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1.
Pediatric asthma: An unmet need for more effective, focused treatments.
Papadopoulos, NG, Čustović, A, Cabana, MD, Dell, SD, Deschildre, A, Hedlin, G, Hossny, E, Le Souëf, P, Matricardi, PM, Nieto, A, et al
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019;(1):7-16
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Abstract
BACKGROUND Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.
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A review on the management of asthma in the Avicenna's Canon of Medicine.
Amini, F, Jaladat, AM, Atarzadeh, F, Mosavat, SH, Parvizi, MM, Zamani, N
Journal of complementary & integrative medicine. 2019;(4)
Abstract
Introduction In this study, we attempted to identify medicinal plants for treating asthma by investigating Persian Medicine (PM) sources. Methods In the present review study, materials concerning asthma were assessed by the (most) reliable source of PM (Canon of Medicine) written by Avicenna. Recommended medicinal plants for treating asthma were extracted from this book. Likewise, the electronic databases were used for investigating the pharmacological properties of offered herbs. Results The signs and symptoms of "Rabv" discussed by Avicenna are very similar to the asthma in modern medicine. Avicenna dichotomized asthma causing into pulmonary and non-pulmonary ones, including asthma with the heart, liver, or stomach origin. Overall, 14 medicinal plants were mentioned for the treatment of asthma presented in Canon of Medicine, including celery, juniper, dodder, chamomile, fennel, quince seed, black caraway, lavender, hyssop, squill, anise, absinthe, asafoetida, and common polypody. Conclusions PM prescribes medicinal plants for treating asthma, based on each patient's symptoms and trigger factors.
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Monoclonal antibodies for severe asthma: Pharmacokinetic profiles.
Matera, MG, Calzetta, L, Rogliani, P, Cazzola, M
Respiratory medicine. 2019;:3-13
Abstract
Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic profiles. These profiles are unique in that they are dependent on their structure as well as can be markedly influenced by the biology of their target antigen, but their general behaviour can still be considered a class property, similar to their endogenous IgG counterpart. They cannot be administered by oral route, have a slow distribution into tissue, are metabolized to peptides and amino acids in several tissues but are protected from degradation by binding to protective receptors (the FcRn), which explains their long elimination half-lives. Their clearance is nonlinear because of the saturation of the target-mediated elimination. Also anti-drug antibody (ADA) response and off-target binding, as well as their glycosylation pattern, can influence the pharmacokinetics of mAbs.
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Asthma pharmacotherapy: an update on leukotriene treatments.
Trinh, HKT, Lee, SH, Cao, TBT, Park, HS
Expert review of respiratory medicine. 2019;(12):1169-1178
Abstract
Introduction: Asthma is a chronic inflammatory disease of the airways with a large heterogeneity of clinical phenotypes. There has been increasing interest regarding the role of cysteinyl leukotriene (LT) and leukotriene receptor antagonists (LTRA) in asthma treatment.Areas covered: This review summarized the data (published in PubMed during 1984-2019) regarding LTRA treatment in asthma and LTs-related airway inflammation mechanisms. Involvement of LTs C4/D4/E4 has been demonstrated in the several aspects of airway inflammation and remodeling. Novel pathways related to LTE4, the most potent mediator, and its respective receptors have recently been studied. Antagonists against cysteinyl leukotriene receptor (CysLTR) type 1, including montelukast, pranlukast and zafirlukast, have been widely prescribed in clinical practices; however, some clinical trials have shown insignificant responses to LTRAs in adult asthmatics, while some phenotypes of adult asthma showed more favorable responses to LTRAs including aspirin-exacerbated respiratory disease, elderly asthma, asthma associated with smoking, obesity and allergic rhinitis.Expert opinion: Further investigations are needed to understand the role of LTs in airway inflammation and remodeling of the asthmatic airways. There is a lack of biomarkers to predict responsiveness to LTRA, especially in adult asthmatics. Besides CysLTR1 antagonists, targets aiming other LT pathways should be considered.
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[Role of non pharmacological Interventions for asthma].
Bousso, A, Chenivesse, C, Barnig, C
Presse medicale (Paris, France : 1983). 2019;(3 Pt 1):282-292
Abstract
Smoking cessation remains a major issue for asthmatic smokers. Respiratory rehabilitation and respiratory physiotherapy have shown a benefit in controlling symptoms, preventing exacerbations and improving the quality of life. The control of the environment is crucial and must be approached in a global way. Management of obesity and psychological disorders should be systematically proposed. Allergen immunotherapy may be discussed in allergic persistent asthma to house dust mites. Certain dietary interventions or alternative medicines have not proved their worth.
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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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Intravenous and Nebulized Magnesium Sulfate for Treating Acute Asthma in Children: A Systematic Review and Meta-Analysis.
Su, Z, Li, R, Gai, Z
Pediatric emergency care. 2018;(6):390-395
Abstract
OBJECTIVE This study aimed to evaluate the efficacy of intravenous (IV) and nebulized magnesium sulfate in acute asthma in children. METHODS The PubMed, Cochrane Library, and EMBASE databases were searched. Randomized controlled trials and quasi-randomized controlled trials of IV and nebulized magnesium sulfate in pediatric acute asthma were included. The outcomes subject to meta-analysis were pulmonary function, hospitalization, and further treatment. If statistical heterogeneity was significant, random-effects models were used for meta-analysis, otherwise, fixed-effects models were applied. RESULTS Ten randomized and quasi-randomized trials (6 IV, 4 nebulized) were identified. Intravenous magnesium sulfate treatment is associated with significant effects on respiratory function (standardized mean difference, 1.94; 95% confidence interval [CI], 0.80-3.08; P = 0.0008) and hospital admission (risk ratio, 0.55; 95% CI, 0.31-0.95; P = 0.03). But nebulized magnesium sulfate treatment shows no significant effect on respiratory function (standardized mean difference, 0.19; 95% CI, -0.01-0.40; P = 0.07) or hospital admission (risk ratio, 1.11; 95% CI, 0.86-1.44; P = 0.42). CONCLUSIONS The meta-analysis revealed that IV magnesium sulfate is an effective treatment in children, with the pulmonary function significantly improved and hospitalization and further treatment decreased. But nebulized magnesium sulfate treatment showed no significant effect on respiratory function or hospital admission and further treatment.
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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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Repurposing excipients as active inhalation agents: The mannitol story.
Anderson, SD, Daviskas, E, Brannan, JD, Chan, HK
Advanced drug delivery reviews. 2018;:45-56
Abstract
The story of how we came to use inhaled mannitol to diagnose asthma and to treat cystic fibrosis began when we were looking for a surrogate for exercise as a stimulus to identify asthma. We had proposed that exercise-induced asthma was caused by an increase in osmolarity of the periciliary fluid. We found hypertonic saline to be a surrogate for exercise but an ultrasonic nebuliser was required. We produced a dry powder of sodium chloride but it proved unstable. We developed a spray dried preparation of mannitol and found that bronchial responsiveness to inhaling mannitol identified people with currently active asthma. We reasoned that mannitol had potential to replace the 'osmotic' benefits of exercise and could be used as a treatment to enhance mucociliary clearance in patients with cystic fibrosis. These discoveries were the start of a journey to develop several registered products that are in clinical use globally today.
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Asthma, Environment and Pollution: Where the Rubber Hits the Road.
Krishnan, S, Panacherry, S
Indian journal of pediatrics. 2018;(10):893-898
Abstract
The detrimental effects of environmental pollution on one's health are undeniable and have been demonstrated time and time again. Breathing in pollutants in ambient air often has consequences throughout the body, including cardiovascular disease, effects on the reproductive system, and oncologic implications. In the respiratory system, chronic exposure yields a number of outcomes, including chronic obstructive pulmonary disease (COPD) and asthma exacerbations, increased rates of hospitalizations, and increased severity of acute illnesses. On a macro-level, this morbidity and mortality then leads to vast and far-reaching public health consequences the world over, including the loss of billions of dollars' worth of labor. This is especially applicable in developing countries, which often undergo rapid growth, industrialization and urbanization with a resultant increase in vehicular traffic, coal combustion, and fuel emissions as a whole. For this reason, environmental pollutants have been studied extensively, and countries around the globe have established laws that regulate ambient air levels of so-called criteria pollutants. This article will explore several of these criteria pollutants, including particulate matter, nitrogen dioxide, sulfur dioxide, and ozone, and their individual relationships to asthma pathophysiology. However, it is also emphasized that though each one of these toxins yields its own effects, the group of them often works together to have cumulative consequences. For these reasons and many more, it is important to remain aware and educated about these omnipresent environmental pollutants.