;&lt;/sup&gt;&amp;nbsp;in patients with moderate-to-very severe COPD and renal impairment in the TONADO&lt;sup&gt;&amp;reg;&lt;/sup&gt; studies

Introduction: The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO (R) studies (NCT01431274; NCT01431287). As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies. Methods: These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat (R)) in patients with moderate-to-very severe COPD. In this analysis…

Lung Transplantation

For patients with terminal lung conditions such chronic obstructive lung disease (COPD), lung transplantation (LuTx) offers treatment to improve quality of life and additionally, in those with certain other diseases—e.g., cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH)—to prolong life (1, 2, e1). It is used at the point when, despite treatment by all available conservative methods, the patient’s quality of life will be clearly impaired or life shortened if transplantation does not take place (3, 4, e2). At present, there are four main surgical options when performing a lung transplantation (5, e3, e4). These are: Unilateral (single lung) …

Analysis of Rescue Medication Use over 1 Year in Patients Receiving LAMA, LABA, or Combination Maintenance Treatment for COPD in the TONADO Studies

Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial

BACKGROUND: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. METHODS: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophil…

Budesonide/formoterol for the treatment of asthma.

Budesonide/formoterol (Symbicort), AstraZeneca plc) is a novel treatment for asthma, combining an inhaled corticosteroid - budesonide, and a long-acting beta(2)-agonist - formoterol, in a single inhaler, the Turbuhaler. Randomised, clinical studies in patients with asthma have demonstrated that budesonide/formoterol is more effective than the inhaled corticosteroids, budesonide and fluticasone alone, and at least as effective as both monocomponents in separate inhalers. Results from clinical studies suggest a synergistic effect when both drugs are administered via one inhaler, although the mechanisms for this are not fully understood. Budesonide/formoterol has a rapid onset of effect, appar…

The Arietta Study: Exploring Severe Asthma Biomarkers in a Real-World Setting

Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications

Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems. A number of well-recognized bioma…

Quantification Of Total Serum IgE In Patients With Asthma Using 3 Different Methods

Fractional exhaled nitric oxide is associated with more severe asthma

Fractional exhaled nitric oxide (FeNO) levels are used as a marker of airway inflammation. The aim of the present work was to evaluate a possible relationship between FeNO and parameters of asthma control and severity in different asthma phenotypes. FeNO was evaluated in 200 asthma patients (37% male, mean age ± SD 54±15 years, 19% controlled (GINA), 30% treated with oral corticosteroids (OCS), median FEV1 (interquartile range) 2,05 L (1,49-2,70), 74% pred. (56-90%)), together with other asthma characteristics (lung function, asthma control, allergies, serum IgE, serum ECP, and blood eosinophils). Patients with poorly controlled asthma had significantly higher FeNO values (ACQ-5≥1.5 vs. 70%…

Determining SGRQ and TDI responder rates across the duration of clinical trials: Results from tiotropium + olodaterol in COPD

Introduction: Patient-reported outcomes (PROs) are important in COPD for understanding patients’ symptoms and experience of the disease. Responder rates at specific timepoints are frequently used to analyse clinically important improvements in PROs. Alternatively, responders can be defined using average PRO improvement vs. baseline over the whole study period or the last two timepoints, as recently discussed by the FDA. Aims and objectives: To compare three techniques for determining responder rates of St. George’s Respiratory Questionnaire (SGRQ) and transition dyspnoea index (TDI). Methods: Two double-blind, replicate, Phase III, 52-week TONADO trials compared tiotropium + olodaterol (T+O…

Evidenz für eine frühzeitige Therapie der COPD mit Tiotropium

Hintergrund: Die Wirksamkeit von Tiotropium versus Kontrolle wurde in einer praspezifizierten Subgruppenanalyse der 4-Jahres-Studie „Understanding Potential Long-term Impacts on Function with Tiotropium“ bei Patienten mit chronisch obstruktiver Lungenerkrankung (COPD) mittleren Schweregrades (GOLD II) untersucht und erstmals den gepoolten Ergebnissen aus den schwereren Krankheitsstadien (GOLD III/IV) gegenubergestellt. Methode: Randomisierte multizentrische, doppelblinde, kontrollierte Studie mit parallelem Gruppenvergleich bei 5993 Patienten uber 4 Jahre. Die Patienten erhielten entweder Tiotropium 18 µg einmal taglich oder Plazebo. Als Endpunkte wurden der jahrliche FEV1-Abfall und weiter…

Indacaterol vs tiotropium in COPD patients classified as GOLD A and B

SummaryIntroductionAccording to current GOLD strategy, patients with COPD classified as groups A and B may be treated with inhaled bronchodilators, either long-acting β2-agonist (LABA) or long-acting muscarinic antagonist (LAMA). However, there is little guidance on which class of agent is preferred and a lack of prospective data to differentiate the two.MethodsIn this study, we performed post-hoc analyses of pooled data from two prospective, controlled clinical trials comparing the LABA indacaterol and LAMA tiotropium in 1422 patients with moderate airflow limitation and no history of exacerbations in the previous year. This population fits the definitions of GOLD A and B groups and could …

The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma

Background:  Patients with severe persistent asthma who are inadequately controlled despite treatment according to current asthma management guidelines have a significant unmet medical need. Such patients are at high risk of serious exacerbations and asthma-related mortality. Methods:  Here, we pooled data from seven studies to determine the effect of omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, on asthma exacerbations in patients with severe persistent asthma. Omalizumab was added to current asthma therapy and compared with placebo (in five double-blind studies) or with current asthma therapy alone (in two open-label studies). The studies included 4308 patients (2511 tre…

Effect of tiotropium/olodaterol combination therapy on long-term heart rate and blood pressure in COPD patients

Introduction: Cardiovascular (CV) comorbidities are common in COPD, and associated with poor prognosis. LABAs and LAMAs are established COPD treatments whose pharmacology would suggest the potential to increase heart rate (HR) and impact blood pressure (BP). However, previous studies indicate that HR and BP are not negatively influenced by tiotropium (Tio) or olodaterol (Olo) monotherapy. Aims: To determine the effect of dual bronchodilation with Tio/Olo (T/O) on HR and BP. Methods: The 52-week, Phase III TONADO® studies (NCT01431274/NCT01431287) evaluated T/O 5/5 µg, Tio 5 µg or Olo 5 µg, via the Respimat® inhaler, in GOLD 2–4 COPD patients. In this post hoc analysis, long-term changes fro…

Patients' perceptions of well-being using a guided self-management plan in asthma

Summary Asthma can place considerable restrictions on the health-related quality of life of asthma patients and their families; this burden may be greatest when symptoms are not adequately controlled. The Symbicort® Adjustable Maintenance Dosing Programme, consisting of studies from several different countries, compared a guided self-management plan that allows adjustable maintenance dosing using budesonide/formoterol in a single inhaler (Symbicort) with fixed dosing. Quality of life was assessed in three countries, using asthma-specific and generic questionnaires. Clinically relevant improvements in mean quality of life scores were observed from the beginning to the end of the 1-month run-…

Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency

Background Vitamin D has effects on the innate and adaptive immune system. In asthmatic children low vitamin D levels are associated with poor asthma control, reduced lung function, increased medication intake, and exacerbations. Little is known about vitamin D in adult asthma patients or its association with asthma severity and control. Methods Clinical parameters of asthma control and 25-hydroxyvitamin D (25(OH)D) serum concentrations were evaluated in 280 adult asthma patients (mean ± SD: 45.0 ± 13.8 yrs., 40% male, FEV1 74.9 ± 23.4%, 55% severe, 51% uncontrolled). Results 25(OH)D concentrations in adult asthmatics were low (25.6 ±11.8 ng/ml) and vitamin D insufficiency or deficiency (vi…

Budesonide/formoterol maintenance and reliever therapy: a new treatment approach for adult patients with asthma.

An inhaled corticosteroid (ICS) or an ICS/long-acting beta(2)-agonist (LABA) combination plus short-acting beta(2)-agonist (SABA) as needed for symptom relief is recommended for persistent asthma. Additionally, budesonide/formoterol maintenance and reliever therapy (Symbicort SMART, AstraZeneca, Sweden) has been approved for adults in the European Union. This option is well tolerated and offers greater reductions in asthma exacerbations together with similar improvements in daily symptom control, at a lower overall steroid load, compared with fixed-dose ICS/LABA plus SABA.Two large clinical trials investigated the use of budesonide/formoterol as maintenance and reliever compared with medium…

Similar Camp Transfer Of Naturally Occurring Regulatory T Cells More Effectively Suppresses Effector Functions Of Th1 Compared To Th2 Cells

Fluticasone/formoterol combination therapy versus budesonide/formoterol for the treatment of asthma: a randomized, controlled, non-inferiority trial of efficacy and safety.

The inhaled corticosteroid fluticasone propionate (fluticasone) and the long-acting β₂ agonist formoterol fumarate (formoterol) have been combined in a single aerosol inhaler fluticasone/formoterol (flutiform(®)). This study compared the efficacy and safety of fluticasone/formoterol with the combination product budesonide/formoterol (Symbicort(®) Turbohaler(®)).A randomized, double-blind, double-dummy, multicenter, Phase 3 study comprising a 7- (± 3) day screening, 2-4-week run-in, and 12-week treatment periods. Patients aged ≥ 12 years with moderate to severe persistent asthma for ≥ 6 months before screening and forced expiratory volume in one second (FEV₁) 50-80% predicted and ≥ 15% rever…

S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma – Addendum 2020

ZusammenfassungDas vorliegende Addendum zur Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma (2017) ergänzt wichtige neue Erkenntnisse zur Diagnostik und Therapie von Asthma sowie zu neu für die Therapie des Asthmas zugelassenen Medikamenten. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

Efficacy of Once-Daily Tiotropium Respimat ® on Lung Function and Asthma Control in Adults with Asthma at GINA Steps 2–5

Predictors Of Asthma Control And A Risk Score For Exacerbations

Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD)

ZusammenfassungDas vorliegende Dokument ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit COPD, die die bisherige Version aus dem Jahr 2007 ablöst. Die Fülle an neuen Erkenntnissen zu Risikofaktoren, Diagnostik, Schweregradeinschätzung, Prävention und medikamentösen sowie nicht medikamentösen Therapiemaßnahmen machten eine umfassende Überarbeitung erforderlich. Die neue Leitlinie baut auf das GOLD-Dokument unter Berücksichtigung von Besonderheiten in Deutschland und Österreich auf.

TA-MUC1 epitope in non-small cell lung cancer

MUC1 (CD227), an established tumor marker, is expressed on glandular epithelia and on epithelial tumors. Tumor MUC1 differs from normal MUC1 by modified glycan side chains. Recently, a novel carbohydrate-induced conformational tumor-associated MUC1 epitope (TA-MUC1) was described, whose clinical relevance in lung cancer is not known. Eighty-five paraffin embedded tissue sections of non-small cell lung cancer (NSCLC) patients (73% male; mean age 64+/-9 years) were stained with the monoclonal antibody PankoMab (against TA-MUC1) and compared with the established antibodies E29 and 214D4 regarding prognostic relevance. TA-MUC1 is virtually absent in bronchial epithelium. As shown by multivariat…

Characterization of COPD Patients Experiencing Clinically Relevant Improvement Vs Worsening in Health Status 2 Years After a Change of Maintenance Treatment in the 'Real-life' Daccord Study

Once-daily tiotropium Respimat® 5 μg is an efficacious 24-h bronchodilator in adults with symptomatic asthma

SummaryIntroductionOnce-daily tiotropium Respimat® 5 μg is an efficacious add-on therapy to inhaled corticosteroids (ICS) with or without long-acting β2-agonists in patients with symptomatic asthma. The objective of this study was to investigate whether the dosing regimen of tiotropium (once- versus twice-daily), delivered via the Respimat® SoftMist™ inhaler, affected 24-h bronchodilator efficacy and safety versus placebo Respimat® in patients with asthma who were symptomatic despite medium-dose ICS therapy.MethodsA randomised, double-blind, placebo-controlled, crossover study with 4-week treatment periods of tiotropium 5 μg (once-daily, evening) and 2.5 μg (twice-daily, morning and evening…

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…

Anti-type2-Antibodies Specifically Inhibit Murine Asthma Features Induced By Intranasal Application of IL-5 and IL-13

Benefits of tiotropium/olodaterol compared with tiotropium in patients receiving COPD LAMA at baseline: pooled analysis of 4 clinical trials

Mometasone furoate delivered via Breezhaler and Twisthaler in patients with asthma

Introduction: Mometasone furoate (MF), an inhaled corticosteroid (ICS), is approved for the treatment of asthma. Previous studies suggest that MF Twisthaler® doses of 800 and 200 µg and MF Breezhaler® doses of 320 and 80 µg would elicit similar lung function effects, respectively. These MF doses are also used in an indacaterol/MF combination in development for asthma. Since sensitivity to ICS is variable, individual patients’ ICS sensitivity (as measured by FEV1 decline on ICS weaning) was used to build a robust analysis model for the study data. Methods: This was a randomized, double-blind, double-dummy, parallel-group, non-inferiority study of 739 adolescents and adults with asthma. MF wa…

SeroGRID: an improved method for the rapid selection of antigens with disease related immunogenicity

Screening of cDNA expression libraries derived from human tumors with autologous sera (SEREX) permits the definition of immunogenic antigens in individual cancer patients. However, only a minority of SEREX-derived cDNA clones show a clear cancer-relatedness in the sense that circulating autoantibodies to them occur exclusively in the sera of tumor patients but not in healthy individuals. Evaluation of multiple SEREX-defined clones in serological assays using panels of allogeneic sera from cancer patients as well as appropriate control groups is an important step towards focussing on the relevant antigens. This in turn is the basis for defining disease parameters of diagnostic and prognostic…

IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease

Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production…

Measurement of exhaled nitric oxide: comparison of 3 different analyzers

Exhaled nitric oxide (FeNO) is used as a surrogate marker to monitor airway inflammation. Aim of this study was to compare the new FeNO analyzer Vivatmo pro from Bosch (BV) with the Niox Vero from Circassia (CN) and the CLD from Ecomedics (EC). In 106 asthma patients (median age 54 years (range 20-87), 60 % female, median ACT of 16, 85 % on inhaled corticosteroids (mean 1300 μg BDP), 36 % on therapy with biologics) 2 FeNO measurements per patient and per device were performed using each analyzer in a random sequence according to the ATS / ERS guidelines. Additionally, the success rate to achieve a valid NO value was evaluated. 70 % of the patients had FeNO values In conclusion, for the rang…

Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma

Background Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less; however, long-term data are lacking. Objective We sought to evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA). Methods COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859 ) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506 ). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-def…

The Wnt/beta-Catenin Pathway Attenuates Experimental Allergic Airway Disease

Abstract Signaling via the Wnt/β-catenin pathway plays crucial roles in embryogenesis and homeostasis of adult tissues. In the lung, the canonical Wnt/β-catenin pathway has been implicated in remodeling processes, development of emphysema, and fibrosis. However, its relevance for the modulation of allergic responses in the lung remains unclear. Using genetically modified mice with lung-specific inducible (doxycycline) Wnt-1 expression (CCSP-rtTA × tetO-Wnt1), the impact of Wnt on the development of allergic airway disease was analyzed. Overexpression of Wnt during the allergen challenge phase attenuated the development of airway inflammation in an acute model, as well as in a more therapeut…

Tiotropium add-on therapy reduces seasonal peaks of asthma worsening in adults with symptomatic severe asthma

Despite the use of preferred controller therapies (including inhaled corticosteroids [ICS] with or without additional long-acting β2-agonists [LABAs]), a large proportion of patients with asthma have poor disease control, leaving them at risk of recurring symptoms and episodes of asthma exacerbations and worsening [1, 2]. Such problems can be triggered by many different environmental factors including pollutants, respiratory infections or allergens [3]. They may occur sporadically, but are often determined by seasons, mirroring seasonal patterns of allergen exposure and prevalence of respiratory viral infection [3, 4]. They can cause reduced quality of life, increase asthma burden [2, 3], a…

Synthesis and preliminary evaluation of (R,R)(S,S) 5-(2-(2-[4-(2-[18F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([18F]FEFE) for the in vivo visualisation and quantification of the β2-adrenergic receptor status in lung

The 18 F-labeled b2-adrenergic receptor ligand (R,R)(S,S) 5-(2-(2-(4-(2-( 18 F)fluoroethoxy)phenyl)-1-methylethylamino)-1- hydroxyethyl)-benzene-1,3-diol, a derivative of the original highly selective racemic fenoterol, was synthesized in an overall radio- chemical yield of 20% after 65 min with a radiochemical purity higher than 98%. The specific activity was in the range of 50-60 GBq/mmol. In vitro testing of the non-radioactive fluorinated fenoterol derivative with isolated guinea pig trachea was conducted to obtain an IC50 value of 60 nM. Preliminary ex vivo organ distribution and in vivo experiments with positron emission tomography (PET) on guinea pigs were performed to study the biod…

The Immunomodulatory Capacity of Wnt on Human Dendritic Cells – Wnt/β-Catenin Signalling as a Potential Target for Bronchial Asthma

Benefits of Tiotropium + Olodaterol Over Tiotropium at Delaying Clinically Significant Events in Patients with COPD Classified as GOLD B

ARIA���EAACI statement on asthma and COVID���19 (June 2, 2020)

Artículo con numerosos autores sólo se mencionan el primero y el de la UAM

Long-Term Safety of Tiotropium/Olodaterol Respimat in Elderly Patients with Moderate to Very Severe COPD in the TONADO Studies

Care pathways for the selection of a biologic in severe asthma.

Physicians need care pathways to select a biologic in type 2 severe asthma (omalizumab, mepolizumab, reslizumab) http://ow.ly/pygw30gB7Bv

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…

The effect of tiotropium/olodaterol versus tiotropium on COPD exacerbation rates in patients with/without frequent exacerbation history

Background: Patients with COPD with a history of frequent exacerbations are at increased risk of future exacerbations. There are limited data as to whether combining LAMA/LABA reduces exacerbation risk in all patients. We investigated whether tiotropium/olodaterol (T/O) reduced exacerbation rate versus tiotropium (tio) in patients with a range of exacerbation histories. Methods: TONADO 1+2 (NCT01431274/NCT01431287) and DYNAGITO (NCT02296138) were 52-week, parallel-group, randomised, double-blind, Phase III trials in COPD patients with FEV1 Results: There was a lower rate of moderate/severe exacerbations with T/O (0.68 per patient-year) than tio (0.77 per patient-year) (rate ratio [RR] vs ti…

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice: Review

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Clinically meaningful FEV1 response with reslizumab achieved early and sustained over 52 weeks

Background: Reslizumab (RES) is a humanized anti-interleukin-5 monoclonal antibody that significantly reduces the risk of asthma exacerbations and improves asthma control, lung function, and quality of life in patients with uncontrolled eosinophilic asthma. The mean difference in FEV 1 in RES treated patients vs placebo (PBO) at 16 and 52 weeks has been shown to be statistically and clinically significant (Castro et al., Lancet Respir Med. 2015; 3:355–366), but individual responders have not been assessed. Aims/Objectives: To assess the proportion of RES-treated patients who achieved a ≥0.1L increase in FEV 1 from baseline and the duration of treatment before response occurs. Methods: This …

&lt;p&gt;Future perspectives of anticholinergics for the treatment of asthma in adults and children&lt;/p&gt;

Despite major advances in therapeutic interventions and the availability of detailed treatment guidelines, a high proportion of patients with symptomatic asthma remain uncontrolled. Asthma management is largely guided by the Global Initiative for Asthma (GINA) strategy and is based on a backbone of inhaled corticosteroid (ICS) therapy with the use of additional therapies to achieve disease control. Inhaled long-acting bronchodilators alone and in combination are the preferred add-on treatment options. Although long-acting muscarinic antagonists (LAMAs) are a relatively recent addition to disease management recommendations for asthma, tiotropium has been extensively studied in a large clinic…

P141 2-year follow-up of COPD patients in the non-interventional ‘real-life’ daccord study in germany

Introduction Although randomised, controlled trials are important in the development of new pharmacological treatments, they provide limited information on the ‘real life’ management of chronic diseases. Here, we analysed two-year follow-up data from the prospective, non-interventional, observational DACCORD study to evaluate the frequency of exacerbations and the evolution of disease severity using GOLD 2011 categorization. Methods COPD out-patients were recruited into DACCORD following either a change or initiation of COPD maintenance medication and followed up for 2 years. Data of 3137 patients that completed the 2-year follow-up were analysed; Exacerbation data were collected from the 6…

Asthma bronchiale: neue Erkenntnisse und Entwicklungen

In mild asthma low-dose steroid inhalation treatment reduces severe exacerbations and exacerbation associated loss of lung function. In patients with mild asthma, symptom-driven use of a combination of inhaled steroid and short-acting beta-2-sympathomimetics in a single inhaler is feasible. In moderate and severe asthma the fixed combination of formoterol and budesonide can be used a maintenance therapy but also as treatment of acute symptoms. Monotherapy with long-acting beta 2-sympathomimetics should be completely avoided. Long-acting anticholinergic drugs are equally efficacious as long-acting beta-2-sympathomimetics, but have not yet been approved for use in patients with asthma. The co…

Real-life effectiveness of anti-IL-5(-receptor) antibody treatment in patients with severe eosinophilic asthma

In patients with uncontrolled, severe eosinophilic asthma treatment with anti-IL-5(-receptor) (anti-IL5(R)) antibodies is a promising therapeutic approach. Results of clinical trials demonstrate a very good effectiveness and safety profile of these drugs. However, there is limited data on real-life effectiveness because the drugs have been approved for just a few years. Aim of the present study was to evaluate the real-life effectiveness of the anti-IL5(R) antibodies mepolizumab, reslizumab and benralizumab in severe eosinophilic asthma shortly after approval in Germany. In 119 patients (n=44 male, mean age 54±14 yrs., BMI 27.5±6.2, FEV1 1.9±0.8L (64±21%), 5±3 exacerbations in the last 12 m…

Eosinophilic and Noneosinophilic Asthma

Background Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a pre…

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…

P285 The ‘real-life’ copd patient in the age of laba/lamas: an expansion of the daccord study

Introduction The prospective, non-interventional DACCORD study collects data from a representative cohort of COPD out-patients across Germany who either initiated or changed COPD maintenance medication prior to entry. Initially, DACCORD consisted of two treatment groups (Glycopyrronium-based therapy vs. any other COPD maintenance medication with the exception of Glycopyrronium). Following the approval of LABA/LAMA fixed-dose combinations (FDC) in 2013, DACCORD was extended to follow an additional cohort of patients receiving any LABA/LAMA FDC over a period of 2 years. Methods 5223 patients with complete baseline data (3815 LAMA/LABA FDC vs. 1408 standard treatment group) were analysed here.…

2 years in the life of COPD patients: Evolution of GOLD 2011 classification in the 'real-life' DACCORD study

Introduction Limited data are available on the progression of COPD categorised according to GOLD 2011. We analysed data from the ongoing, non-interventional, observational DACCORD study and compared baseline GOLD 2011 categorisation with that of 1 and 2-years after inclusion. Methods Patients with a diagnosis of COPD were recruited into DACCORD following either a change or initiation of maintenance medication. Baseline exacerbations data (collected over 6 months) were annualised for GOLD categorisation at baseline; COPD symptoms were evaluated using the COPD Assessment Test (CAT) at baseline as well as the 1 year and 2 year visit. Data on exacerbations were collected every 3 months up to 2 …

Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations

This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 μg/day) received budesonide/formoterol 160/4.5 μg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 μg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 μg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first sev…

P46 Frequency of COPD exacerbations in the German DACCORD Registry

Introduction In patients with COPD, exacerbations are among the most relevant safety measures. In this analysis of data from the observational DACCORD study, we report the frequency of exacerbations in a COPD population. Methods To get insights into occurrence and frequency of exacerbations, data from 4,123 patients were obtained from 349 primary and secondary care centres in Germany. To be eligible for entry into DACCORD, all patients had to have a COPD diagnosis (consistent with the German Disease Management Programme definition), and had to have a change in bronchodilator maintenance medication, prior to entry. Data collected included history and treatment of exacerbations 6 months prior…

One-year follow up of asthmatic patients newly initiated on treatment with medium- or high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings

Abstract Introduction Global Initiative for Asthma (GINA) recommends medium- or high-dose inhaled corticosteroid-long-acting β2-agonist (ICS-LABA) as preferred treatments for patients with moderate-to-severe asthma. Limited data is available on how step 4/5 patients respond to ICS-LABA and how they step up/down in clinical practice. Methods This retrospective cohort study assessed the characteristics, control status, treatment pathways, and healthcare resource utilization in patients with asthma during one year after initiating medium- or high-dose ICS-LABA. Data from the United Kingdom Clinical Practice Research Datalink were analysed between January 01, 2006 and February 28, 2016. Results…

Effective Management of Severe Asthma with Biologic Medications in Adult Patients: A Literature Review and International Expert Opinion

International audience; Severe asthma often remains uncontrolled despite effective treatments and evidence-based guidelines. A group of global experts in asthma and biologic medications from nine countries considered the most relevant clinical variables to manage severe asthma in adult patients and guide treatment choice. The resulting recommendations address the investigation of biomarker levels (blood eosinophil count along with fractional concentration of exhaled nitric oxide [FeNO]), clinical features (oral corticosteroid [OCS] dependency, specific comorbid disease entities associated with severe type 2 asthma), and safety considerations. Current evidence suggests that biomarkers, inclu…

Differences of airway dimensions between patients with and without bronchiolitis obliterans syndrome after lung transplantation-Computer-assisted quantification of computed tomography.

Abstract Background The aim of our retrospective study was to determine whether a dedicated software for assessment of airway morphology can detect differences in airway dimensions between patients with and without bronchiolitis obliterans syndrome (BOS), regarded as the clinical correlate of chronic lung allograft rejection. Methods 12 patients with and 14 patients without diagnosis of BOS were enrolled in the study. Evaluation of bronchial wall area percentage (WA%) and bronchial wall thickness (WT) in all follow-up CT scans was performed using a semiautomatic airway assessment tool. We assessed temporal changes (ΔWA%, ΔWT) and compared these morphological parameters with forced expirator…

Inhibition of cAMP Degradation Improves Regulatory T Cell-Mediated Suppression

Abstract Naturally occurring regulatory T cells (nTreg cells) are crucial for the maintenance of peripheral tolerance. We have previously shown that a key mechanism of their suppressive action is based on a contact-dependent transfer of cAMP from nTreg cells to responder T cells. Herein, we further elucidate the important role of cAMP for the suppressive properties of nTreg cells. Prevention of cAMP degradation by application of the phosphodiesterase 4 inhibitor rolipram led to strongly increased suppressive potency of nTreg cells for Th2 cells in vitro and in vivo. Detailed analyses revealed that rolipram caused, in the presence of nTreg cells, a synergistic increase of cAMP in responder T…

Omalizumab (Xolair®) improves quality of life in adult patients with allergic asthma: a review

Abstract Physicians are increasingly aware that asthma causes significant impairment of the patient's physical, psychological, and social well-being. Whilst standard clinical endpoints provide significant information on airway status during treatment, it is important to determine whether such improvements overcome the functional impairment that patients have to deal with on a daily basis. As such, assessment of health-related quality of life (QoL) is an important aspect of asthma management in clinical practice. Omalizumab (Xolair ® ) is a recombinant humanized monoclonal anti-immunoglobulin E (IgE) antibody that represents a new therapeutic approach to IgE-mediated diseases such as allergi…

Safety of tiotropium and olodaterol fixed-dose combination for COPD in patients on β-blockers

Introduction: The TONADO studies (NCT01431274; NCT01431287) established the efficacy and safety of a new once-daily fixed-dose combination (FDC) with tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, for the treatment of COPD. This post hoc analysis evaluates T+O safety in the subgroup of patients (pts) receiving β-blockers (BBs) in these studies. Methods: These were randomised, double-blind, parallel-group, 52-week, Phase III trials comparing T+O FDC (2.5/5 µg; 5/5 µg) with the monocomponents. Adverse events (AEs) and serious AEs (SAEs) were recorded and SAEs independently adjudicated. Pooled safety data from pts receiving BBs at baseline …

Absence of Adverse Effects of Tiotropium/Olodaterol Compared with the Monocomponents on Long-Term Heart Rate and Blood Pressure in Patients with Moderate-to-Very-Severe COPD

Stefan Andreas,1,2 Lorcan McGarvey,3 Ulrich Bothner,4 Matthias Trampisch,4 Alberto de la Hoz,4 Matjaz Fležar,5 Roland Buhl,6 Peter Alter7 1Department of Cardiology and Pneumology, University Medical Center G&amp;ouml;ttingen, G&amp;ouml;ttingen, Germany; 2LungClinic Immenhausen, Immenhausen, Germany, Member of the German Center for Lung Research (DZL); 3Queen&amp;rsquo;s University Belfast, Belfast, UK; 4Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 5Klinika Golnik, Golnik, Slovenia; 6Pulmonary Department, Johannes Gutenberg University Mainz, Mainz, Germany; 7Department of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg (UMR); Member o…

P256 Safety Of Once-daily Tiotropium And Olodaterol Fixed-dose Combination Via The Respimat In Chronic Obstructive Pulmonary Disease In Two 1-year Studies

Introduction The fixed-dose combination (FDC) of tiotropium (T), a once-daily long-acting muscarinic antagonist, and olodaterol (O), a once-daily long-acting β 2 -agonist, is currently being evaluated in chronic obstructive pulmonary disease (COPD). Two 52-week, Phase III replicate pivotal studies were conducted to assess the efficacy and safety of FDCs of T and O (T+O) delivered via Respimat® Soft Mist™ inhaler in patients (pts) with GOLD Stage 2–4 COPD. Pooled safety data from the two studies are presented here. Methods These were double-blind, randomised, parallel-group studies with 5 arms: O 5 µg, T 2.5 µg, T 5 µg, T+O 2.5/5 µg, T+O 5/5 µg. Key inclusion criteria were: age ≥40 years, di…

Photobiologie und klinische Immunologie (V 66–V 70)

&amp;ldquo;Real-life&amp;rdquo; inhaled corticosteroid withdrawal in COPD: a subgroup analysis of DACCORD

Claus Vogelmeier,1 Heinrich Worth,2 Roland Buhl,3 Carl-Peter Cri&amp;eacute;e,4 Nadine S Lossi,5 Claudia Mail&amp;auml;nder,5 Peter Kardos6 1Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, 2Facharzt Forum F&amp;uuml;rth, F&amp;uuml;rth, 3Pulmonary Department, Mainz University Hospital, Mainz, 4Department of Sleep and Respiratory Medicine, Evangelical Hospital G&amp;ouml;ttingen-Weende, Bovenden, 5Clinical Research, Respiratory, Novartis Pharma GmbH, N&amp;uuml;rnberg, 6Group Practice and Centre for Allergy, Respiratory and Sleep Medicine, Re…

Monotherapy with indacaterol once daily reduces the rate of exacerbations in patients with moderate-to-severe COPD: Post-hoc pooled analysis of 6 months data from three large phase III trials

Summary Background In patients with COPD, exacerbations are associated with poor quality of life and may shorten survival. Prevention of exacerbations is, therefore, a key objective in COPD management. Indacaterol, a once-daily ultra-long-acting β 2 -agonist, has been shown to reduce exacerbations in various studies. This pooled analysis evaluated the effect of indacaterol on exacerbations versus placebo. Methods Six-month data were pooled from three randomized, double-blind, and placebo-controlled studies: indacaterol 300 μg versus placebo (1 year); indacaterol 150 μg and 300 μg versus placebo (6 months); and indacaterol 150 μg versus placebo (6 months). All treatments were administered on…

&lt;p&gt;Assessment of physical functioning and handling of tiotropium/olodaterol Respimat® in patients with COPD in a real-world clinical setting&lt;/p&gt;

Background Patients with chronic obstructive pulmonary disease (COPD) show signs of reduced physical activity from the early stages of the disease, impacting morbidity and mortality. Data suggest treatment with tiotropium, a long-acting muscarinic antagonist, and olodaterol, a long-acting s2-agonist (LABA), as monotherapies and in combination, increases exercise capacity. This study assessed the effects of fixed-dose tiotropium/olodaterol (delivered via Respimat®) on physical function in Global Initiative for Chronic Obstructive Lung Disease A-D patients requiring long-acting dual bronchodilation treatment in a real-world setting. Methods This open-label, single arm, noninterventional study…

Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with moderate-to-severe COPD (QUANTIFY): a randomised, non-inferiority study

Background QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD. The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD. Methods This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o…

Studienendpunkte bei der chronisch-obstruktiven Lungenerkrankung (COPD): „Minimal Clinically Important Difference”

The concept of the minimal clinically important difference (MCID) is intended to provide a measure of relevance for a statistically applied in patients with COPD. Clinically important differences are those differences relevant to the individual patient and important to the patient's life. However, people's difference in a diagnostic parameter perception of what is important vary. Furthermore, physicians may rate the significance of a particular marker and its difference which can be achieved by a pharmacological intervention differently from the patient. Thus, the major problem with defining an MCID for any measure is that the most important differences, which require the most subtle measur…

Reply to the Letter Entitled "FeNO Variability when Using Different Analyzers at the Joint ATS/ERS Guideline Cutoff".

Short-Term Reproducibility Of Non-Invasive Clinical And Inflammatory Parameters In Asthma

The ARIETTA study: baseline demographics in a real-world setting in patients with severe asthma

Introduction and Aim: As recognition of asthma heterogeneity increases and targeted treatment options are introduced, the future role of biomarkers (BM) in patient (pt) selection, monitoring and risk prediction will be important. We report baseline demographic and clinical characteristics from ARIETTA, an ongoing, prospective, longitudinal study assessing the relationship between BM and disease-related health outcomes in the real world. Methods: Pts with severe asthma (GINA steps 4-5) receiving daily inhaled corticosteroids (CS; fluticasone propionate ≥500 μg or equivalent) and ≥1 second controller medication were enrolled. Study enrollment is now complete. BM, clinical characteristics and …

Safety and tolerability of omalizumab

Summary Background Omalizumab (Xolair®) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. Objective To review clinical study data to assess the safety profile of omalizumab. Methods We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic in…

Small airway disease (SAD) is associated with respiratory symptoms and relevant for therapy in early COPD

Background: SAD is common in patients with COPD. Occurring early in the course of the disease, it is frequently missed by currently used diagnostic tests. Multiple breath washout (MBW) testing detects ventilation heterogeneity (VH) while oscillometry (OS) assesses peripheral obstruction, both associated with SAD. We therefore set out to evaluate the presence and symptoms of SAD in patients with early COPD. Methods: We prospectively evaluated 26 patients (FEV1 77±19% pred., 88% GOLD I/II). In an 8-week cross-over design, the effect of dual bronchodilatation (tiotropium/olodaterol, T/O) on lung function and symptoms (CAT) was compared to monotherapy (formoterol). Lung function was assessed by…

Anti-IgE antibodies for the treatment of asthma

Purpose of review Allergic asthma is a hypersensitivity reaction initiated by immunologic mechanisms mediated by IgE antibodies. IgE plays a central role in the initiation and propagation of the inflammatory cascade and thus the allergic response. Targeting factors involved in the allergic response, such as IgE, is a novel strategy for new therapies. Attenuating allergic disease by specifically inhibiting IgE and the development of the monoclonal anti-IgE antibody, omalizumab, were major breakthroughs in asthma management. Recent findings Several studies have shown that omalizumab has significant anti-inflammatory effects and that it may act on multiple components of the inflammatory cascad…

Impact of tiotropium + olodaterol on physical functioning in COPD: results of an open-label observational study

R&amp;uuml;diger Sauer,1 Michaela H&amp;auml;nsel,2 Roland Buhl,3 Roman A Rubin,4 Marcel Frey,5 Thomas Glaab2,3 1Lung Centre Ulm, Ulm, Germany; 2Boehringer Ingelheim Pharma GmbH&amp;nbsp;&amp;amp; Co. KG, Ingelheim, Germany; 3Pulmonary Department, Mainz University Hospital, Mainz, Germany; 4Pulmonary Specialist Practice, Wiesbaden, Germany; 5Biometrics, Alcedis GmbH, Gie&amp;szlig;en, Germany Background: Maintaining and improving physical functioning is key to mitigating the cycle of deconditioning associated with chronic obstructive pulmonary disease (COPD). We evaluated the impact of free combination of the long-acting anticholinergic tiotropium plus the long-acting &amp;beta;2-agonist ol…

Type 2-High and Type 2-Low Airway Inflammation in Severe Asthma

COPD in elderly patients – an analysis of the DACCORD observational study

Introduction: In elderly patients COPD is frequently complicated by the presence of several comorbidities and the many non-COPD-related medications prescribed to treat these conditions. This analysis aims to characterize COPD patients above the age of 75 in a real-world cohort in Germany. Methods: DACCORD is a prospective, non-interventional study collecting data from COPD patients treated in primary and secondary care. Prior to study entry, patients either initiated or changed COPD maintenance medication. Moderate/severe exacerbations, COPD-medication and non-COPD medication were documented at baseline and every 3 months. Comorbidities were documented at baseline. Results: Baseline charact…

CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease

Background Based on their potency to control allergic diseases, regulatory T (Treg) cells represent a promising target for novel strategies to interfere with allergic airway inflammation. We have previously demonstrated that stimulation of the CD4 molecule on human Treg cells activates their suppressive activity in vitro and in vivo . Objective We sought to determine the effect of CD4-mediated Treg-cell activation on pulmonary inflammation in a humanized mouse model of allergic airway inflammation. Methods PBMCs obtained from donors allergic to birch pollen or from healthy donors were injected into NOD-severe combined immunodeficiency γc −/− mice, followed by allergen airway challenges and …

Long-term general and cardiovascular safety of tiotropium/olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease

Abstract Background Long-term safety, particularly cardiovascular safety, is of special interest in maintenance treatment of chronic obstructive pulmonary disease (COPD) with long-acting β 2 -agonists and long-acting muscarinic antagonists, given potential cardiovascular effects. Methods Two 52-week Phase III trials (TONADO ® ) investigated tiotropium/olodaterol (5/5 and 2.5/5 μg) versus tiotropium 2.5, 5 μg and olodaterol 5 μg. In a pre-specified safety analysis, investigator-reported treatment-emergent adverse events (AEs), electrocardiogram and laboratory data were pooled. All serious AE (SAE) reports were reviewed by an independent Adjudication Committee, which assessed whether deaths, …

Single and Synergistic Effects of Type 2 Cytokines on Eosinophils and Asthma Hallmarks

Abstract The type 2 cytokines IL-5, IL-13, and IL-4 play an important role in the induction and progression of asthma. According to the Global Initiative for Asthma guidelines, blood eosinophil numbers are one marker that helps to guide treatment decisions in patients suffering from severe forms of asthma. Effects of type 2 cytokines were analyzed, alone or in combination, on eosinophils in blood and other compartments and on the development of asthma symptoms. C57BL/6 mice received a single intranasal application of equimolar amounts of IL-5, IL-13, and IL-4, alone or in combination. Numbers, activation state, and migratory behavior of eosinophils in bone marrow (BM), blood, lung, and bron…

Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD.

Two, once daily (q.d.) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the β(2)-agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability. Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 μg q.d. (n=797) or tiotropium 18 μg q.d. (n=801) for 12 weeks. After 12 weeks, the two treatments had similar overall effects on "trough" (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.0…

Anti-interleukin-5 therapy (mepolizumab) in life-threatening asthma attack: A case-based discussion

We report about a case of a compassionate off-label use of the anti-interleukin-5-agent mepolizumab in a ventilated patient with life-threatening asthma attack in eosinophilic asthma. The patient suffered from severe eosinophilic asthma and was transmitted to our hospital with an asthma attack and a life-threatening respiratory state under ventilation. Since high dose steroids had not yielded a sufficient respiratory improvement mepolizumab was administered subcutaneously. After administration of mepolizumab respiratory state and ventilation parameter improved significantly. Two days after administration the patient was weaned could be extubated 8 days later and recovered completely from th…

Current and future pharmacologic therapy of exacerbations in chronic obstructive pulmonary disease and asthma.

Exacerbations are an important cause of the morbidity and mortality associated with asthma and chronic obstructive pulmonary disease. Newer therapies include long-acting beta(2)-agonists, which are more effective than short-acting bronchodilators. Inhaled corticosteroids and, in asthma, leukotriene receptor antagonists may have roles in the early phase of exacerbation as an alternative to or added to oral prednisolone. In the future, combinations of long-acting beta(2)-agonists and anticholinergic bronchodilators may offer additive clinical benefits. However, although the treatment and prevention of exacerbations of chronic obstructive pulmonary disease and asthma have been improved by usin…

Is the patient's baseline inhaled steroid dose a factor for choosing the budesonide/formoterol maintenance and reliever therapy regimen?

Objective: Baseline inhaled corticosteroid (ICS) dose may be a factor for prescribers to consider when they select a budesonide/formoterol maintenance and reliever therapy regimen for symptomatic asthmatics. Methods: A 6-month randomized study compared two maintenance doses of budesonide/formoterol 160/4.5 µg, 1 × 2 and 2 × 2, plus as needed, in 8424 asthma patients with symptoms when treated with ICS ± an inhaled long-acting β2-agonist (LABA). In the total study population, 1339 (17%) were high-dose ICS (HD) users (≥1600 µg/day budesonide). This HD stratum was compared with the rest of the study population, divided into low-dose (LD; 400 µg/day) and medium-dose strata (MD; 401–1599 µg/day…

Characterization of the interstitial lung and peripheral blood T cell receptor repertoire in cigarette smokers.

T lymphocytes modulate the pulmonary inflammatory response. The aim of this study was to evaluate the clonality within the interstitial lung and peripheral blood T cell receptor (TCR) repertoire in smokers. Interstitial T lymphocytes were isolated from surplus tissue of 16 patients (63 +/- 9 [+/- SD] yr old, 11 male) undergoing surgery due to lung cancer (n = 15) or emphysema. TCR clonality was assessed by PCR amplification followed by spectratyping. Nearly all TCR of interstitial lung lymphocytes showed oligoclonal bands (CD4(+) subset 13/16 patients, 81%; CD8(+) 100%) indicating a specific differentiation. Peripheral blood T lymphocytes (PBL) TCR (especially CD4(+)) had less oligoclonal b…

Exposure to Toll like Receptor 7 (TLR7)-Ligand Supports Sensitization to an Inhaled Allergen.

Efficacy of a fixed combination of ciclesonide and formoterol: the EXCITED-study.

SummaryRecommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta2-agonist. The present study was designed to evaluate the efficacy of a newly developed fixed combination of ciclesonide and formoterol in comparison to the marketed fixed combination of fluticasone and salmeterol in patients with moderate asthma.This was a phase II, multi-centre, randomized, parallel-group, double-blind, double-dummy study. After a 2-week run-in period, 160 patients with moderate asthma were randomized to a 6-week treatment with ciclesonide/formoterol 320/9 μg bid (CIC/F) or fluticasone propionate/salmeterol 250/50 μg bid (FP/S), both delivered a…

Measurement of Fractional Exhaled Nitric Oxide: Comparison of Three Different Analysers

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Fractional exhaled nitric oxide (FeNO) is a surrogate marker for airway inflammation, supporting the diagnostic pathway and treatment decisions for asthma patients. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; Aim of this study was to compare the new analyser Vivatmo pro (Bosch, BV) with NIOX VERO (Circassia, CN) and CLD (Ecomedics, EC). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In 100 asthmatics (median 53 years [range 20–87], 62% female, 86% on inhaled corticosteroids [mean 1,300 μg beclomethasone dipropionate or equivalent], 35% treated with biologics) 2 FeNO measurements per device were performed. Additionally, the success rate…

P121 Characteristics of COPD patients with and without maintenance treatment at baseline, by GOLD stage: TONADO: Abstract P121 Table 1

Rationale The efficacy and safety of the once-daily combination of tiotropium (T), a long-acting muscarinic antagonist (LAMA), and olodaterol (O), a long-acting β 2 -agonist (LABA), for the treatment of chronic obstructive pulmonary disease (COPD) has been established. We investigated whether there was a difference in the characteristics of COPD patients with and without baseline maintenance treatment. Methods Two replicate, randomised, 52-week, double-blind, parallel-group, Phase III trials (NCT01431274; NCT01431287; n = 5162) assessed the efficacy and safety of once-daily treatment with T+O (2.5/5 μg; 5/5 μg; Respimat® inhaler) compared to the individual components. Baseline characteristi…

S2K-Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose

Die idiopathische pulmonale Fibrose (IPF) ist eine schwerwiegende und in der Regel zum Tod fuhrende Erkrankung, die bisher nur unzureichend behandelt werden kann. Empfehlungen zur Diagnostik und Therapie wurden erstmals im ATS-ERS-Statement im Jahr 2000 publiziert 1 . Seither haben sich die diagnostischen Standards geandert und es liegen zahlreiche Therapiestudien zu diesem Krankheitsbild vor, die es erforderlich machten, die bestehenden Empfehlungen zu uberarbeiten und eine wissenschaftlich begrundete Leitlinie zu erstellen. Diese wurde von einer internationalen Expertengruppe in den Jahren 2006 – 2010 erarbeitet und publiziert 2 . Die folgenden Ausfuhrungen beinhalten eine Ubersetzung wes…

THE RECOVERY-ELISA—A NOVEL ASSAY TECHNIQUE TO MONITOR THERAPY WITH HUMANIZED ANTIBODIES: THE EXAMPLE OF OMALIZUMAB

The therapeutic use of antibodies has grown exponentially, providing new treatment options for various diseases. Monitoring treatment with therapeutic antibodies is a particular challenge because often the target antigen is no longer measurable or the results are unreliable. To overcome this problem, a recovery-ELISA was developed to quantify therapeutic antibody and antigen by a modification of the traditional sandwich immunoassay using omalizumab as an example. Standard serum samples were spiked with IgE and omalizumab in a certain concentration range to create standard curves. After incubation and washout procedures, the reaction was stopped and the plate read with bichromatic absorbance…

Dose bridging data for mometasone furoate in once-daily fixed-dose inhaled combinations of mometasone furoate/indacaterol and mometasone furoate/ indacaterol/glycopyrronium in patients with asthma

Once-daily (o.d.) fixed-dose combinations of mometasone furoate/indacaterol acetate (MF/IND) and mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY), both delivered via the Breezhaler® device, are approved for the maintenance treatment of asthma. Across these fixed-dose combinations, while the doses of bronchodilators remain the same, the nominal doses of mometasone furoate in micrograms differ. This article presents the steps followed in bridging the mometasone furoate doses at the corresponding dose strengths in the mometasone furoate formulation delivered via the Twisthaler® and mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glyco…

Tiotropium+olodaterol chez les patients atteints de BPCO modérée à sévère avec la bronchite chronique et/ou l’emphysème

Introduction La bronchite chronique et l’emphyseme sont deux phenotypes de la BPCO qui peuvent influer sur les decisions de traitement pharmacologiques. Objectifs Tiotropium (T) + olodaterol (O) a ete etabli en tant que traitement de la BPCO dans deux grands essais de phase III. Cette analyse post hoc a evalue l’effet de T + O sur la fonction pulmonaire, les symptomes et la qualite de vie (QdV) chez les patients (pts) selon la definition de la bronchite et/ou l’emphyseme portee par l’investigateur ( Fig. 1 ). Methodes Tonado® 1 + 2 etait dupliquee en 2 etudes jumelles, en double aveugle, controles vs traitement actif, les patients Gold 2–4 etaient randomises en 5 groupes paralleles (ratio 1…

Characterising individual response to mepolizumab treatment

Background: Patients with severe eosinophilic asthma (SEA) often have heterogenous phenotypes with periods of asthma worsening, making it difficult to assess mepolizumab treatment response. Aims: To define patient level variables for mepolizumab treatment response. Methods: In this post-hoc analysis we examined mepolizumab response in patients with SEA (≥2 exacerbations in prior year) in the 32-week, randomised, placebo-controlled MENSA study and the following 52-week, open-label COSMOS study. Patients who completed both studies and received mepolizumab throughout were included (n=311). Results: In MENSA, 67% and 21% of patients had 0 or 1 exacerbations, respectively, and were considered re…

Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease

Aqueous extract of Kalanchoe pinnata (Kp) have been found effective in models to reduce acute anaphylactic reactions. In the present study, we investigate the effect of Kp and the flavonoid quercetin (QE) and quercitrin (QI) on mast cell activation in vitro and in a model of allergic airway disease in vivo. Treatment with Kp and QE in vitro inhibited degranulation and cytokine production of bone marrow-derived mast cells following IgE/FcɛRI crosslinking, whereas treatment with QI had no effect. Similarly, in vivo treatment with Kp and QE decreased development of airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and production of IL-5, IL-13 and TNF. In contrast, treatm…

Pooled safety analysis of the fixed-dose combination of indacaterol and glycopyrronium (QVA149), its monocomponents, and tiotropium versus placebo in COPD patients

BACKGROUND: To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium (QVA149) and its monocomponents; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety databases.METHODS: Data from 11,404 patients with chronic obstructive pulmonary disease (COPD) were pooled from 14 clinical studies of QVA149, indacaterol and glycopyrronium of ≥3 month's duration with at least two of the treatment groups: QVA149 110/50 μg, glycopyrronium 50 μg, indacaterol 150 μg, placebo or tiotr…

A New Dosimeter Methacholine Challenge Protocol Based On A Single Methacholine Concentration

P125 Tiotropium plus olodaterol combination therapy provides lung-function benefits when compared to tiotropium alone, irrespective of prior treatment with a long-acting bronchodilator: post hoc analyses of two 1-year studies: Abstract P125 Table 1

Rationale Tiotropium plus olodaterol (T+O) is a novel once-daily combination of the long-acting muscarinic antagonist (LAMA) tiotropium (T) and the recently approved long-acting β 2 -agonist (LABA) olodaterol, for use as maintenance treatment in chronic obstructive pulmonary disease (COPD). These post hoc analyses of data from the two pivotal 1-year TONADO studies determined whether treatment with a long-acting bronchodilator (LABD) prior to randomisation affected the lung-function benefits of T+O 5/5 µg (via Respimat®) compared to T 5 µg (via Respimat®). Methods In the studies, 2124 patients had not received prior LABD treatment (T+O n = 426; T n = 454) and 3038 patients had (T+O n = 603, …

Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study.

PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in patients undergoing first-line chemotherapy for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable NSCLC were enrolled in an open-label, multicenter phase II study of three cycles of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175 mg/m2, day 1), or regimen B, cisplatin (100 mg/m2, day 1) plus vinorelbine (25 mg/m2, days 1, 8, 15, and 22) in combination with intratumoral injection of 7.5 × 1012 particles of SCH 58500 (rAd/p53, day 1). Responses of individual tumor lesions were assessed after each cycle, and gene transfer was examin…

Switch from LABA+ICS to a LABA/LAMA combination in symptomatic women with COPD – an analysis of the observational DACCORD study

Introduction: COPD prevalence in women has increased in recent years and the importance of avoiding ICS use in this group, because of its potential negative impact on comorbidities such as osteoporosis and diabetes, has become a topic of interest. In this real-life cohort women with COPD that were switched from LABA+ICS treatment to a fixed combination of LABA/LAMA were followed for 1 year. Methods: DACCORD is a prospective, non-interventional 2-year study in the primary and secondary care setting throughout Germany. Patients were recruited after a change in, or initiation of COPD maintenance medication. Data collected at baseline and every 3 months included moderate/severe exacerbations an…

Analysis Of Pulmonary Inflammation Using Humanized Mouse Models

Molekulare Zielstrukturen f�r die Therapie des Bronchialkarzinoms

Comparison of Exhaled Nitric Oxide (eNO) Measurements with 5 Different Analyzers.

A two-year evaluation of the ‘real life’ impact of COPD on patients in Germany: The DACCORD observational study

Abstract Introduction DACCORD is an observational, non-interventional study being conducted in German primary and secondary care centres. The study aims to describe the impact of disease (including exacerbations) and treatments over 2 years on ‘real-life' patients with chronic obstructive pulmonary disease (COPD). Materials and methods Patients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years and, on recruitment, were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and randomised clinical trial participation. Exacerbations data were collected every 3 months. COPD medication, COPD Assessment Test (CAT) and forced expiratory volu…

Two pathways, one patient; UK asthma guidelines

The first widely disseminated ‘asthma guideline’ came out of Australia and New Zealand in 1989,1 followed shortly by the British Thoracic Society (BTS) in 1990,2 the United States National Heart, Lung, and Blood Institute Expert Panel Report in 19913 and the Global Initiative for Asthma (GINA) strategy document in 1995.4 All have benefited from regular updates, the BTS collaborating with the Scottish Intercollegiate Guideline Network (SIGN) since 2003, most recently in 2016.5 Each new iteration of the asthma guidelines was written by experts in the field and based on best available evidence. It is not known whether these guidelines (or any others) have improved the care of people with asthm…

The frequent exacerbator in real-life: an analysis of the DACCORD study

Introduction: Exacerbation prevention is a major treatment goal in COPD. Hence, exacerbations are a decisive diagnostic and prognostic factor when it comes to therapy. The non-interventional prospective DACCORD study was following COPD patients for 2 years. Here, we compare patients with frequent exacerbations, non-frequent exacerbations and no exacerbations in the 6 months prior to study entry. Methods: DACCORD recruited COPD patients following a change or initiation of COPD maintenance. Data collected at baseline and every 3 months include exacerbations and COPD medication use. COPD Assessment Test (CAT) data were collected anually. Results: Out of 6527 patients, 7.1% were frequent exacer…

Inhibition of cAMP Degradation Improves Regulatory T Cell-Mediated Suppression of Allergic Airway Disease.

Profile of glycopyrronium for once-daily treatment of moderate-to-severe COPD

Bronchodilators are central in the symptomatic management of chronic obstructive pulmonary disease (COPD). Long-acting muscarinic antagonists (LAMAs) and long-acting β(2)-agonists (LABAs) are the main classes of long-acting bronchodilators. To date, tiotropium is the only once-daily LAMA available for the treatment of COPD. Glycopyrronium is a novel LAMA, currently in development for COPD. Phase II studies have shown that glycopyrronium 50 μg once daily provides clinically significant 24-hour bronchodilation with a rapid onset of action, which is faster than that of tiotropium, and a favorable safety and tolerability profile. The Phase III GLycopyrronium bromide in COPD airWays (GLOW) progr…

Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: a focused review of the impact data in the literature

This review provides an overview of the role of long-term treatment of severe asthma with oral corticosteroids (OCS) and its associated side-effects in adults. It is based on a systematic literature search conducted in MEDLINE, Embase and the Cochrane Library to identify relevant studies. After a short overview of severe asthma and its treatment we present studies showing a dose–response relationship in asthmatic patients treated with OCS and then consider by organ systems the undesired effects demonstrated in clinical and epidemiological studies in patients with OCS-dependent asthma. It was found that the risk of developing various OCS-related complications, including infections, diabetes …

A year in the life of German patients with COPD: the DACCORD observational study

Roland Buhl,1 Carl-Peter Cri&amp;eacute;e,2 Peter Kardos,3 Claus Vogelmeier,4,5 Nadine Lossi,6 Claudia Mail&amp;auml;nder,6 Heinrich Worth7 1Pulmonary Department, Mainz University Hospital, Mainz, 2Department of Sleep and Respiratory Medicine, Evangelical Hospital G&amp;ouml;ttingen-Weende, Bovenden, 3Group Practice and Centre for Allergy, Respiratory and Sleep Medicine, Red Cross Maingau Hospital, Frankfurt am Main, 4Department of Medicine, Pulmonary, and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, 5German Center for Lung Research, Marburg, 6Clinical Research Primary Care, Novartis Pharma GmbH, N&amp;uuml;rnberg, 7Facharztforum F&amp;…

Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany

Omalizumab is a humanized monoclonal anti-immunoglobulin E (IgE) antibody indicated in Europe for the treatment of uncontrolled severe persistent allergic (IgE-mediated) asthma despite optimal therapy with inhaled corticosteroids and long-acting beta(2) agonists. Between 2005 and 2007 280 patients (58% female, mean age 44+/-16 yrs., 46% on oral corticosteroids, median serum IgE level 235IU/ml) who met the EU criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab by 134 physicians as part of a post-marketing surveillance trial and were followed-up for 6 months. The median follow-up time was 195 days, the patients were treated with a median dose of 450mg omalizum…

Corrigendum to “The use of omalizumab in the treatment of severe allergic asthma: A clinical experience update” [Respiratory Medicine 103 (2009) 1098–1113]

a Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, D level Centre Block (MP810), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK Mainz University Hospital, 55131 Mainz, Germany Hopital Arnaud de Villeneuve, FR-34000 Montpellier, France Novartis Horsham Research Centre, Horsham, RH12 5AB, UK Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, USA

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 …

An open-label, prospective phase I/II study evaluating the immunogenicity and safety of a ras peptide vaccine plus GM-CSF in patients with non-small cell lung cancer.

Mutations of the ras gene have been reported in 20-40% of NSCLC patients. If present, they are critical for the malignant phenotype of these tumors. Therefore, targeting them by specific vaccination is a promising therapeutic approach. In a clinical trial we screened for ras mutations in patients with NSCLC. Patients with ras-positive tumors were immunized six times intradermally with a mixture of seven peptides representing the most common ras mutations. Objectives of the study were the feasibility, efficacy and safety of the vaccination. In addition, the induction of a specific immune reaction was investigated by DTH tests, and the induction of peptide-specific T cells was tested in ex vi…

Exceptional LAS Requests in Eurotransplant: Analysis of an 8-year Effort to Improve Lung Allocation for Precarious Patients

PURPOSE: Following introduction of the lung allocation score (LAS) in 2011, Eurotransplant member centers can apply for an exceptional LAS (eLAS) if the calculated LAS insufficiently reflects the perceived transplant benefit for a patient, specifically in case of primary pulmonary hypertension group 1 and 4; combined lung+non-renal transplantation; rare diseases; or extracorporeal support. Each eLAS proposal is evaluated by a LAS Review Board, consisting of ≥3 lung transplant experts, which subsequently declines or approves the eLAS request in consensus of ≥3 votes. In case of a lower than accepted score, predefined business rules to assign LAS percentiles are used. METHODS: A retrospective…

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second c…

P123 Inhaled corticosteroid plus long-acting β2-agonist therapy is overused in the treatment of patients with chronic obstructive pulmonary disease: post hoc analyses of two 1-year studies: Abstract P123 Table 1

Rationale Inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) therapy is indicated for different patient groups with chronic obstructive pulmonary disease (COPD) in the USA and Europe. In the previous version of the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations, the use of ICS plus LABA therapy was restricted to patients with severe and very severe lung-function impairment and frequent exacerbations, with overtreatment in milder patient populations well documented. The current GOLD document recommends the use of ICS plus LABA maintenance therapy for patients in categories C and D. Methods We present post hoc analyses from the two pivotal 1-year TO…

The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial.

BackgroundTiotropium, a once-daily long-acting anticholinergic bronchodilator, has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids (ICS).ObjectiveThe objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat (5 μg or 2.5 μg), compared with placebo Respimat, as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma.MethodsA phase III, double-blind, placebo-controlled trial was conducted (NCT01316380). Adults with symptomatic asthma receiving low- to medium-dose ICS (200-400 μg budesonide or equivalent dose) and a pre-bronchodilator forced expira…

Budesonide/Formoterol Maintenance And Reliever Therapy In Patients With Difficult-To-Control Asthma

Prevention Of COPD Exacerbations With Tiotropium Versus Salmeterol: Pooled Analysis From Clinical Studies

EXPRESSION OF T-CELL TRANSCRIPTION FACTOR T-BET IS INCREASED IN COPD

Measurement of exhaled nitric oxide: Comparison of different analysers

Background and objective:  Exhaled nitric oxide (NO) is used as a surrogate marker to monitor eosinophilic airway inflammation, assist in diagnosis, and support treatment decisions for asthma patients. The aim of this study was to compare five NO analysers: Medisoft (M), Aerocrine Niox (N), Aerocrine Niox flex (NF), Aerocrino Niox mino (NM) and EcoMedics (E). Methods:  In 85 subjects (25 asthma patients, 25 COPD patients, 35 healthy volunteers; median age 36.5 years, range 23–79, 47% female), three NO measurements per individual were performed, using each analyser according to the American Thoracic Society/European Respiratory Society guidelines. Subjects evaluated the devices on the basis …

Indacaterol Provides Effective Bronchodilation In Patients With Chronic Obstructive Pulmonary Disease Irrespective Of Patient Age (&lt;65 Or e65 Years)

The effect of adjustable dosing with budesonide/formoterol on health-related quality of life and asthma control compared with fixed dosing

Budesonide/formoterol in a single inhaler is an effective therapy for asthma. We investigated whether adjustable maintenance dosing with budesonide/formoterol could maintain health-related quality of life (HRQL) and asthma control.Asthma patients (n = 4025) received budesonide/formoterol (Symbicort 160/4.5 microg) 2 inhalations twice daily (b.i.d.) for 4 weeks during run-in of this open, multicentre study. Patients were randomised to adjustable dosing (budesonide/formoterol 1 inhalation b.i.d.; stepping up to 2 or 4 inhalations bid for 1 week if asthma worsened) or fixed dosing (budesonide/formoterol 2 inhalations b.i.d.), for 12 weeks. Change in HRQL (standardised Asthma Quality of Life Qu…

The Treatment of Mild and Moderate Asthma in Adults

BACKGROUND: Asthma is a chronic inflammatory airway disease that usually causes variable airway obstruction. It affects 5–10% of the German population. METHODS: This review is based on relevant publications retrieved by a selective search, as well as on national and international guidelines on the treatment of mild and moderate asthma in adults. RESULTS: The goal of treatment is to attain optimal asthma control with a minimal risk of exacerbations and mortality, loss of pulmonary function, and drug side effects. This can be achieved with a combination of pharmacotherapy and non-drug treatment including patient education, exercise, smoking cessation, and rehabilitation. Pharmacohterapy is ba…

Do asthmatic smokers benefit as much as non-smokers on budesonide/formoterol maintenance and reliever therapy? Results of an open label study

SummaryBackgroundStudies with inhaled corticosteroids (ICS) in smoking asthmatics have mostly shown poorer treatment responses than in non-smoking asthmatics.MethodsEuroSMART, an open, randomised, 6-month study, compared budesonide/formoterol (Symbicort ® Turbuhaler®)hhNeither the Symbicort SMART posology nor the dry powder formulation, Turbuhaler, is currently approved in the US. maintenance and reliever therapy (Symbicort SMART®) at two maintenance doses of budesonide/formoterol (160/4.5 μg), 1 × 2 and 2 × 2, in patients with asthma who were symptomatic despite treatment with ICS ± long-acting β2-agonists. The 8424 randomised patients included 886 smokers (11%; aged <40 years or with a sm…

New fixed bronchodilator combinations of a long-acting β2-agonist and a long-acting anticholinergic

The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy.

Abstract Background Divergent strategies have emerged for the management of severe asthma. One strategy utilises high and fixed doses of maintenance treatment, usually inhaled corticosteroid/long-acting β2-agonist (ICS/LABA), supplemented by a short-acting β2-agonist (SABA) as needed. Alternatively, budesonide/formoterol is used as both maintenance and reliever therapy. The latter is superior to fixed-dose treatment in reducing severe exacerbations while achieving similar or better asthma control in other regards. Exacerbations may be reduced by the use of budesonide/formoterol as reliever medication during periods of unstable asthma. We examined the risk of a severe exacerbation in the per…

P260 Tiotropium Respimat(R) Add-on To Inhaled Corticosteroids Improves Lung Function In Patients With Symptomatic Mild Asthma: Results From A Phase Iii Trial

Background Despite currently available therapies and detailed guidelines, many people with mild asthma remain symptomatic; it is important to establish the efficacy and safety of new treatments in this group. Methods A Phase III, randomised, double-blind, parallel-group trial (GraziaTinA-asthma ® ; NCT01316380) evaluated the efficacy and safety of once-daily tiotropium 5 µg or 2.5 µg versus placebo (all delivered via the Respimat ® SoftMist™ inhaler) for 12 weeks in patients with symptomatic asthma on low-dose inhaled corticosteroids (200–400 µg budesonide or equivalent). The primary end point was peak forced expiratory volume in 1 second (FEV 1 ) within 3 h of dosing (0–3h) response (chang…

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)…

Wirksamkeit und Verträglichkeit von Salmeterol in der Langzeit-therapie bei Patienten mit obstruktiver Atemwegserkrankung

BACKGROUND Salmeterol is a long-acting inhaled beta 2-agonist with a bronchodilating effect lasting over 10 to 12 hours. METHODS A prospective, open, multi-centre study was performed to evaluate the efficacy and safety of inhaled salmeterol (50 micrograms BID) over a mean treatment period of 29 months (range: 4-1145 days) in 634 patients (54% male, age 45 +/- 15 years) with mild to moderate asthma or chronic obstructive pulmonary disease (COPD). Peak expiratory flow rates, rescue use of short acting beta 2-agonists and safety were study objectives. Patients were critically monitored for a possible loss of bronchodilator efficacy of salmeterol during long-term treatment. RESULTS During the f…

Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma.

The role of IgE in patients with severe asthma is not fully understood.We sought to investigate whether IgE to Staphylococcus aureus enterotoxins might be relevant to disease severity in adult asthmatic patients.Specific IgE antibody concentrations in serum against enterotoxins, grass pollen (GP), and house dust mite allergens and total IgE levels were measured in adult cohorts of 69 control subjects, 152 patients with nonsevere asthma, and 166 patients with severe asthma. Severe asthma was defined as inadequately controlled disease despite high-dose inhaled corticosteroids plus at least 2 other controller therapies, including oral steroids.Enterotoxin IgE positivity was significantly great…

Tiotropium reduces airflow obstruction in asthma patients, independent of body mass index

Vitamin D Insufficiency In Adult Asthma Is Associated With Asthma Severity And Control

Data in asthmatic children suggest that low vitamin D levels are associated with poor asthma control, reduced lung function, and increased medication intake. To investigate the role of vitamin D insufficiency in adult asthmatics 25-hydroxyvitamin D was measured in 280 adult patients with asthma (mean±SEM: 45.0±0.8 yrs., 40% male, FEV1 74.9±1.4%) and correlated with clinical parameters of asthma control. The majority of patients had severe asthma (n=155, 55%) and were uncontrolled (n=144, 51%). Serum levels of vitamin D were significantly related to asthma severity (mean±SEM: intermittent 31.1±3.2 ng/ml, mild 27.3±1.6 ng/ml, moderate 26.5±1.5, severe 24.0±0.9, p=0.046) and asthma control (co…

P149 Once-daily tiotropium Respimat® add-on to at least ICS in adult patients with symptomatic asthma: pooled safety analysis: Abstract P149 Table 1

Background A high proportion of patients with asthma are symptomatic despite at least ICS maintenance therapy. Five trials aimed to evaluate the safety of tiotropium Respimat® compared with placebo Respimat®, each as add-on to at least ICS in adult patients with symptomatic asthma. Methods Five Phase III and one Phase II randomised, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-asthma® (48 weeks): tiotropium Respimat® 5 µg add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-asthma® (24 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (400–800 µg budesonide or equivalent); GraziaTinA-asthma® (12 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on t…

Omalizumab and the risk of malignancy: results from a pooled analysis.

Background Since initial registration, the omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%). The previous analysis was based on limited available data, warranting further investigation. Objective We sought to examine the incidence of malignancy using comprehensive pooled data from clinical trials of omalizumab-treated patients. Methods This pooled analysis included data from 67 phase I to IV clinical trials. The prespeci…

Psychological distress in lung cancer survivors at least 1 year after diagnosis-Results of a German multicenter cross-sectional study.

Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

International audience; Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance …

Against all odds: anti-IgE for intrinsic asthma?

For many years, pathogenetic concepts and the results of clinical trials supported the view that anti-IgE treatment is specifically effective in allergic asthma. However, there is now growing clinical and mechanistic evidence suggesting that treatment with the anti-IgE antibody omalizumab can be effective in patients with intrinsic asthma. Therefore, large and well-controlled clinical trials with anti-IgE are urgently warranted in patients with intrinsic asthma. In addition, there is a need to find new biomarkers which can identify patients with asthma who respond to anti-IgE treatment.

&lt;p&gt;Switch from IL-5 to IL-5-Receptor α Antibody Treatment in Severe Eosinophilic Asthma&lt;/p&gt;

Background Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy. Methods In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under …

Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial

Chronic non-specific respiratory symptoms are difficult to manage. This trial aimed to evaluate the association between baseline fractional exhaled nitric oxide (FeNO) and the response to inhaled corticosteroids in patients with non-specific respiratory symptoms.In this double-blind randomised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, wheeze, or dyspnoea and less than 20% bronchodilator reversibility across 26 primary care centres and hospitals in the UK and Singapore. Patients were assessed for 2 weeks before being randomly assigned (1:1) to 4 weeks of treatment with extrafine inhaled corticosteroids (QVAR 80 μg, two puffs twice per day, equi…

Clinical Development of Mepolizumab for the Treatment of Severe Eosinophilic Asthma: On the Path to Personalized Medicine.

The development of mepolizumab, an anti-IL-5 monoclonal antibody for the treatment of severe eosinophilic asthma, is an example of a clinical development program that evolved over time based on sound, basic scientific principles. Initial clinical data on the effects of mepolizumab on lung function in a general asthmatic population were disappointing. However, it became clear that mepolizumab may be more effective against other clinical endpoints, particularly asthma exacerbations, in patients with more severe disease. Furthermore, a developing understanding of asthma disease pathobiology led to the identification of an appropriate target population and predictive biomarker for mepolizumab t…

P294 Benefits of tiotropium/olodaterol over tiotropium at delaying clinically significant events in patients with copd classified as gold B

Rationale The once-daily combination of tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, has demonstrated efficacy and safety in COPD. Two large clinical studies (TONADO ® 1 + 2) have also demonstrated the benefits of T/O compared to the monocomponents in patients with moderate to very severe COPD. This post hoc analysis investigated whether T/O is more effective than T at delaying clinically significant events in patients with GOLD stage B COPD. Methods A total of 5162 patients were randomised to O 5 µg, T 2.5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg (delivered via Respimat ® inhaler) in two 52-week, parallel-group, double-blind studies (NC…

Assessing biomarkers in a real-world severe asthma study (ARIETTA)

AbstractThe prognostic value of asthma biomarkers in routine clinical practice is not fully understood. ARIETTA (NCT02537691) is an ongoing, prospective, longitudinal, international, multicentre real-world study designed to assess the relationship between asthma biomarkers and disease-related health outcomes. The trial aims to enrol and follow for 52 weeks approximately 1200 severe asthma patients from approximately 160 sites in more than 20 countries. Severe asthmatics, treated with daily inhaled corticosteroid (≥500 μg of fluticasone propionate or equivalent) and at least 1 second controller medication are to be included. In this real-world study, patients will be treated according to the…

Patient Baseline Characteristics Predict An Increased Risk Of Future Asthma Exacerbations

Predicting Responders to Reslizumab after 16 Weeks of Treatment Using an Algorithm Derived from Clinical Studies of Patients with Severe Eosinophilic Asthma.

Reslizumab is a humanized anti-IL-5 monoclonal antibody used as add-on maintenance treatment for patients with uncontrolled eosinophilic asthma.To predict response and nonresponse to intravenous reslizumab at 52 weeks with an algorithm we developed based on clinical indicators from pivotal clinical trials.Patients aged 18 years and older who met Global Initiative for Asthma 4 or 5 criteria and received intravenous reslizumab (n = 321) in two trials ( www.clinicaltrials.gov identifiers, NCT01287039 and NCT01285323) were selected as the data source. A mathematical model was constructed that was based on change from baseline to 16 weeks in Asthma Control Questionnaire and Asthma Quality of Lif…

Tiotropium + olodaterol in patients with moderate to severe COPD with chronic bronchitis and/or emphysema

Introduction: Chronic bronchitis and emphysema are two COPD phenotypes that can affect pharmacologic treatment decisions. Aims: Tiotropium (T) + olodaterol (O) was established for COPD treatment in two large Phase III trials. This post hoc analysis assessed the effect of T+O on lung function, symptoms and health-related quality of life (QoL) in patients (pts) with investigator-defined bronchitis and/or emphysema. Methods: TONADO ® 1+2 were replicate, randomised, double-blind, parallel-group trials. Pts with GOLD 2–4 COPD were randomised to once-daily T+O 2.5/5 or 5/5 µg, T 2.5 or 5 µg, or O 5 µg via Respimat ® inhaler. 1 End points included forced expiratory volume in 1 second (FEV 1 ) area…

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…

c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. e…

Future Directions in the Pharmacologic Therapy of Chronic Obstructive Pulmonary Disease

Current therapy for chronic obstructive pulmonary disease (COPD) fails to alter its relentless progression. This remains a significant challenge and unmet need. A recent advance is the demonstration that treatment with a fixed dose of an inhaled corticosteroid and a long-acting beta2-agonist in COPD improves lung function and quality of life, and reduces exacerbation more effectively than either drug alone. Other improvements include the introduction of tiotropium, a once-daily anticholinergic. In advanced clinical development are other once-daily bronchodilators and combinations of anticholinergic drugs and beta2-agonists. Increased understanding of the pathogenesis of COPD has led to nove…

P128 Pooled safety analysis of adjudicated serious adverse events with the combination of tiotropium + olodaterol: Abstract P128 Table 1

Rationale This analysis aimed to obtain a comprehensive and objective safety assessment of the combination of tiotropium (T), a long-acting muscarinic antagonist, with olodaterol (O), a long-acting β2-agonist, (T+O) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Methods Data from two, 52-week, pivotal Phase III trials investigating T+O 5/5 µg and T+O 2.5/5 µg versus T 2.5 µg, 5 µg and O 5 µg were pooled, and patient narratives and profiles of serious adverse-event (SAE) reports were reviewed by an independent Adjudication Committee. The committee members independently assessed all SAEs to determine if any deaths, hospitalisations or intubations were r…

Late Breaking Abstract - Predictive value of FeNO in patients with non-specific respiratory symptoms: a randomised controlled trial

Background: Fractional exhaled nitric oxide (FeNO) can predict treatment response in asthma, but little is known of its utility in patients with non-specific respiratory symptoms (NSRS). Aims and objectives: To evaluate the association between baseline FeNO and response to treatment with inhaled corticosteroids (ICS) in patients with NSRS. Methods: This was a multi-centre randomised, placebo-controlled trial, carried out in UK and Singapore. It consisted of a 2-week assessment period to establish baseline measurements and a 4-week treatment period with either extrafine ICS (200 µ beclomethasone bid) or placebo. NIOX VERO (Circassia) was used to measure baseline FeNO. The primary endpoint wa…

The whole story: treatment outcomes with SymbicortS

Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort (budesonide and formoterol in a single inhaler), a t…

Efficacy of once-daily tiotropium Respimat in adults with asthma at GINA Steps 2-5.

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4–5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2–5, a post hoc analysis of five double-blind trials (12–48-weeks; patients aged 18–75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0–3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients’ background treatment regi…