scholarly journals Long-acting muscarinic antagonists: a potential add-on therapy in the treatment of asthma?

2016 ◽  
Vol 25 (139) ◽  
pp. 54-64 ◽  
Author(s):  
William W. Busse ◽  
Ronald Dahl ◽  
Christine Jenkins ◽  
Alvaro A. Cruz
Keyword(s):  
Clinical Trials ◽  
Treatment Guidelines ◽  
Alternative Therapy ◽  
Significant Proportion ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Global Initiative For Asthma ◽  
Children With Asthma ◽  
Global Initiative ◽  
Long Acting

Asthma is a chronic inflammatory disorder of the airways that is a major global burden on both individuals and healthcare systems. Despite guideline-directed treatment, a significant proportion of patients with asthma do not achieve control. This review focuses on the potential use of long-acting anticholinergics as bronchodilators in the treatment of asthma, with results published from clinical trials of glycopyrrolate, umeclidinium and tiotropium. The tiotropium clinical trial programme is the most advanced, with data available from a number of phase II and III studies of tiotropium as an add-on to inhaled corticosteroid maintenance therapy, with or without a long-acting β2-agonist, in patients across asthma severities. Recent studies using the Respimat Soft Mist inhaler have identified 5 µg once daily as the preferred dosing regimen, which has shown promising results in adults, adolescents and children with asthma. Tiotropium Respimat has recently been incorporated into the Global Initiative for Asthma 2015 treatment strategy as a recommended alternative therapy at steps 4 and 5 in adult patients with a history of exacerbations. The increasing availability of evidence from ongoing and future clinical trials will be beneficial in determining where long-acting anticholinergic agents fit in future treatment guidelines across a variety of patient populations and disease severities.

scholarly journals First analysis of the Severe Paediatric Asthma Collaborative in Europe registry

2020 ◽  
Vol 6 (4) ◽  
pp. 00566-2020
Author(s):  
Norrice M. Liu ◽  
Karin C.L. Carlsen ◽  
Steve Cunningham ◽  
Grazia Fenu ◽  
Louise J. Fleming ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Suboptimal Control ◽  
High Dose ◽  
Asthma Control Test ◽  
European Respiratory Society ◽  
Paediatric Asthma ◽  
Global Initiative For Asthma ◽  
Global Initiative ◽  
Long Acting

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe.Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination.Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic.We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching.

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

2021 ◽  
pp. 2102730
Author(s):  
Helen K. Reddel ◽  
Leonard B. Bacharier ◽  
Eric D. Bateman ◽  
Christopher E. Brightling ◽  
Guy G. Brusselle ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Age Groups ◽  
Skills Training ◽  
Mild Asthma ◽  
Executive Summary ◽  
Global Initiative For Asthma ◽  
Global Initiative ◽  
Long Acting ◽  
Beta2 Agonist

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes.GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting beta2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as- needed combination ICS-formoterol reduces severe exacerbations by >60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function and inflammatory outcomes as daily ICS plus as-needed SABA.Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as-needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, MART) in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting beta2-agonist (LABA) (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11  years, new treatment options are added at Steps 3-4.Across all age-groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment and review remain essential to optimize asthma outcomes.

scholarly journals Comparing LAMA with LABA and LTRA as add-on therapies in primary care asthma management

2020 ◽  
Vol 30 (1) ◽  
Author(s):  
Alan Kaplan ◽  
J. Mark FitzGerald ◽  
Roland Buhl ◽  
Christian Vogelberg ◽  
Eckard Hamelmann
Keyword(s):  
Primary Care ◽  
Lung Function ◽  
Inhaled Corticosteroids ◽  
Asthma Management ◽  
Global Initiative For Asthma ◽  
Control Asthma ◽  
Global Initiative ◽  
Long Acting ◽  
Randomised Controlled ◽  
Meta Analyses

Abstract The Global Initiative for Asthma recommends a stepwise approach to adjust asthma treatment to the needs of individual patients; inhaled corticosteroids (ICS) remain the core pharmacological treatment. However, many patients remain poorly controlled, and evidence-based algorithms to decide on the best order and rationale for add-on therapies are lacking. We explore the challenges of asthma management in primary care and review outcomes from randomised controlled trials and meta-analyses comparing the long-acting muscarinic antagonist (LAMA) tiotropium with long-acting β2-agonists (LABAs) or leukotriene receptor antagonists (LTRAs) as add-on to ICS in patients with asthma. In adults, LAMAs and LABAs provide a greater improvement in lung function than LTRAs as add-on to ICS. In children, results were positive and comparable between therapies, but data are scarce. This information could aid decision-making in primary care, supporting the use of add-on therapy to ICS to help improve lung function, control asthma symptoms and prevent exacerbations.

scholarly journals Prevalence of overuse of short-acting beta-2 agonists (SABA) and associated factors among patients with asthma in Germany

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Heinrich Worth ◽  
Carl-Peter Criée ◽  
Claus F. Vogelmeier ◽  
Peter Kardos ◽  
Eva-Maria Becker ◽  
...  
Keyword(s):  
Beta Agonist ◽  
General Physician ◽  
Short Acting ◽  
Healthcare Data ◽  
Global Initiative For Asthma ◽  
Multivariable Regression ◽  
Beta 2 ◽  
Global Initiative ◽  
Long Acting ◽  
Underlying Inflammation

Abstract Background Overuse of short-acting beta-2 agonists (SABA), which do not treat the underlying inflammation of asthma, is linked to poor clinical outcomes such as increased exacerbation risk. This study, as part of the SABINA program, estimated the prevalence of SABA overuse and associated variables in outpatients in Germany. Methods This retrospective study used anonymized electronic healthcare data from the Disease Analyzer database (IQVIA). A total of 15,640 patients aged ≥ 12 years with asthma who received ≥ 1 SABA prescription(s) between July 2017 and June 2018 in 924 general physician and 22 pneumologist (PN) practices were included. SABA overuse was defined as ≥ 3 prescribed inhalers (~ 200 puffs each) during the study period. The associations between SABA overuse and physician specialty, Global Initiative for Asthma (GINA) steps (based on asthma medications), age, sex, and inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) use were estimated using multivariable regression for patients with probable moderate (GINA step 2) and probable severe (GINA steps 3–5) asthma. Results Annually, 36% of all patients (GINA steps 1–5) in general and 38% in PN practices received ≥ 3 SABA inhalers. The risk of SABA overuse was 14% higher in patients treated by a general practitioner vs. a PN; 34% and 85% higher in GINA steps 4 and 5, respectively, vs. GINA step 3; and 40% higher in male vs. female patients. Conclusions SABA overuse is prevalent among patients with asthma across all GINA steps in Germany, which may indicate suboptimal asthma control. Further studies are needed to investigate the reasons behind SABA overuse.

scholarly journals Tiotropium bromide: additional options for the treatment of bronchial asthma

2019 ◽  
Vol 16 (3) ◽  
pp. 67-74
Author(s):  
O M Kurbacheva ◽  
M E Dyneva
Keyword(s):  
Bronchial Asthma ◽  
Inhaled Corticosteroids ◽  
Biological Properties ◽  
Additional Treatment ◽  
Tiotropium Bromide ◽  
Inhalation Therapy ◽  
Global Initiative For Asthma ◽  
Successful Control ◽  
Global Initiative ◽  
Long Acting

Bronchial asthma (BA) is one of the most common chronic diseases, characterized by airway inflammation and bronchospasm. Symptoms of BA are wheezing, shortness of breath, a feeling of constriction in the chest and cough, the frequency and severity of which vary greatly over time. Today studies of BA phenotypes allow selecting treatment depending on the particular pathogenesis of each phenotype individually, thereby helping to achieve control, which is the main goal of BA therapy. However, it is necessary to take into account the peculiarities of airway innervation, since an increased parasympathetic tone is characteristics of all BA phenotypes and plays an important role in the development of bronchoconstriction and inflammation. Therefore, tiotropium bromide, which is a long-acting blocker of muscarinic cholinergic receptors, is one of the main bronchodilators in the treatment of BA. It blocks bronchoconstriction, hypersecretion and swelling of the mucous membrane of the airway, which in turn prevents the progression of inflammation, and the prolonged action of tiotropium bromide, which allows it to be used once a day helps to achieve control of asthma in addition to basic inhalation therapy - inhaled corticosteroids (ICS) long-acting P2-agonists (LABA). According to GINA (Global Initiative for Asthma), tiotropium bromide is recommended as an additional treatment, starting from step 4, and in accordance with the Russian Federal Clinical Guidelines for Bronchial Asthma - from step 3. Currently, according to clinical studies, much is known about the mechanisms of action and biological properties of tiotropium bromide, which made it possible to substantiate the needs for its administration to patients with BA regardless of its phenotype. This strategy will contribute to a more successful control of BA considering risk factors and comorbidity, thereby reducing needs of increasing ICS dose.

scholarly journals Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials

2021 ◽  
Vol 16 ◽  
Author(s):  
Alberto J Lorenzatti
Keyword(s):  
Clinical Trials ◽  
Arterial Wall ◽  
Plaque Formation ◽  
Phase Iii ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Phase Iii Clinical Trials ◽  
Cytokines And Chemokines ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a chronic inflammatory disorder of the vasculature where cholesterol accumulates in the arterial wall stimulating infiltration of immune cells. This plays an important role in plaque formation, as well as complications caused by its build up. Pro-inflammatory cytokines and chemokines are implicated throughout the progression of the disease and different therapies that aim to resolve this chronic inflammation, reduce cardiovascular (CV) events and improve clinical outcomes have been tested. The results from the pivotal CANTOS trial show that targeting the pro-inflammatory cytokine IL-1β successfully reduces the incidence of secondary CV events. This review briefly assesses the role of inflammation in atherosclerosis, providing a picture of the multiple players involved in the process and offering a perspective on targeting inflammation to prevent atherosclerotic CV events, as well as focusing on the results of the latest Phase III clinical trials.

scholarly journals Leukotriene B4 levels in sputum from asthma patients

2016 ◽  
Vol 2 (4) ◽  
pp. 00088-2015 ◽  
Author(s):  
Andrew Higham ◽  
Paul Cadden ◽  
Thomas Southworth ◽  
Matthew Rossall ◽  
Umme Kolsum ◽  
...  
Keyword(s):  
Leukotriene B4 ◽  
Healthy Controls ◽  
Asthma Treatment ◽  
Inhaled Corticosteroid ◽  
Global Initiative For Asthma ◽  
Treatment Stage ◽  
Asthma Patients ◽  
Global Initiative ◽  
Long Acting ◽  
The Relationship

Poor asthma control is associated with increased airway neutrophils. Leukotriene B4 (LTB4) is a potent neutrophil chemoattractant. We examined the levels of LTB4 levels in the sputum of asthma patients and the relationship with disease severity.47 asthma patients (categorised according to Global Initiative for Asthma treatment stage) and 12 healthy controls provided sputum samples that were processed first with PBS to obtain supernatants and secondly with dithiothreitol (DTT) to obtain supernatants. LTB4 levels were determined by ELISA.LTB4 levels were significantly higher in step 1 (steroid naïve) and step 3 (inhaled corticosteroid (ICS) plus long acting β-agonist) patients than step 2 patients (ICS alone) (p=0.02 and p=0.01, respectively). There was very good correlation when comparing PBS processed to DTT processed supernatants.High LTB4 levels were found in the sputum of asthmatics at step 3 despite ICS use.

scholarly journals Prevalence of Respiratory Viral Infections in Children with Asthma in Kermanshah

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Farhad Babaei ◽  
Hamid Reza Mortazavi ◽  
Nasim Kondori ◽  
Bahareh Cheshmenooshi ◽  
Mohsen Moghoofei
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Influenza Viruses ◽  
Inflammatory Disorder ◽  
Seasonal Incidence ◽  
Chronic Inflammatory Disorder ◽  
Children With Asthma ◽  
Respiratory Viral Infections ◽  
Syncytial Virus

Background: Asthma is a chronic inflammatory disorder of lung airways, affecting about 300 million people worldwide. Several risk factors are involved in asthma development, such as environmental allergens, genetic susceptibility, and respiratory viral infections. Viral infections induce NF-kB and inflammatory pathways that lead to the production of cytokines, chemokines, and inflammatory proteins and, finally, a reduction of lung volume and function. Objectives: The aim of this study was to evaluate viral infections’ prevalence in children with asthma from 2016 to 2017. Methods: One hundred throat swab samples were collected from asthmatic children. Extraction of RNA and cDNA synthesis were performed to recognize parainfluenza viruses, rhinoviruses, influenza viruses, and respiratory syncytial virus (RSV) using real-time PCR. Also, the associations of age, sex, and other studied factors with asthmatic attacks were evaluated. Results: In this study, 41 viruses were detected, including 21 cases of rhinoviruses (51.22%), 10 cases of parainfluenza (24.39%), seven cases of respiratory syncytial virus (17.07%), and three cases of the influenza virus (7.32%). Regarding seasonal incidence, the prevalence of the viruses was high in autumn and winter, and there was a significant relationship between seasonal incidence and gender. However, there were no statistically significant relationships between the prevalence of the viruses and age or gender. Conclusions: The most important viral causes of childhood asthma in this study were found to be rhinoviruses, followed by parainfluenza. The lowest prevalence was related to the RSV and influenza virus, which the two viruses also showed the lowest seasonal outbreaks. Therefore, it can be said that with an increase in the seasonal incidence of respiratory viruses, the effects of these viruses will be greater on asthma.

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

2020 ◽  
Vol 26 ◽  
Author(s):  
Felix-Martin Werner ◽  
Rafael Coveñas
Keyword(s):  
Clinical Trials ◽  
Maintenance Therapy ◽  
Antipsychotic Drug ◽  
Cognitive Functions ◽  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Therapeutic Effects ◽  
Treatment Resistant ◽  
Long Acting ◽  
Novel Antipsychotic

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.

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