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Treatment Resistent Asthma

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
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
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
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
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
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
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
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...
September 6, 2016: European Journal of Endocrinology
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
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
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...
2016: G3: Genes—Genomes—Genetics
Izabela Kupryś-Lipińska, Katarzyna Molińska, Piotr Kuna
Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically...
2016: Pneumonologia i Alergologia Polska
Terufumi Shimoda, Yasushi Obase, Reiko Kishikawa, Tomoaki Iwanaga
BACKGROUND: Cigarette smoking induces neutrophilic airway inflammation and relative resistance to inhaled corticosteroids (ICS). OBJECTIVE: We evaluated the influence of cigarette smoking on airway inflammation in patients with asthma and also compared the effect of ICS between smoking and nonsmoking in patients with asthma. METHODS: Smokers with asthma (n = 81) and nonsmokers with asthma (n = 52) were recruited for the study. We examined lung function, fractional exhaled nitric oxide (FeNO) concentration, induced sputum, and acetylcholine inhalation before and 6 months after inhaling budesonide at 800 μg/day...
July 2016: Allergy and Asthma Proceedings:
Robyn L Jones, Peter B Noble, John G Elliot, Alan L James
COPD is defined as airflow limitation that is not reversed by treatment. In asthma, airflow limitation is not only reversible, but also inducible. This is called 'airway hyperresponsiveness' (AHR) and is associated with thickening of the airway wall, predominantly the layer of airway smooth muscle, due to more cells, bigger cells and more extracellular matrix (ECM) in proportion to the increase in smooth muscle. AHR is also observed in COPD if the changes in airflow are expressed as a percent of the baseline lung function...
July 5, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Diana Majolli André, Marina Ciarallo Calixto, Carolina Sollon, Eduardo Costa Alexandre, Luiz O Leiria, Natalia Tobar, Gabriel Forato Anhê, Edson Antunes
Obesity and insulin resistance have been associated with deterioration in asthma outcomes. High oxidative stress and deficient activation of AMP-activated protein kinase (AMPK) have emerged as important regulators linking insulin resistance and inflammation. This study aimed to evaluate the effects of resveratrol on obesity-associated allergic pulmonary inflammation. Male C57/Bl6 mice fed with high-fat diet to induce obesity (obese group) or standard-chow diet (lean group) were treated or not with resveratrol (100mg/kg/day, two weeks)...
September 2016: International Immunopharmacology
Yi Jia, Xu Fang, Xuehua Zhu, Chunxue Bai, Lei Zhu, Meiling Jin, Xiangdong Wang, Min Hu, Renhong Tang, Zhihong Chen
RATIONALE: Type 2 innate lymphoid cells (ILC2s) have been shown to produce large amounts of type 2 cytokines in a non-antigen specific manner. These cytokines act upstream and downstream of ILC2 and are increasingly popular in asthma drug development, thus warranting a closer investigation of the mechanism-related clinical manifestations of ILC2 from asthma patient selection perspective. OBJECTIVES: We hypothesized that IL-13+ ILC2s in the circulation might correlate with asthma control status as a result of persistent Th2 inflammation in the lung...
June 17, 2016: American Journal of Respiratory Cell and Molecular Biology
Sona Franova, Ivana Kazimierova, Lenka Pappova, Marta Joskova, Lukas Plank, Martina Sutovska
OBJECTIVE: Using an experimental model of allergic asthma, we evaluated the anti-asthmatic potential of polyphenol flavonol derivate morin after either acute or long-term treatment of male OVA-sensitised guinea pigs. METHODS: The following methods were used in experiments: the in-vitro tracheal smooth muscle contraction induced by histamine; the changes in specific airway resistance (sRaw) to histamine and the sensitivity of a chemically induced cough reflex both via an in-vivo method; the serum and BALF concentrations' analysis of the inflammatory cytokines interleukin IL-4, IL-5, IL-13; and lung tissue infiltration by eosinophils and mastocytes...
August 2016: Journal of Pharmacy and Pharmacology
Abdul Rehman Khan, Fazli Rabbi Awan
CONTEXT: Under normal physiological conditions, leptin regulates body weight by creating a balance between food intake and energy expenditure. However, in obesity, serum leptin levels increase and become defective to retain energy balance. EVIDENCE ACQUISITION: Elevated serum leptin levels are regarded as an established marker of obesity. It is also reported that obese asthmatic patients have maximum serum leptin levels compared to other groups such as non-obese asthmatics, and normal obese and non obese subjects without asthma...
January 2016: International Journal of Endocrinology and Metabolism
Emma Raywood, Sooky Lum, Paul Aurora, Katharine Pike
BACKGROUND: The bronchodilator response (BDR) is frequently used to support diagnostic and therapeutic decision-making for children who wheeze. However, there is little evidence-based guidance describing the role of BDR testing in preschool children and it is unclear whether published cut-off values, which are derived from adult data, can be applied to this population. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases (inception-September 2015) for studies reporting response to a bronchodilator in healthy preschool children, response following placebo inhalation, and the diagnostic efficacy of BDR compared with a clinical diagnosis of asthma/recurrent wheezing...
June 6, 2016: Pediatric Pulmonology
Sahdeo Prasad, Amit K Tyagi
BACKGROUND: Spice and spice-derived compounds have been identified and explored for their health benefits since centuries. One of the spice long pepper has been traditionally used to treat chronic bronchitis, asthma, constipation, gonorrhea, paralysis of the tongue, diarrhea, cholera, malaria, viral hepatitis, respiratory infections, stomach ache, diseases of the spleen, cough, and tumors. METHODS: In this review, the evidences for the chemopreventive and chemotherapeutic potential of piperlongumine have been described...
2016: Current Pharmaceutical Design
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