{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:51:55Z","timestamp":1789681915680,"version":"4.0.1"},"reference-count":81,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","journal.chestnet.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Chest"],"published-print":{"date-parts":[[2017,6]]},"DOI":"10.1016\/j.chest.2016.07.035","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T03:45:27Z","timestamp":1470973527000},"page":"1345-1355","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":58,"title":["Dilemmas, Confusion, and Misconceptions Related to Small Airways Directed Therapy"],"prefix":"10.1016","volume":"151","author":[{"given":"Federico","family":"Lavorini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar S.","family":"Usmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.J.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Corbetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.J.","family":"Corrigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.L.","family":"Chawes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.N.R.","family":"Dekhuijzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Hausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Lavorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.L.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Roche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sanchis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.S.","family":"Usmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Vincken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib1","first-page":"1","article-title":"Bridging the gap between science and clinical efficacy: physiology, imaging and modelling of\u00a0aerosol in the lung","volume":"29","author":"Darquenne","year":"2016","journal-title":"J\u00a0Aerosol Med Pulm Drug Deliv"},{"key":"10.1016\/j.chest.2016.07.035_bib2","series-title":"Morphometry of the Human Lung","first-page":"p4","author":"Weibel","year":"1963"},{"issue":"26","key":"10.1016\/j.chest.2016.07.035_bib3","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1056\/NEJMoa032158","article-title":"The nature of small-airway obstruction in chronic obstructive pulmonary disease","volume":"350","author":"Hogg","year":"2004","journal-title":"N\u00a0Engl J Med"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib4","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0091-6749(97)70193-3","article-title":"Inflammation of small airways in asthma","volume":"100","author":"Hamid","year":"1997","journal-title":"J\u00a0Allergy Clin Immunol"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib5","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1152\/jappl.1992.72.3.1016","article-title":"Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure","volume":"72","author":"Yanai","year":"1992","journal-title":"J\u00a0Appl Physiol"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib6","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1164\/ajrccm.161.6.9906075","article-title":"Recurrent exacerbations in severe asthma are associated with enhanced airway closure during stable episodes","volume":"161","author":"in\u2019t Veen","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib7","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.jaci.2013.03.009","article-title":"Alveolar nitric oxide and asthma control in mild untreated asthma","volume":"131","author":"Scichilone","year":"2013","journal-title":"J\u00a0Allergy Clin Immunol"},{"issue":"9537","key":"10.1016\/j.chest.2016.07.035_bib8","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/S0140-6736(06)69290-8","article-title":"Asthma: defining of the persistent adult phenotypes","volume":"368","author":"Wenzel","year":"2006","journal-title":"Lancet"},{"issue":"5","key":"10.1016\/j.chest.2016.07.035_bib9","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1164\/ajrccm.154.5.8912772","article-title":"Alveolar tissue inflammation in asthma","volume":"154","author":"Kraft","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"issue":"7","key":"10.1016\/j.chest.2016.07.035_bib10","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1164\/ajrccm.163.7.2008013","article-title":"Distal lung dysfunction at night in nocturnal asthma","volume":"163","author":"Kraft","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"issue":"6 pt 1","key":"10.1016\/j.chest.2016.07.035_bib11","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1164\/ajrccm.152.6.8520737","article-title":"Peripheral airways responsiveness to cool, dry air in normal and asthmatic individuals","volume":"152","author":"Kaminsky","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib12","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1183\/09031936.02.00401402","article-title":"Outdoor air pollution climatic changes and allergic bronchial asthma","volume":"20","author":"D\u2019Amato","year":"2002","journal-title":"Eur Respir J"},{"issue":"5","key":"10.1016\/j.chest.2016.07.035_bib13","doi-asserted-by":"crossref","first-page":"376","DOI":"10.4168\/aair.2014.6.5.376","article-title":"Small airways dysfunction in asthma: evaluation and management to improve asthma control","volume":"6","author":"Usmani","year":"2014","journal-title":"Allergy Asthma Immunol Res"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib14","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/MCP.0000000000000115","article-title":"Small-airway disease in asthma: pharmacological considerations","volume":"21","author":"Usmani","year":"2015","journal-title":"Curr Opin Pulm Med"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1159\/000343629","article-title":"Treating the small airways","volume":"84","author":"Usmani","year":"2012","journal-title":"Respiration"},{"key":"10.1016\/j.chest.2016.07.035_bib16","first-page":"353","article-title":"Delivery characteristics and patients\u2019 handling of two single-dose dry-powder inhalers used in COPD","volume":"6","author":"Chapman","year":"2011","journal-title":"Int J Obstruct Pulmon Dis"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3109\/21556660.2013.766197","article-title":"Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium","volume":"2","author":"Colthorpe","year":"2013","journal-title":"J\u00a0Drug Assess"},{"key":"10.1016\/j.chest.2016.07.035_bib18","unstructured":"Lock DJ, Watkins A, Munro A. DPI performance modelling using an\u00a0inhalation simulator and oropharyngeal model: a more patient-relevant approach for device development. Paper presented at: Drug Delivery to the Lungs DDL25 Conference; December 10, 2014; Edinburgh, UK."},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000363390","article-title":"New inhaler devices; the good, the bad and the ugly","volume":"88","author":"Lavorini","year":"2014","journal-title":"Respiration"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib20","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1046\/j.1365-2125.2003.01892.x","article-title":"Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications","volume":"56","author":"Labiris","year":"2003","journal-title":"Br J Clin Pharmacol"},{"issue":"9","key":"10.1016\/j.chest.2016.07.035_bib21","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1517\/17425247.2014.928282","article-title":"NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma","volume":"11","author":"Corradi","year":"2014","journal-title":"Exp Opin Drug Deliv"},{"key":"10.1016\/j.chest.2016.07.035_bib22","first-page":"145","article-title":"Development of Respimat Soft Mist inhaler and its clinical utility in respiratory disorders","volume":"4","author":"Dalby","year":"2011","journal-title":"Med Devices (Auckl)"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2332\/allergolint.09-OA-0122","article-title":"Comparison of effectiveness in ciclesonide and fluticasone propionate on small airway function in mild asthma","volume":"59","author":"Hoshino","year":"2010","journal-title":"Allergol Int"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.rmed.2008.09.002","article-title":"Lung function and asthma control with beclomethasone and formoterol in a single inhaler","volume":"103","author":"Huchon","year":"2009","journal-title":"Respir Med"},{"issue":"10","key":"10.1016\/j.chest.2016.07.035_bib25","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1111\/j.1398-9995.2007.01493.x","article-title":"Beclomethasone\/formoterol vs\u00a0fluticasone\/salmeterol inhaled combination in moderate to severe asthma","volume":"62","author":"Papi","year":"2007","journal-title":"Allergy"},{"key":"10.1016\/j.chest.2016.07.035_bib26","first-page":"1163","article-title":"Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD","volume":"9","author":"Postma","year":"2014","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"10.1016\/j.chest.2016.07.035_bib27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejpb.2015.07.016","article-title":"Can \u2018extrafine\u2019 dry powder aerosols improve lung deposition?","volume":"96","author":"de Boer","year":"2015","journal-title":"Eur J Pharm Biopharm"},{"issue":"4","key":"10.1016\/j.chest.2016.07.035_bib28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.4104\/pcrj.2009.00029","article-title":"Not all asthma inhalers are the same: factors to consider when prescribing an inhaler","volume":"18","author":"Chrystyn","year":"2009","journal-title":"Prim Care Respir J"},{"issue":"4","key":"10.1016\/j.chest.2016.07.035_bib29","doi-asserted-by":"crossref","first-page":"E110","DOI":"10.1208\/pt0804110","article-title":"In\u00a0vitro and in\u00a0vivo aspects of cascade impactor tests and inhaler performance: a review","volume":"8","author":"Mitchell","year":"2007","journal-title":"AAPS PharmSciTech"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib30","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1183\/09031936.00166410","article-title":"What the pulmonary specialist should know about the new inhalation therapies","volume":"37","author":"Laube","year":"2011","journal-title":"Eur Respir J"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib31","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1378\/chest.122.2.510","article-title":"Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers","volume":"122","author":"Leach","year":"2002","journal-title":"Chest"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib32","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/ppul.10238","article-title":"Influence of particle size on lung deposition and pharmacokinetics of beclomethasone dipropionate in children","volume":"35","author":"Agertoft","year":"2003","journal-title":"Pediatr Pulmonol"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib33","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1183\/09031936.98.12061346","article-title":"Improved airway targeting with the CFC-free HFA beclomethasone metered-dose inhaler compared with CFC-beclomethasone","volume":"12","author":"Leach","year":"1998","journal-title":"Eur Respir J"},{"key":"10.1016\/j.chest.2016.07.035_bib34","series-title":"Drug Delivery to the Lungs","first-page":"211","article-title":"Targeting the lungs with therapeutic aerosols","author":"Zanen","year":"2001"},{"issue":"5","key":"10.1016\/j.chest.2016.07.035_bib35","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1152\/japplphysiol.00525.2003","article-title":"Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols","volume":"95","author":"Usmani","year":"2003","journal-title":"J\u00a0Appl Physiol (1985)"},{"issue":"12","key":"10.1016\/j.chest.2016.07.035_bib36","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1164\/rccm.200410-1414OC","article-title":"Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size","volume":"172","author":"Usmani","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"issue":"10","key":"10.1016\/j.chest.2016.07.035_bib37","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1136\/thx.51.10.977","article-title":"Optimal particle size for beta 2 agonist and anticholinergic aerosols in patients with severe airflow obstruction","volume":"51","author":"Zanen","year":"1996","journal-title":"Thorax"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib38","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1365-2125.2007.03013.x","article-title":"The use of plethysmography and oscillometry to compare long-acting bronchodilators in patients with COPD","volume":"65","author":"Borrill","year":"2008","journal-title":"Br J Clin Pharmacol"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib39","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1378\/chest.76.1.83","article-title":"Single-breath nitrogen washout: effects of alterations of lung volumes and elastic recoil","volume":"76","author":"Al-Bazzaz","year":"1979","journal-title":"Chest"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib40","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1398-9995.2006.00970.x","article-title":"Nitrogen washout slope in poorly controlled asthma","volume":"61","author":"Bourdin","year":"2006","journal-title":"Allergy"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib41","doi-asserted-by":"crossref","first-page":"S250","DOI":"10.1016\/S0091-6749(99)70041-2","article-title":"Effect of formulation parameters on hydrofluoroalkane-beclomethasone dipropionate drug deposition in humans","volume":"104","author":"Leach","year":"1999","journal-title":"J\u00a0Allergy Clin Immunol"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/jam.2006.19.117","article-title":"Two-dimensional and three-dimensional imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers","volume":"19","author":"Leach","year":"2006","journal-title":"J\u00a0Aerosol Med"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib43","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.rmed.2005.09.027","article-title":"High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma","volume":"100","author":"Newman","year":"2006","journal-title":"Respir Med"},{"issue":"8","key":"10.1016\/j.chest.2016.07.035_bib44","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.rmed.2009.02.010","article-title":"Comparative in\u00a0vitro evaluation of four corticosteroid metered dose inhalers: consistency of delivered dose and particle size distribution","volume":"103","author":"de Vries","year":"2009","journal-title":"Respir Med"},{"issue":"suppl 1","key":"10.1016\/j.chest.2016.07.035_bib45","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1089\/jam.1999.12.Suppl_1.S-19","article-title":"Optimizing the in\u00a0vitro performance of Respimat","volume":"12","author":"Zierenberg","year":"1999","journal-title":"J\u00a0Aerosol Med"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib46","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1089\/jam.2005.18.264","article-title":"Deposition of corticosteroid aerosol in the human lung by Respimat Soft Mist inhaler compared to deposition by metered dose inhaler or by Turbuhaler dry powder inhaler","volume":"18","author":"Pitcairn","year":"2005","journal-title":"J\u00a0Aerosol Med"},{"issue":"5","key":"10.1016\/j.chest.2016.07.035_bib47","first-page":"855","article-title":"Beclomethasone\/formoterol fixed combination for the management of asthma: patient considerations","volume":"4","author":"Nicolini","year":"2008","journal-title":"Ther Clin Risk Manag"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib48","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.anai.2012.01.010","article-title":"Characterization of respiratory deposition of fluticasone-salmeterol hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic patients","volume":"108","author":"Leach","year":"2012","journal-title":"Ann Allergy Asthma Immunol"},{"issue":"4","key":"10.1016\/j.chest.2016.07.035_bib49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1046\/j.1365-2125.2001.01304.x","article-title":"Methods to identify drug deposition in the lungs following inhalation","volume":"51","author":"Chrystyn","year":"2001","journal-title":"Br J Clin Pharmacol"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib50","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1046\/j.1365-2125.1996.00493.x","article-title":"Pharmacokinetics of inhaled drugs","volume":"42","author":"Lipworth","year":"1996","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib51","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.pupt.2007.05.002","article-title":"Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma","volume":"21","author":"Bateman","year":"2008","journal-title":"Pulm Pharmacol Ther"},{"issue":"5","key":"10.1016\/j.chest.2016.07.035_bib52","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.pupt.2005.01.004","article-title":"Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5\u2019monophosphate in asthmatic patients","volume":"18","author":"Derom","year":"2005","journal-title":"Pulm Pharmacol Ther"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib53","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1183\/09031936.00079908","article-title":"Effects of ciclesonide and fluticasone on cortisol secretion in patients with persistent asthma","volume":"33","author":"Derom","year":"2009","journal-title":"Eur Respir J"},{"issue":"4","key":"10.1016\/j.chest.2016.07.035_bib54","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1152\/jappl.1979.47.4.867","article-title":"Calculated deposition of inhaled particles in the airway generations of normal subjects","volume":"47","author":"Gerrity","year":"1979","journal-title":"J\u00a0Appl Physiol"},{"key":"10.1016\/j.chest.2016.07.035_bib55","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1089\/jam.1989.2.89","article-title":"Assessment of airway geometry with inert aerosols","volume":"2","author":"Heyder","year":"1989","journal-title":"J\u00a0Aerosol Sci"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1089\/08942680252908548","article-title":"Gamma scintigraphic evaluation of a novel budesonide dry powder inhaler using a validated radiolabeling technique","volume":"15","author":"Warren","year":"2002","journal-title":"J\u00a0Aerosol Med"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib57","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3109\/07853890.2011.585656","article-title":"Assessing and treating small airways disease in asthma and chronic obstructive pulmonary disease","volume":"44","author":"Usmani","year":"2012","journal-title":"Ann Med"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib58","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.pupt.2012.10.001","article-title":"Assessing and accessing the small airways: implications for asthma management","volume":"26","author":"Scichilone","year":"2013","journal-title":"Pulm Pharmacol Ther"},{"issue":"5","key":"10.1016\/j.chest.2016.07.035_bib59","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.jaip.2015.06.012","article-title":"Ultrafine-particle inhalers, the Holy Grail of inhaled corticosteroid therapy, or not!","volume":"3","author":"Kelly","year":"2015","journal-title":"J\u00a0Allergy Clin Immunol Pract"},{"key":"10.1016\/j.chest.2016.07.035_bib60","series-title":"Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma\u2014Full Report No.: 07-4051","year":"2007"},{"issue":"10","key":"10.1016\/j.chest.2016.07.035_bib61","doi-asserted-by":"crossref","first-page":"e29","DOI":"10.1016\/S2213-2600(13)70199-1","article-title":"Integrating real-life studies in the global therapeutic research framework","volume":"1","author":"Roche","year":"2013","journal-title":"Lancet Respir Med"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib62","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.rmed.2004.03.026","article-title":"How representative are clinical study patients with asthma or COPD for a larger \u2018real life\u2019 population of patients with obstructive lung disease?","volume":"99","author":"Herland","year":"2005","journal-title":"Respir Med"},{"issue":"5","key":"10.1016\/j.chest.2016.07.035_bib63","article-title":"Small-particle inhaled corticosteroid as first-line or step-up controller therapy in childhood asthma","volume":"3","author":"van Aalderen","year":"2015","journal-title":"J\u00a0Allergy Clin Immunol Pract"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib64","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1067\/mai.2000.111582","article-title":"Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane-beclomethasone extrafine inhalation aerosol), in asthma","volume":"106","author":"VandenBurgt","year":"2000","journal-title":"J\u00a0Allergy Clin Immunol"},{"issue":"suppl A","key":"10.1016\/j.chest.2016.07.035_bib65","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0954-6111(98)90215-3","article-title":"Safety of hydrofluoalkane-134a beclomethasone dipropionate extrafine aerosol","volume":"92","author":"Thompson","year":"1998","journal-title":"Respir Med"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib66","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.pupt.2008.01.001","article-title":"Tolerability of high cumulative doses of the HFA modulite beclomethasone dipropionate\/formoterol combination inhaler in asthmatic patients","volume":"21","author":"Singh","year":"2008","journal-title":"Pulm Pharmacol Ther"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib67","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/S0091-6749(99)70016-3","article-title":"Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant","volume":"104","author":"Busse","year":"1999","journal-title":"J\u00a0Allergy Clin Immunol"},{"issue":"suppl A","key":"10.1016\/j.chest.2016.07.035_bib68","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0954-6111(98)90214-1","article-title":"Hydrofluroalkane-134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose","volume":"92","author":"Davies","year":"1998","journal-title":"Respir Med"},{"issue":"7","key":"10.1016\/j.chest.2016.07.035_bib69","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1368-5031.2004.00273.x","article-title":"The efficacy and safety of QVAR (hydrofluoroalkane-beclomethasone dipropionate extrafine aerosol) in asthma (part I): an update of clinical experience in adults","volume":"58","author":"van Schayck","year":"2004","journal-title":"Int J Clin Pract"},{"key":"10.1016\/j.chest.2016.07.035_bib70","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1183\/09031936.00095906","article-title":"Beclomethasone\/formoterol vs. budesonide\/formoterol combination therapy in asthma","volume":"29","author":"Papi","year":"2007","journal-title":"Eur Respir J"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib71","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2165\/00003088-200948060-00001","article-title":"Systemic exposure and implications for lung deposition with an extra-fine hydrofluoroalkane beclomethasone dipropionate\/formoterol fixed combination","volume":"48","author":"Bousquet","year":"2009","journal-title":"Clin Pharmacokinet"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2332\/allergolint.O-07-522","volume":"57","author":"Ohbayashi","year":"2008","journal-title":"Allergol Int"},{"issue":"1","key":"10.1016\/j.chest.2016.07.035_bib73","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1517\/17425240802637862","article-title":"Targeting drugs to the airways: the role of spacer devices","volume":"6","author":"Lavorini","year":"2009","journal-title":"Expert Opin Drug Deliv"},{"issue":"suppl 1","key":"10.1016\/j.chest.2016.07.035_bib74","doi-asserted-by":"crossref","first-page":"S-4","DOI":"10.1089\/jamp.2013.1076","article-title":"The evolution of spacers and valved holding chambers","volume":"27","author":"Nikander","year":"2014","journal-title":"J\u00a0Aerosol Med Pulm Drug Deliv"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib75","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1183\/09031936.00051106","article-title":"Spacer inhalation technique and deposition of extrafine aerosol in asthmatic children","volume":"29","author":"Roller","year":"2007","journal-title":"Eur Respir J"},{"issue":"2","key":"10.1016\/j.chest.2016.07.035_bib76","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2500\/aap.2015.36.3835","article-title":"Flunisolide hydrofluoroalkane with integrated spacer for treating asthma: an updated review","volume":"36","author":"Berger","year":"2015","journal-title":"Allergy Asthma Proc"},{"issue":"6","key":"10.1016\/j.chest.2016.07.035_bib77","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/j.1365-2125.2011.04024.x","article-title":"Effect of\u00a0AeroChamber Plus\u2122 on the lung and systemic bioavailability of\u00a0beclomethasone dipropionate\/formoterol pMDI","volume":"72","author":"Singh","year":"2011","journal-title":"Br J Clin Pharmacol"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib78","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/bcp.12640","article-title":"Pharmacokinetics and pharmacodynamics of an extrafine fixed pMDI combination of beclomethasone dipropionate\/formoterol fumarate in adolescent asthma","volume":"80","author":"Kuna","year":"2015","journal-title":"Br J Clin Pharmacol"},{"issue":"3","key":"10.1016\/j.chest.2016.07.035_bib79","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1183\/09031936.00067711","article-title":"Is it really time to look at distal airways to improve asthma phenotyping and treatment","volume":"38","author":"Perez","year":"2011","journal-title":"Eur Respir J"},{"issue":"4","key":"10.1016\/j.chest.2016.07.035_bib80","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.anai.2013.02.009","article-title":"Targeting the small airways asthma phenotype: if we can reach it, should we treat it?","volume":"110","author":"Lipworth","year":"2013","journal-title":"Ann Allergy Asthma Immunol"},{"issue":"4","key":"10.1016\/j.chest.2016.07.035_bib81","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jaci.2010.07.040","article-title":"Alveolar nitric oxide concentration, small airways inflammation, and targeted asthma therapy: are we there yet?","volume":"126","author":"Kelly","year":"2010","journal-title":"J\u00a0Allergy Clin Immunol"}],"container-title":["Chest"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012369216537532?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012369216537532?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T07:32:54Z","timestamp":1757921574000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0012369216537532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":81,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["S0012369216537532"],"URL":"https:\/\/doi.org\/10.1016\/j.chest.2016.07.035","relation":{},"ISSN":["0012-3692"],"issn-type":[{"value":"0012-3692","type":"print"}],"subject":[],"published":{"date-parts":[[2017,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dilemmas, Confusion, and Misconceptions Related to Small Airways Directed Therapy","name":"articletitle","label":"Article Title"},{"value":"Chest","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.chest.2016.07.035","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}