Optimizing the Development Strategy of Combination Therapy in Respiratory Medicine: From Isolated Airways to Patients

AbstractThe current recommendations for the treatment of chronic obstructive pulmonary disease (COPD) are pushing towards triple combination therapy based on the combination of an inhaled corticosteroid (ICS) associated with two bronchodilator agents. However, dual bronchodilation remains the cornerstone for the treatment of most COPD patients. Combining a long-acting β2 adrenoceptor agonist (LABA) with a long-acting muscarinic antagonist (LAMA) induces appreciable synergistic bronchorelaxant effect in human airways, especially when the medications are combined at isoeffective concentrations. Thus, each LABA/LAMA combination is characterized by a specific range of concentration-ratio at which the drug mixture may induce sustained synergistic interaction. Results of a recent randomized controlled trial (RCT, NCT00696020) and evidences from pre-clinical studies in human isolated airways poses the question whether combining tiotropium 5  μg with olodaterol 5 μg is the best combination option: tiotropium/olodaterol 5/5 μg has the same efficacy profile of tiotropium/olodaterol 5/2 μg, and it is less effective than tiotropium/olodaterol 5/10 μg. Furthermore, tiotropium/olodaterol 5/2 μg, 5/5 μg, and 5/10 μg combination s are generally characterized by the same safety profile. Indeed tiotropium/olodaterol 5/5 μg is effective and safe in COPD, but a different development strategy based on solid data obtained...
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research

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Authors: Zhao Z, Chang MY, Frerichs I, Zhang JH, Chang HT, Gow CH, Möller K Abstract BACKGROUND: Since bronchial abnormalities often exhibit spatial non-uniformity which may be not correctly assessed by conventional global lung function measures, regional information may help to characterize the disease progress. We hypothesized that regional air trapping during mechanical ventilation could be characterized by regional end-expiratory flow (EEF) derived from electrical impedance tomography (EIT). METHODS: Twenty-five patients suffering from chronic obstructive pulmonary disease (COPD grade 3 or 4) or severe...
Source: Minerva Anestesiologica - Category: Anesthesiology Tags: Minerva Anestesiol Source Type: research
Conclusion: In this group of pulmonologists confirmed COPD or ACO patients, a substantial proportion would be considered to have signs of asthma. In the personalized approach of airway disease management, these patients might benefit from ICS containing treatment. Prospective studies are needed to guide personalized care in this patient group.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: General practice and primary care Source Type: research
Conclusions: The presence of a wheeze seems to be the only clinical indicator to predict physician decision to prescribe SCS at exacerbation.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Monitoring airway disease Source Type: research
Background: Obese-related asthma (OBA) is an asthma sub-phenotype that often is severe. Inflamed adipose tissue may release pro (leptin) and anti-inflammatory (adiponectin) adipokines implicated in OBA. The effects of treatment with oral corticosteroids (OCS) on systemic levels of adipokines remains unknown.Subjects and Methods: Patients with mild to moderate asthma (MMA, n=55), severe asthma (SA= 72) and COPD (n=41) were from BIOAIR, a European multicenter study. After recruitment (visit 1), patients were optimized with medium doses of inhaled glucocorticosteroids (ICS) and LABA for four weeks (visit 2), then included in ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Allergy and immunology Source Type: research
Background: It is not clear how many patients with bronchiectasis without a history of asthma or COPD have actual airway hyperresponsiveness (AHR) and would benefit from inhaled corticosteroids (ICS).The aim of this study is to assess the presence of AHR in non-CF bronchiectasis excluding patients with a history of asthma or COPD.Design: For this study we used the data from the screening of the FORZA study. The FORZA study is a prospective double-blind randomized controlled trial comparing formoterol-beclomethasone versus placebo to evaluate the reduction in cough in patients with non-CF bronchiectasis without an underlyin...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory infections Source Type: research
Objectives: Few reports have investigated the efficacy of using inhaled corticosteroid (ICS)-containing inhalers to treat patients with asthma–COPD overlap (ACO). We assessed the effect of ICS treatment on patients with ACO using five sets of diagnostic criteria to identify predictors of the response.Methods: Patients with stable COPD enrolled in the Korean COPD subgroup study cohort were assessed for asthma overlap. Patients who were prospectively followed-up for 1 year.Measurements and Main Results: Among 1,067 COPD patients, 138 (12.9%), 32 (3.0%), 171 (16%), 221 (20.7%), and 264 (24.7%) were classified as having ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway pharmacology and treatment Source Type: research
The aim of this study was to evaluate the risk of moderate and/or severe exacerbations and all-cause mortality in a large primary care population after withdrawal of ICS compared to continued users stratified by elevated blood eosinophil counts. We included subjects’ aged 40 or more who had a diagnosis of COPD. We excluded subjects with a history of asthma, pulmonary fibrosis, cardiac arrhythmia and bronchiectasis, COPD exacerbations or with a myocardial infarction. We evaluated the risk of COPD outcomes among subjects by various blood eosinophil thresholds that withdrew from ICS using Cox regression analysis adjuste...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway pharmacology and treatment Source Type: research
Conclusion: Further studies are needed to characterize this group of patients in order to improve our clinical practice.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Clinical Problems Source Type: research
Background: This real-world cohort study was performed in chronic obstructive pulmonary disease (COPD) patients to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the GOLD guidelines.Methods: A total of 1144 patients from KOLD and KOCOSS cohorts, whose final follow-up visits were between 2017 and 2018, were analyzed. Features supporting ICS usage were: a history of asthma, blood eosinophils ≥300 cells/µl, or ≥2 exacerbations in the previous year. Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdra...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway pharmacology and treatment Source Type: research
Background: Inadequately controlled asthma and underuse of inhaled corticosteroids (ICS) may lead to SABA reliance. Association of SABA reliance and asthma exacerbation risk in a nationwide Swedish asthma population was examined.Methods: Linking drug- and patient-registries identified 365,324 asthma patients, defined as individuals aged 12–45 years prescribed 2 medications for obstructive lung disease in any 12-month period from 2006-2014 (inclusion: date of 2nd claim). Patients with COPD or an oral corticosteroid (OCS)-treated comorbidity were excluded. SABA reliance was defined as claims for>2 SABA canisters in ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway pharmacology and treatment Source Type: research
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