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Review of the British Thoracic Society Winter Meeting 2012, 5 to 7 Thorax Online First, published on January 12, 2013 as 10.1136/thoraxjnl-2012-203165 Review Thorax: first published as 10.1136/thoraxjnl-2012-203165 on 12 January 2013. Downloaded from Review of the British Thoracic Society Winter Meeting 2012, 5 to 7 December, London, UK Hannah Kelly Bayes,1 Alistair Colin Church,2 Andrew J Fisher,3 on behalf of the BTS Science and Research Committee 1Department of Inflammation ABSTRACT airways.34Work is also ongoing to use the lungs, and Immunology, Institute of This review highlights new developments in scientific with their rich vascular bed, to deliver a range of Infection, University of Glasgow, Glasgow, UK and clinical research presented at the British Thoracic therapies including inhaled chemotherapy, vaccines, 2Department of Respiratory, Society Winter Scientific Meeting held from 5 to 7 biologicals and analgesics. Scottish Pulmonary Vascular December 2012. Although a wide spectrum of Nanomedicine uses the enhanced magnetic and Unit, Glasgow, UK 3 respiratory research was presented at the meeting the electrical properties and increased surface area: Institute of Cellular Medicine, content of the review focuses specifically on the key volume ratio of particles less than 100 nm in size. Newcastle University, Newcastle, UK themes of pleural disease, interstitial lung disease and Dr Andrew Thorley (London) provided examples future therapies in respiratory medicine. Advances in of inhaled nanomedicine currently in development. Correspondence to clinical and translational respiratory research presented in Inhaled anti-tuberculosis nanomedicines allow Professor Andrew J Fisher, the major symposia and spoken sessions related to these delivery to the site of disease, potential for phago- Institute of Cellular Medicine, Newcastle University Medical areas are summarised. Additional sessions covering cytosis by macrophages and formulation to allow School, Framlington Place, lifestyle dilemmas in the context of respiratory disease delivery as a single combination therapy, with Newcastle Upon Tyne NE2 and the early career investigator awards are also promising preclinical in vivo work. Cancer thera- 4HH, UK; a.j.fi[email protected] highlighted. peutics may be particularly amenable to nanomedi- cine due to increased permeability of tumours to HKB and ACC contributed equally nanosized particles and enhanced retention of This review aims to encapsulate the exciting and agents due to poor vascular and lymphatic drain- Received 19 December 2012 important new developments in respiratory medi- age. For example, tumour necrosis factor α (TNFα) Revised 19 December 2012 cine presented at the annual British Thoracic coated gold nanoparticles reduce tumour size in Accepted 20 December 2012 Society (BTS) Winter Scientific Meeting. As a sig- murine models and have now entered phase I clin- nificant breadth of scientific and clinical research ical trials. Finally, with manmade and natural nano- was presented at the 23 major symposia and in 430 particles eliciting toxic effects,5 Dr Thorley urged submitted abstracts, the review focuses on key judicious use of nanomedicine to balance beneficial themes: future therapies in respiratory medicine, and potential adverse effects. pleural disease, and interstitial lung disease (ILD). Gene therapy for cystic fibrosis lung disease has http://thorax.bmj.com/ Additional well received sessions covering lifestyle explored both virus and liposome-mediated lung dilemmas in the context of respiratory disease and delivery. Professor Eric Alton (London) presented the the early career investigator awards are also scientific and clinical research programme of the UK highlighted. CF Gene Consortium (http://www.cfgenetherapy.org. uk). This has lead to a trial of liposome-delivered EVOLVING THERAPIES FOR RESPIRATORY gene therapy in patients over 12 years of age who DISEASE receive multidose treatment over a 12-month period, This year’s BTS conference included several excel- the results of which are expected in spring 2014. on September 28, 2021 by guest. Protected copyright. lent sessions highlighting novel treatments and Professor Alton also described promising results from means of drug delivery in respiratory disease. A the next stage in gene therapy via the use of a modi- two-part symposium run in association with the fied lentivirus, which achieves significantly better and British Association for Lung Research (BALR) sustained delivery compared with liposome-mediated covered emerging strategies of therapeutic delivery treatment. to the lungs. Inhaled therapies date back to the Moving from the current therapies available, the ancient Egyptians, however Dr Omar Usmani second part of this symposium detailed advances in (London) discussed how effective drug delivery to use of cells as delivery systems to areas of disease. the lungs remains problematic, with current devices Professor Claire Lewis (Sheffield, UK) detailed the achieving only 10–20% lung deposition.1 In add- identification of tumour active macrophages ition confusion over inhaler devices remained (TAMS), which home to areas of hypoxia and their prevalent in both healthcare professionals and manipulation to target lung metastases of prostate patients, which was described separately by Mak cancer. The macrophages were cotransfected with et al2 in a survey of over 1200 healthcare profes- an adenoviral E1A-dependent oncolytic virus and a sionals. Dr Usmani highlighted that the input of hypoxia-inducible factor (HIF)-responsive plasmid design engineers and formulation chemists had encoding E1A. When the transfected macrophages To cite: Bayes HK, now resulted in introduction of innovative inhaler were introduced into a murine model with a pros- Church AC, Fisher AJ, et al. Thorax Published Online devices, an example being intelligent nebulisers tate tumour attached, the cells homed to the First: [please include Day which adapt to breathing patterns to achieve 50– hypoxic areas within the tumour. This activated the Month Year] doi:10.1136/ 70% drug deposition, and manipulation of particle HIF-responsive genes and led to upregulation of thoraxjnl-2012-203165 size to allow effective treatment of small and large EIA and replication of the virus. However, for the CopyrightBayes HK, et Article al. Thorax 2013;author0:1–6. (or doi:10.1136/thoraxjnl-2012-203165 their employer) 2013. Produced by BMJ Publishing Group Ltd (& BTS) under licence.1 Review Thorax: first published as 10.1136/thoraxjnl-2012-203165 on 12 January 2013. Downloaded from virus to be able to further replicate it requires the cell to contain this meeting that over 50% of these costs are attributable to a prostate-specific factor, thus limiting further viral replication drug costs.910New therapies are emerging, for example, anti- to prostate tissue. Convincing data were presented showing interleukin (IL)-13 and bronchial thermoplasty, but will require tumour regression and prevention of metastases after introduc- judicious use. Dr Andrew Menzies-Gow (London) highlighted tion of these TAMS into the mice. This seems a very exciting the need for asthma biomarkers to help direct these novel ther- and novel method to allow the introduction of tumouricidal apies. This was exemplified by the recent use of the systemic cells to target a cancerous cell population. biomarker periostin which predicts eosinophilic airways Next Dr Sam Janes (London) discussed mesenchymal stem disease11 and can be used to direct therapies targeting T helper cells (MSCs) as a potential vehicle for delivery of TNF-related 2 disease, including inhaled corticosteroids and the anti-IL13 apoptosis inducing ligand (TRAIL) to a murine model of lung monoclonal antibody, lebribizumab.12 Bronchial thermoplasty is cancer. Again these cells home to areas of inflammation and now being performed in the clinical setting for severe asthma, damage and within 24 h of administration mesenchymal cells as described separately by Bicknell et al.13 However, Dr were identified within the tumour. Although the size of the Menzies-Gow stressed there is a pressing need to develop better tumour was not reduced there was a definite reduction in the biomarkers to predict response to such treatment. In a compli- number of pulmonary satellite metastases observed within mentary session, Professor Richard Knowles (Stevenage, UK) the animals. This approach was also presented separately by described the U-BIOPRED project, which is collecting biochem- Sage et al6 in the context of mesothelioma. These presentations ical, genetic and clinical data from infants with recurrent suggest an exciting new opportunity for treating lung cancer. wheeze through to adults with asthma (http://www.ubiopred. Finally, Professor John Simpson (Newcastle, UK) described european-lung-foundation.org).14 Such work should enable the alternative approach of targeting cell removal. He exempli- improved phenotyping of patients with asthma, development of fied this via experimental data showing that removal of blood biomarkers and direction of novel therapies. monocytes can result in a reduction of the development of acute lung injury from inhaled lipopolysaccharide in murine PLEURAL DISEASE models. The proposed mechanism being reduced recruitment of There is increasing interest in the area of pleural disease and neutrophils to sites of inflammation due to loss of monocyte- this was reflected in a number of excellent sessions dedicated to derived chemoattractants. However, in subsequent human that topic. Although relatively uncommon (10% of parapneu- experiments, removal of monocytes
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