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Anti-IL-5 monoclonal antibodies for the treatment of asthma: an update.
Walsh, GM
Expert opinion on biological therapy. 2020;(10):1237-1244
Abstract
INTRODUCTION Asthma exhibits marked heterogeneity in symptoms with severe or refractory asthma representing a clear area of unmet medical need. These patients require more specifically targeted treatments with monoclonal antibody-based biologics targeted at inhibition of the type 2 cytokines IL-4, IL-5 and IL-13 having considerable potential as effective treatments for severe asthma. For the most part, anti-cytokine-based biologic therapies are more likely to give significant clinical benefit in carefully selected patient populations that take asthma phenotypes and endotypes into account. AREAS COVERED This review is based on recent English-language original articles in Pub Med or MedLine that reported significant clinical findings on the current status, therapeutic potential and safety of the anti-IL-5 biologics mepolizumab, reslizumab and benralizumab in the treatment of severe refractory asthma. EXPERT OPINION Anti-IL-5 treatment appears effective in patients with eosinophilic asthma through exacerbation prevention with accumulating evidence of glucocorticoid-sparing effects with an acceptable safety profile for these biologics.
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Limitations of the results from randomized clinical trials involving intravenous and nebulised magnesium sulphate in adults with severe acute asthma.
Javor, E, Grle, SP
Pulmonary pharmacology & therapeutics. 2019;:31-37
Abstract
The role of intravenous (IV) or nebulised magnesium sulphate (MgSO4) in the treatment of severe acute asthma in adults is unclear. A controversy exists regarding its efficacy. In children MgSO4 has a more evident clinical effect, but the child population has not been considered in this work. The applicability of the results from randomized clinical trials (RCTs) involving MgSO4 in adult population is questioned in the optimal treatment of asthma exacerbations. According to the newest guidelines from the Global Initiative for Asthma (GINA), optimal treatment in the emergency department (ED) is based on short-acting beta2-agonists (SABA), oral or IV corticosteroids (CS), short acting muscarinic antagonists (SAMA) and the controlled oxygen therapy. Further improvements with IV or nebulised MgSO4 were assessed in a recent large multicentre, double-blind, placebo-controlled randomized 3 Mg trial, which failed to demonstrate clinical benefit. Several other RCTs found some benefit with MgSO4, although the majority lacked some treatment options that are used in the optimal treatment of asthma exacerbations. Therefore, we reviewed the limitations of RCTs of IV or nebulised MgSO4 in adults with acute asthma, with the aim to answer in which subpopulation MgSO4 could be beneficial.
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What is New in the Management of Childhood Asthma?
Gupta, A, Bhat, G, Pianosi, P
Indian journal of pediatrics. 2018;(9):773-781
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Abstract
Asthma still causes considerable morbidity and mortality globally and minimal improvement has been seen in key outcomes over the last decade despite increasing treatment costs. This review summarizes recent advances in the management of asthma in children and adolescents. It focuses on the need for personalized treatment plans based on heterogenous asthma pathophysiology, the use of the terminology 'asthma attack' over exacerbation to instill widespread understanding of severity, and the need for every attack to trigger a structured review and focused strategy. The authors discuss difficulties in diagnosing asthma, accuracy and use of Fractional exhaled nitric oxide both as second line test and as a method to monitor treatment adherence or guide the choice of pharmacotherapy. The authors discuss acute and long-term management of asthma. Asthma treatment goals are to minimize symptom burden, prevent attacks and (where possible) reduce risk and impact of progressive pathophysiology and adverse outcomes. The authors discuss pharmacological management; optimal use of short acting β2 agonists, long acting muscarinic antagonist (tiotropium), use of which is relatively new in pediatrics, allergen specific immunotherapy, biological monoclonal antibody treatment, azalide antibiotic azithromycin, and the use of vitamin D. They also discuss electronic monitoring and adherence devices, direct observation of therapy via mobile device, temperature controlled laminar airflow device, and the importance of considering when symptoms may actually result from dysfunctional breathing rather than asthma.
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Guideline on management of the acute asthma attack in children by Italian Society of Pediatrics.
Indinnimeo, L, Chiappini, E, Miraglia Del Giudice, M, ,
Italian journal of pediatrics. 2018;(1):46
Abstract
BACKGROUND Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. METHODS The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted. A literature search was performed using the Cochrane Library and Medline/PubMed databases, retrieving studies in English or Italian and including children over age 2 year. RESULTS Inhaled ß2 agonists are the first line drugs for acute asthma attack in children. Ipratropium bromide should be added in moderate/severe attacks. Early use of systemic steroids is associated with reduced risk of ED visits and hospitalization. High doses of inhaled steroids should not replace systemic steroids. Aminophylline use should be avoided in mild/moderate attacks. Weak evidence supports its use in life-threatening attacks. Epinephrine should not be used in the treatment of acute asthma for its lower cost / benefit ratio, compared to β2 agonists. Intravenous magnesium solphate could be used in children with severe attacks and/or forced expiratory volume1 (FEV1) lower than 60% predicted, unresponsive to initial inhaled therapy. Heliox could be administered in life-threatening attacks. Leukotriene receptor antagonists are not recommended. CONCLUSIONS This Guideline is expected to be a useful resource in managing acute asthma attacks in children over age 2.
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Medication Regimens for Managing Acute Asthma.
Maselli, DJ, Peters, JI
Respiratory care. 2018;(6):783-796
Abstract
Asthma exacerbation is defined as a progressive increase in symptoms of shortness of breath, cough, or wheezing sufficient to require a change in therapy. After ruling out diagnoses that mimic an asthma exacerbation, therapy should be initiated. Short-acting β2 agonists and short-acting muscarinic antagonists are effective as bronchodilators for asthma in the acute setting. Systemic corticosteroids to reduce airway inflammation continue to be the mainstay therapy for asthma exacerbations, and, unless there is a contraindication, the oral route is favored. Based on the current evidence, nebulized magnesium should not be routinely used in acute asthma. The evidence favors the use of intravenous magnesium sulfate in selected cases, particularly in severe exacerbations. Methylxanthines have a minimum role as therapy for asthma exacerbations but may be considered in refractory cases of status asthmaticus with careful monitoring of toxicity. Current guidelines recommend the use of helium-oxygen mixtures in patients who do not respond to standard therapies or those with severe disease.
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Recent developments in the use of biologics targeting IL-5, IL-4, or IL-13 in severe refractory asthma.
Walsh, GM
Expert review of respiratory medicine. 2018;(11):957-963
Abstract
Severe or refractory asthma is seen in approximately 5% of asthmatic subjects who have unsatisfactory symptom control despite adherence to high-dose inhaled glucocorticoid therapies resulting in significant morbidity, reduced quality of life and health-care cost implications. Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level requiring specifically targeted treatments to block the key pathways of the disease. Monoclonal antibody-based biologics targeted at inhibition of the type 2 cytokines IL-4, IL-5, and IL-13 have considerable potential as effective treatments for severe asthma. Areas covered: This review is based on recent English-language original articles in PubMed or Medline that reported significant clinical findings on the current status, therapeutic potential, and safety of biologics targeted at IL-4, IL-5, and IL-13 in the treatment of asthma together with the potential utility of simple reproducible non-invasive biomarkers to guide the effective use of biologic-based therapy that do not require direct sampling of the airways Expert commentary: The further development of reproducible and straightforward discriminatory non-invasive biomarkers may aid identification of those patients most likely to benefit from treatment with these interventions.
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Reslizumab in the treatment of severe eosinophilic asthma: an update.
Walsh, GM
Immunotherapy. 2018;(8):695-698
Abstract
A marked heterogeneity is exhibited by asthma both clinically and at the molecular level with different phenotypes driven by diverse mechanistic pathways that require specifically targeted treatments. Biologics aimed at IL-4/13, IL-5 or IgE are proven or potentially effective treatments for patients with difficult to treat eosinophilic asthma. Importantly, it is now widely accepted that biologic-based therapies give significant clinical improvements in those patient populations where asthma phenotypes are taken into account. Such asthma phenotypes have been identified by reproducible and straightforward discriminatory biomarkers. This short review discusses recent studies of the effectiveness of the anti-IL-5 reslizumab in relation to the use of simple reproducible biomarkers in eosinophilic asthma.
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Adjunct Therapies for Refractory Status Asthmaticus in Children.
Rehder, KJ
Respiratory care. 2017;(6):849-865
Abstract
Asthma exacerbation is a common reason for children to present to the emergency department. If primary therapies fail to halt the progression of an asthma flare, status asthmaticus often leads to hospital, and potentially ICU, admission. Following the initial administration of inhaled β agonists and systemic corticosteroids, a wide array of adjunct medical therapies may be used to treat status asthmaticus. Unfortunately, the data supporting the use of these adjunct therapies are often unclear, conflicting, or absent. This review will present the physiologic basis and summarize the supporting data for a host of adjunct therapies, including ipratropium, intravenous β agonists, methylxanthines, intravenous and inhaled magnesium, heliox (helium-oxygen mixture), ketamine, antibiotics, noninvasive ventilation, inhaled anesthetics, and extracorporeal membrane oxygenation. Finally, we present a suggested care map for escalating to these therapies in children with refractory status asthmaticus.
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IV Magnesium Sulfate for Treating Children with Acute Asthma in the ED.
Bidwell, J
The American journal of nursing. 2017;(2):59
Abstract
Editor's note: This is a summary of a nursing care-related systematic review from the Cochrane Library.
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10.
Pharmacogenetic and pharmacogenomic considerations of asthma treatment.
Matera, MG, Rinaldi, B, Calzetta, L, Cazzola, M
Expert opinion on drug metabolism & toxicology. 2017;(11):1159-1167
Abstract
Pharmacogenetic and pharmacogenomic approaches are already utilized in some areas, such as oncology and cardiovascular disease, for selecting appropriate patients and/or establishing treatment and dosing guidelines. This is not true in asthma although many patients have different responses to drug treatment due to genetic factors. Areas covered: Several genetic factors that affect the pharmacotherapeutic responses to asthma medications, such as β2-AR agonists, corticosteroids, and leukotriene modifiers and could contribute to significant between-person variability in response are described. Expert opinion: An expanding number of genetic loci have been associated with therapeutic responses to asthma drugs but the individual effect of one single-nucleotide polymorphism is partial. In fact, epigenetic changes can modify genetic effects in time-, environment-, and tissue-specific manners, genes interact together in networks, and nongenetic components such as environmental exposures, gender, nutrients, and lifestyle can significantly interact with genetics to determine the response to therapy. Therefore, well-designed randomized controlled trials or observational studies are now mandatory to define if response to asthma medications in individual patients can be improved by using pharmacogenetic predictors of treatment response. Meanwhile, routine implementation of pharmacogenetics and pharmacogenomics into clinical practice remains a futuristic, far-off challenge for many clinical practices.