{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:47:09Z","timestamp":1786996029535,"version":"build-2736575974"},"reference-count":101,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"Boehringer Ingelheim International GmbH"},{"name":"Department of Experimental Medicine"},{"DOI":"10.13039\/501100007642","name":"University of Rome \u201cTor Vergata","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pulmonary Pharmacology & Therapeutics"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1016\/j.pupt.2019.03.004","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T03:04:53Z","timestamp":1552359893000},"page":"39-50","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"special_numbering":"C","title":["Pharmacological characterization of the interaction between tiotropium bromide and olodaterol on human bronchi and small airways"],"prefix":"10.1016","volume":"56","author":[{"given":"Luigino","family":"Calzetta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rogliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Rinaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Cazzola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriella","family":"Matera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pupt.2019.03.004_bib1","doi-asserted-by":"crossref","first-page":"1750214","DOI":"10.1183\/13993003.00214-2017","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary","volume":"49","author":"Vogelmeier","year":"2017","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib2","author":"GOLD"},{"key":"10.1016\/j.pupt.2019.03.004_bib3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/17476348.2018.1442216","article-title":"Dual LABA\/LAMA bronchodilators in chronic obstructive pulmonary disease: why, when, and how","volume":"12","author":"Calzetta","year":"2018","journal-title":"Expert Rev. Respir. Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.rmed.2017.01.006","article-title":"Optimizing drug delivery in COPD: the role of inhaler devices","volume":"124","author":"Rogliani","year":"2017","journal-title":"Respir. Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4104\/pcrj.2011.00102","article-title":"Beyond lung function in COPD management: effectiveness of LABA\/LAMA combination therapy on patient-centred outcomes","volume":"21","author":"van der Molen","year":"2012","journal-title":"Prim. Care Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib6","first-page":"785","article-title":"Dual therapy strategies for COPD: the scientific rationale for LAMA + LABA","volume":"11","author":"Cohen","year":"2016","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"10.1016\/j.pupt.2019.03.004_bib7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.coph.2018.03.011","article-title":"Pharmacological mechanisms leading to synergy in fixed-dose dual bronchodilator therapy","volume":"40","author":"Calzetta","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3109\/15412555.2014.922172","article-title":"Translational study searching for synergy between glycopyrronium and indacaterol","volume":"12","author":"Cazzola","year":"2015","journal-title":"COPD"},{"key":"10.1016\/j.pupt.2019.03.004_bib9","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.rmed.2015.08.005","article-title":"Searching for the synergistic effect between aclidinium and formoterol: from bench to bedside","volume":"109","author":"Cazzola","year":"2015","journal-title":"Respir. Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.rmed.2016.01.001","article-title":"Magnitude of umeclidinium\/vilanterol lung function effect depends on monotherapy responses: results from two randomised controlled trials","volume":"112","author":"Donohue","year":"2016","journal-title":"Respir. Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ejphar.2014.10.025","article-title":"Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi","volume":"745","author":"Cazzola","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12931-016-0386-8","article-title":"Pharmacological characterisation of the interaction between glycopyrronium bromide and indacaterol fumarate in human isolated bronchi, small airways and bronchial epithelial cells","volume":"17","author":"Cazzola","year":"2016","journal-title":"Respir. Res."},{"key":"10.1016\/j.pupt.2019.03.004_bib13","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ejphar.2017.07.026","article-title":"Pharmacological characterization of the interaction between umeclidinium and vilanterol in human bronchi","volume":"812","author":"Calzetta","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib14","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/jvp.12504","article-title":"Combining long-acting bronchodilators with different mechanisms of action: a pharmacological approach to optimize bronchodilation of equine airways","volume":"41","author":"Calzetta","year":"2018","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"10.1016\/j.pupt.2019.03.004_bib15","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1080\/15412555.2017.1344627","article-title":"Pharmacological characterization of the interaction between tiotropium and olodaterol administered at 5:5 concentration-ratio in equine bronchi","volume":"14","author":"Calzetta","year":"2017","journal-title":"COPD"},{"key":"10.1016\/j.pupt.2019.03.004_bib16","first-page":"PA1055","article-title":"Interaction between tiotropium bromide and olodaterol in small human airways","volume":"50","author":"Calzetta","year":"2017","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib17","first-page":"PA1810","article-title":"Interaction between tiotropium bromide and olodaterol in human bronchial smooth muscle","volume":"50","author":"Cazzola","year":"2017","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib18","first-page":"A6275","article-title":"Interaction between tiotropium bromide and olodaterol in small human airways","volume":"195","author":"Rogliani","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib19","first-page":"A6274","article-title":"Interaction between tiotropium bromide and olodaterol in human bronchial smooth muscle","volume":"195","author":"Calzetta","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib20","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.pupt.2009.04.005","article-title":"Relaxant effect of brain natriuretic peptide in nonsensitized and passively sensitized isolated human bronchi","volume":"22","author":"Matera","year":"2009","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib21","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1164\/ajrccm.156.2.96-12079","article-title":"Acetylcholine via muscarinic receptors inhibits histamine release from human isolated bronchi","volume":"156","author":"Reinheimer","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib22","first-page":"L722","article-title":"Acetylcholine in isolated airways of rat, Guinea pig, and human: species differences in role of airway mucosa","volume":"270","author":"Reinheimer","year":"1996","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.pupt.2019.03.004_bib23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1006\/pupt.2001.0308","article-title":"Auxotonic contractile responses of rat tracheal and bronchial airway smooth muscle","volume":"14","author":"van Lunteren","year":"2001","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib24","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1164\/ajrccm.163.6.2007138","article-title":"Immediate allergic response in small airways","volume":"163","author":"Wohlsen","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib25","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1517\/17460441.2014.909403","article-title":"Advances in asthma drug discovery: evaluating the potential of nasal cell sampling and beyond","volume":"9","author":"Calzetta","year":"2014","journal-title":"Expert Opin. Drug Discov."},{"key":"10.1016\/j.pupt.2019.03.004_bib26","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1165\/rcmb.2011-0056OC","article-title":"Pharmacological characterization of adenosine receptors in isolated human bronchi","volume":"45","author":"Calzetta","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.pupt.2019.03.004_bib27","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1111\/j.1476-5381.2011.01339.x","article-title":"Epithelium integrity is crucial for the relaxant activity of brain natriuretic peptide in human isolated bronchi","volume":"163","author":"Matera","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib28","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1152\/japplphysiol.00415.2001","article-title":"Methacholine responsiveness of proximal and distal airways of monkeys and rats using videomicrometry","volume":"92","author":"Kott","year":"2002","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.pupt.2019.03.004_bib29","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1183\/09031936.96.09122479","article-title":"Videomicroscopy of methacholine-induced contraction of individual airways in precision-cut lung slices","volume":"9","author":"Martin","year":"1996","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1085\/jgp.119.2.187","article-title":"Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices","volume":"119","author":"Bergner","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"10.1016\/j.pupt.2019.03.004_bib31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1465-9921-7-65","article-title":"Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse","volume":"7","author":"Kummer","year":"2006","journal-title":"Respir. Res."},{"key":"10.1016\/j.pupt.2019.03.004_bib32","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1183\/09031936.03.00027502","article-title":"The early allergic response in small airways of human precision-cut lung slices","volume":"21","author":"Wohlsen","year":"2003","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib33","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00210-010-0533-6","article-title":"Efficacy is a contributing factor to the clinical onset of bronchodilation of inhaled \u03b2 2-adrenoceptor agonists","volume":"382","author":"Rosethorne","year":"2010","journal-title":"N. Schmied. Arch. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pupt.2015.03.007","article-title":"Pharmacological characterization of the interaction between the dual phosphodiesterase (PDE) 3\/4 inhibitor RPL554 and glycopyrronium on human isolated bronchi and small airways","volume":"32","author":"Calzetta","year":"2015","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib35","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0034-5687(01)00252-3","article-title":"High strength stimulation of the vagus nerve in awake humans: a lack of cardiorespiratory effects","volume":"127","author":"Binks","year":"2001","journal-title":"Respir. Physiol."},{"key":"10.1016\/j.pupt.2019.03.004_bib36","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1165\/rcmb.2010-0306OC","article-title":"Protein prenylation contributes to the effects of LPS on EFS-induced responses in human isolated bronchi","volume":"45","author":"Cazzola","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.pupt.2019.03.004_bib37","doi-asserted-by":"crossref","first-page":"S154","DOI":"10.1164\/ajrccm.158.supplement_2.13tac120","article-title":"Muscarinic receptors and control of airway smooth muscle","volume":"158","author":"Fryer","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0014-2999(88)90155-0","article-title":"Muscarinic M1, M2 receptor binding. Relationship with functional efficacy","volume":"156","author":"Freedman","year":"1988","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib39","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.pupt.2008.02.003","article-title":"Effects of neuraminidase on equine isolated bronchi","volume":"21","author":"Matera","year":"2008","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib40","series-title":"Fitting Models to Biological Data Using Linear and Nonlinear Regression : a Practical Guide to Curve Fitting","author":"Motulsky","year":"2004"},{"key":"10.1016\/j.pupt.2019.03.004_bib41","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1183\/09031936.02.00275702","article-title":"Relaxation of proximal and distal isolated human bronchi by halothane, isoflurane and desflurane","volume":"20","author":"Mercier","year":"2002","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib42","series-title":"Translational Study Searching for Synergy between Glycopyrronium and Indacaterol","author":"Cazzola","year":"2014"},{"key":"10.1016\/j.pupt.2019.03.004_bib43","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1124\/jpet.113.204644","article-title":"Effect of the mixed phosphodiesterase 3\/4 inhibitor RPL554 on human isolated bronchial smooth muscle tone","volume":"346","author":"Calzetta","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.pupt.2019.03.004_bib44","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.pupt.2013.01.002","article-title":"The influence of propofol, remifentanil and lidocaine on the tone of human bronchial smooth muscle","volume":"26","author":"Rogliani","year":"2013","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib45","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.tiv.2007.03.003","article-title":"A mathematical approach to study combined effects of toxicants in vitro: evaluation of the Bliss independence criterion and the Loewe additivity model","volume":"21","author":"Goldoni","year":"2007","journal-title":"Toxicol. Vitro"},{"key":"10.1016\/j.pupt.2019.03.004_bib46","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/sim.3005","article-title":"Quantifying synergism\/antagonism using nonlinear mixed-effects modeling: a simulation study","volume":"27","author":"Boik","year":"2008","journal-title":"Stat. Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib47","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.diagmicrobio.2006.01.024","article-title":"Mathematical formulation of additivity for antimicrobial agents","volume":"55","author":"Boucher","year":"2006","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"10.1016\/j.pupt.2019.03.004_bib48","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0031-6997(25)06847-4","article-title":"The search for synergy: a critical review from a response surface perspective","volume":"47","author":"Greco","year":"1995","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.pupt.2019.03.004_bib49","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4097\/kjae.2010.58.5.421","article-title":"Drug interaction: focusing on response surface models","volume":"58","author":"Lee","year":"2010","journal-title":"Korean J Anesthesiol"},{"key":"10.1016\/j.pupt.2019.03.004_bib50","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1128\/AAC.47.1.106-117.2003","article-title":"In vitro drug interaction modeling of combinations of azoles with terbinafine against clinical Scedosporium prolificans isolates","volume":"47","author":"Meletiadis","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.pupt.2019.03.004_bib51","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.pupt.2019.03.004_bib52","first-page":"H655","article-title":"Contractile properties of isolated vascular smooth muscle after photoradiation","volume":"256","author":"Freas","year":"1989","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.pupt.2019.03.004_bib53","first-page":"61","article-title":"Ethanol suppresses L-arginine-induced relaxation response of rat aorta stimulated with bacterial lipopolysaccharide","volume":"35","author":"Hatake","year":"2000","journal-title":"Nihon Arukoru Yakubutsu Igakkai Zasshi"},{"key":"10.1016\/j.pupt.2019.03.004_bib54","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1124\/jpet.110.167007","article-title":"Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models","volume":"334","author":"Bouyssou","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.pupt.2019.03.004_bib55","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/17476348.2018.1442216","article-title":"Dual LABA\/LAMA bronchodilators in chronic obstructive pulmonary disease: why, when and how","volume":"12","author":"Calzetta","year":"2018","journal-title":"Expert Rev. Respir. Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib56","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1165\/rcmb.2013-0119OC","article-title":"Brain natriuretic peptide protects against hyperresponsiveness of human asthmatic airway smooth muscle via an epithelial cell-dependent mechanism","volume":"50","author":"Calzetta","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.pupt.2019.03.004_bib57","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pupt.2012.09.003","article-title":"Epithelial-smooth muscle cooperation is needed for brain natriuretic peptide-dependent bronchorelaxant activity","volume":"26","author":"Matera","year":"2013","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib58","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/bjp.2008.185","article-title":"Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans","volume":"154","author":"Wessler","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib59","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ddmec.2006.02.008","article-title":"Non-neuronal acetylcholine release and its contribution to COPD pathology","volume":"3","author":"Kummer","year":"2006","journal-title":"Drug Discov. Today Dis. Mech."},{"key":"10.1016\/j.pupt.2019.03.004_bib60","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.coph.2014.03.001","article-title":"Non-neuronal cholinergic airway epithelium biology","volume":"16","author":"Kummer","year":"2014","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib61","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.rmed.2017.06.020","article-title":"Impact of LABA\/LAMA combination on exercise endurance and lung hyperinflation in COPD: a pair-wise and network meta-analysis","volume":"129","author":"Calzetta","year":"2017","journal-title":"Respir. Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib62","first-page":"PA1814","article-title":"Clinical synergism of LABA\/LAMA combinations in COPD patients","volume":"50","author":"Rogliani","year":"2017","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib63","first-page":"1805","article-title":"Differential pharmacology and clinical utility of long-acting bronchodilators in COPD - focus on olodaterol","volume":"11","author":"Matera","year":"2015","journal-title":"Therapeut. Clin. Risk Manag."},{"key":"10.1016\/j.pupt.2019.03.004_bib64","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.coph.2018.03.011","article-title":"Pharmacological mechanisms leading to synergy in fixed-dose dual bronchodilator therapy","volume":"40","author":"Calzetta","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib65","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12931-016-0386-8","article-title":"Pharmacological characterisation of the interaction between glycopyrronium bromide and indacaterol fumarate in human isolated bronchi, small airways and bronchial epithelial cells","volume":"17","author":"Cazzola","year":"2016","journal-title":"Respir. Res."},{"key":"10.1016\/j.pupt.2019.03.004_bib66","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ejphar.2017.07.026","article-title":"Pharmacological characterization of the interaction between umeclidinium and vilanterol in human bronchi","volume":"812","author":"Calzetta","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib67","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/1465-9921-7-73","article-title":"Muscarinic receptor signaling in the pathophysiology of asthma and COPD","volume":"7","author":"Gosens","year":"2006","journal-title":"Respir. Res."},{"key":"10.1016\/j.pupt.2019.03.004_bib68","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/2040622313518227","article-title":"Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases","volume":"5","author":"Alagha","year":"2014","journal-title":"Ther. Adv. Chronic. Dis."},{"key":"10.1016\/j.pupt.2019.03.004_bib69","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1476-5381.2010.01190.x","article-title":"Muscarinic receptor antagonists, from folklore to pharmacology; finding drugs that actually work in asthma and COPD","volume":"163","author":"Moulton","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib70","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ejphar.2011.01.017","article-title":"Characterization of bencycloquidium bromide, a novel muscarinic M(3) receptor antagonist in Guinea pig airways","volume":"655","author":"Jiang","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib71","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1513\/pats.200409-045MS","article-title":"Distribution of receptor targets in the lung","volume":"1","author":"Barnes","year":"2004","journal-title":"Proc. Am. Thorac. Soc."},{"key":"10.1016\/j.pupt.2019.03.004_bib72","first-page":"OA4407","article-title":"Protein tyrosin kinase and KCa++ cannel: two faces of the same coin in LABA\/LAMA synergy","volume":"50","author":"Calzetta","year":"2017","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib73","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1111\/j.1476-5381.1996.tb15300.x","article-title":"Paradoxical facilitation of acetylcholine release from parasympathetic nerves innervating Guinea-pig trachea by isoprenaline","volume":"117","author":"Belvisi","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib74","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.pupt.2010.03.003","article-title":"The scientific rationale for combining long-acting beta2-agonists and muscarinic antagonists in COPD","volume":"23","author":"Cazzola","year":"2010","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib75","doi-asserted-by":"crossref","first-page":"L1037","DOI":"10.1152\/ajplung.00145.2007","article-title":"Functional effects of 20-HETE on human bronchi: hyperpolarization and relaxation due to BKCa channel activation","volume":"293","author":"Morin","year":"2007","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.pupt.2019.03.004_bib76","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/sj.bjp.0706724","article-title":"Pharmacological assessment of the duration of action of glycopyrrolate vs tiotropium and ipratropium in Guinea-pig and human airways","volume":"148","author":"Villetti","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib77","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pupt.2018.01.003","article-title":"Comparison of the in vitro pharmacological profiles of long-acting muscarinic antagonists in human bronchus","volume":"49","author":"Naline","year":"2018","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib78","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.2147\/COPD.S138540","article-title":"Small airways disease: time for a revisit?","volume":"12","author":"Stockley","year":"2017","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"10.1016\/j.pupt.2019.03.004_bib79","first-page":"1289","article-title":"Neural control of human airways in health and disease","volume":"134","author":"Barnes","year":"1986","journal-title":"Am. Rev. Respir. Dis."},{"key":"10.1016\/j.pupt.2019.03.004_bib80","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1164\/ajrccm.150.6.7952627","article-title":"Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in Guinea pig and human airways","volume":"150","author":"Takahashi","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib81","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/1056-8719(93)90034-C","article-title":"Studies of human airways in vitro: a review of the methodology","volume":"30","author":"Hulsmann","year":"1993","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"10.1016\/j.pupt.2019.03.004_bib82","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jclinane.2016.09.013","article-title":"Glycopyrrolate: it's time to review","volume":"36","author":"Howard","year":"2017","journal-title":"J. Clin. Anesth."},{"key":"10.1016\/j.pupt.2019.03.004_bib83","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1600-0773.1989.tb01138.x","article-title":"Intramuscular atropine in elderly people: pharmacokinetic studies using the radioreceptor assay and some pharmacodynamic responses","volume":"65","author":"Kentala","year":"1989","journal-title":"Pharmacol. Toxicol."},{"key":"10.1016\/j.pupt.2019.03.004_bib84","author":"FDA"},{"key":"10.1016\/j.pupt.2019.03.004_bib85","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1165\/rcmb.2011-0056OC","article-title":"Pharmacological characterization of adenosine receptors on isolated human bronchi","volume":"45","author":"Calzetta","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.pupt.2019.03.004_bib86","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1183\/09031936.99.14243999","article-title":"Endothelin-1 potentiates cholinergic nerve-mediated contraction in human isolated bronchus","volume":"14","author":"Fernandes","year":"1999","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.pupt.2019.03.004_bib87","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ejphar.2015.04.042","article-title":"Pharmacological assessment of the onset of action of aclidinium and glycopyrronium versus tiotropium in COPD patients and human isolated bronchi","volume":"761","author":"Rogliani","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.pupt.2019.03.004_bib88","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1124\/jpet.109.151639","article-title":"Characterization of aclidinium bromide, a novel inhaled muscarinic antagonist, with long duration of action and a favorable pharmacological profile","volume":"331","author":"Gavalda","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.pupt.2019.03.004_bib89","series-title":"Functional Activity (Potency). The Challenge of CMC Regulatory Compliance for Biopharmaceuticals and Other Biologics","first-page":"239","author":"Geigert","year":"2013"},{"key":"10.1016\/j.pupt.2019.03.004_bib90","doi-asserted-by":"crossref","first-page":"L119","DOI":"10.1152\/ajplung.1992.262.2.L119","article-title":"Assessment of signal transduction mechanisms regulating airway smooth muscle contractility","volume":"262","author":"Schramm","year":"1992","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.pupt.2019.03.004_bib91","series-title":"Coupling Microscale Transport and Tissue Mechanics: Modeling Strategies for Arterial Multiphysics. Modeling of Microscale Transport in Biological Processes","first-page":"77","author":"Marino","year":"2017"},{"key":"10.1016\/j.pupt.2019.03.004_bib92","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.tips.2011.04.003","article-title":"Novel bronchodilators for the treatment of chronic obstructive pulmonary disease","volume":"32","author":"Matera","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.pupt.2019.03.004_bib93","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1378\/chest.12-1766","article-title":"Small airway obstruction in COPD: new insights based on micro-CT imaging and MRI imaging","volume":"143","author":"Hogg","year":"2013","journal-title":"Chest"},{"key":"10.1016\/j.pupt.2019.03.004_bib94","first-page":"7","article-title":"Dysfunctional lung anatomy and small airways degeneration in COPD","volume":"8","author":"Martin","year":"2013","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"10.1016\/j.pupt.2019.03.004_bib95","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.2147\/COPD.S115886","article-title":"In vitro dose comparison of Respimat((R)) inhaler with dry powder inhalers for COPD maintenance therapy","volume":"12","author":"Ciciliani","year":"2017","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"10.1016\/j.pupt.2019.03.004_bib96","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S2213-2600(18)30102-4","article-title":"Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial","volume":"6","author":"Calverley","year":"2018","journal-title":"Lancet.Res.Med"},{"key":"10.1016\/j.pupt.2019.03.004_bib97","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S2213-2600(18)30139-5","article-title":"Is ICS\u2013LAMA an alternative option to treat patients with COPD?","volume":"6","author":"Rogliani","year":"2018","journal-title":"Lancet.Res.Med."},{"key":"10.1016\/j.pupt.2019.03.004_bib98","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12931-018-0770-7","article-title":"Beclomethasone dipropionate and formoterol fumarate synergistically interact in hyperresponsive medium bronchi and small airways","volume":"19","author":"Calzetta","year":"2018","journal-title":"Respir. Res."},{"key":"10.1016\/j.pupt.2019.03.004_bib99","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.pupt.2018.01.010","article-title":"Effect of lipopolysaccharide on the responsiveness of equine bronchial tissue","volume":"49","author":"Calzetta","year":"2018","journal-title":"Pulm. Pharmacol. Therapeut."},{"key":"10.1016\/j.pupt.2019.03.004_bib100","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.pupt.2010.12.008","article-title":"Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi","volume":"24","author":"Matera","year":"2011","journal-title":"Pulm Pharmacol. Ther."},{"key":"10.1016\/j.pupt.2019.03.004_bib101","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ejphar.2015.09.007","article-title":"Propofol protects against opioid-induced hyperresponsiveness of airway smooth muscle in a horse model of target-controlled infusion anaesthesia","volume":"765","author":"Calzetta","year":"2015","journal-title":"Eur. J. Pharmacol."}],"container-title":["Pulmonary Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1094553919300367?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1094553919300367?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T21:28:37Z","timestamp":1761082117000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1094553919300367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":101,"alternative-id":["S1094553919300367"],"URL":"https:\/\/doi.org\/10.1016\/j.pupt.2019.03.004","relation":{},"ISSN":["1094-5539"],"issn-type":[{"value":"1094-5539","type":"print"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pharmacological characterization of the interaction between tiotropium bromide and olodaterol on human bronchi and small airways","name":"articletitle","label":"Article Title"},{"value":"Pulmonary Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pupt.2019.03.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}