{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:57:43Z","timestamp":1792508263608,"version":"4.5.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"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":[[2022,11]]},"DOI":"10.1016\/j.chest.2022.03.033","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T20:21:45Z","timestamp":1649103705000},"page":"1030-1047","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"title":["V\u0307\/Q\u0307 Mismatch"],"prefix":"10.1016","volume":"162","author":[{"given":"J. Alberto","family":"Neder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Kirby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giles","family":"Santyr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Pourafkari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reginald","family":"Smyth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin B.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Crinion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-4894","authenticated-orcid":false,"given":"Juan Pablo","family":"de-Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis E.","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.chest.2022.03.033_bib1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/j.2040-4603.2011.tb00323.x","article-title":"Spatial distribution of ventilation and perfusion: mechanisms and regulation","volume":"1","author":"Glenny","year":"2011","journal-title":"Compr Physiol"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0034-5687(78)90104-4","article-title":"The normal human lung: ultrastructure and morphometric estimation of diffusion capacity","volume":"32","author":"Gehr","year":"1978","journal-title":"Respir Physiol"},{"key":"10.1016\/j.chest.2022.03.033_bib3","series-title":"Comprehensive Physiology","first-page":"113","article-title":"Ventilation: total, alveolar, and dead space","author":"Anthonisen","year":"2011"},{"issue":"4","key":"10.1016\/j.chest.2022.03.033_bib4","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1183\/09031936.00037014","article-title":"Gas exchange and ventilation-perfusion relationships in the lung","volume":"44","author":"Petersson","year":"2014","journal-title":"Eur Respir J"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib5","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1152\/jappl.1985.58.3.978","article-title":"Ventilation-perfusion inequality in normal humans during exercise at sea level and simulated altitude","volume":"58","author":"Gale","year":"1985","journal-title":"J\u00a0Appl Physiol"},{"issue":"12","key":"10.1016\/j.chest.2022.03.033_bib6","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1513\/AnnalsATS.202004-398FR","article-title":"Residual exertional dyspnea in cardiopulmonary disease","volume":"17","author":"Neder","year":"2020","journal-title":"Ann Am Thorac Soc"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib7","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1080\/15412555.2021.1913110","article-title":"Recent advances in the physiological assessment of dyspneic patients with mild COPD","volume":"18","author":"Neder","year":"2021","journal-title":"COPD"},{"issue":"9435","key":"10.1016\/j.chest.2022.03.033_bib8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(04)16900-6","article-title":"Pathophysiology of airflow limitation in chronic obstructive pulmonary disease","volume":"364","author":"Hogg","year":"2004","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib9","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1152\/physrev.00025.2015","article-title":"The contribution of small airway obstruction to the pathogenesis of chronic obstructive pulmonary disease","volume":"97","author":"Hogg","year":"2017","journal-title":"Physiol Rev"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1172\/JCI108630","article-title":"Ventilation-perfusion inequality in chronic obstructive pulmonary disease","volume":"59","author":"Wagner","year":"1977","journal-title":"J\u00a0Clin Invest"},{"issue":"7 suppl","key":"10.1016\/j.chest.2022.03.033_bib11","doi-asserted-by":"crossref","first-page":"S647","DOI":"10.1097\/00005768-200107001-00002","article-title":"Ventilatory limitations in chronic obstructive pulmonary disease","volume":"33","author":"O\u2019Donnell","year":"2001","journal-title":"Med Sci Sports Exerc"},{"issue":"1","key":"10.1016\/j.chest.2022.03.033_bib12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12325-019-01128-9","article-title":"Dyspnea in COPD: new mechanistic insights and management implications","volume":"37","author":"O\u2019Donnell","year":"2020","journal-title":"Adv Ther"},{"issue":"4","key":"10.1016\/j.chest.2022.03.033_bib13","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1378\/chest.08-0820","article-title":"Pulmonary vascular involvement in COPD","volume":"134","author":"Peinado","year":"2008","journal-title":"Chest"},{"issue":"8","key":"10.1016\/j.chest.2022.03.033_bib14","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1164\/rccm.201801-0095PP","article-title":"Pulmonary vascular involvement in COPD\u2014is there a pulmonary vascular phenotype?","volume":"198","author":"Kovacs","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"10.1016\/j.chest.2022.03.033_bib15","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1152\/japplphysiol.00008.2009","article-title":"Pulmonary characteristics in COPD and mechanisms of increased work of breathing","volume":"107","author":"Loring","year":"2009","journal-title":"J\u00a0Appl Physiol"},{"issue":"5","key":"10.1016\/j.chest.2022.03.033_bib16","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S2213-2600(18)30054-7","article-title":"Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial","volume":"6","author":"Hohlfeld","year":"2018","journal-title":"Lancet Respir Med"},{"issue":"6","key":"10.1016\/j.chest.2022.03.033_bib17","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1152\/japplphysiol.00774.2020","article-title":"The effect of long-acting dual bronchodilator therapy on exercise tolerance, dynamic hyperinflation, and dead space during constant work rate exercise in COPD","volume":"130","author":"Stringer","year":"2021","journal-title":"J\u00a0Appl Physiol"},{"key":"10.1016\/j.chest.2022.03.033_bib18","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.resp.2018.03.012","article-title":"Acute bronchodilator therapy does not reduce wasted ventilation during exercise in COPD","volume":"252-253","author":"Elbehairy","year":"2018","journal-title":"Respir Physiol Neurobiol"},{"issue":"8","key":"10.1016\/j.chest.2022.03.033_bib19","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1053\/rmed.2001.1124","article-title":"Effects on diffusing capacity and ventilation\u2014perfusion relationships of budesonide inhalations for 2\u00a0months in chronic obstructive pulmonary disease (COPD)","volume":"95","author":"Sandek","year":"2001","journal-title":"Respir Med"},{"issue":"11","key":"10.1016\/j.chest.2022.03.033_bib20","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1164\/rccm.201001-0038PP","article-title":"Airway endothelial dysfunction in asthma and chronic obstructive pulmonary disease: a challenge for future research","volume":"182","author":"Wanner","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"issue":"5 suppl","key":"10.1016\/j.chest.2022.03.033_bib21","doi-asserted-by":"crossref","first-page":"192S","DOI":"10.1378\/chest.121.5_suppl.192S","article-title":"Phosphodiesterase 4 inhibitors for the treatment of COPD","volume":"121","author":"Sturton","year":"2002","journal-title":"Chest"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib22","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S0022-3565(24)35320-0","article-title":"Subthreshold doses of specific phosphodiesterase type 3 and 4 inhibitors enhance the pulmonary vasodilatory response to nebulized prostacyclin with improvement in gas exchange","volume":"292","author":"Schermuly","year":"2000","journal-title":"J\u00a0Pharmacol Exp Ther"},{"issue":"5","key":"10.1016\/j.chest.2022.03.033_bib23","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1183\/09031936.00096511","article-title":"Physiological effects of roflumilast at rest and during exercise in COPD","volume":"39","author":"O\u2019Donnell","year":"2012","journal-title":"Eur Respir J"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib24","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1183\/09031936.00011714","article-title":"The effect of roflumilast in addition to LABA\/LAMA\/ICS treatment in COPD patients","volume":"44","author":"Backer","year":"2014","journal-title":"Eur Respir J"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib25","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1148\/radiol.10100322","article-title":"Validation of computational fluid dynamics in CT-based airway models with SPECT\/CT","volume":"257","author":"De Backer","year":"2010","journal-title":"Radiology"},{"key":"10.1016\/j.chest.2022.03.033_bib26","first-page":"263","article-title":"Functional respiratory imaging to assess the interaction between systemic roflumilast and inhaled ICS\/LABA\/LAMA","volume":"11","author":"Vos","year":"2016","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3109\/15412555.2011.651180","article-title":"Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial","volume":"9","author":"Lederer","year":"2012","journal-title":"COPD"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1164\/rccm.200907-0988OC","article-title":"Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension","volume":"181","author":"Blanco","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"issue":"7","key":"10.1016\/j.chest.2022.03.033_bib29","doi-asserted-by":"crossref","first-page":"597","DOI":"10.21037\/atm-20-4895","article-title":"Inhaled pulmonary vasodilators: a narrative review","volume":"9","author":"Liu","year":"2021","journal-title":"Ann Transl Med"},{"issue":"2 pt 1","key":"10.1016\/j.chest.2022.03.033_bib30","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1164\/ajrccm.156.2.9607114","article-title":"Effects of inhaled nitric oxide on gas exchange in lungs with shunt or poorly ventilated areas","volume":"156","author":"Hopkins","year":"1997","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"10.1016\/j.chest.2022.03.033_bib31","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1378\/chest.11-2798","article-title":"Ventilatory and cardiocirculatory exercise profiles in COPD: the role of pulmonary hypertension","volume":"142","author":"Boerrigter","year":"2012","journal-title":"Chest"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib32","doi-asserted-by":"crossref","first-page":"391","DOI":"10.7326\/0003-4819-93-3-391","article-title":"Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group","volume":"93","year":"1980","journal-title":"Ann Intern Med"},{"issue":"8222","key":"10.1016\/j.chest.2022.03.033_bib33","first-page":"681","article-title":"Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party","volume":"1","year":"1981","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib34","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1124\/mol.53.2.330","article-title":"Effects of almitrine bismesylate on the ionic currents of chemoreceptor cells from the carotid body","volume":"53","author":"L\u00f3pez-L\u00f3pez","year":"1998","journal-title":"Mol Pharmacol"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib35","first-page":"288","article-title":"Enhancement of hypoxic pulmonary vasoconstriction by almitrine in the dog","volume":"128","author":"Romaldini","year":"1983","journal-title":"Am Rev Respir Dis"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib36","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1378\/chest.83.3.528","article-title":"Improvement in ventilation-perfusion matching by almitrine in COPD","volume":"83","author":"M\u00e9lot","year":"1983","journal-title":"Chest"},{"issue":"5","key":"10.1016\/j.chest.2022.03.033_bib37","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1164\/arrd.1986.134.5.910","article-title":"Improvement in ventilation-perfusion relationships by almitrine in patients with chronic obstructive pulmonary disease during mechanical ventilation","volume":"134","author":"Castaing","year":"1986","journal-title":"Am Rev Respir Dis"},{"issue":"6585","key":"10.1016\/j.chest.2022.03.033_bib38","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0140-6736(49)91459-2","article-title":"Neurological effects of oxygen in chronic cor pulmonale","volume":"2","author":"Davies","year":"1949","journal-title":"Lancet"},{"issue":"5","key":"10.1016\/j.chest.2022.03.033_bib39","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1164\/ajrccm.161.5.9904119","article-title":"The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease","volume":"161","author":"Robinson","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"issue":"1-2","key":"10.1016\/j.chest.2022.03.033_bib40","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/jocn.15957","article-title":"Effect of high-flow nasal cannula oxygen therapy in patients with chronic obstructive pulmonary disease: a meta-analysis","volume":"31","author":"Duan","year":"2022","journal-title":"J\u00a0Clin Nurs"},{"issue":"4","key":"10.1016\/j.chest.2022.03.033_bib41","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01574-2021","article-title":"ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure","volume":"59","author":"Oczkowski","year":"2021","journal-title":"Eur Respir J"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib42","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1152\/japplphysiol.00173.2012","article-title":"Imaging regional PA02 and gas exchange","volume":"113","author":"Petersson","year":"2012","journal-title":"J\u00a0Appl Physiol"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib43","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1148\/radiol.2021203711","article-title":"Pulmonary functional imaging: part 1. State-of-the-art technical and physiologic underpinnings","volume":"299","author":"Ohno","year":"2021","journal-title":"Radiology"},{"issue":"3","key":"10.1016\/j.chest.2022.03.033_bib44","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1148\/radiol.2021204033","article-title":"Pulmonary functional imaging: part 2. State-of-the-art clinical applications and opportunities for improved patient care","volume":"299","author":"Gefter","year":"2021","journal-title":"Radiology"},{"issue":"5","key":"10.1016\/j.chest.2022.03.033_bib45","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1183\/09031936.00085612","article-title":"Haemodynamic responses to exercise in patients with COPD","volume":"41","author":"Hilde","year":"2013","journal-title":"Eur Respir J"},{"issue":"11","key":"10.1016\/j.chest.2022.03.033_bib46","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1053\/rmed.2002.1371","article-title":"Relationship between lung function, ventilation-perfusion inequality and extent of emphysema as assessed by high-resolution computed tomography","volume":"96","author":"Sandek","year":"2002","journal-title":"Respir Med"},{"issue":"12","key":"10.1016\/j.chest.2022.03.033_bib47","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1513\/AnnalsATS.201606-448FR","article-title":"The clinical significance of collateral ventilation","volume":"13","author":"Terry","year":"2016","journal-title":"Ann Am Thorac Soc"},{"issue":"9","key":"10.1016\/j.chest.2022.03.033_bib48","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.4187\/respcare.07237","article-title":"The relevance of targeting treatment to small airways in asthma and COPD","volume":"65","author":"Santus","year":"2020","journal-title":"Respir Care"},{"issue":"13","key":"10.1016\/j.chest.2022.03.033_bib49","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.4155\/fmc.11.133","article-title":"Novel cosuspension metered-dose inhalers for the combination therapy of chronic obstructive pulmonary disease and asthma","volume":"3","author":"Lechuga-Ballesteros","year":"2011","journal-title":"Future Med Chem"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib50","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3390\/antiox10020155","article-title":"Oxygen-sensitivity and pulmonary selectivity of vasodilators as potential drugs for pulmonary hypertension","volume":"10","author":"Morales-Cano","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"2","key":"10.1016\/j.chest.2022.03.033_bib51","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1183\/09031936.00048514","article-title":"Pathophysiology of human ventilatory control","volume":"44","author":"Dempsey","year":"2014","journal-title":"Eur Respir J"}],"container-title":["CHEST"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012369222005773?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012369222005773?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T23:03:33Z","timestamp":1762124613000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0012369222005773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":51,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["S0012369222005773"],"URL":"https:\/\/doi.org\/10.1016\/j.chest.2022.03.033","relation":{},"ISSN":["0012-3692"],"issn-type":[{"value":"0012-3692","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"V\u0307\/Q\u0307 Mismatch","name":"articletitle","label":"Article Title"},{"value":"CHEST","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.chest.2022.03.033","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}