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https://www.readbyqxmd.com/read/28743094/a-personalized-medicine-approach-to-the-design-of-dry-powder-inhalers-selecting-the-optimal-amount-of-bypass
#1
Thomas Kopsch, Darragh Murnane, Digby Symons
In dry powder inhalers (DPIs) the patient's inhalation manoeuvre strongly influences the release of drug. Drug release from a DPI may also be influenced by the size of any air bypass incorporated in the device. If the amount of bypass is high less air flows through the entrainment geometry and the release rate is lower. In this study we propose to reduce the intra- and inter-patient variations of drug release by controlling the amount of air bypass in a DPI. A fast computational method is proposed that can predict how much bypass is needed for a specified drug delivery rate for a particular patient...
July 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28741229/inhaled-antimicrobials-for-ventilator-associated-pneumonia-practical-aspects
#2
Garyphallia Poulakou, Dimitrios K Matthaiou, David P Nicolau, Georgios Siakallis, George Dimopoulos
Positive experience with inhaled antibiotics in pulmonary infections of patients with cystic fibrosis has paved the way for their utilization in mechanically ventilated, critically ill patients with lower respiratory tract infections. A successful antibiotic delivery depends upon the size of the generated particle and the elimination of drug impaction in the large airways and the ventilator circuit. Generated droplet size is mainly affected by the type of the nebulizer employed. Currently, jet, ultrasonic, and vibrating mesh nebulizers are marketed; the latter can deliver optimal antibiotic particle size...
July 24, 2017: Drugs
https://www.readbyqxmd.com/read/28738364/risk-factors-for-community-acquired-pneumonia-in-adults-a-systematic-review-of-observational-studies
#3
Jordi Almirall, Mateu Serra-Prat, Ignasi Bolíbar, Valentina Balasso
We performed a systematic review of the literature to establish conclusive evidence of risk factors for community-acquired pneumonia (CAP). Observational studies (cross-sectional, case-control, and cohort studies) the primary outcome of which was to assess risk factors for CAP in both hospitalized and ambulatory adult patients with radiologically confirmed pneumonia were selected. The Newcastle-Ottawa Scale specific for cohort and case-control designs was used for quality assessment. Twenty-nine studies (20 case-control, 8 cohort, and 1 cross-sectional) were selected, with 44...
July 25, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28738158/efficient-interfacially-driven-vehiculization-of-corticosteroids-by-pulmonary-surfactant
#4
Alberto Hidalgo, Fabrizio Salomone, Nieves Fresno, Guillermo Orellana, Antonio Cruz, Jesus Perez-Gil
Pulmonary surfactant is a crucial system to stabilize the respiratory air-liquid interface. Furthermore, pulmonary surfactant has been proposed as an effective method for targeting drugs to the lungs. However, few studies have examined in detail the mechanisms of incorporation of drugs into surfactant, the impact of the presence of drugs on pulmonary surfactant performance at the interface under physiologically-meaningful conditions, or the ability of pulmonary surfactant to use the air-liquid interface to vehiculise drugs to long distances...
July 24, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28737971/fluticasone-furoate-vilanterol-and-lung-function-decline-in-patients-with-moderate-copd-and-heightened-cardiovascular-risk
#5
Peter M A Calverley, Julie A Anderson, Robert D Brook, Courtney Crim, Natacha Gallot, Sally Kilbride, Fernando Martinez, Julie Yates, David E Newby, Jørgen Vestbo, Robert Wise, Bartolome R Celli
RATIONALE: Many patients with chronic obstructive pulmonary disease (COPD) have an accelerated loss of lung function. It is unclear whether drug treatment can modify this in moderately severe disease. OBJECTIVES: In a pre-specified analysis of the key secondary outcome in the Study to Understand Mortality and MorbidITy (SUMMIT), we investigated whether the inhaled corticosteroid fluticasone furoate 100 μg (FF), the long-acting beta-agonist vilanterol 25 µg (VI) or the combination (FF/VI) modified the rate of decline in FEV1 compared with placebo...
July 24, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28737431/the-analysis-of-pneumatic-atomization-of-newtonian-and-non-newtonian-fluids-for-different-medical-nebulizers
#6
Marek Ochowiak, Magdalena Matuszak, Sylwia Włodarczak
OBJECTIVE: The paper contains results of the experimental studies on atomization process of inhaled drugs and aqueous solutions of glycerol with aqueous solutions of glycerol-polyacrylamide (Rokrysol WF1) in pneumatic nebulizers. In experiments the different concentration of aqueous solutions of glycerol-polyacrylamide have been tested. In addition, the effect of nebulizer design on atomization process has been determined. The one of the main elements of medical pneumatic nebulizer is nebulizer cup...
July 24, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28736268/differential-connectivity-of-gene-regulatory-networks-distinguishes-corticosteroid-response-in-asthma
#7
Weiliang Qiu, Feng Guo, Kimberly Glass, Guo Cheng Yuan, John Quackenbush, Xiaobo Zhou, Kelan G Tantisira
BACKGROUND: Variations in drug response between individuals have prevented us from achieving high drug efficacy in treating many complex diseases, including asthma. Genetics plays an important role in accounting for such inter-individual variations in drug response. However, systematic approaches for addressing how genetic factors and their regulators determine variations in drug response in asthma treatment are lacking. METHODS: We used PANDA (Passing Attributes between Networks for Data Assimilations) to construct the gene regulatory networks associated with good responders and poor responders to inhaled corticosteroids based on a subset of 145 Caucasian asthmatic children who participated in the Childhood Asthma Management Cohort (CAMP)...
July 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28735415/cfd-simulation-of-aerosol-delivery-to-a-human-lung-via-surface-acoustic-wave-nebulization
#8
Morteza Yousefi, Oveis Pourmehran, Mofid Gorji-Bandpy, Kiao Inthavong, Leslie Yeo, Jiyuan Tu
Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning...
July 22, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28734855/effects-of-constant-rate-infusions-of-dexmedetomidine-or-mk-467-on-the-minimum-alveolar-concentration-of-sevoflurane-in-dogs
#9
Rachel C Hector, Marlis L Rezende, Khursheed R Mama, Eugene P Steffey, Heather K Knych, Ann M Hess, Juhana M Honkavaara, Marja R Raekallio, Outi M Vainio
OBJECTIVE: To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α2-adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs. STUDY DESIGN: Crossover experimental study. ANIMALS: Six healthy, adult Beagle dogs weighing 12.6±0.9 kg (mean±standard deviation). METHODS: Dogs were anesthetized with sevoflurane in oxygen. After a 60-minute instrumentation and equilibration period, the MAC of sevoflurane was determined in triplicate using the tail clamp technique...
March 4, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28732821/optimizing-inhalation-technique-using-web-based-videos-in-obstructive-lung-diseases
#10
Tobias Müller, Annegret Müller, Christian Hübel, Verena Knipel, Wolfram Windisch, Christian Gabriel Cornelissen, Michael Dreher
BACKGROUND: Inhaled agents are widely used in the treatment of chronic airway diseases. Correct technique is required to ensure appropriate drug deposition, but poor technique is common. This study investigated whether inhalation technique could be improved by patient training using short videos from the German Airway League. METHODS: Outpatients from a university hospital respiratory clinic who had incorrect inhalation technique were asked to demonstrate this again immediately after viewing the training videos, and after 4-8 weeks' follow-up...
August 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28730936/an-industry-update-what-is-the-latest-news-in-therapeutic-delivery
#11
Iain Simpson
This Industry Update covers the period from 1 through 30 April 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. Biogen expanded its portfolio of developmental drugs targeting neurological diseases by licensing a drug from Bristol-Myers Squibb which is currently under investigation for the treatment of progressive supranuclear palsy. Takeda announced a deal with NuBiyota focused on developing treatments for gastrointestinal disorders, based on the manipulation of microbes living in the gut...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28730933/drug-delivery-to-the-lungs-challenges-and-opportunities
#12
Stephen P Newman
Pulmonary drug delivery is relatively complex because the respiratory tract has evolved defense mechanisms to keep inhaled drug particles out of the lungs and to remove or inactivate them once deposited. In addition to these mechanical, chemical and immunological barriers, pulmonary drug delivery is adversely affected by the behavioral barriers of poor adherence and poor inhaler technique. Strategies to mitigate the effects of these barriers include use of inhaler devices and formulations that deliver drug to the lungs efficiently, appropriate inhaler technique and improved education of patients...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28727920/ballistic-penetration-of-highly-charged-nanoaerosol-particles-through-a-lipid-monolayer
#13
Victor N Morozov, Yuri M Shlyapnikov, Igor L Kanev, Elena Andreevna Shlyapnikova
To be used as a drug, inhaled nanoaerosol particles (NAPs) must first penetrate the lipid layer on top of the lung fluid before they will be able to reach the lung epithelium. We investigated how the penetration of NAPs through a model lipid monolayer (LM) depends upon their charging level and size. It was shown that deposition of NAPs 20-200 nm in diameter and charged to the Rayleigh limit gradually increased the surface tension of a dipalmitoylphosphatidylcholine monolayer (DPPC), indicating a loss of lipid molecules from the monolayer...
July 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28721208/new-perspectives-on-the-regulation-of-type-ii-inflammation-in-asthma
#14
REVIEW
Mireya Becerra-Díaz, Marsha Wills-Karp, Nicola M Heller
Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. β-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation...
2017: F1000Research
https://www.readbyqxmd.com/read/28721202/defining-the-inflammatory-signature-of-human-lung-explant-tissue-in-the-presence-and-absence-of-glucocorticoid
#15
Tracy L Rimington, Emily Hodge, Charlotte K Billington, Sangita Bhaker, Binaya K C, Iain Kilty, Scott Jelinsky, Ian P Hall, Ian Sayers
BACKGROUND:  Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help study the mechanisms underlying inflammatory responses and which can provide a tool to aid drug discovery for inflammatory respiratory diseases such as asthma and COPD. METHOD:  Parenchymal lung tissue from 6 individual donors was dissected and cultured with two pro-inflammatory stimuli, lipopolysaccharide (LPS) (1 µg/ml) and interleukin-1 beta (IL-1β) (10 ng/ml) in the presence or absence of dexamethasone (1 µM)...
2017: F1000Research
https://www.readbyqxmd.com/read/28720675/the-effect-of-nebulizer-position-on-aerosolized-epoprostenol-delivery-in-an-adult-lung-model
#16
Allison C Anderson, Meagan N Dubosky, Kelly A Fiorino, Vanessa Quintana, Carl A Kaplan, David L Vines
BACKGROUND: Aerosolized epoprostenol is an alternative for inhaled nitric oxide in the management of pulmonary arterial hypertension and possibly acute hypoxemia. Our objective was to determine differences in drug deposition based on different nebulizer positions in the ventilator circuit, using a vibrating mesh nebulizer. METHODS: An 8.0-mm inner diameter endotracheal tube (ETT) was connected to a training test lung, compliance of 30 mL/cm H2O, with a collecting filter placed at the ETT-test lung junction...
July 18, 2017: Respiratory Care
https://www.readbyqxmd.com/read/28720405/persistent-cognitive-and-morphological-alterations-induced-by-repeated-exposure-of-adolescent-rats-to-the-abused-inhalant-toluene
#17
K M Braunscheidel, J T Gass, P J Mulholland, S B Floresco, J J Woodward
While thepsychoactive inhalant toluene causes behavioral effects similarto those produced by other drugs of abuse, the persistent behavioral and anatomical abnormalities induced by toluene exposure are not well known. To mimic human "binge-like" inhalant intoxication, adolescent, male Sprague-Dawley rats were exposed to toluene vapor (57,000ppm) twice daily for five consecutive days. These rats remained in their home cages until adulthood (P60), when they were trained in operant boxes to respond to a palatable food reward and then challenged with several different cognitive tasks...
July 15, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28718908/death-from-butane-inhalation-abuse-in-teenagers-two-new-case-studies-and-review-of-the-literature
#18
Véronique Alunni, Yvan Gaillard, François Castier, Marie-Dominique Piercecchi-Marti, Gérald Quatrehomme
The ready availability of butane makes butane abuse frequent. Fatalities are rare. This study presents two cases of death by butane overdose. The postmortem analyses were carried out using headspace gas chromatography-mass spectrometry. It revealed femoral blood butane concentrations of 18 and 22 mg/L, respectively, as well as specific combinations of adjuvants in each victim. In one of the victims, brain and fatty tissue also contained butane, pointing to chronic consumption. The originality of this study is to show that the identification of specific combinations of adjuvants can be helpful for identifying the brand of deodorant used...
July 18, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28718049/good-things-in-small-packages-an-innovative-delivery-approach-for-inhaled-insulin
#19
James B Fink, Lisa Molloy, John S Patton, Valdecir Castor Galindo-Filho, Jacqueline de Melo Barcelar, Luciana Alcoforado, Simone Cristina Soares Brandão, Armèle Dornelas de Andrade
PURPOSE: The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3-6 μm particle size distribution. METHODS: In silico modeling with computational fluid dynamics (CFD) and in vitro testing of device components were assessed using an Alberta idealized adult airway (Copley, UK) to optimize mouthpiece and aerosol path design for dose delivered distal to the trachea...
July 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28717881/a-retrospective-comparison-of-inhaled-milrinone-and-iloprost-in-post-bypass-pulmonary-hypertension
#20
Kassiani Theodoraki, Apostolos Thanopoulos, Panagiota Rellia, Evangelos Leontiadis, Dimitrios Zarkalis, Konstantinos Perreas, Theophani Antoniou
During cardiac operations, weaning from cardiopulmonary bypass (CPB) may prove challenging as a result of superimposed acute right ventricular dysfunction in the setting of elevated pulmonary vascular resistance (PVR). The aim of this study was to retrospectively evaluate the effect of inhaled milrinone versus inhaled iloprost in patients with persistent pulmonary hypertension following discontinuation of CPB. Eighteen patients with elevated PVR post-bypass were administered inhaled milrinone at a cumulative dose of 50 μg kg(-1)...
July 17, 2017: Heart and Vessels
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