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Pulmonary Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/29158154/tiotropium-inhibits-mucin-production-stimulated-by-neutrophil-elastase-but-not-by-il-13
#1
Kosaku Komiya, Shuichi Kawano, Isao Suzaki, Tomohiro Akaba, Jun-Ichi Kadota, Bruce K Rubin
Tiotropium, a muscarinic antagonist, is approved for the treatment of chronic obstructive pulmonary disease and poorly controlled asthma. Because mucus hypersecretion is characteristic of both of these diseases, and muscarinic agonists stimulate mucus secretion, we hypothesized that tiotropium would attenuate airway MUC5AC expression. We grew normal human bronchial epithelial (NHBE) cells to a goblet cell phenotype with 1 or 5 ng/mL of IL-13 and exposed these cells to 10 nM tiotropium or excipient for the full 14 days...
November 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29158153/m3-receptor-is-involved-in-the-effect-of-penehyclidine-hydrochloride-reduced-endothelial-injury-in-lps-stimulated-human-pulmonary-microvascular-endothelial-cell
#2
Qinghong Yuan, Fei Xiao, Qiangsheng Liu, Fei Zheng, Shiwen Shen, Qianwen He, Kai Chen, Yanlin Wang, Zongze Zhang, Jia Zhan
LPS has been recently shown to induce muscarinic acetylcholine 3 receptor (M3 receptor) expression and penehyclidine hydrochloride (PHC) is an anticholinergic drug which could block the expression of M3 receptor. PHC has been demonstrated to perform protective effect on cell injury. This study is to investigate whether the effect of PHC on microvascular endothelial injury is related to its inhibition of M3 receptor or not. HPMVECs were treated with specific M3 receptor shRNA or PBS, and randomly divided into LPS group (A group), LPS+PHC group (B group), LPS + M3 shRNA group (C group) and LPS + PHC + M3 shRNA group (D group)...
November 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29133080/population-pharmacokinetics-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#3
Ulrike Schmid, Christiane Doege, Claudia Dallinger, Matthias Freiwald
BACKGROUND: Nintedanib is a potent intracellular inhibitor of tyrosine kinases, including the receptor kinases vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor. A previous model assessed the population pharmacokinetics of nintedanib and its main metabolite BIBF 1202 in patients with non-small cell lung cancer and idiopathic pulmonary fibrosis (IPF). The objective of this analysis was to further characterise the population pharmacokinetics of nintedanib in patients with IPF by including data from the Phase III trials...
November 10, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29133079/baicalein-attenuates-monocrotaline-induced-pulmonary-arterial-hypertension-by-inhibiting-vascular-remodeling-in-rats
#4
Ruizan Shi, Zehui Wei, Diying Zhu, Naijie Fu, Wang Chang, Sha Yin, Yueqin Liang, Jianfeng Xing, Xuening Wang, Yan Wang
BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder characterized by elevated pulmonary arterial pressure (PAP) and right ventricular hypertrophy (RVH) driven by progressive vascular remodeling. Reversing adverse vascular remodeling is an important concept in the treatment of PAH. Endothelial injury, inflammation, and oxidative stress are three main contributors to pulmonary vascular remodeling. Baicalein is a natural flavonoid that has been shown to possess anti-proliferative, anti-inflammatory, anti-oxidative, and cardioprotective properties...
November 10, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29129801/activating-prostaglandin-e2-receptor-subtype-ep4-increases-secreted-mucin-from-airway-goblet-cells
#5
Tomohiro Akaba, Kosaku Komiya, Isao Suzaki, Yuji Kozaki, Jun Tamaoki, Bruce K Rubin
Prostaglandin E2 (PGE2) is a ligand of the E-type prostanoid receptors, EP1-4. PGE2 secretion is increased in the airways of patients with asthma by secretory phospholipases A2, which also increases MUC5AC mucin in goblet cells. We hypothesized that PGE2 would also increase MUC5AC mRNA and secreted protein through specific EP receptor activation. We sought to assess the effect of specific EP receptor activation on MUC5AC secretion from ciliated-enriched cells or goblet-enriched cells induced by IL-13. We develop an enriched goblet cell epithelium by growing normal human bronchial epithelial cells at air liquid interface for 14 days in the presence of IL-13...
November 9, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29128622/efficacy-and-tolerability-of-pharmacological-interventions-for-pulmonary-arterial-hypertension-a-network-meta-analysis
#6
Hongjing Lin, Mupeng Wang, Ying Yu, Zeyu Qin, Xin Zhong, Jiahui Ma, Fangbo Zhao, Xueli Zhang
PURPOSE: This network meta-analysis (NMA) is designed to compare the efficacy and tolerability of various therapies and combinations for pulmonary arterial hypertension (PAH). METHOD: We conducted a systematic search in databases PubMed, Embase, and Cochrane Library. Treatment efficacy and tolerability were compared by synthesizing direct and indirect evidence. The surface under the curve ranking area was utilized to rank multiple interventions. RESULT: A total of 43 randomized clinical trials were included in our NMA...
November 8, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29107090/inhibition-of-angiotensin-ii-and-calpain-attenuates-pleural-fibrosis
#7
Lin-Jie Song, Fei Xiang, Hong Ye, Hai Huang, Jie Yang, Fan Yu, Liang Xiong, Juan-Juan Xu, Peter A Greer, Huan-Zhong Shi, Jian-Bao Xin, Yunchao Su, Wan-Li Ma
Pleural fibrosis is associated with various inflammatory processes such as tuberculous pleurisy and bacterial empyema. There is currently no ideal therapeutic to attenuate pleural fibrosis. Some pro-fibrogenic mediators induce fibrosis through inflammatory processes, suggesting that blockage of these mediators might prevent pleural fibrosis. The MeT-5A human pleural mesothelial cell line (PMC) was used in this study as an in vitro model of fibrosis; and intra-pleural injection of bleomycin with carbon particles was used as an in vivo mouse model of pleural fibrosis...
October 26, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29066215/treatment-with-long-acting-muscarinic-antagonists-stimulates-serum-levels-of-irisin-in-patients-with-copd
#8
Jyotshna Mandal, Michael Roth, Eleni Papakonstantinou, Qingzhu Sun, Luigi Costa, Lucas Boeck, Andreas Scherr, Janko Rakic, Renaud Louis, Branislava Milenkovic, Wim Boersma, Konstantinos Kostikas, Francesco Blasi, Joachim Aerts, Gernot Rohde, Alicia Lacoma, Antoni Torres, Tobias Welte, Michael Tamm, Daiana Stolz
Long acting muscarinic antagonists (LAMA) are currently considered the therapeutic mainstay for patients with COPD and have been shown to improve clinical outcomes including symptoms, exercise capacity and airflow limitation. Irisin, is a newly discovered hormone-like myokine generated by skeletal muscle cells in response to exercise and it is suggested to regulate energy expenditure and exercise capacity. The aim of the present study was to investigate if treatment with LAMA alters serum irisin levels in patients with COPD...
October 21, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29056509/the-effect-of-l-arginine-on-ciliary-beat-frequency-in-pcd-patients-non-pcd-respiratory-patients-and-healthy-controls
#9
Panayiotis Kouis, Andreas Hadjisavvas, Nicos Middleton, Stefania I Papatheodorou, Kyriacos Kyriacou, Panayiotis K Yiallouros
OBJECTIVES: Few studies have examined the potentially therapeutic effect of increasing the production of endogenous nitric oxide (NO) in Primary Ciliary Dyskinesia (PCD) and other chronic respiratory conditions. Nasal NO is low in PCD and has been found to correlate with compromised Ciliary Beat Frequency (CBF). In this study we assessed the effect of increasing l-Arginine, as the substrate of NO synthases, on CBF in biopsies of human respiratory ciliated epithelium. METHODOLOGY: A total of 28 suspect cases with chronic respiratory manifestations referred for PCD diagnostic testing and 8 healthy controls underwent nasal brushing...
October 19, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29054517/size-distribution-of-salbutamol-ipratropium-aerosols-produced-by-different-nebulizers-in-the-absence-and-presence-of-heat-and-humidification
#10
Ssu-Han Yang, Tsung-Ming Yang, Hui-Ling Lin, Ying-Huang Tsai, Tien-Pei Fang, Gwo-Hwa Wan
BACKGROUND: Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. METHODS: We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0...
October 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29031617/steroid-sparing-effects-of-doxofylline
#11
Yanira Riffo-Vasquez, Radhakrishnan Venkatasamy, Clive P Page
Glucocorticosteroids are widely used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). However, there are growing concerns about the side effect profile of this class of drug, particularly an increased risk of pneumonia. Over the last two decades there have been many attempts to find drugs to allow a reduction of glucocorticosteroids, including xanthines such as theophylline. Use of xanthines has been shown to lead to a reduction in the requirement for glucocorticosteroids, although xanthines also have a narrow therapeutic window limiting their wider use...
October 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29031616/factors-affecting-the-selection-of-an-inhaler-device-for-copd-and-the-ideal-device-for-different-patient-profiles-results-of-epoca-delphi-consensus
#12
Marc Miravitlles, Juan José Soler-Cataluña, Bernardino Alcázar, José Luis Viejo, Francisco García-Río
BACKGROUND: This study aimed to identify the relevant factors for the choice of an inhaler device by physicians and the selection of the most important characteristics of a device according to different characteristics of patients with COPD. METHOD: In this two-round Delphi survey, 96 Spanish COPD-expert pulmonologists completed an internet-based, self-administered questionnaire, which consisted of a first part with 19 items related to the prioritization of the drug or the device, the experience, ability and preference of the patient, and the experience and preferences of the healthcare professional...
October 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29031615/the-leukotriene-receptor-antagonist-pranlukast-attenuates-airway-remodeling-by-suppressing-tgf-%C3%AE-signaling
#13
Jung Hur, Ji Young Kang, Chin Kook Rhee, Young Kyoon Kim, Sook Young Lee
BACKGROUND/OBJECTIVE: Asthma is a chronic airway disease characterized by airway eosinophilic inflammation and remodeling, which are associated with a loss in lung function. Although both contribute significantly to asthma pathogenesis, mechanistic studies and drug discovery have focused on inflammatory targets. In this study, we investigated the effect of the leukotriene receptor antagonist pranlukast on allergic airway inflammation and remodeling in vivo and in vitro. METHOD: Four groups of female BALB/c mice (control; ovalbumin [OVA]-sensitized and -challenged; dimethyl sulfoxide [DMSO]-treated OVA; and pranlukast-treated OVA) were examined...
October 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29024795/are-valved-holding-chambers-vhcs-interchangeable-an-in-vitro-evaluation-of-vhc-equivalence
#14
Sanjeeva Dissanayake, Mark Nagel, Emanuela Falaschetti, Jason Suggett
INTRODUCTION: The European Medicines Agency (EMA) requires that a specific valved holding chamber (VHC) is designated for use with a given pressurised metered dose inhaler (pMDI). No other regulatory authorities impose similar requirements, implying that VHCs are interchangeable. This in vitro study, employing EMA assessment criteria, assessed the equivalence of four anti-static VHCs (aVHCs) versus the non-conducting VHC most widely referenced in pMDI monographs, the AeroChamber Plus™ (AC+) VHC...
October 9, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28987804/pharmacodynamics-pharmacokinetics-and-safety-of-revefenacin-td-4208-a-long-acting-muscarinic-antagonist-in-patients-with-chronic-obstructive-pulmonary-disease-copd-results-of-two-randomized-double-blind-phase-2-studies
#15
Dean Quinn, Christopher N Barnes, Wayne Yates, David L Bourdet, Edmund J Moran, Peter Potgieter, Andrew Nicholls, Brett Haumann, Dave Singh
BACKGROUND: Revefenacin (TD-4208) is a potent, lung-selective, long-acting muscarinic antagonist currently in development for once-daily treatment of chronic obstructive pulmonary disease (COPD). We evaluated the pharmacodynamics (bronchodilator activity), pharmacokinetics (PK) and safety of single- and multiple-dose administrations of nebulized revefenacin in two clinical trials (Study 0059 and Study 0091) in patients with moderate to severe COPD. METHODS: In Study 0059, 32 patients were randomized to receive a single dose of revefenacin (350 or 700 μg), active control ipratropium (500 μg) or placebo inhalation solution administered via standard jet nebulizer in a double-blind, crossover fashion...
October 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28987803/long-acting-%C3%AE-2-adrenoreceptor-agonists-suppress-type-1-interferon-expression-in-human-plasmacytoid-dendritic-cells-via-epigenetic-regulation
#16
Chang-Hung Kuo, San-Nan Yang, Yi-Giien Tsai, Chong-Chao Hsieh, Wei-Ting Liao, Li-Chen Chen, Min-Sheng Lee, Hsuan-Fu Kuo, Ching-Hsiung Lin, Chih-Hsing Hung
The combination of inhaled long-acting β2-adrenoreceptor (LABA) and inhaled glucocorticoid (ICS) is a major therapy for asthma. However, the increased risk of infection is still a concern. Plasmacytoid dendritic cells (pDCs) are the predominant cells producing type 1 interferon (IFN) against infection. The effect of LABA/ICS on type 1 IFN expression in human pDCs is unknown. Circulating pDCs were isolated from healthy human subjects and were pretreated with glucocorticoid (GCS), LABA or a cAMP analog, and were stimulated with Toll-like receptor (TLR) agonist CpG (TLR9) or imiquimod (TLR7) in the presence of IL-3...
October 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28986204/cough-and-severe-asthma
#17
REVIEW
Liam G Heaney
No abstract text is available yet for this article.
October 3, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28986203/inhaled-nebulised-unfractionated-heparin-improves-lung-function-in-moderate-to-very-severe-copd-a-pilot-study
#18
Janis K Shute, Luigino Calzetta, Vittorio Cardaci, Stefania di Toro, Clive P Page, Mario Cazzola
BACKGROUND: COPD is an inflammatory airway disease characterised by progressive airflow limitation and air trapping, leading to lung hyperinflation and exercise limitation. Acute worsening of symptoms, including dyspnea, cough and sputum production, occurs during exacerbations which are associated with significantly reduced health related quality of life, and increased morbidity and mortality. Chronic bronchial mucus production and productive cough are risk factors for exacerbations. Medicines targeting bronchoconstriction and airway inflammation are the current mainstays of COPD therapy...
October 3, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28964817/adrb2-gene-polymorphism-and-emphysema-heterogeneity-can-modulate-bronchodilator-response-in-patients-with-emphysema
#19
Masafumi Nojiri, Shiro Mizuno, Kazuaki Nishiki, Ryo Kato, Ken Nakagawa, Taku Oikawa, Masaharu Iguchi, Kazuhiro Osanai, Takeshi Ishizaki, Hirohisa Toga
BACKGROUND: Genetic variation in the β2-adrenergic receptor (ADRB2) gene has been thought to have an important role in the differential response to β2-agonist therapy for asthma. However, previous studies have shown little evidence for an association between these ADRB2 variants and the bronchial dilator response (BDR) in chronic obstructive pulmonary disease (COPD) patients. This discrepancy could be explained by differences in the distribution and heterogeneity of pulmonary emphysema in COPD patients, since emphysema distribution and heterogeneity are thought to have a role in pulmonary function in COPD patients...
September 27, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28951192/role-of-prostaglandin-e2-in-bronchoconstriction-triggered-cough-response-in-guinea-pigs
#20
Akihito Okazaki, Johsuke Hara, Noriyuki Ohkura, Masaki Fujimura, Tamami Sakai, Miki Abo, Nobuyuki Katayama, Kazuo Kasahara, Shinji Nakao
A feature of cough variant asthma is a heightened cough response to bronchoconstriction. The mediators of this response are unknown. This study was designed to elucidate the role of lipid mediators in bronchoconstriction-triggered cough response in an experimental animal model. We examined the influence of bronchoconstriction on cell components and mediators including prostaglandin E2 (PGE2) in bronchoalveolar lavage fluid (BALF). We studied the cough response to bronchoconstriction (CRB) by measuring the correlation between the increase in enhanced pause (Penh), an index of bronchoconstriction, and cough counts induced by methacholine (Mch) inhalation in conscious guinea pigs...
September 22, 2017: Pulmonary Pharmacology & Therapeutics
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