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Difficult to treat asthma

Kenneth Wysocki
Research and application of genomic medicine in lung disease during the past century has clarified our understanding and focus on specific phenotypes, helping clinicians tailor treatment for individual patients. Cystic fibrosis and lung cancer have been researched extensively; specific genotypes have been instrumental in precision medicine to treat these lung diseases. Asthma and chronic obstructive pulmonary disease are more complex and heterogeneous in their pathogenesis, genotypic profile, and phenotypic expression, making treatment more difficult with increasing disease severity...
2018: AACN Advanced Critical Care
Michal Shteinberg, Emilia Hardak, Matthew Koslow, Dario Prais, Malena Cohen-Cymberkno, David Shoseyov, Adi Dagan, Yochai Adir, David Shitrit
Bronchiectasis is anatomically defined by irreversible distortion of the bronchi. Clinically, its manifestations are cough with sputum production and a predisposition to pulmonary infections. Unlike asthma and COPD, where ample clinical data are present regarding the course and effective treatment, knowledge of bronchiectasis has yet to evolve. Lately, bronchiectasis is gaining renewed attention among the medical community, with growing basic and clinical research-based data. In Israel, no registered treatments exist for bronchiectasis, which makes it difficult to treat these patients...
February 2018: Harefuah
Nadia L Krupp, Andrea Weist, Cindy D Fiscus, James Slaven, Andrew Harner, Gregory S Montgomery, Michelle S Howenstine
AIM: At our institution, a pediatric High Risk Asthma clinic has been in operation for over 15 years, targeting children with poorly controlled, and difficult to treat asthma. This study evaluates the outcomes and cost-effectiveness of the High Risk Asthma clinic from 2000 through 2014. METHODS: A retrospective chart review was performed on all patients entering High Risk Asthma clinic from 2000-2014, and total hospitalizations and Emergency Department visits were tallied for the year prior to entering clinic and the year after...
February 27, 2018: Pediatric Pulmonology
Virginia Mirra, Silvia Montella, Francesca Santamaria
BACKGROUND: The primary goal of asthma management is to achieve disease control for reducing the risk of future exacerbations and progressive loss of lung function. Asthma not responding to treatment may result in significant morbidity. In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong or adherence to treatment may be poor. It is then crucial to distinguish these cases from the truly "severe therapy-resistant" asthmatics by a proper filtering process...
February 21, 2018: BMC Pediatrics
Kian Fan Chung
Severe therapy-resistant asthma has been defined as "asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy". Patients who usually present with 'difficult-to-treat asthma' should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant...
February 2018: Seminars in Respiratory and Critical Care Medicine
William C Anderson, Stanley J Szefler
Strategies to control the risk domain of NHLBI EPR-3 (National Heart, Lung, and Blood Institute Expert Panel Report-3) asthma guidelines, which includes exacerbations requiring systemic corticosteroids, reduction in lung growth, and progressive loss of lung function, and treatment-related adverse effects, are evolving in children and adolescents. Increasing evidence demonstrates that children and adolescents with asthma are at risk of a reduction in lung growth, leading to lower lung function and potentially chronic obstructive pulmonary disease as adults...
February 2018: Seminars in Respiratory and Critical Care Medicine
Lei Chong, Weixi Zhang, Gang Yu, Hailin Zhang, Lili Zhu, Haiyan Li, Youyou Shao, Changchong Li
CD38 is a plasma membrane bound multifunctional enzyme. It can be activated by inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-13, inducing calcium responses to agonist in airway smooth muscle cells (ASMC). Previous studies have found that high-fat-diet (HFD) induced obesity exhibited innate airway hyperresponsiveness (AHR). This study aimed to detect the effect of CD38 signaling pathway on the AHR of overweight/obese mice. The HFD-fed mice exhibited a significantly higher baseline airway resistance (Rn), and the increasing rates of Rn responded to increasing doses of methacholine compared with the LFD-fed mice...
February 1, 2018: International Immunopharmacology
Michael D Shields, Fahad ALQahtani, Michael P Rivey, James C McElnay
We describe, for the first time, the use of a mobile device platform for remote direct observation of inhaler use and technique. The research programme commenced with a rapid systematic review of mobile device (or videophone) use for direct observation of therapy (MDOT). Ten studies (mainly pilots) were identified involving patients with tuberculosis, sickle cell disease and Alzheimer's disease. New studies are ongoing ( website) in TB, stroke, sickle cell disease, HIV and opioid dependence...
2018: PloS One
Michael E Hyland, Joseph W Lanario, Jill Pooler, Matthew Masoli, Rupert C Jones
BACKGROUND: Previous research shows that existing asthma quality of life questionnaires fail to measure the burden of oral corticosteroids that can be used to treat severe asthma, and are therefore not fit for purpose for severe asthma according to the USA's Federal Drug Authority's (FDA) criteria for content validity. Patient input and documentation of that input is key to achieving content validity according to FDA guidelines. This paper describes the process of constructing a new questionnaire to measure the burden of asthma symptoms and burden of treatment in severe asthma, using criteria specified by the FDA...
January 27, 2018: Health and Quality of Life Outcomes
Jianguo Hong, Yixiao Bao, Aihuan Chen, Changchong Li, Li Xiang, Chuanhe Liu, Zhimin Chen, Deyu Zhao, Zhou Fu, Yunxiao Shang
OBJECTIVE: With increased industrialization and urbanization in China, pediatric asthma is becoming more prevalent. Despite a growing body of evidence, there remains a significant unmet need for adequate management of childhood asthma. The Subspecialty Group of Respiratory Diseases of the Society of Pediatrics, the Chinese Medical Association, and the editorial board of the Chinese Journal of Pediatrics have recently updated the "Guidelines for diagnosis and optimal management of asthma in children," first published in 2008...
December 11, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Emily E Barsky, Lauren M Giancola, Sachin N Baxi, Jonathan M Gaffin
Severe asthma accounts for only a small proportion of the children with asthma, but a disproportionately high amount of resource utilization and morbidity. It is a heterogeneous entity and requires a step-wise, evidence based approach to evaluation and management by pediatric subspecialists. The first step is to confirm the diagnosis by eliciting confirmatory history and objective evidence of asthma and excluding possible masquerading diagnoses. The next step is to differentiate difficult-to-treat asthma, asthma which can be controlled with appropriate management, from asthma which requires the highest level of therapy to maintain control or remains uncontrolled despite management optimization...
December 8, 2017: Annals of the American Thoracic Society
Danilo Di Bona, Irene Fiorino, Marialuisa Taurino, Flavia Frisenda, Elena Minenna, Carlo Pasculli, Georgios Kourtis, Anna Simona Rucco, Andrea Nico, Marcello Albanesi, Lucia Giliberti, Luciana D'Elia, Maria Filomena Caiaffa, Luigi Macchia
BACKGROUND: Randomized Controlled Trials showed that omalizumab exhibited a good safety and tolerability profile in patients with moderate-to-severe asthma. However, safety data of long-term treatment with omalizumab are scarce. Our aim was to assess the safety of omalizumab in patients under long-term treatment in a real-life setting. METHODS: Difficult-to-control asthmatic patients treated with omalizumab up to 9 years were retrospectively evaluated. Mild to severe adverse events any and reasons for discontinuation were recorded...
September 2017: Respiratory Medicine
Rachel Knightly, Stephen J Milan, Rodney Hughes, Jennifer A Knopp-Sihota, Brian H Rowe, Rebecca Normansell, Colin Powell
BACKGROUND: Asthma exacerbations can be frequent and range in severity from mild to life-threatening. The use of magnesium sulfate (MgSO₄) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO₄ has been demonstrated, the role of inhaled MgSO₄ is less clear. OBJECTIVES: To determine the efficacy and safety of inhaled MgSO₄ administered in acute asthma. SPECIFIC AIMS: to quantify the effects of inhaled MgSO₄ I) in addition to combination treatment with inhaled β₂-agonist and ipratropium bromide; ii) in addition to inhaled β₂-agonist; and iii) in comparison to inhaled β₂-agonist...
November 28, 2017: Cochrane Database of Systematic Reviews
Stephanie A Shore
Obesity is a risk factor for asthma, especially nonallergic asthma. Ozone, a common air pollutant, is a nonallergic asthma trigger. Importantly, ozone-induced decrements in lung function are greater in obese and overweight human subjects than in lean individuals. Obese mice also exhibit exaggerated pulmonary responses to ozone. Ozone causes greater increases in pulmonary resistance, in bronchoalveolar lavage neutrophils, and in airway hyperresponsiveness in obese than in lean mice. Our data indicate that IL-33 plays a role in mediating these events...
November 2017: Annals of the American Thoracic Society
Corrado Pelaia, Alessandro Vatrella, Maria Teresa Busceti, Luca Gallelli, Rosa Terracciano, Rocco Savino, Girolamo Pelaia
Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that has been recently approved as an add-on biological treatment for severe eosinophilic asthma, by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Moreover, mepolizumab is also currently included within the step 5 of the Global Initiative for Asthma guidelines, as an add-on therapy for severe uncontrolled asthma. The relevant therapeutic benefits detectable in patients with refractory eosinophilic asthma receiving mepolizumab depend on the pivotal pathogenic role played by IL-5 in these subjects...
2017: Drug Design, Development and Therapy
Oana Joean, Anja Hueber, Felix Feller, Adan Chari Jirmo, Matthias Lochner, Anna-Maria Dittrich, Melanie Albrecht
Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation...
November 10, 2017: Scientific Reports
Karin Fieten, Renske Schappin, Wieneke Zijlstra, Lilian Figee, Jos Beutler, Florine Raymakers, Harmieke van Os-Medendorp, Rebecca Stellato, Maartje Vandewall, Joan Winkelhof, Monica Uniken Venema, Carla Bruijnzeel-Koomen, Lucia Rijssenbeek-Nouwens, Cornelis van der Ent, Els van Hoffen, Yolanda Meijer, Suzanne Pasmans
BACKGROUND: Alpine climate treatment has historically been used in Europe to treat atopic dermatitis (AD), but no randomized trials have been conducted to provide evidence for its effectiveness. OBJECTIVE: To investigate the long-term effectiveness of alpine climate treatment for children with difficult to treat AD. MATERIALS & METHODS: A pragmatic, open, randomized controlled trial was conducted. Children diagnosed with AD that was considered difficult to treat, aged between 8 and 18 years and willing to be treated in Switzerland were randomized to a six week personalized integrative multidisciplinary treatment period in a clinical setting in the alpine climate (Switzerland) or an outpatient setting in moderate maritime climate (Netherlands)...
November 9, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
B Storlie Curtis, E Branda Megan, R Gionfriddo Michael, D Shah Nilay, A Rank Matthew
We consider the problem of individual-specific medication level recommendation (initiation, removal, increase, or decrease) for asthma sufferers. Asthma is one of the most common chronic diseases in both adults and children, affecting 8% of the US population and costing $37-63 billion/year in the United States of America. Asthma is a complex disease, whose symptoms may wax and wane, making it difficult for clinicians to predict outcomes and prognosis. Improved ability to predict prognosis can inform decision making and may promote conversations between clinician and provider around optimizing medication therapy...
November 6, 2017: Biostatistics
Michael S Blaiss, Mario Castro, Bradley E Chipps, Myron Zitt, Reynold A Panettieri, Michael B Foggs
BACKGROUND: Severe asthma poses significant disease-related and economic burdens in the United States. Challenges in practice include how to define "severe asthma" for a given patient, knowing which are the right tests to perform and when, and having a better understanding of a patient's asthma phenotype. Furthermore, current guidelines do not address a clear, practical approach to treatment that is based on a patient's asthma phenotype. OBJECTIVE: To develop a consensus on the definition of severe asthma, the role of biomarkers and phenotyping severe asthma, and the use of newer biologic therapies and bronchial thermoplasty to help guide practicing clinicians...
December 2017: Annals of Allergy, Asthma & Immunology
Yuan Zhang, Elien Gevaert, Hongfei Lou, Xiangdong Wang, Luo Zhang, Claus Bachert, Nan Zhang
Chronic rhinosinusitis (CRS), although possibly overdiagnosed, is associated with a high burden of disease and is often difficult to treat in those truly affected. Recent research has demonstrated that inflammatory signatures of CRS vary around the world, with less eosinophilic and more neutrophilic inflammation found in Asia compared with Europe and North America. Although in the Western world about 80% of nasal polyps carry a type 2 signature, this might be between 20% and 60% in China and Korea or Thailand, respectively...
November 2017: Journal of Allergy and Clinical Immunology
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