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Pulmonary Pharmacology & Therapeutics

Patrick Darken, Paolo DePetrillo, Colin Reisner, Earl St Rose, Paul Dorinsky
The budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) is an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2 -agonist fixed-dose combination formulated with innovative co-suspension delivery technology that is in clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, Phase I, single-dose, six-treatment, four-period, crossover study (NCT01980615) examined the pharmacokinetic (PK) and safety profile of three doses of BGF MDI (320/14...
March 12, 2018: Pulmonary Pharmacology & Therapeutics
Andreas Krause, Jochen Zisowsky, Jasper Dingemanse
BACKGROUND: Macitentan is the first endothelin receptor antagonist with demonstrated efficacy on morbidity and mortality in pulmonary arterial hypertension (PAH) in the pivotal study SERAPHIN. METHODS: The pharmacokinetics (PK) of macitentan and its active metabolite, ACT-132577, were characterized in a population model. Efficacy and hemodynamics (pharmacodynamics, PD) were related to PK based on PK/PD modeling. RESULTS: Sex, age, and body weight influenced the PK to a statistically significant extent...
February 28, 2018: Pulmonary Pharmacology & Therapeutics
Shin-Hwar Wu, Lih-Jen Shyu, Chin-Hsing Li, Chao-Hung Yu, Huang-Chi Chen, Chew-Teng Kor, Chu-Hsien Wang, Kai-Huang Lin
INTRODUCTION: The optimal dose of inhaled metered-dose bronchodilators for intubated patients with chronic obstructive pulmonary disease (COPD) is unknown. In this study, we proposed a bronchodilator dosing schedule based on an individual's airway resistance (Raw ) and tested its efficacy in reducing Raw . METHODS: A total of 51 newly admitted patients with invasively ventilated COPD were randomly assigned to receive personalized or fixed bronchodilator dosing. Personal target Raw was defined by measuring each individual's Raw after maximal pharmacologic bronchodilatation...
February 20, 2018: Pulmonary Pharmacology & Therapeutics
Sarah Petite
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death in the United States. Guideline recommendations for medication therapy include the use of inhaled medications for management of stable COPD. There are limited data available describing prescribing percentages of medications in patients with COPD. AIM: To determine the prescribing percentages of medications for COPD in a national, cross-sectional study. METHODS: This was a national, cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) in 2013...
February 15, 2018: Pulmonary Pharmacology & Therapeutics
Ewa-Lena Johansson, Ewa Ternesten-Hasséus, Per Gustafsson, Teet Pullerits, Monica Arvidsson, Eva Millqvist
BACKGROUND: Chronic cough is a common symptom and related to several pulmonary, airway and heart diseases. When all likely medical explanations for the coughing are excluded, there remains a large group of patients with chronic coughing, which is mostly a cough reflex easily triggered by environmental irritants and noxious stimuli. The main aim of this study was to improve the diagnostic ability to differentiate chronic idiopathic cough (CIC) from asthma. METHODS: Twenty-three patients with CIC, 16 patients with mild asthma and 21 control participants were included...
February 10, 2018: Pulmonary Pharmacology & Therapeutics
Maria Theresa Voelker, Andreas Bergmann, Thilo Busch, Nora Jahn, Sven Laudi, Katharina Noreikat, Philipp Simon, Sven Bercker
INTRODUCTION: Hemoglobin-based oxygen carriers (HBOC) have been developed as an alternative to blood transfusions. Their nitric-oxide-scavenging properties HBOC also induce vasoconstriction. In acute lung injury, an excess of nitric oxide results in a general vasodilation, reducing oxygenation by impairing the hypoxic pulmonary vasoconstriction. Inhaled nitric oxide (iNO) is used to correct the ventilation perfusion mismatch. We hypothesized that the additional use of HBOC might increase this effect...
February 6, 2018: Pulmonary Pharmacology & Therapeutics
Jana Graf, Tanja Lucke, Ronald Herrera, Henrik Watz, Rolf Holle, Claus Vogelmeier, Joachim H Ficker, Rudolf A Jörres
Patients with COPD are often of advanced age and have a high number of medications due to their lung disease and comorbidities. Thus they are at risk for unwanted effects from drugs, either due to age or due to interactions between drugs. These issues are not clarified. We therefore assessed the number of medications and potential adverse effects in a large cohort of patients with COPD. The analysis was performed in 2741 patients of the German COPD cohort COSYCONET, using baseline data (visit 1) and follow-up data after about 1...
February 5, 2018: Pulmonary Pharmacology & Therapeutics
Richard W Chapman, Zhili Li, Michel R Corboz, Helena Gauani, Adam J Plaunt, Donna M Konicek, Franziska G Leifer, Charles E Laurent, Han Yin, Dany Salvail, Chad Dziak, Walter R Perkins, Vladimir Malinin
INS1009 is a long acting pulmonary vasodilator prodrug of treprostinil (TRE) that is formulated in a lipid nanoparticle for inhaled delivery by nebulization. This study examined the ability of INS1009 to inhibit vasoconstriction in the pulmonary vasculature of rats and dogs and the extent to which local activity within the lung contributes to its activity. Rats received a single dose of INS1009 by nose-only inhalation or were given a continuous intravenous (i.v.) infusion of TRE, followed by an i.v. challenge of the thromboxane mimetic pulmonary vasoconstrictor U46619 and the increase in pulmonary arterial pressure (PAP) was measured...
February 5, 2018: Pulmonary Pharmacology & Therapeutics
Michel R Corboz, Jimin Zhang, Daniel LaSala, Keith DiPetrillo, Zhili Li, Vladimir Malinin, Jeremy Brower, Philip J Kuehl, Ted E Barrett, Walter R Perkins, Richard W Chapman
Idiopathic pulmonary fibrosis is a progressive and lethal disease and while there are now two approved drugs (Esbriet® and Ofev®) additional effective treatments are still needed. Recently, prostacyclin analogs such as iloprost and treprostinil (TRE) have been shown to exert some protection against bleomycin-induced pulmonary fibrosis in mice when administered in a prophylactic regimen. In this study, we evaluated the effect of the inhaled treprostinil prodrug hexadecyl-treprostinil (C16TR) formulated in a lipid nanoparticle (INS1009) administered therapeutically in a fibrotic rat model...
February 1, 2018: Pulmonary Pharmacology & Therapeutics
Luigino Calzetta, Paola Rogliani, Elena Pistocchini, Maurizio Mattei, Giuseppe Cito, Pietro Alfonsi, Clive Page, Maria Gabriella Matera
Recurrent airway obstruction (RAO) is a main characteristic of horses with severe equine asthma syndrome. The presence of bacterial lipopolysaccharide (LPS) in the airways of horses is thought to play a crucial role in the clinical expression of this disorder. This study pharmacologically characterized the effect of LPS on the responsiveness of equine bronchial tissue. Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml) and then stimulated by electrical field stimulation (EFS). The role of capsaicin sensitive-sensory nerves (capsaicin desensitization treatment), neurokinin-2 (NK2 ) receptors (blocked by GR159897), transient receptor potential vanilloid type 1 receptors (TRPV1; blocked by SB366791), and neurokinin A (NKA) were investigated...
January 30, 2018: Pulmonary Pharmacology & Therapeutics
Leonard F Lebender, Laura Prünte, Nowshin N Rumzhum, Alaina J Ammit
Arachidonic acid is metabolized by cyclooxygenases (COX-1 and COX-2) into various prostanoids which exert different functions in mammalian physiology. One of these prostanoids, prostaglandin E2 (PGE2 ), interacts with four different G protein-coupled receptors, named EP1 , EP2 , EP3 and EP4 , to initiate different downstream signalling pathways. Prostanoid receptors are diversely expressed throughout different tissues all over the body and PGE2 is responsible for a large variety of beneficial and disadvantageous effects...
January 30, 2018: Pulmonary Pharmacology & Therapeutics
Argyrios Tzouvelekis, Theodoros Karampitsakos, Maria Kontou, Andreas Granitsas, Ioanna Malliou, Aris Anagnostopoulos, Paschalis Ntolios, Vasilios Tzilas, Evangelos Bouros, Paschalis Steiropoulos, Serafeim Chrysikos, Katerina Dimakou, Nikolaos Koulouris, Demosthenes Bouros
BACKGROUND: Nintedanib represents an antifibrotic compound able to slow down disease progression of patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To investigate the safety and efficacy of nintedanib in patients with IPF in a real-life setting. METHODS: This was a multicentre, retrospective, observational, real-life study for patients with IPF receiving nintedanib between October 2014 and October 2016. RESULTS: We identified 94 patients with IPF receiving nintedanib (72 males, mean age±SD: 73...
January 20, 2018: Pulmonary Pharmacology & Therapeutics
Evelyn Thais Fantozzi, Sara Garbin, Fernanda Yamamoto-Ricardo-da-Silva, Ricardo Martins Oliveira-Filho, Domenico Spina, Wothan Tavares-de-Lima, Yanira Riffo-Vasquez
RATIONAL: Acute lung injury (ALI) is a common complication after intestinal ischemia and reperfusion (I/R) injury that can lead to acute respiratory distress syndrome (ARDS). We have previously demonstrated that females are protected against lung damage induced by intestinal I/R through an estrogen mediated mechanism. OBJECTIVES: to investigate the effect of obesity on ALI induced by intestinal I/R in female mice. METHODS: C57Bl/6 female mice were fed with a standard low-fat diet (SD) or a high-fat diet (HFD) for 9 weeks...
January 11, 2018: Pulmonary Pharmacology & Therapeutics
Emmanuel Naline, Stanislas Grassin Delyle, Hélène Salvator, Marion Brollo, Christophe Faisy, Tatiana Victoni, Charlotte Abrial, Philippe Devillier
BACKGROUND AND PURPOSE: Long-acting muscarinic antagonists (LAMAs) have been recommended for the treatment of chronic obstructive pulmonary disease and (more recently) asthma. However, the in vitro pharmacological profiles of the four LAMAs currently marketed (tiotropium, umeclidinium, aclidinium and glycopyrronium) have not yet been compared (relative to ipratropium) by using the same experimental approach. EXPERIMENTAL APPROACH: With a total of 560 human bronchial rings, we investigated the antagonists' potency, onset and duration of action for inhibition of the contractile response evoked by electrical field stimulation...
January 11, 2018: Pulmonary Pharmacology & Therapeutics
Rahul Dhande, Amit Tyagi, Rakesh Kumar Sharma, Hetal Thakkar
Vinorelbine Tartrate (VLB) is the first line chemotherapeutic agent for treatment of Non-Small Cell Lung Cancer, whose non-specific distribution causes unwanted side effects. The aim of the present investigation was to formulate VLB loaded spherulites intended for targeting the lung. Spherulites were composed of Soyabean Phosphatidylcholine (SPC), Cholesterol (Chol), Potassium oleate and Mannitol. Lipid film prepared using SPC, Chol and Potassium oleate, was dispersed in aqueous phase comprising Mannitol and VLB, followed by controlled shearing and extrusion...
January 11, 2018: Pulmonary Pharmacology & Therapeutics
Anne J Lexmond, Dave Singh, Henderik W Frijlink, Graham W Clarke, Clive P Page, Ben Forbes, Maarten van den Berge
Inhaled airway challenges provoke bronchoconstriction in susceptible subjects and are a pivotal tool in the diagnosis and monitoring of obstructive lung diseases, both in the clinic and in the development of new respiratory medicines. This article reviews the main challenge agents that are in use today (methacholine, mannitol, adenosine, allergens, endotoxin) and emphasises the importance of controlling how these agents are administered. There is a danger that the optimal value of these challenge agents may not be realised due to suboptimal inhaled delivery; thus considerations for effective and reproducible challenge delivery are provided...
January 10, 2018: Pulmonary Pharmacology & Therapeutics
Jaya Muneswarao, Ashutosh Kumar Verma, Mohamed Azmi Ahmad Hassali
No abstract text is available yet for this article.
January 5, 2018: Pulmonary Pharmacology & Therapeutics
Paola Rogliani, Josuel Ora, Ermanno Puxeddu, Luigino Calzetta, Francesco Cavalli, Maria Gabriella Matera, Mario Cazzola
COPD is a chronic inflammatory disease characterized by partially reversible airflow limitation. Currently, phosphodiesterase4 inhibitors and inhaled corticosteroids are anti-inflammatory agents that can be used in patients with severe COPD, always added to at least one bronchodilator. In this prospective interventional pilot study, we investigated the effect of adding oral roflumilast 500 μg once-daily or inhaled ciclesonide 160 μg once-daily to glycopyrronium 44 μg once-daily on lung volumes and exercise tolerance in 16 patients with severe COPD, of which 8 received roflumilast and 8 ciclesonide for 8 weeks...
December 30, 2017: Pulmonary Pharmacology & Therapeutics
Jaya Muneswarao, Ashutosh Kumar Verma, Mohamed Azmi Ahmad Hassali
No abstract text is available yet for this article.
December 28, 2017: Pulmonary Pharmacology & Therapeutics
Li Zhang, Tieying Sun, Longteng Liu, Lifang Wang
Unexplained chronic cough (UCC) affects millions of patients worldwide. New therapeutic approaches to this condition are urgently needed, since current treatment options provide only symptomatic relief. Cough reflex hypersensitivity has been shown to play an important role in the pathogenesis of UCC. The transient receptor potential vanilloid type 1 (TRPV1) is present on peripheral terminals of airway sensory nerves and modulation of its activity represents a potential target for the pharmacological treatment of UCC...
December 27, 2017: Pulmonary Pharmacology & Therapeutics
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