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Treatment Resistent Asthma

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https://www.readbyqxmd.com/read/28523172/roles-of-roflumilast-a-selective-phosphodiesterase-4-inhibitor-in-airway-diseases
#1
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
#2
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
#3
Ana R Sousa, Richard P Marshall, Linda C Warnock, Sarah Bolton, Annette Hastie, Fiona Symon, Beverley Hargadon, Hilary Marshall, Matthew Richardson, Christopher E Brightling, Pranab Haldar, Roberta Milone, Peter Chalk, Rick Williamson, Reynold Panettieri, Richard Knowles, Eugene R Bleecker, Andrew 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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 hyperreactivity) is an intrinsic component of 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 non-asthmatic individuals with SCD...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28314658/management-of-chronic-inducible-urticaria-according-to-the-guidelines-a-prospective-controlled-study
#11
Emek Kocatürk, Pelin Kuteyla Can, Pırıl Etikan Akbas, Mehmet Copur, Ece Nur Degirmentepe, Kübra Kızıltac, Ralfi Singer
BACKGROUND: The recommended treatment approach in chronic inducible urticarias (CIndU) is the same as that for chronic spontaneous urticaria (CSU). But there is a lack of controlled trials assessing efficacy of available treatment options. OBJECTIVE: We aimed to evaluate the efficacy of treatment algorithm recommended by the guidelines and comparison of treatment responses in CIndU vs CSU. METHODS: This prospective parallel group controlled study included 70 CIndU and 66 CSU patients...
March 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28295526/pharmacological-treatments-in-asthma-affected-horses-a-pair-wise-and-network-meta-analysis
#12
L Calzetta, P Roncada, D di Cave, L Bonizzi, A Urbani, E Pistocchini, P Rogliani, M G Matera
BACKGROUND: Equine asthma is a disease characterised by reversible airflow obstruction, bronchial hyperresponsiveness and airway inflammation following exposure of susceptible horses to specific airborne agents. Although clinical remission can be achieved in a low-airborne dust environment, repeated exacerbations may lead to irreversible airway remodelling. The available data on the pharmacotherapy of equine asthma results from several small studies, and no head-to-head clinical trials have been conducted among the available medications...
March 10, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28282577/therapeutic-efficacy-of-a-co-blockade-of-il-13-and-il-25-on-airway-inflammation-and-remodeling-in-a-mouse-model-of-asthma
#13
Fang-Qi Zhang, Xin-Peng Han, Fang Zhang, Xuan Ma, Dong Xiang, Xue-Min Yang, Hai-Feng Ou-Yang, Zhikui Li
Repeated airway inflammation and unremitting remodeling provoke irreversible pulmonary dysfunction and resistance to current drugs in patients with chronic bronchial asthma. Interleukin (IL)-13 and IL-25 play an important role in airway inflammation and remodeling in asthma. We aimed to investigate whether co-inhibiting IL-13 and IL-25 can effectively down-regulate allergen-induced airway inflammation and remodeling in mice. Mice with asthma induced by chronic exposure to ovalbumin (OVA) were given soluble IL-13 receptor α2 (sIL-13R) or soluble IL-25 receptor (sIL-25R) protein alone and in combination to neutralize the bioactivity of IL-13 and IL-25, and relevant airway inflammation and remodeling experiments were performed...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28275137/a-ceacam6-high-airway-neutrophil-phenotype-and-ceacam6-high-epithelial-cells-are-features-of-severe-asthma
#14
Aarti Shikotra, David F Choy, Salman Siddiqui, Greer Arthur, Deepti R Nagarkar, Guiquan Jia, Adam K A Wright, Chandra M Ohri, Emma Doran, Claire A Butler, Beverley Hargadon, Alexander R Abbas, Janet Jackman, Lawren C Wu, Liam G Heaney, Joseph R Arron, Peter Bradding
Severe asthma represents a major unmet clinical need; understanding the pathophysiology is essential for the development of new therapies. Using microarray analysis, we previously found three immunological clusters in asthma: Th2-high, Th17-high, and Th2/17-low. Although new therapies are emerging for Th2-high disease, identifying molecular pathways in Th2-low disease remains an important goal. Further interrogation of our previously described microarray dataset revealed upregulation of gene expression for carcinoembryonic Ag cell adhesion molecule (CEACAM) family members in the bronchi of patients with severe asthma...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28267764/ex-vivo-modulation-of-the-foxo1-phosphorylation-state-does-not-lead-to-dysfunction-of-t-regulatory-cells
#15
Kristen Kelley Penberthy, Monica Weaver Buckley, Sanja Arandjelovic, Kodi Ravichandran
Peripheral regulatory CD4+ T cells (Treg cells) prevent maladaptive inflammatory responses to innocuous foreign antigens. Treg cell dysfunction has been linked to many inflammatory diseases, including allergic airway inflammation. Glucocorticoids that are used to treat allergic airway inflammation and asthma are thought to work in part by promoting Treg cell differentiation; patients who are refractory to these drugs have defective induction of anti-inflammatory Treg cells. Previous observations suggest that Treg cells deficient in the transcription factor FoxO1 are pro-inflammatory, and that FoxO1 activity is regulated by its phosphorylation status and nuclear localization...
2017: PloS One
https://www.readbyqxmd.com/read/28260934/peak-inspiratory-flow-rate-measurement-by-using-in-check-dial-for-the-different-inhaler-devices-in-elderly-with-obstructive-airway-diseases
#16
Theerasuk Kawamatawong, Supattra Khiawwan, Prapaporn Pornsuriyasak
BACKGROUND: Inhaler device technique is a common cause of treatment failure in patients with asthma and chronic obstructive pulmonary disease. Dry powder inhaler (DPI) requires optimal peak inspiratory flow rate (PIFR) for drug delivery. Low PIFR generation is common in the elderly. Patient lung function and intrinsic inhaler resistance are factors for determining generated PIFR and drug delivery from DPI. OBJECTIVES: We aimed to identify the PIFR of the older (aged >60 years) and the younger (aged ≤60 years) patients with obstructive airway diseases for the different inhaler devices (Turbuhaler(®) and Accuhaler)...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28258348/neutralization-of-nerve-growth-factor-ngf-inhibits-the-th2-response-and-protects-against-the-respiratory-syncytial-virus-rsv-infection
#17
Xiaorong Wu, Xiong Zhou, Yuxiang Hu, Chao Liu, Jun Wang
Increasing evidence suggests that respiratory syncytial virus (RSV) infection during the early life is an important risk factor for the development of asthma. RSV infection is associated with neurogenic inflammation in the airways along with the increased expression of nerve growth factor (NGF). However, the role of NGF in RSV infection is not clear. In this study, we infected the rat with RSV and treated these animals with anti-NGF neutralization antibody. We found that anti-NGF treatment significantly alleviated the lung inflammation as evidenced by decreased inflammatory infiltration and decreased airway resistance...
March 3, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28252317/role-for-nlrp3-inflammasome-mediated-il-1%C3%AE-dependent-responses-in-severe-steroid-resistant-asthma
#18
Richard Y Kim, James W Pinkerton, Ama T Essilfie, Avril Ab Robertson, Katherine J Baines, Alexandra C Brown, Jemma R Mayall, Md Khadem Ali, Malcolm R Starkey, Nicole G Hansbro, Jeremy A Hirota, Lisa G Wood, Jodie L Simpson, Darryl A Knight, Peter A Wark, Peter G Gibson, Luke A J O'Neill, Matthew A Cooper, Jay C Horvat, Philip M Hansbro
RATIONALE: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive NLRP3 inflammasome and concomitant IL-1β responses occur in COPD, respiratory infections and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma...
March 2, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28245238/impacts-of-allergic-airway-inflammation-on-lung-pathology-in-a-mouse-model-of-influenza-a-virus-infection
#19
Akira Kawaguchi, Tadaki Suzuki, Yuki Ohara, Kenta Takahashi, Yuko Sato, Akira Ainai, Noriyo Nagata, Masato Tashiro, Hideki Hasegawa
Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood...
2017: PloS One
https://www.readbyqxmd.com/read/28223414/the-flavonoid-cyanidin-blocks-binding-of-the-cytokine-interleukin-17a-to-the-il-17ra-subunit-to-alleviate-inflammation-in-vivo
#20
Caini Liu, Liang Zhu, Koichi Fukuda, Suidong Ouyang, Xing Chen, Chenhui Wang, Cun-Jin Zhang, Bradley Martin, Chunfang Gu, Luke Qin, Suguna Rachakonda, Mark Aronica, Jun Qin, Xiaoxia Li
Cyanidin, a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, including asthma, diabetes, atherosclerosis, and cancer, through its anti-inflammatory effects. We investigated the molecular basis of cyanidin action. Through a structure-based search for small molecules that inhibit signaling by the proinflammatory cytokine interleukin-17A (IL-17A), we found that cyanidin specifically recognizes an IL-17A binding site in the IL-17A receptor subunit (IL-17RA) and inhibits the IL-17A/IL-17RA interaction...
February 21, 2017: Science Signaling
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