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Treatment Resistent Asthma

Verónica Giubergia, María J Ramirez Farías, Verónica Pérez, Adriana González, Nancy Crespi, Nora Fridman, Claudio Castaños
INTRODUCTION: Severe asthma accounts for 5-7% of all asthma cases. The World Health Organization proposed a follow-up protocol to classify cases into severe, treatment-resistant asthma (STRA) or severe, difficult-to-control asthma (SDCA). OBJECTIVE: To analyze the clinical, functional, and therapeutic characteristics of patients with STRA or SDCA. METHODS: Cross-sectional, observational, and analytical study to assess the diagnosis, the extent of control (clinical and functional), comorbidities, treatment adherence, inhalation technique, and environmental factors in patients with severe asthma...
April 1, 2018: Archivos Argentinos de Pediatría
Seyed Hamid Borsi, Homeira Rashidi, Maryam Shaabanpour, Hanieh Raji
Asthma is an inflammatory disease, which causes airflow limitation and increase insulin resistance. The present study was carried out in order to investigate insulin resistance and the effect of inhaled corticosteroid (ICS) on insulin sensitivity in asthmatic patients. A registered (IRCT201605247411N2) interventional, quasi-experimental trial was performed from 2014 to 2015 in Imam Khomeini hospital Ahvaz, Iran. Patients with mild to moderate asthma participated in this study. Spirometry, fasting blood sugar (FBS), blood sugar 2 hour post prandial (BS2HPP), HbA1C, low density lipoprotein (LDL), high density lipoprotein (HDL), Insulin Level, and C reactive protein (CRP) were measured...
February 19, 2018: Monaldi Archives for Chest Disease, Archivio Monaldi Per le Malattie del Torace
Michael C Peters, Sheena Kerr, Eleanor M Dunican, Prescott G Woodruff, Merritt L Fajt, Bruce D Levy, Elliot Israel, Brenda R Phillips, David T Mauger, Suzy A Comhair, Serpil C Erzurum, Mats W Johansson, Nizar N Jarjour, Andrea M Coverstone, Mario Castro, Annette T Hastie, Eugene R Bleecker, Sally E Wenzel, John V Fahy
BACKGROUND: Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain. OBJECTIVE: To determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation. METHODS: We used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, "T2GM") in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non-severe asthma patients on ICS (n=85)...
March 7, 2018: Journal of Allergy and Clinical Immunology
Matthew Morten, Adam Collison, Vanessa E Murphy, Daniel Barker, Christopher Oldmeadow, John Attia, Joseph Meredith, Heather Powell, Paul D Robinson, Peter D Sly, Peter G Gibson, Joerg Mattes
BACKGROUND: The single-centre double-blind, randomised controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FeNO) in combination with asthma symptoms (FeNO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (ANZ Clinical Trials Registry, number 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FeNO group...
March 7, 2018: Journal of Allergy and Clinical Immunology
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
Nadia Galizzi, Laura Galli, Andrea Poli, Nicola Gianotti, Elisabetta Carini, Alba Bigoloni, Giuseppe Tambussi, Silvia Nozza, Adriano Lazzarin, Antonella Castagna, Daniela Mancusi, Roberta Termini
INTRODUCTION: A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. METHODS: Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015...
2018: PloS One
Zeyu Zeng, Xixi Lin, Rongying Zheng, Hui Zhang, Weixi Zhang
Severe airway hyperresponsiveness (AHR) is a clinical feature of asthma, which has been associated with obesity and has shown a poor response to standard asthma treatments such as glucocorticoids. Numerous studies have shown that Interleukin (IL)-17 producing CD4 + T cells (Th17 cells), which could be inhibited by celastrol, is essential in mediating steroid-resistant AHR. The following study investigates the impact of celastrol and its mechanism on the regulation of AHR in murine model of obesity and asthma...
2018: Frontiers in Pharmacology
Tsunahiko Hirano, Kazuto Matsunaga
Because the pathophysiology of asthma has diverse characteristics, to manage the disease effectively, it is important for clinicians to distinguish among the clinical phenotypes. Among them, adult-onset asthma, that is, late-onset asthma (LOA), is increasing because of the aging of the population. The phenotype of LOA is largely divided into two types according to the presence or absence of eosinophilic inflammation, T-helper (Th)2- and non-Th2-associated LOA. Especially in Th2 LOA related to rhinosinusitis, as pulmonary function at onset is poor and asthma exacerbations occur frequently, it is important to detect this phenotype in the early phase by using a biomarker of Th2-type inflammation such as fractional exhaled nitric oxide (FE NO )...
2018: Journal of Asthma and Allergy
Patrícia Duarte Freitas, Aline Grandi Silva, Palmira Gabriele Ferreira, Analuci da Silva, João Marcos Salge, Regina Maria Carvalho-Pinto, Alberto Cukier, Claudia M Brito, Marcio C Mancini, Celso R F Carvalho
INTRODUCTION: Obese adults with asthma have an increased number of comorbidities and reduced daily life physical activity (DLPA), which may worsen asthma symptoms. Exercise is recommended to improve asthma outcomes; however, the benefits of exercise for psychosocial comorbidities and physical activity levels in obese adults with asthma have been poorly investigated. OBJECTIVE: To assess the effects of exercise on DLPA, asthma symptoms and psychosocial comorbidities in obese adults with asthma...
February 9, 2018: Medicine and Science in Sports and Exercise
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
Sara Olenich, Graeme Waterworth, Gary J Badger, Bruce Levy, Elliot Israel, Helene M Langevin
OBJECTIVE: Although less is known about musculoskeletal factors that may contribute to asthma symptoms, body-based treatments addressing movement restrictions of the chest and shoulders may be a useful adjunct to asthma pharmacotherapy. In this pilot study, we compared asthma symptoms, pulmonary function tests, and medication use before and after a course of resistance flexibility and strength training (RFST) treatments in human subjects with asthma. METHODS: Patients with asthma (n = 10; mean age 23 years) completed questionnaires (Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT)), spirometry, chest wall excursion, and shoulder range of motion (ROM) before and after a series of four RFST treatments over 47 ± 21 days...
February 8, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
José Carlos Rodríguez-Jiménez, Fernanda Judith Moreno-Paz, Luis Manuel Terán, Eduardo Guaní-Guerra
Aspirin-exacerbated respiratory disease is a chronic and treatment-resistant disease, characterized by the presence of eosinophilic rhinosinusitis, nasal polyposis, bronchial asthma, and nonsteroidal anti-inflammatory drugs hypersensitivity. Alterations in arachidonic acid metabolism may induce an imbalance between pro-inflammatory and anti-inflammatory substances, expressed as an overproduction of cysteinyl leukotrienes and an underproduction of prostaglandin E2. Although eosinophils play a key role, recent studies have shown the importance of other cells and molecules in the development of the disease like mast cells, basophils, lymphocytes, platelets, neutrophils, macrophages, epithelial respiratory cells, IL-33 and thymic stromal lymphopoietin, making each of them promissory diagnostic and treatment targets...
February 2018: Respiratory Medicine
Morgan Gazzola, Samuel Mailhot-Larouche, Clémentine Beucher, Ynuk Bossé
The mechanisms whereby anti-cholinergics improve asthma outcomes, such as lung function, symptoms and rate of exacerbation, can be numerous. The most obvious is by affecting the contraction of airway smooth muscle (ASM). The acetylcholine released from the cholinergic nerves is the most important bronchoconstrictor that sets the baseline degree of contractile activation of ASM in healthy individuals. Although the degree of ASM's contractile activation can also be fine-tuned by a plethora of other bronchoconstrictors and bronchodilators in asthma, blocking the ceaseless effect of acetylcholine on ASM by anti-cholinergics reduces, at any given moment, the overall degree of contractile activation...
February 7, 2018: Canadian Journal of Physiology and Pharmacology
Michael J McGeachie, George L Clemmer, Boris Hayete, Heming Xing, Karl Runge, Ann Chen Wu, Xiaofeng Jiang, Quan Lu, Bruce Church, Iya Khalil, Kelan Tantisira, Scott Weiss
BACKGROUND: Variation in response to the most commonly used class of asthma controller medication, inhaled corticosteroids (ICS), presents a serious challenge in asthma management, particularly for steroid-resistant patients who display little or no response to treatment. OBJECTIVE: We applied a systems-biology approach to primary clinical and genomic data to identify and validate genes that modulate steroid response in children with asthma. METHODS: We selected 104 ICS-treated asthmatic non-Hispanic white children and determined a Steroid Responsiveness Endophenotype (SRE) using observations of six clinical measures over four years...
January 30, 2018: Journal of Allergy and Clinical Immunology
Samuel N Uwaezuoke, Adaeze C Ayuk, Joy N Eze
Severe asthma or therapy-resistant asthma in children is a heterogeneous disease that affects all age-groups. Given its heterogeneity, precision in diagnosis and treatment has become imperative, in order to achieve better outcomes. If one is thus able to identify specific patient phenotypes and endotypes using the appropriate biomarkers, it will assist in providing the patient with more personalized and appropriate treatment. However, there appears to be a huge diagnostic gap in severe asthma, as there is no single test yet that accurately determines disease phenotype...
2018: Journal of Asthma and Allergy
Leah R Reznikov, David K Meyerholz, Shin-Ping Kuan, Maria V Guevara, Kalina R Atanasova, Mahmoud H Abou Alaiwa
Airway hyperreactivity is a hallmark feature of asthma and can be precipitated by airway insults, such as ozone exposure or viral infection. A proposed mechanism linking airway insults to airway hyperreactivity is augmented cholinergic transmission. In the current study, we tested the hypothesis that acute potentiation of cholinergic transmission is sufficient to induce airway hyperreactivity. We atomized the cholinergic agonist bethanechol to neonatal piglets and forty-eight hours later measured airway resistance...
January 29, 2018: Lung
Youming Zhang, Thanushiyan Poobalasingam, Laura L Yates, Simone A Walker, Martin S Taylor, Lauren Chessum, Jackie Harrison, Loukia Tsaprouni, Ian M Adcock, Clare M Lloyd, William O Cookson, Miriam F Moffatt, Charlotte H Dean
We previously identified dipeptidyl-peptidase 10 (DPP10) on chromosome 2 as a human asthma susceptibility gene, through positional cloning. Initial association results were confirmed in many subsequent association studies but the functional role of DPP10 in asthma remains unclear. Using the MRC Harwell N-ethyl-N-nitrosourea (ENU) DNA archive, we identified a point mutation in Dpp10 that caused an amino acid change from valine to aspartic acid in the β propeller region of the protein. Mice carrying this point mutation were recovered and a congenic line was established (Dpp10145D )...
December 28, 2017: Disease Models & Mechanisms
Angela M Fonceca, Graeme R Zosky, Elizabeth M Bozanich, Erika N Sutanto, Anthony Kicic, Paul S McNamara, Darryl A Knight, Peter D Sly, Debra J Turner, Stephen M Stick
BACKGROUND: Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure...
January 22, 2018: Respiratory Research
M Sánchez-Borges, A Capriles-Hulett, F Caballero-Fonseca, L González-Aveledo
Background. Currently there are no biomarkers useful to predict the future evolution and the therapeutic response in patients with chronic spontaneous urticaria (CSU). Objective. To review the available information on biomarkers that might be applied for the follow up of the response to guideline recommended therapies for CSU. Methods. A review of the medical literature on CSU potential clinical and laboratory biomarkers in PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine (CyA), and treatment...
January 2018: European Annals of Allergy and Clinical Immunology
Tai Joon An, Chin Kook Rhee, Ji Hye Kim, Young Rong Lee, Jin Young Chon, Chan Kwon Park, Hyoung Kyu Yoon
BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids...
January 2018: Tuberculosis and Respiratory Diseases
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