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Treatment Resistent Asthma

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https://www.readbyqxmd.com/read/27887950/cyslt2-receptor-activation-is-involved-in-ltc4-induced-lung-air-trapping-in-guinea-pigs
#1
Tomohiko Sekioka, Michiaki Kadode, Yasuo Yonetomi, Akihiro Kamiya, Manabu Fujita, Takeshi Nabe, Kazuhito Kawabata
CysLT1 receptors are known to be involved in the pathogenesis of asthma. However, the functional roles of CysLT2 receptors in this condition have not been determined. The purpose of this study is to develop an experimental model of CysLT2 receptor-mediated LTC4-induced lung air-trapping in guinea pigs and use this model to clarify the mechanism underlying response to such trapping. Because LTC4 is rapidly converted to LTD4 by γ-glutamyltranspeptidase (γ-GTP) under physiological conditions, S-hexyl GSH was used as a γ-GTP inhibitor...
November 22, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27884795/forced-oscillation-technique-as-a-predictor-of-fev1-improvement-in-asthma
#2
Taisuke Akamatsu, Toshihiro Shirai, Yukiko Shimoda, Takahito Suzuki, Ichiro Hayashi, Rie Noguchi, Eisuke Mochizuki, Shogo Sakurai, Mika Saigusa, Akito Yamamoto, Yuichiro Shishido, Takefumi Akita, Satoru Morita, Kazuhiro Asada
The usefulness of the forced oscillation technique (FOT) for predicting the treatment outcomes in untreated asthmatic patients is unknown. We investigated whether FOT could predict an improvement in FEV1 following treatment. FOT, spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients before and after undergoing a minimum of two months combination therapy of inhaled corticosteroids and long-acting β2-agonists. The patients were classified as responders or nonresponders to treatment based on the presence or absence of a 10% improvement in the FEV1...
November 21, 2016: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/27853177/difference-in-resistance-to-humidity-between-commonly-used-dry-powder-inhalers-an-in-vitro-study
#3
Christer Janson, Thomas Lööf, Gunilla Telg, Georgios Stratelis, Folke Nilsson
Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at -0 °C...
November 17, 2016: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/27852250/impaired-anti-inflammatory-action-of-glucocorticoid-in-neutrophil-from-patients-with-steroid-resistant-asthma
#4
Meijia Wang, Pengfei Gao, Xiaojie Wu, Yuetao Chen, Yikuan Feng, Qun Yang, Yongjian Xu, Jianping Zhao, Jungang Xie
BACKGROUND: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics. METHODS: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment...
November 16, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27830033/anti-inflammatory-effects-of-boletus-edulis-polysaccharide-on-asthma-pathology
#5
Songquan Wu, Guangli Wang, Ruhui Yang, Yubao Cui
Asthma is a chronic airway disease common around the world. The burden of this disease could be reduced with new and effective treatments. Here, the efficacy of a polysaccharide extract from the Boletus edulis (BEP) mushroom, which has demonstrated anti-inflammatory properties, was tested in a mouse model of asthma. Five groups of BaLB/C mice were developed; one group served as a control and did not have asthma induction. The other four groups of mice were sensitized by ovalbumin challenge. FinePointe™ RC animal airway resistance and pulmonary compliance was used to assess airway function in asthma models...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27815425/stat6-regulates-the-development-of-eosinophilic-versus-neutrophilic-asthma-in-response-to-alternaria-alternata
#6
Andrea C Valladao, Charles W Frevert, Lisa K Koch, Daniel J Campbell, Steven F Ziegler
Human asthma is a heterogeneous disease characterized by the expression of both Th2 and Th17 cytokines. In vitro and in vivo studies have shown a reciprocal regulation between Th2 and Th17 pathways, suggesting a potential induction of neutrophil-promoting Th17 inflammation in the absence of a Th2 response. Alternaria alternata is a clinically relevant allergen that is associated with severe and fatal asthma exacerbations. Exposure to A. alternata is characterized by a predominant Th2 response, but can also induce the production of factors associated with Th17 responses (e...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27798418/t2-low-asthma-current-approach-to-diagnosis-and-therapy
#7
Konstantinos Samitas, Eleftherios Zervas, Mina Gaga
PURPOSE OF REVIEW: Asthma is a heterogeneous disease not only on a clinical but also on a mechanistic level. For a long time, the molecular mechanisms of asthma were considered to be driven by type 2 helper T cells (Th2) and eosinophilic airway inflammation; however, extensive research has revealed that T2-low subtypes that differ from the dominant T2 paradigm are also common. RECENT FINDINGS: Research into asthma pathways has led to the recognition that some asthma phenotypes show absence of T2 inflammation or alternate between T2 and non-T2 responses...
January 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27796513/glucocorticosteroids
#8
Peter J Barnes
Glucocorticosteroids are the most effective anti-inflammatory therapy for asthma but are relatively ineffective in COPD. Glucocorticoids are broad-spectrum anti-inflammatory drugs that suppress inflammation via several molecular mechanisms. Glucocorticoids suppress the multiple inflammatory genes that are activated in asthma by reversing histone acetylation of activated inflammatory genes through binding of ligand-bound glucocorticoid receptors (GR) to coactivator molecules and recruitment of histone deacetylase-2 (HDAC2) to the activated inflammatory gene transcription complex (trans-repression)...
October 28, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27789120/effect-of-curcumin-on-nasal-symptoms-and-airflow-in-patients-with-perennial-allergic-rhinitis
#9
Sihai Wu, Dajiang Xiao
BACKGROUND: Allergic rhinitis (AR) is a common disorder that can significantly affect patient quality of life. Previous studies have found that curcumin had anti-inflammatory and antioxidant effects and clinical benefits in cancer and asthma. OBJECTIVE: To determine the efficacy of curcumin in the treatment of AR and to explore the molecular mechanisms involved. METHODS: In a randomized, double-blind study, 241 patients with AR received either placebo or oral curcumin for 2 months...
October 24, 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27741157/the-role-of-vitamin-d-in-allergic-diseases-in-children
#10
Michele Miraglia Del Giudice, Annalisa Allegorico
The role of vitamin D in calcium and phosphate homeostasis is well known; however, in addition to traditional functions, vitamin D modulates a variety of processes, and evidence shows that it has an important role in different allergic diseases such as asthma, atopic dermatitis, and food allergy. Vitamin D acts by binding to the vitamin D receptor, which is present in a variety of tissues; for this reason it is considered a hormone. One of the most important functions is to modulate the immune system response, both innate and adaptive, by suppressing Th2-type response and increasing natural killer cells...
November 2016: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/27718262/a-12-week-randomized-parallel-group-proof-of-concept-study-of-tulobuterol-patch-and-salmeterol-inhaler-as-add-on-therapy-in-adult-onset-mild-to-moderate-asthma
#11
Hideki Inoue, Akio Niimi, Hisako Matsumoto, Isao Ito, Tsuyoshi Oguma, Kojiro Otsuka, Tomoshi Takeda, Hitoshi Nakaji, Tomoko Tajiri, Toshiyuki Iwata, Tadao Nagasaki, Michiaki Mishima
Patch formulation of tulobuterol has been used in asthma treatment as a long-acting β2 -agonist (LABA) through sustained skin absorption. Its treatment efficacy, especially in small airways, remains poorly understood. The study aim was to investigate LABA add-on effects of tulobuterol patch (TP) and salmeterol inhaler (SA) on pulmonary function, asthma control, and health status. Patients who had adult-onset under-controlled asthma, despite taking inhaled corticosteroids, were enrolled in a randomized, open-label, parallel-group, proof-of-concept study of 12-week add-on treatment with TP (n = 16) or SA (n = 17)...
October 8, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27713399/a-novel-anti-il4r%C3%AE-nanoparticle-efficiently-controls-lung-inflammation-during-asthma
#12
Rabih Halwani, Asma Sultana Shaik, Elaref Ratemi, Sibtain Afzal, Rosan Kenana, Saleh Al-Muhsen, Achraf Al Faraj
Drug resistance and the harmful side effects accompanying the prolonged corticosteroid treatment of chronic pulmonary diseases prompted the development of more specific anti-inflammatory approaches. Several strategies aiming to block IL4Rα, the receptor for a key pro-inflammatory pathway, were investigated. However, their efficiency was limited, mostly due to the systemic or subcutaneous route of administrations. In this paper, we examined the ability of an intranasal treatment with biocompatible nanoparticles targeting IL4Rα to control lung inflammation in ovalbumin (OVA)-sensitized mice...
October 7, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27698668/radioactive-merano-spa-treatment-for-allergic-rhinitis-therapy
#13
Desiderio Passali, Giacomo Gabelli, Giulio Cesare Passali, Roberto Magnato, Stefan Platzgummer, Lorenzo Salerni, Salvatore Lo Cunsolo, Alexandra Joos, Luisa Maria Bellussi
Allergic rhinitis is a common nasal disorder with a high impact on quality of life, high social costs in therapies, and a natural development towards asthma. Pharmacological therapy is based on several genres of medications, of which intranasal corticosteroids are currently the most widespread. Thermal water treatment has traditionally been used as adjunctive treatment for chronic rhinitis and sinusitis. The present study was carried out to assess the clinical efficacy of nasal inhalation of radioactive oligomineral water vapours from the Merano hot spring and to compare it with the clinical efficacy of mometasone furoate nasal spray...
2016: International Journal of Otolaryngology
https://www.readbyqxmd.com/read/27687913/il-27-attenuates-airway-inflammation-in-a-mouse-asthma-model-via-the-stat1-and-gadd45%C3%AE-p38-mapk-pathways
#14
Xiaoqiong Su, Jue Pan, Fengxi Bai, Honglei Yuan, Nian Dong, Dandan Li, Xiangdong Wang, Zhihong Chen
BACKGROUND: Asthma is prone to Th2-mediated chronic airway inflammation. Interleukin-27 (IL-27) is a member of the IL-12 family that promotes the differentiation of Th1 cells and inhibits Th2 cells. We use human/mouse CD4(+) T cells to see whether IL-27 could inhibit IL-4 production in vitro and then observe whether IL-27 administration could alleviate allergic airway inflammation in vivo by mice asthma model. METHODS: We isolated and cultured CD4(+) T cells from healthy humans and mice to test whether IL-27 could inhibit IL-4 production under different conditions...
September 29, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27658760/high-resolution-metabolomics-to-identify-urine-biomarkers-in-corticosteroid-resistant-asthmatic-children
#15
Youngja H Park, Anne M Fitzpatrick, Carl Angelo Medriano, Dean P Jones
BACKGROUND: Corticosteroid (CS) treatment has been established as the first anti-inflammatory treatment for adults and children with asthma. However, a subset of patients fails to respond to combined systemic and inhaled CS treatment. OBJECTIVE: This study is aimed at further understanding CS resistance among severe asthmatic children. METHODS: High resolution metabolomics (HRM) was performed on urine samples from CS-respondent (n=15) and CS-nonrespondent (n=15) children to determine possible urine biomarkers related to CS resistance...
September 19, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27621904/evaluation-of-airway-resistance-in-primary-small-cell-carcinoma-of-the-trachea-by-mostgraph-a-case-study
#16
Eri Hagiwara, Yasuhiro Gon, Kentaro Hayashi, Mai Takahashi, Yuko Iida, Hisato Hiranuma, Yoshiko Nakagawa, Tsukasa Hataoka, Kenji Mizumura, Shuichiro Maruoka, Tetsuo Shimizu, Noriaki Takahashi, Shu Hashimoto
The case subject was a 58-year-old woman who presented to our hospital with a chief complaint of respiratory discomfort. Wheezing could be heard in both lungs; treatment was initiated with inhaled steroids for suspected bronchial asthma. However, 1 week later, the respiratory discomfort had not improved and the wheezing sound had progressed to the neck area. Upper airway obstruction was suspected; therefore, chest computed tomography (CT) was performed, revealing tracheal stenosis caused by a tumor in the upper airway...
August 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27601016/management-of-endocrine-disease-morbidity-in-polycystic-ovary-syndrome
#17
REVIEW
Dorte Glintborg, Marianne Andersen
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition in premenopausal women. The syndrome is characterized by hyperandrogenism, irregular menses and polycystic ovaries when other etiologies are excluded. Obesity, insulin resistance and low vitamin D levels are present in more than 50% patients with PCOS, these factors along with hyperandrogenism could have adverse effects on long-term health. Hyperinflammation and impaired epithelial function were reported to a larger extent in women with PCOS and could particularly be associated with hyperandrogenism, obesity and insulin resistance...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27525064/elucidating-novel-disease-mechanisms-in-severe-asthma
#18
REVIEW
Richard Y Kim, Brittany Rae, Rachel Neal, Chantal Donovan, James Pinkerton, Lohis Balachandran, Malcolm R Starkey, Darryl A Knight, Jay C Horvat, Philip M Hansbro
Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure...
July 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27468424/sweet-p-inhibition-of-glucocorticoid-receptor-%C3%AE-as-a-potential-cancer-therapy
#19
Assumpta C Nwaneri, Lucien McBeth, Terry D Hinds
The need for the development of new cancer therapies and push for the design of new targeting techniques is on the rise, and would be useful for cancers that are resistant to current drug treatments. The understanding of the genome has significantly advanced cancer therapy, as well as prevention and earlier detection. This research highlight discusses a potential new type of cancer-targeting molecule, Sweet-P, which is the first of its kind. Sweet-P specifically targets the microRNA-144 binding site in the 3' untranslated region (3' UTR) of the human glucocorticoid receptor β (GRβ), which has been demonstrated to increase expression...
2016: Cancer Cell & Microenvironment
https://www.readbyqxmd.com/read/27449512/plethysmography-phenotype-qtl-in-mice-before-and-after-allergen-sensitization-and-challenge
#20
Samir N P Kelada
Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene-environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains...
September 8, 2016: G3: Genes—Genomes—Genetics
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