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Treatment Resistent Asthma

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https://www.readbyqxmd.com/read/28679952/severe-asthma-in-humans-and-mouse-model-suggests-a-cxcl10-signature-underlies-corticosteroid-resistant-th1-bias
#1
Marc Gauthier, Krishnendu Chakraborty, Timothy B Oriss, Mahesh Raundhal, Sudipta Das, Jie Chen, Rachael Huff, Ayan Sinha, Merritt Fajt, Prabir Ray, Sally E Wenzel, Anuradha Ray
We previously showed that Th1/type 1 inflammation marked by increased IFN-γ levels in the airways can be appreciated in 50% of patients with severe asthma, despite high dose corticosteroid (CS) treatment. We hypothesized that a downstream target of IFN-γ, CXCL10, which recruits Th1 cells via the cognate receptor CXCR3, is an important contributor to Th1high asthma and CS unresponsiveness. We show high levels of CXCL10 mRNA closely associated with IFNG levels in the BAL cells of 50% of severe asthmatics and also in the airways of mice subjected to a severe asthma model, both in the context of high-dose CS treatment...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28666799/ovatodiolide-suppresses-allergic-airway-inflammation-and-hyperresponsiveness-in-a-murine-model-of-asthma
#2
Chien-Neng Wang, Yueh-Lun Lee, Yu-Pei Lin, Wen-Hui Chung, Yew-Min Tzeng, Chen-Chen Lee
Asthma, a complex pulmonary allergic disease, major therapy is applied of drugs to control the disease, but quickly recur after the drugs are stopped. In patients with severe asthma may show steroid resistance and would benefit from the development of novel therapeutic drugs. Ovatodiolide, a unique macrocyclic diterpenoid isolated from Anisomeles indica, showed therapeutic potential for the treatment of allergic asthma. As a model of allergic inflammation, we used ovalbumin (OVA)-immunized mice, which displayed T helper cell type 2 (TH2) cytokine expression in bronchoalveolar lavage fluid (BALF), as well as airway inflammation and hyperresponsiveness (AHR)...
June 27, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28658552/mechanisms-and-treatments-for-severe-steroid-resistant-allergic-airway-disease-and-asthma
#3
REVIEW
Philip M Hansbro, Richard Y Kim, Malcolm R Starkey, Chantal Donovan, Kamal Dua, Jemma R Mayall, Gang Liu, Nicole G Hansbro, Jodie L Simpson, Lisa G Wood, Jeremy A Hirota, Darryl A Knight, Paul S Foster, Jay C Horvat
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28658551/spectrum-of-t-lymphocyte-activities-regulating-allergic-lung-inflammation
#4
REVIEW
Erwin W Gelfand, Anthony Joetham, Meiqin Wang, Katsuyuki Takeda, Michaela Schedel
Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients, research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid-resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28642859/exercise-induced-bronchospasm-and-allergy
#5
REVIEW
Serena Caggiano, Renato Cutrera, Antonio Di Marco, Attilio Turchetta
Sport is an essential part of childhood, with precious and acknowledged positive health effects but the impact of exercise-induced bronchoconstriction (EIB) significantly reduces participation in physical activity. It is important to recognize EIB, differentiating EIB with or without asthma if the transient narrowing of the airways after exercise is associated with asthmatic symptoms or not, in the way to select the most appropriate treatment among the many treatment options available today. Therapy is prescribed based on symptoms severity but diagnosis of EIB is established by changes in lung function provoked by exercise evaluating by direct and indirect tests...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28641517/the-case-for-cannabinoid-cb1-receptors-as-a-target-for-bronchodilator-therapy-for-%C3%AE-agonist-resistant-asthma
#6
John Ashton, Robert J Hancox
Although b2-receceptor agonists are powerful bronchodilators and are at the forefront of asthma symptom relief, patients who use them frequently develop partial resistance to them. This can be a particularly serious problem during severe attacks, where high dose b2-agonist treatment is the front line therapy. Alternative bronchodilators are urgently needed. In this article we review the evidence for the bronchodilator effects of the cannabinoid CB1 receptor tetrahydrocannabinol (THC) and suggest that the mechanism of action for these effects are sufficiently independent of the mechanisms of standard bronchodilators to warrant clinical investigation...
June 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28572736/asthma-like-airway-inflammation-and-responses-in-a-rat-model-of-atopic-dermatitis-induced-by-neonatal-capsaicin-treatment
#7
Rafael Taeho Han, Sewon Kim, Kyungmin Choi, Hyeonseok Jwa, JaeHee Lee, Hye Young Kim, Hee Jin Kim, Hang-Rae Kim, Seung Keun Back, Heung Sik Na
Recent studies have shown that approximately 70% of patients with severe atopic dermatitis (AD) develop asthma. Development of AD in infancy and subsequent other atopic diseases such as asthma in childhood is referred to as atopic march. However, a causal link between the diseases of atopic march has remained largely unaddressed, possibly due to lack of a proper animal model. Recently, we developed an AD rat model showing chronically relapsing dermatitis and scratching behaviors induced by neonatal capsaicin treatment...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28558721/extracellular-heat-shock-protein-90%C3%AE-mediates-hdm-induced-bronchial-epithelial-barrier-dysfunction-by-activating-rhoa-mlc-signaling
#8
Hang-Ming Dong, Yan-Qing Le, Yan-Hong Wang, Hai-Jin Zhao, Chao-Wen Huang, Ya-Hui Hu, Li-Shan Luo, Xuan Wan, Yi-Lan Wei, Zi-Qiang Chu, Wei Li, Shao-Xi Cai
BACKGROUND: The disruption and hyperpermeability of bronchial epithelial barrier are closely related to the pathogenesis of asthma. House dust mite (HDM), one of the most important allergens, could increase the airway epithelial permeability. Heat shock protein (Hsp) 90α is also implicated in the lung endothelial barrier dysfunction by disrupting RhoA signaling. However, the effect of extracellular Hsp90α (eHsp90α) on the bronchial epithelial barrier disruption induced by HDM has never been reported...
May 30, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28552257/-allergic-bronchopulmonary-aspergillosis-evaluation-of-a-maintenance-therapy-with-nebulized-ambisome-%C3%A2
#9
C Godet, F Couturaud, S Ragot, F Laurent, A L Brun, A Bergeron, J Cadranel
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) affects 3-13% of patients with asthma. Its natural history includes possibly life-threatening exacerbations and evolution towards fixed obstructive ventilatory disorders or even irreversible lung fibrosis lesions. ABPA prognosis is directly associated with exacerbation control and the main objective of the treatment is to decrease their frequency and duration. Recommendations regarding dosage and duration of treatment are not very precise...
May 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28543931/severe-asthma-in-children
#10
REVIEW
Andrew Bush, Louise Fleming, Sejal Saglani
Most children with asthma have their disease easily controlled if low-dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high-dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed...
May 25, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28523172/roles-of-roflumilast-a-selective-phosphodiesterase-4-inhibitor-in-airway-diseases
#11
REVIEW
Theerasuk Kawamatawong
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases. Both diseases have incompletely distinct pathophysiology, clinical manifestation, and treatment responsiveness. Pulmonary and systemic inflammations are the hallmarks of COPD. Most asthma responds to inhaled corticosteroid (ICS) treatment. In contrast, COPD is a corticosteroid-resistant disease. Bronchodilators are a preferred treatment method of COPD, with the aim of improving symptoms and preventing exacerbation...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28512018/nanoencapsulation-of-a-glucocorticoid-improves-barrier-function-and-anti-inflammatory-effect-on-monolayers-of-pulmonary-epithelial-cell-lines
#12
Lucas A Rigo, Cristiane S Carvalho-Wodarz, Adriana R Pohlmann, Silvia S Guterres, Nicole Schneider-Daum, Claus-Michael Lehr, Ruy C R Beck
The anti-inflammatory effect of polymeric deflazacort nanocapsules (NC-DFZ) was investigated, and possible improvement of epithelial barrier function using filter grown monolayers of A549 and Calu-3 using as models was assessed. NC prepared from poly(ε-caprolactone) (PCL) had a mean size around 200 nm, slightly negative zeta potential (∼ - 8 mV), and low polydispersity index (< 0.10). Encapsulation of DFZ had an efficiency of 85%. No cytotoxic effects were observed at particle concentration of 9.85 x 10(11) NC/ml, which was therefore chosen to evaluate the effect of NC-DFZ at 1% (w/v) of PCL and 0...
May 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28493293/responsiveness-to-oral-prednisolone-in-severe-asthma-is-related-to-the-degree-of-eosinophilic-airway-inflammation
#13
A R Sousa, R P Marshall, L C Warnock, S Bolton, A Hastie, F Symon, B Hargadon, H Marshall, M Richardson, C E Brightling, P Haldar, R Milone, P Chalk, R Williamson, R Panettieri, R Knowles, E R Bleecker, A J Wardlaw
BACKGROUND: Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear. OBJECTIVE: To relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation...
May 10, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28469725/asthma-like-attacks-terminated-by-slow-pathway-ablation
#14
Selcuk Ozturk, Hasan Turhan, Ertan Yetkin
Asthma is a chronic airway disease in which the pathological mechanisms are reversible airway obstruction, bronchial hyper reactivity, and constriction of the lower airways. Supraventricular tachycardia (SVT) is a common arrhythmia which originates above the bundle of His and causing heart rates exceeding 150 beats/min. SVT patients present with palpitation, chest pain, chest discomfort, dyspnea, hyperventilation, and lightheadedness, occasionally. Besides, extraordinary presentations of SVT are available in literature...
April 2017: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/28461761/managing-the-pediatric-patient-with-refractory-asthma-a-multidisciplinary-approach
#15
REVIEW
James Cook, Fran Beresford, Valentina Fainardi, Pippa Hall, Georgie Housley, Angela Jamalzadeh, Michelle Nightingale, David Winch, Andrew Bush, Louise Fleming, Sejal Saglani
Children with asthma that is refractory to high levels of prescribed treatment are described as having problematic severe asthma. Those in whom persistent symptoms result from a failure of basic asthma management are described as having "difficult asthma", while those who remain symptomatic despite these factors having been addressed are described as having "severe therapy-resistant asthma" (STRA). The majority of children have difficult asthma; asthma that is poorly controlled because of a failure to get the basics of asthma management right...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28442499/absorption-distribution-metabolism-and-excretion-of-the-oral-prostaglandin-d2-receptor-2-dp2-antagonist-fevipiprant-qaw039-in-healthy-volunteers-and-in-vitro
#16
David Pearson, H Markus Weiss, Yi Jin, Jan Jaap van Lier, Veit J Erpenbeck, Ulrike Glaenzel, Peter End, Ralph Woessner, Fabian Eggimann, Gian Camenisch
Fevipiprant is a novel oral prostaglandin D2 receptor 2 (DP2; also known as CRTh2) antagonist, which is currently in development for the treatment of severe asthma and atopic dermatitis. We investigated the absorption, distribution, metabolism, and excretion properties of fevipiprant in healthy subjects after a single 200 mg oral dose of [(14)C]-radiolabeled fevipiprant. Fevipiprant and metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and radioactivity measurements, and mechanistic in vitro studies were performed to investigate clearance pathways and covalent plasma protein binding...
April 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28401621/mouse-models-of-severe-asthma-understanding-the-mechanisms-of-steroid-resistance-tissue-remodelling-and-disease-exacerbation
#17
REVIEW
Steven Maltby, Hock L Tay, Ming Yang, Paul S Foster
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e...
April 11, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28399782/the-effects-of-chrysophanol-on-ovalbumin-ova-induced-chronic-lung-toxicology-by-inhibiting-th17-response
#18
Chunyan Zhang, Yafan Song, Congxia Wang, Ling Zhao, Huafeng Kang, Xiaobin Ma, Jing Wang, Tianzhu Zhang, Wang Shumin, Chunhua Ma
Chrysophanol (CH), extracted from plants of Rheum genus, possesses various pharmacological effects including anti-inflammatory activity. The purpose of the present study was to evaluate the protective effects and the underlying mechanisms of CH on ovalbumin (OVA)-induced asthma in mice. Fifty mice were randomly assigned to five experimental groups: control group, model group, dexamethasone (2 mg/kg) group and CH (5 and 10 mg/kg) groups. The number of eosinophil cells and the production of interleukin-6 (IL-6), IL-1β, IL-17 A and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) were measured...
June 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28389065/nattokinase-profibrinolytic-enzyme-effectively-shrinks-the-nasal-polyp-tissue-and-decreases-viscosity-of-mucus
#19
Tetsuji Takabayashi, Yoshimasa Imoto, Masafumi Sakashita, Yukinori Kato, Takahiro Tokunaga, Kanako Yoshida, Norihiko Narita, Tamotsu Ishizuka, Shigeharu Fujieda
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is often comorbid with asthma and resistant to therapeutic interventions. We recently reported that excessive fibrin deposition caused by impairment of fibrinolysis might play pivotal role in forming nasal polyp. Nattokinase (NK), a serine protease produced by Bacillus subtilis, has been reported to be a strong fibrinolytic enzyme. NK could be a promising drug candidate for use in the treatment of both CRSwNP and asthma. The objective of this study was to investigate the effects of NK on nasal polyp tissues from patients with CRSwNP...
April 4, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28370266/inhaled-steroids-reduce-pain-and-svcam-levels-in-individuals-with-sickle-cell-disease-a-triple-blind-randomized-trial
#20
Jeffrey Glassberg, Caterina Minnitti, Caroline Cromwell, Lawrence Cytryn, Thomas Kraus, Gwen S Skloot, Jason T Connor, Adeeb H Rahman, William J Meurer
Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance, and hyper-reactivity) is an intrinsic component of Sickle Cell Disease (SCD) and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 nonasthmatic individuals with SCD...
July 2017: American Journal of Hematology
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