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Pulmonary Pharmacology & Therapeutics

Luigino Calzetta, Nicola A Hanania, Frank L Dini, Marc F Goldstein, William R Fairweather, William W Howard, Mario Cazzola
This pooled analysis of double-blind, randomized, placebo-controlled trials aimed to investigate the Impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Patients with asthma ≥16 years of age with (forced expiratory volume in 1 s [FEV1 ] ≥50% and <80% and with ≥15% post-bronchodilator increase in FEV1 ) were randomized in a 1:1:1:1 ratio in DOROTHEO 1 to receive doxofylline 200 mg, doxofylline 400 mg, theophylline 250 mg, or placebo; in DOROTHEO 2 patients were randomized in a 1:1:1 ratio to receive doxofylline 400 mg, theophylline 250 mg, or placebo...
September 13, 2018: Pulmonary Pharmacology & Therapeutics
Colin Reisner, Joel Miller, Paolo DePetrillo, Andrea Maes, Shahid Siddiqui, Ubaldo J Martin
BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes significant mortality in Japan. GFF MDI is a long-acting muscarinic antagonist/long-acting β2 -agonist fixed-dose combination of glycopyrronium (GP) and formoterol fumarate dihydrate (FF), delivered by a metered dose inhaler (MDI) using co-suspension delivery technology, for the long-term maintenance treatment of COPD. METHODS: This randomized, Phase I, single-dose, four-treatment, four-period, crossover study (NCT02196714) examined the pharmacokinetic (PK) and safety profile of two doses of GFF MDI (28...
September 12, 2018: Pulmonary Pharmacology & Therapeutics
Corrado Pelaia, Maria Teresa Busceti, Sabina Solinas, Rosa Terracciano, Girolamo Pelaia
Mepolizumab is a humanized monoclonal antibody which targets interleukin-5 (IL-5) and is nowadays available in many countries for add-on biological therapy of severe eosinophilic asthma. Although the approval of mepolizumab use in clinical practice has been made possible by several successful pre-marketing controlled trials, so far only a very few studies have been performed in a real-life setting. Within such a context, our present observational investigation refers to 14 patients with refractory eosinophilic asthma, currently treated with mepolizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy, whose anti-IL-5 treatment began between June 2017 and January 2018...
September 11, 2018: Pulmonary Pharmacology & Therapeutics
Mariam Ba, Shanti Rawat, Ronna Lao, Marilyn Grous, Michael Salmon, Andrew J Halayko, William T Gerthoffer, Cherie A Singer
BACKGROUND: Airway smooth muscle (ASM) contributes to local inflammation and plays an immunomodulatory role in airway diseases. This is partially regulated by p38 mitogen-activated protein kinase (MAPK), which further activates two closely related isoforms of the MAPK-activated protein kinases (MKs), MK2 and MK3. The MKs have similar substrate specificities but less is known about differences in their functional responses. This study was undertaken to identify differential downstream inflammatory targets of MK2 and MK3 signaling and assess cross-talk between the MAPK pathway and NF-κB signaling relevant to ASM function...
September 8, 2018: Pulmonary Pharmacology & Therapeutics
Steven Kesten, Elliot Israel, Guangxi Li, Jolyon Mitchell, Robert Wise, Tom Stern
BACKGROUND: Delivery of inhaled respiratory medications have been associated with variable delivery of drug due to errors in device operations and have not been designed to monitor true delivery of medication. A fully digital breath-activated inhaled (DBAI) delivery platform has been developed with integrated firmware and software to address these limitations. METHODS: the device was designed to produce similar aerosol particle output to a marketed albuterol MDI and to the albuterol/ipratropium combination in a soft mist inhaler (SMI)...
September 7, 2018: Pulmonary Pharmacology & Therapeutics
Ioanna Ninou, Eleanna Kaffe, Stefan Müller, David C Budd, Christopher S Stevenson, Christoph Ullmer, Vassilis Aidinis
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease with a dismal prognosis and a largely unknown etiology. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for extracellular production of lysophosphatidic acid (LPA), a bioactive phospholipid. LPA has numerous effects in most cell types, signaling through at least 6 receptors (LPAR) exhibiting wide spread distribution and overlapping specificities. The ATX/LPA axis has been suggested as a therapeutic target in different chronic inflammatory and fibroproliferative disorders, including pulmonary fibrosis...
September 7, 2018: Pulmonary Pharmacology & Therapeutics
Sebastiano Emanuele Torrisi, Ada Vancheri, Mauro Pavone, Gianluca Sambataro, Stefano Palmucci, Carlo Vancheri
Idiopathic Pulmonary Fibrosis (IPF) is a severe parenchymal lung disease characterized by an intense deposition of collagen in the interstitial spaces. The introduction of anti-fibrotic drugs increased patients' life expectancy highlighting the role of comorbidities in patients' management and prognosis. IPF is frequently associated with other diseases mainly because of its onset during middle age and sometimes because of the presence of common pathogenic pathways such as in the case of lung cancer. Comorbidities may differently influence prognosis of IPF patients...
September 4, 2018: Pulmonary Pharmacology & Therapeutics
Gino Scalone, Stefano Nava, Francesco Ventrella, Guglielmo Bussoli, Giosuè Angelo Catapano, Alfio Pennisi, Francesco Dadduzio, Pietro Schino, Riccardo Pela, Marta Bartezaghi, Paolo Morini, Alberto Porpiglia, Elisa Muscianisi
Several documents and guidelines provide recommendations for effective management of COPD patients. However, there is often a significant imbalance between recommended treatment of COPD patients and the actual care provided both in primary care and specialty setting. This imbalance could result in a significant negative impact on patients' health status and quality of life, leading to increased hospitalisations and health resource utilisation in COPD patients METHODS: MISTRAL was an observational, longitudinal, prospective cohort study, designed to assess the overall pharmacological approach of COPD in routine clinical practice in Italy...
September 4, 2018: Pulmonary Pharmacology & Therapeutics
Sneha Dhapare, Hua Li, Masahiro Sakagami
Emphysema progressively destroys alveolar structures, leading to disability and death, yet remains irreversible and incurable to date. Impaired vascular endothelial growth factor (VEGF) signaling is an emerging pathogenic mechanism, thereby proposing a hypothesis that VEGF stimulation/elevation enables recovery from alveolar structural destruction and loss of emphysema. Our previous in vitro study identified that salvianolic acid B (Sal-B), a polyphenol of traditional Chinese herbal danshen, stimulated lung cell proliferation and migration, and protected against induced lung cell death, by virtue of signal transducer and activator of transcription 3 (STAT3) activation and VEGF stimulation/elevation...
September 4, 2018: Pulmonary Pharmacology & Therapeutics
Diego Jose Maselli, Nicola Alexander Hanania
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic pulmonary conditions worldwide which often coexist. Patients with asthma COPD overlap (ACO) may have worse outcomes than those with either disease alone, for example, more respiratory symptoms and frequent exacerbations, and worse lung function. Additionally, there is a growing interest in factors that affect the disease including comorbid conditions. Indeed, recent studies have demonstrated higher rates of comorbid conditions in the ACO population, but the mechanisms behind these observations remain unclear...
August 30, 2018: Pulmonary Pharmacology & Therapeutics
Luane Marques de Mello, Álvaro A Cruz
The prevalence of non-communicable chronic diseases has been on the rise and the co-occurrence of morbidities is becoming more common. Multimorbidities are found more frequently among women, those with a history of mental disorders, lower level of schooling, and unfavorable socioeconomic condition. Physical inactivity, smoking and obesity are also associated with multimorbidities. Its occurrence is directly related to the age, affecting the majority of the individuals with more than 50 years. It is important to consider the possibility of comorbid conditions that aggravate, complicate or simulate the symptoms of the disease in the face of a patient with asthma and poor response to treatment...
August 24, 2018: Pulmonary Pharmacology & Therapeutics
Liming He, Ying Dong, Wenqian Wu, Ling Zhang, Bo Sun
BACKGROUND: Dexamethasone (DEX) is widely used for antenatal lung maturation and has been investigated to prevent premature lung injury by inhibiting postnatal inflammation. Its pharmacological mechanisms in the treatment of bacterial infection-induced injury of neonatal lung parenchymal cells remain to be clarified. We hypothesized that DEX pretreatment may attenuate endotoxin-induced growth suppression and regulate cytokine mRNA expression in cultured neonatal type II alveolar epithelial cells (AEC-II)...
August 18, 2018: Pulmonary Pharmacology & Therapeutics
Stefan Andreas, Ulrich Bothner, Matthias Trampisch, Michaela Haensel, Roland Buhl, Peter Alter
BACKGROUND: Cardiovascular comorbidities are common in chronic obstructive pulmonary disease (COPD), and elevated heart rate reflects increased cardiovascular risk over time, which is associated with unfavourable neurohumoral activation. Long-acting β2 -agonists (LABAs) are established treatments in COPD, but potentially increase heart rate. We report a post hoc pooled analysis of the effect of olodaterol (5 or 10 μg) or formoterol (12 μg) on heart rate and blood pressure (BP) in Global Initiative for Chronic Obstructive Lung Disease Stage 2-4 COPD patients...
August 2, 2018: Pulmonary Pharmacology & Therapeutics
Michael Gillen, Pablo Forte, Jan Olof Svensson, Rosa Lamarca, Joanna Burke, Karolina Rask, Ulrika Larsdotter Nilsson, Göran Eckerwall
INTRODUCTION: Many patients with chronic obstructive pulmonary disease or asthma experience difficulties in coordinating inhalation with pressurized metered-dose inhaler (pMDI) actuation. The use of a spacer device can improve drug delivery in these patients. The aim of this study was to establish the relative bioavailability of single doses of Symbicort® (budesonide/formoterol) pMDI 160/4.5 μg/actuation (2 actuations) used with and without a spacer device. In addition, an in vitro study was conducted to characterize performance of the inhaler when used in conjunction with a spacer device...
August 2, 2018: Pulmonary Pharmacology & Therapeutics
Julia Budde, Gwen S Skloot
The aging population is growing at an unparalleled rate. Asthma is common in the elderly (age over 65 years) and can be more severe with little chance for remission. Asthma in older individuals is often under-diagnosed, misdiagnosed and frequently under-treated. Concomitant medical and psychosocial conditions are more prevalent in the elderly and can obfuscate the presentation of asthma and make it more difficult to assess and manage. While these comorbidities are important in understanding elderly asthma, aging itself can be considered a "comorbidity" since it impacts structural and functional changes in the lung...
July 4, 2018: Pulmonary Pharmacology & Therapeutics
Takashi Nojiri, Hiroshi Hosoda, Takeshi Tokudome, Koichi Miura, Shin Ishikane, Toru Kimura, Yasushi Shintani, Masayoshi Inoue, Noriyoshi Sawabata, Mikiya Miyazato, Meinoshin Okumura, Kenji Kangawa
No abstract text is available yet for this article.
August 2018: Pulmonary Pharmacology & Therapeutics
R Carrington, S Jordan, S C Pitchford, C P Page
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a poor prognosis and limited treatment options. Many compounds have shown efficacy in preclinical models of this condition, but only pirfenidone and nintedanib have been approved for clinical use. It is widely accepted that the current animal models of IPF need to be improved and in this review we have critically evaluated the current state of play of preclinical models of IPF and discuss the challenges facing this field. The popular model of a single intratracheal (I...
August 2018: Pulmonary Pharmacology & Therapeutics
Dave Hassall, Noushin Brealey, Wayne Wright, Steve Hughes, Andy West, Ramiya Ravindranath, Francis Warren, Peter Daley-Yates
BACKGROUND: Poor adherence to inhaled drug therapy in individuals with asthma and/or chronic obstructive pulmonary disease (COPD) may be associated with suboptimal therapeutic outcomes. Measurement of drug residues in hair samples has been employed to assess oral medication use over time. Here, we test the feasibility of analyzing hair samples from patients with asthma and/or COPD for assessing adherence to prescribed inhaled medication. METHODS: In total, 200 male and female subjects, ≥ 18 years of age, with stable asthma and/or COPD who were receiving an acceptable standard of care daily inhaled product consistently, were recruited...
August 2018: Pulmonary Pharmacology & Therapeutics
Umberto Vespasiani-Gentilucci, Claudio Pedone, Moises Muley-Vilamu, Raffaele Antonelli-Incalzi
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is commonly associated with other chronic diseases, which poses several diagnostic and therapeutic problems. Indeed, important comorbidities frequently remain unrecognized and, then, untreated, whereas respiratory drugs may have non respiratory side effects, and selected non respiratory drugs may variably affect the respiratory function. OBJECTIVE: to describe: how COPD affects the presentation and contributes to the diagnostic challenges of its most common comorbidities; how coexisting COPD impacts the therapeutic approach to selected comorbidities and viceversa...
August 2018: Pulmonary Pharmacology & Therapeutics
Katarzyna Luczak-Wozniak, Marta Dabrowska, Izabela Domagala, Marta Miszczuk, Wojciech Lubanski, Andrzej Leszczynski, Rafal Krenke
BACKGROUND: Pharmacological treatment of asthma and chronic obstructive pulmonary disease (COPD) is based mainly on inhaled medications. There is a continuous need to examine and train patients in their inhalation technique. The objective of the presented study is to determine whether the errors which patients made during inhalations are repetitive, and therefore easier to eradicate, or rather accidental, hence require more attention and effort from the health care professionals. METHODS: It was a prospective, cohort study which included adults with asthma or COPD, who have used at least one inhaler daily on a regular basis...
August 2018: Pulmonary Pharmacology & Therapeutics
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