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<br /> RESPIRATORY<br /> ISSN 2054-3166 October 2013 • emjreviews.com<br /> INSIDE<br /> Review of the<br /> ERS Annual Congress 2013<br /> Barcelona, Spain<br /> CONTENTS<br /> EDITORIAL PANEL................................................................................................................................... 4<br /> CONGRESS REVIEW................................................................................................................................ 8<br /> • Review of the Annual ERS Congress, held in Barcelona, Spain,<br /> 7th-11th September 2013<br /> POOR ASTHMA CONTROL, DEVICE HANDLING AND PHENOTYPE................................. 30<br /> • Roberto Rodiguez-Roisin, Christian Virchow, Cynthia Rand, Richard Dekhuijzen,<br /> Michael Wechsler<br /> LONG-TERM NON-INVASIVE VENTILATION (NIV) FOR COPD PATIENTS WITH<br /> CHRONIC RESPIRATORY FAILURE .....<a title="EMJ - Respiratory page 1" href="http://viewer.zmags.com/publication/4ead80ac?page=1"> RESPIRATORY ISSN 2054-3166 </a> <a title="EMJ - Respiratory page 2" href="http://viewer.zmags.com/publication/4ead80ac?page=2"> CONTENTS EDITORIAL PANEL.......................</a> <a title="EMJ - Respiratory page 3" href="http://viewer.zmags.com/publication/4ead80ac?page=3"> RESPIRATORY ASTHMA IN PREGNANCY................</a> <a title="EMJ - Respiratory page 4" href="http://viewer.zmags.com/publication/4ead80ac?page=4"> EDITORIAL BOARD RESPIRATORY Dr Peter Barnes He</a> <a title="EMJ - Respiratory page 5" href="http://viewer.zmags.com/publication/4ead80ac?page=5"> Welcome It gives me great pleasure to welcome you</a> <a title="EMJ - Respiratory page 6" href="http://viewer.zmags.com/publication/4ead80ac?page=6"> Designed for Emphysema RePneu® Lung Volume Reduct</a> <a title="EMJ - Respiratory page 7" href="http://viewer.zmags.com/publication/4ead80ac?page=7"> Foreword Professor Nicholas Hill </a> <a title="EMJ - Respiratory page 8" href="http://viewer.zmags.com/publication/4ead80ac?page=8"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 9" href="http://viewer.zmags.com/publication/4ead80ac?page=9"> Welcome to the European Medical Journal review of</a> <a title="EMJ - Respiratory page 10" href="http://viewer.zmags.com/publication/4ead80ac?page=10"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 11" href="http://viewer.zmags.com/publication/4ead80ac?page=11"> Congress being over for another year, we are stil</a> <a title="EMJ - Respiratory page 12" href="http://viewer.zmags.com/publication/4ead80ac?page=12"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 13" href="http://viewer.zmags.com/publication/4ead80ac?page=13"> ERS relaunches White Book ‘THE EUROPEAN </a> <a title="EMJ - Respiratory page 14" href="http://viewer.zmags.com/publication/4ead80ac?page=14"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 15" href="http://viewer.zmags.com/publication/4ead80ac?page=15"> motivational videos, are all designed t</a> <a title="EMJ - Respiratory page 16" href="http://viewer.zmags.com/publication/4ead80ac?page=16"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 17" href="http://viewer.zmags.com/publication/4ead80ac?page=17"> New electronic tool helping to reduce pneumonia d</a> <a title="EMJ - Respiratory page 18" href="http://viewer.zmags.com/publication/4ead80ac?page=18"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 19" href="http://viewer.zmags.com/publication/4ead80ac?page=19"> Kicking the habit: e-cigarettes versus nicotine p</a> <a title="EMJ - Respiratory page 20" href="http://viewer.zmags.com/publication/4ead80ac?page=20"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 21" href="http://viewer.zmags.com/publication/4ead80ac?page=21"> to improve the situation for patie</a> <a title="EMJ - Respiratory page 22" href="http://viewer.zmags.com/publication/4ead80ac?page=22"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 23" href="http://viewer.zmags.com/publication/4ead80ac?page=23"> Lead author Dr Francisco Campos-Rodriguez, from t</a> <a title="EMJ - Respiratory page 24" href="http://viewer.zmags.com/publication/4ead80ac?page=24"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 25" href="http://viewer.zmags.com/publication/4ead80ac?page=25"> Cancer breathalyser: Diagnosing lung cancer via p</a> <a title="EMJ - Respiratory page 26" href="http://viewer.zmags.com/publication/4ead80ac?page=26"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 27" href="http://viewer.zmags.com/publication/4ead80ac?page=27"> Obstructive lung disease patients experience cogn</a> <a title="EMJ - Respiratory page 28" href="http://viewer.zmags.com/publication/4ead80ac?page=28"> ERS ANNUAL CONGRESS 2013 CONVENTION CENTRE DE GRA</a> <a title="EMJ - Respiratory page 29" href="http://viewer.zmags.com/publication/4ead80ac?page=29"> From a host of fourteen therapeutical areas, EURO</a> <a title="EMJ - Respiratory page 30" href="http://viewer.zmags.com/publication/4ead80ac?page=30"> POOR ASTHMA CONTROL, DEVICE HANDLING </a> <a title="EMJ - Respiratory page 31" href="http://viewer.zmags.com/publication/4ead80ac?page=31"> that are ‘inhalation experts’ due to patients who</a> <a title="EMJ - Respiratory page 32" href="http://viewer.zmags.com/publication/4ead80ac?page=32"> after one-on-one instruction this increased </a> <a title="EMJ - Respiratory page 33" href="http://viewer.zmags.com/publication/4ead80ac?page=33"> successful treatment in 19.7% of patients in the </a> <a title="EMJ - Respiratory page 34" href="http://viewer.zmags.com/publication/4ead80ac?page=34"> may be more than they need for their personal fee</a> <a title="EMJ - Respiratory page 35" href="http://viewer.zmags.com/publication/4ead80ac?page=35"> number of asthma hospitalisations and emergency r</a> <a title="EMJ - Respiratory page 36" href="http://viewer.zmags.com/publication/4ead80ac?page=36"> and objective data in 5-to 12-year-old children w</a> <a title="EMJ - Respiratory page 37" href="http://viewer.zmags.com/publication/4ead80ac?page=37"> Asthma  treatment  failure  with  symptom</a> <a title="EMJ - Respiratory page 38" href="http://viewer.zmags.com/publication/4ead80ac?page=38"> The  impact  of  adherence  with  thera</a> <a title="EMJ - Respiratory page 39" href="http://viewer.zmags.com/publication/4ead80ac?page=39"> 3) using patient adherence levels and patterns to</a> <a title="EMJ - Respiratory page 40" href="http://viewer.zmags.com/publication/4ead80ac?page=40"> Patient has uncontrolled asthma and/or Frequent </a> <a title="EMJ - Respiratory page 41" href="http://viewer.zmags.com/publication/4ead80ac?page=41"> syndrome etc.39 Another consideration is tha</a> <a title="EMJ - Respiratory page 42" href="http://viewer.zmags.com/publication/4ead80ac?page=42"> Patient Conscious inhalation possible Consci</a> <a title="EMJ - Respiratory page 43" href="http://viewer.zmags.com/publication/4ead80ac?page=43"> be addressed, but additional new therapies need t</a> <a title="EMJ - Respiratory page 44" href="http://viewer.zmags.com/publication/4ead80ac?page=44"> the patients with stable asthma controlled with m</a> <a title="EMJ - Respiratory page 45" href="http://viewer.zmags.com/publication/4ead80ac?page=45"> integrin may contribute to the increased activati</a> <a title="EMJ - Respiratory page 46" href="http://viewer.zmags.com/publication/4ead80ac?page=46"> FEV /FVC (forced vital capacity) ratio, peak flow,</a> <a title="EMJ - Respiratory page 47" href="http://viewer.zmags.com/publication/4ead80ac?page=47"> asthma in 61 patients.76 The patients were treate</a> <a title="EMJ - Respiratory page 48" href="http://viewer.zmags.com/publication/4ead80ac?page=48"> process for measuring sputum cell counts requires</a> <a title="EMJ - Respiratory page 49" href="http://viewer.zmags.com/publication/4ead80ac?page=49"> Question: What do the other speakers think about </a> <a title="EMJ - Respiratory page 50" href="http://viewer.zmags.com/publication/4ead80ac?page=50"> unique barriers and the phenotype underlying the </a> <a title="EMJ - Respiratory page 51" href="http://viewer.zmags.com/publication/4ead80ac?page=51"> 12. Price D, et al. Inhaler competence in asthma:</a> <a title="EMJ - Respiratory page 52" href="http://viewer.zmags.com/publication/4ead80ac?page=52"> 61. Wenzel SE. Asthma: defining of the persistent </a> <a title="EMJ - Respiratory page 53" href="http://viewer.zmags.com/publication/4ead80ac?page=53"> CALL FOR PAPERS IF YOU ARE INTERESTED IN SUBMITT</a> <a title="EMJ - Respiratory page 54" href="http://viewer.zmags.com/publication/4ead80ac?page=54"> LONG-TERM NON-INVASIVE VENTILATION (NIV) FOR C</a> <a title="EMJ - Respiratory page 55" href="http://viewer.zmags.com/publication/4ead80ac?page=55"> COPD also places a significant demand </a> <a title="EMJ - Respiratory page 56" href="http://viewer.zmags.com/publication/4ead80ac?page=56"> Table 1. NIV in chronic hypercapnic COPD: RCTs wi</a> <a title="EMJ - Respiratory page 57" href="http://viewer.zmags.com/publication/4ead80ac?page=57"> •Improved survival, sleep-related hypercapnia and</a> <a title="EMJ - Respiratory page 58" href="http://viewer.zmags.com/publication/4ead80ac?page=58"> *6MWD: 6 minute walking distance; COPD: chronic o</a> <a title="EMJ - Respiratory page 59" href="http://viewer.zmags.com/publication/4ead80ac?page=59"> Table 2. NIV in chronic hypercapnic COPD: non-ran</a> <a title="EMJ - Respiratory page 60" href="http://viewer.zmags.com/publication/4ead80ac?page=60"> able to significantly improve PaCO and work of </a> <a title="EMJ - Respiratory page 61" href="http://viewer.zmags.com/publication/4ead80ac?page=61"> 2000;118(6):1582-90. 24. Clini E, Sturani C, Ross</a> <a title="EMJ - Respiratory page 62" href="http://viewer.zmags.com/publication/4ead80ac?page=62"> Thorax. 2004;59(12):1020-5. 61. Windisch W, Walte</a> <a title="EMJ - Respiratory page 63" href="http://viewer.zmags.com/publication/4ead80ac?page=63"> From a host of fourteen therapeutical areas, EURO</a> <a title="EMJ - Respiratory page 64" href="http://viewer.zmags.com/publication/4ead80ac?page=64"> EFFECTIVENESS OF INHALER DEVICES IN ADULT </a> <a title="EMJ - Respiratory page 65" href="http://viewer.zmags.com/publication/4ead80ac?page=65"> can be used with spacers, and breath-actuated pMD</a> <a title="EMJ - Respiratory page 66" href="http://viewer.zmags.com/publication/4ead80ac?page=66"> 90 80 70 60 50 40 30 20 10 0 81 </a> <a title="EMJ - Respiratory page 67" href="http://viewer.zmags.com/publication/4ead80ac?page=67"> on the criteria used to define proper technique. F</a> <a title="EMJ - Respiratory page 68" href="http://viewer.zmags.com/publication/4ead80ac?page=68"> inhalation technique: research to improve inhaler</a> <a title="EMJ - Respiratory page 69" href="http://viewer.zmags.com/publication/4ead80ac?page=69"> Of note, some testing and training devices have b</a> <a title="EMJ - Respiratory page 70" href="http://viewer.zmags.com/publication/4ead80ac?page=70"> 7. Leach CL, Davidson PJ, Boudreau RJ. Impr</a> <a title="EMJ - Respiratory page 71" href="http://viewer.zmags.com/publication/4ead80ac?page=71"> Respir J. 2011;20:92–6. 42. Bynum A, Hopkins </a> <a title="EMJ - Respiratory page 72" href="http://viewer.zmags.com/publication/4ead80ac?page=72"> BRONCHOSCOPIC NITINOL COIL IMPLANTATION: A NEW </a> <a title="EMJ - Respiratory page 73" href="http://viewer.zmags.com/publication/4ead80ac?page=73"> Over the past decade, there have been significant </a> <a title="EMJ - Respiratory page 74" href="http://viewer.zmags.com/publication/4ead80ac?page=74"> measured using radiopaque markers on the guide wi</a> <a title="EMJ - Respiratory page 75" href="http://viewer.zmags.com/publication/4ead80ac?page=75"> Table 1. Main inclusion criteria for three publis</a> <a title="EMJ - Respiratory page 76" href="http://viewer.zmags.com/publication/4ead80ac?page=76"> Table 2. Results of three published studies on LV</a> <a title="EMJ - Respiratory page 77" href="http://viewer.zmags.com/publication/4ead80ac?page=77"> During the next 2 months, and until completion of</a> <a title="EMJ - Respiratory page 78" href="http://viewer.zmags.com/publication/4ead80ac?page=78"> applying this treatment into routine clinical pra</a> <a title="EMJ - Respiratory page 79" href="http://viewer.zmags.com/publication/4ead80ac?page=79"> COPD NOCTURNAL DESATURATOR PATIENTS WITH OB</a> <a title="EMJ - Respiratory page 80" href="http://viewer.zmags.com/publication/4ead80ac?page=80"> INTRODUCTION Chronic obstructive pulmonary disea</a> <a title="EMJ - Respiratory page 81" href="http://viewer.zmags.com/publication/4ead80ac?page=81"> oxidative stress obesity with airway closure gas</a> <a title="EMJ - Respiratory page 82" href="http://viewer.zmags.com/publication/4ead80ac?page=82"> showed that clinical parameter predictors, when a</a> <a title="EMJ - Respiratory page 83" href="http://viewer.zmags.com/publication/4ead80ac?page=83"> Figure 2. Simultaneous recording of nocturnal oxi</a> <a title="EMJ - Respiratory page 84" href="http://viewer.zmags.com/publication/4ead80ac?page=84"> leading to relative hypoxaemia. Risk of sle</a> <a title="EMJ - Respiratory page 85" href="http://viewer.zmags.com/publication/4ead80ac?page=85"> in NREM sleep in hypercapnic chronic obstructive </a> <a title="EMJ - Respiratory page 86" href="http://viewer.zmags.com/publication/4ead80ac?page=86"> SUBSCRIBE TO THE EMJ NEWSLETTER www.news.emjrevie</a> <a title="EMJ - Respiratory page 87" href="http://viewer.zmags.com/publication/4ead80ac?page=87"> BRONCHIAL ALLERGEN CHALLENGES IN ASTHMA RESEARCH </a> <a title="EMJ - Respiratory page 88" href="http://viewer.zmags.com/publication/4ead80ac?page=88"> In comparison with human models, the mouse </a> <a title="EMJ - Respiratory page 89" href="http://viewer.zmags.com/publication/4ead80ac?page=89"> Table 1. Low dose challenges and symptoms. Clinic</a> <a title="EMJ - Respiratory page 90" href="http://viewer.zmags.com/publication/4ead80ac?page=90"> challenge mild asthmatics who were allergic </a> <a title="EMJ - Respiratory page 91" href="http://viewer.zmags.com/publication/4ead80ac?page=91"> 8. Corazza N, Kaufmann T. Novel insights into me</a> <a title="EMJ - Respiratory page 92" href="http://viewer.zmags.com/publication/4ead80ac?page=92"> ASTHMA IN PREGNANCY István Ivancsó, Anikó Bohács,</a> <a title="EMJ - Respiratory page 93" href="http://viewer.zmags.com/publication/4ead80ac?page=93"> Controlling trophoblast invasion and vascul</a> <a title="EMJ - Respiratory page 94" href="http://viewer.zmags.com/publication/4ead80ac?page=94"> lymphocyte activation that characterises asthma.2</a> <a title="EMJ - Respiratory page 95" href="http://viewer.zmags.com/publication/4ead80ac?page=95"> Table 1. The already established immunological ch</a> <a title="EMJ - Respiratory page 96" href="http://viewer.zmags.com/publication/4ead80ac?page=96"> PREGNANCY-INDUCED CHANGES IN ASTHMA CONTROL As </a> <a title="EMJ - Respiratory page 97" href="http://viewer.zmags.com/publication/4ead80ac?page=97"> Pharmacological therapy Because safety data of</a> <a title="EMJ - Respiratory page 98" href="http://viewer.zmags.com/publication/4ead80ac?page=98"> REFERENCES 1. Kwon H, Belanger K, Bracken </a> <a title="EMJ - Respiratory page 99" href="http://viewer.zmags.com/publication/4ead80ac?page=99"> 37. Firoozi F, Lemière C, Ducharme FM, Beauchesne</a> <a title="EMJ - Respiratory page 100" href="http://viewer.zmags.com/publication/4ead80ac?page=100"> Congenital malformations after the use of inhaled</a> <a title="EMJ - Respiratory page 101" href="http://viewer.zmags.com/publication/4ead80ac?page=101"> RECOMBINANT ALLERGENS IN DIAGNOSIS AND </a> <a title="EMJ - Respiratory page 102" href="http://viewer.zmags.com/publication/4ead80ac?page=102"> marker allergens for important Mediterranean poll</a> <a title="EMJ - Respiratory page 103" href="http://viewer.zmags.com/publication/4ead80ac?page=103"> sensitisation in grass pollen allergy in ch</a> <a title="EMJ - Respiratory page 104" href="http://viewer.zmags.com/publication/4ead80ac?page=104"> OLEA POLLEN ALLERGY Olive (Olea europaea) pollen</a> <a title="EMJ - Respiratory page 105" href="http://viewer.zmags.com/publication/4ead80ac?page=105"> depend on its heat-stability and protease digesti</a> <a title="EMJ - Respiratory page 106" href="http://viewer.zmags.com/publication/4ead80ac?page=106"> al. The IgE repertoire in children and adolescent</a> <a title="EMJ - Respiratory page 107" href="http://viewer.zmags.com/publication/4ead80ac?page=107"> the pollen pan-allergen profilin. Is the detection</a> <a title="EMJ - Respiratory page 108" href="http://viewer.zmags.com/publication/4ead80ac?page=108"> PHARMACOLOGICAL TREATMENT OF IDIOPATHIC </a> <a title="EMJ - Respiratory page 109" href="http://viewer.zmags.com/publication/4ead80ac?page=109"> suppress inflammatory or immune responses,</a> <a title="EMJ - Respiratory page 110" href="http://viewer.zmags.com/publication/4ead80ac?page=110"> Figure 2. High-resolution computed tomography (HR</a> <a title="EMJ - Respiratory page 111" href="http://viewer.zmags.com/publication/4ead80ac?page=111"> Azathioprine, an antimetabolite, blocks most T ce</a> <a title="EMJ - Respiratory page 112" href="http://viewer.zmags.com/publication/4ead80ac?page=112"> ANTIOXIDANTS The IFIGENIA (Idiopathic Pulmo</a> <a title="EMJ - Respiratory page 113" href="http://viewer.zmags.com/publication/4ead80ac?page=113"> 390 patients, confirmed that treatment with I</a> <a title="EMJ - Respiratory page 114" href="http://viewer.zmags.com/publication/4ead80ac?page=114"> of pulmonary arterial hypertension.31,32 In a sma</a> <a title="EMJ - Respiratory page 115" href="http://viewer.zmags.com/publication/4ead80ac?page=115"> the efficacy of oral pirfenidone over 72 weeks.45</a> <a title="EMJ - Respiratory page 116" href="http://viewer.zmags.com/publication/4ead80ac?page=116"> pathways activated by tyrosine kinases have also </a> <a title="EMJ - Respiratory page 117" href="http://viewer.zmags.com/publication/4ead80ac?page=117"> in patients with IPF (weak recommendation, very l</a> <a title="EMJ - Respiratory page 118" href="http://viewer.zmags.com/publication/4ead80ac?page=118"> and symptoms.77 There are data suggesting also a </a> <a title="EMJ - Respiratory page 119" href="http://viewer.zmags.com/publication/4ead80ac?page=119"> Am J Respir Crit Care Med. 1998;157:199- 203. 3. </a> <a title="EMJ - Respiratory page 120" href="http://viewer.zmags.com/publication/4ead80ac?page=120"> label Phase II study. Am J Respir Crit Care Med. </a> <a title="EMJ - Respiratory page 121" href="http://viewer.zmags.com/publication/4ead80ac?page=121"> clinical trials. Am J Respir Crit Care Med. 2012;</a> <a title="EMJ - Respiratory page 122" href="http://viewer.zmags.com/publication/4ead80ac?page=122"> NOVEL TREATMENT OPTIONS FOR AUTOIMMUNE </a> <a title="EMJ - Respiratory page 123" href="http://viewer.zmags.com/publication/4ead80ac?page=123"> autoantibody measurement could be a clinical tool</a> <a title="EMJ - Respiratory page 124" href="http://viewer.zmags.com/publication/4ead80ac?page=124"> PAP lung, by enhancing alveolar macrophage f</a> <a title="EMJ - Respiratory page 125" href="http://viewer.zmags.com/publication/4ead80ac?page=125"> Randomisation 1st level control group (WLL) </a> <a title="EMJ - Respiratory page 126" href="http://viewer.zmags.com/publication/4ead80ac?page=126"> Initial failure of the GM-CSF inhalation seems to</a> <a title="EMJ - Respiratory page 127" href="http://viewer.zmags.com/publication/4ead80ac?page=127"> Acknowledgement This paper was, in part, suppo</a> <a title="EMJ - Respiratory page 128" href="http://viewer.zmags.com/publication/4ead80ac?page=128"> Pulmonol. 2008;43(8):828–30. 29. Bonfield TL, Kavu</a> <a title="EMJ - Respiratory page 129" href="http://viewer.zmags.com/publication/4ead80ac?page=129"> ADVANCES IN THE DIAGNOSIS OF TUBERCULOSIS AND </a> <a title="EMJ - Respiratory page 130" href="http://viewer.zmags.com/publication/4ead80ac?page=130"> (of 3 weeks or more), sputum production (sometime</a> <a title="EMJ - Respiratory page 131" href="http://viewer.zmags.com/publication/4ead80ac?page=131"> diagnosed bacteriologically, therefore the qualit</a> <a title="EMJ - Respiratory page 132" href="http://viewer.zmags.com/publication/4ead80ac?page=132"> PCR is the first developed method. There are two c</a> <a title="EMJ - Respiratory page 133" href="http://viewer.zmags.com/publication/4ead80ac?page=133"> drug sensitivity results. WHO subsequently issued</a> <a title="EMJ - Respiratory page 134" href="http://viewer.zmags.com/publication/4ead80ac?page=134"> Surveillance 2002-2007. http:/www. who.int/</a> <a title="EMJ - Respiratory page 135" href="http://viewer.zmags.com/publication/4ead80ac?page=135"> AIRWAY CLEARANCE IN THE INTENSIVE CARE UNIT Dewi </a> <a title="EMJ - Respiratory page 136" href="http://viewer.zmags.com/publication/4ead80ac?page=136"> Dimassi et al.18 studied patients at high risk fo</a> <a title="EMJ - Respiratory page 137" href="http://viewer.zmags.com/publication/4ead80ac?page=137"> resistance. PEP and postural drainage a</a> <a title="EMJ - Respiratory page 138" href="http://viewer.zmags.com/publication/4ead80ac?page=138"> Table 1. Safety, effectiveness, and pros and cons</a> <a title="EMJ - Respiratory page 139" href="http://viewer.zmags.com/publication/4ead80ac?page=139"> disease. 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