{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:22:38Z","timestamp":1780330958582,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AR 071046; RO1 GM119174; RO1 DK113196; P50 AA024333; RO1 AA021890; 3U01AA026976 - 03S1; UO1 AA 026976; R56HL141744;UO1 DK061732; 5U01DK062470-17S2 (SD); K12 HL141952 (AA)"],"award-info":[{"award-number":["R21 AR 071046; RO1 GM119174; RO1 DK113196; P50 AA024333; RO1 AA021890; 3U01AA026976 - 03S1; UO1 AA 026976; R56HL141744;UO1 DK061732; 5U01DK062470-17S2 (SD); K12 HL141952 (AA)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Differences in oxygen delivery methods to treat hypoxemia have the potential to worsen CO2 retention in chronic obstructive lung disease (COPD). Oxygen administration using high flow nasal cannula (HFNC) has multiple physiological benefits in treating respiratory failure including reductions in PaCO2 in a flow-dependent manner. We hypothesized that patients with COPD would develop worsening hypercapnia if oxygen fraction was increased without increasing flow rate. We evaluated the acute response to HFNC in subjects with severe COPD when flow remained constant and inspired oxygen was increased. In total, 11 subjects with severe COPD (FEV1 &lt; 50%) on supplemental oxygen with baseline normocapnia (PaCO2 &lt; 45 mm Hg; n = 5) and hypercapnia (PaCO2 \u2265 45 mm Hg; n = 6) were studied. Arterial blood gas responses were studied at three timepoints: Baseline, HFNC at a flow rate of 30 L\/min at resting oxygen supplementation for 1 h, and FiO2 30% above baseline with the same flow rate for the next hour. The primary endpoint was the change in PaCO2 from baseline. No significant changes in PaCO2 were noted in response to HFNC applied at baseline FiO2 in the normocapnic and hypercapnic group. At HFNC with FiO2 30% above baseline, the normocapnic group did not show a change in PaCO2 (baseline: 38.9 \u00b1 1.8 mm Hg; HFNC at higher FiO2: 38.8 \u00b1 3.1 mm Hg; p = 0.93), but the hypercapnic group demonstrated significant increase in PaCO2 (baseline: 58.2 \u00b1 9.3 mm Hg; HFNC at higher FiO2: 63.3 \u00b1 10.9 mm Hg; p = 0.025). We observed worsening hypercapnia in severe COPD patients and baseline hypercapnia who received increased oxygen fraction when flow remained constant. These data show the need for careful titration of oxygen therapy in COPD patients, particularly those with baseline hypercapnia when flow rate is unchanged.<\/jats:p>","DOI":"10.3390\/jcm10091814","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T12:47:07Z","timestamp":1619009227000},"page":"1814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Acute Responses to Oxygen Delivery via High Flow Nasal Cannula in Patients with Severe Chronic Obstructive Pulmonary Disease\u2014HFNC and Severe COPD"],"prefix":"10.3390","volume":"10","author":[{"given":"Amy H.","family":"Attaway","sequence":"first","affiliation":[{"name":"Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue, NE4 208, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihane","family":"Faress","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Jacono","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1774-0104","authenticated-orcid":false,"given":"Srinivasan","family":"Dasarathy","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, NE4 208, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1056\/NEJMoa1503326","article-title":"High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure","volume":"372","author":"Frat","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1001\/jama.2016.14194","article-title":"Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: A randomized clinical trial","volume":"316","author":"Hernandez","year":"2016","journal-title":"J. Am. Med Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.aucc.2007.08.001","article-title":"High flow nasal oxygen generates positive airway pressure in adult volunteers","volume":"20","author":"Groves","year":"2007","journal-title":"Aust. Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1159\/000342027","article-title":"Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients","volume":"850","author":"Braunlich","year":"2013","journal-title":"Respiration"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1136\/thoraxjnl-2015-207962","article-title":"Nasal high flow oxygen therapy in patients with COPD reduces respiratory rate and tissue carbon dioxide while increasing tidal and end-expiratory lung volumes: A randomised crossover trial","volume":"71","author":"Fraser","year":"2016","journal-title":"Thorax"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1164\/rccm.201605-0916OC","article-title":"Physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure","volume":"195","author":"Mauri","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","first-page":"A3007","article-title":"Physiological Effect of High-Flow Nasal Cannula on Respiratory Pattern and Work of Breathing in Severe COPD Patients","volume":"195","author":"Dziura","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1152\/japplphysiol.00279.2016","article-title":"Nasal high-flow therapy reduces work of breathing compared with oxygen during sleep in COPD and smoking controls: A prospective observational study","volume":"122","author":"Biselli","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1378\/chest.14-2871","article-title":"Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Implications","volume":"148","author":"Spoletini","year":"2015","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1001\/jama.2016.2711","article-title":"Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial","volume":"315","author":"Hernandez","year":"2016","journal-title":"J. Am. Med. Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1007\/s00134-020-06177-1","article-title":"Contributors, Prediction of outcome of nasal high flow use during COVID-19-related acute hypoxemic respiratory failure","volume":"46","author":"Zucman","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1079","DOI":"10.1097\/CCM.0000000000004558","article-title":"High-Flow Nasal Oxygen in Coronavirus Disease 2019 Patients With Acute Hypoxemic Respiratory Failure: A Multicenter, Retrospective Cohort Study","volume":"48","author":"Xia","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Panadero, C., Abad-Fern\u00e1ndez, A., Rio-Ramirez, M.T., Acosta Gutierrez, C.M., Calderon-Alcala, M., Lopez-Riolobos, C., Matesanz-Lopez, C., Garcia-Prieto, F., Diaz-Garcia, J.M., and Raboso-Moreno, B. (2020). High-flow nasal cannula for Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Multidiscip. Respir. Med., 15.","DOI":"10.4081\/mrm.2020.693"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1136\/thoraxjnl-2020-214993","article-title":"High-flow nasal cannula oxygen therapy to treat patients with hypoxemic acute respiratory failure consequent to SARS-CoV-2 infection","volume":"75","author":"Vianello","year":"2020","journal-title":"Thorax"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2001154","DOI":"10.1183\/13993003.01154-2020","article-title":"High-flow nasal oxygen: A safe, efficient treatment for COVID-19 patients not in an ICU","volume":"5","author":"Guy","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Duan, J., Chen, B., Liu, X., Shu, W., Zhao, W., Li, J., Li, Y., Hong, Y., Pan, L., and Wang, K. (2020). Use of high-flow nasal cannula and noninvasive ventilation in patients with COVID-19: A multicenter observational study. Am. J. Emerg. Med.","DOI":"10.1016\/j.ajem.2020.07.071"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13613-020-00653-z","article-title":"The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China","volume":"10","author":"Wang","year":"2020","journal-title":"Ann. Intensive Care"},{"key":"ref_18","first-page":"623","article-title":"The Impact of High-Flow Nasal Cannula Use on Patient Mortality and the Availability of Mechanical Ventilators in COVID-19","volume":"4","author":"Gershengorn","year":"2020","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tran, K., Cimon, K., Severn, M., Pessoa-Silva, C.L., and Conly, J. (2012). Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: A systematic review. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035797"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Braunlich, J., Mauersberger, F., and Wirtz, H. (2018). Effectiveness of nasal highflow in hypercapnic COPD patients is flow and leakage dependent. BMC Pulm. Med., 18.","DOI":"10.1186\/s12890-018-0576-x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/15412555.2019.1672637","article-title":"Nasal High Flow for Stable Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis","volume":"16","author":"Bonnevie","year":"2019","journal-title":"J. Chronic Obstr. Pulm. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1513\/AnnalsATS.201706-425OC","article-title":"Domiciliary High-Flow Nasal Cannula Oxygen Therapy for Patients with Stable Hypercapnic Chronic Obstructive Pulmonary Disease. A Multicenter Randomized Crossover Trial","volume":"15","author":"Nagata","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.2147\/COPD.S159666","article-title":"Long-term effects of oxygen-enriched high-flow nasal cannula treatment in COPD patients with chronic hypoxemic respiratory failure","volume":"13","author":"Storgaard","year":"2018","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40248-015-0019-y","article-title":"Nasal High-flow versus non-invasive ventilation in stable hypercapnic COPD: A preliminary report","volume":"10","author":"Braunlich","year":"2015","journal-title":"Multidiscip. Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1136\/thoraxjnl-2016-209673","article-title":"Change in pulmonary mechanics and the effect on breathing pattern of high flow oxygen therapy in stable hypercapnic COPD","volume":"72","author":"Pisani","year":"2017","journal-title":"Thorax"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-94-007-4546-9_4","article-title":"Effects of nasal insufflation on arterial gas exchange and breathing pattern in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure","volume":"755","author":"Nilius","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1097\/CCM.0000000000002693","article-title":"Effects of High-Flow Nasal Cannula on the Work of Breathing in Patients Recovering From Acute Respiratory Failure","volume":"45","author":"Delorme","year":"2017","journal-title":"Crit. Care Med."},{"key":"ref_28","first-page":"S12","article-title":"High Flow Nasal Cannula, Is There a Role in COPD?","volume":"16","author":"Hill","year":"2017","journal-title":"Tanaffos"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00348-011-1044-z","article-title":"Unsteady flow in the nasal cavity with high flow therapy measured by stereoscopic PIV","volume":"52","author":"Spence","year":"2011","journal-title":"Exp. Fluids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1152\/japplphysiol.00934.2014","article-title":"Nasal high flow clears anatomical dead space in upper airway models","volume":"118","author":"Moller","year":"2015","journal-title":"J. Appl Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1164\/arrd.1980.122.5.747","article-title":"Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure","volume":"122","author":"Aubier","year":"1980","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/00003246-199601000-00007","article-title":"Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease","volume":"24","author":"Hanson","year":"1996","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1183\/09031936.04.00113204","article-title":"Flow limitation and dynamic hyperinflation: Key concepts in modern respiratory physiology","volume":"25","author":"Calverley","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.5664\/jcsm.7258","article-title":"The Epworth Sleepiness Scale: Validation of One-Dimensional Factor Structure in a Large Clinical Sample","volume":"14","author":"Lapin","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Caraballo, C., Desai, N.R., Mulder, H., Alhanti, B., Wilson, F.P., Fiuzat, M., Felker, G.M., Pina, I.L., O\u2019Connor, C.M., and Lindenfeld, J. (2019). Clinical Implications of the New York Heart Association Classification. J. Am. Heart Assoc., 8.","DOI":"10.1161\/JAHA.119.014240"},{"key":"ref_36","first-page":"79","article-title":"Body mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: Findings from the Copenhagen City Heart Study","volume":"173","author":"Vestbo","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"98","DOI":"10.4187\/respcare.03917","article-title":"Comparison of Transcutaneous and Capillary Measurement of PCO2 in Hypercapnic Subjects","volume":"61","author":"Stieglitz","year":"2016","journal-title":"Respir. Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1111\/resp.13050","article-title":"Physiological effects of titrated oxygen via nasal high-flow cannulae in COPD exacerbations: A randomized controlled cross-over trial","volume":"22","author":"Pilcher","year":"2017","journal-title":"Respirology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"882","DOI":"10.21037\/jtd.2018.01.125","article-title":"Effectiveness of high-flow nasal cannula oxygen therapy for acute respiratory failure with hypercapnia","volume":"10","author":"Kim","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"British Thoracic Society Standards of Care Committee (2002). Non-invasive ventilation in acute respiratory failure. Thorax, 57, 192\u2013211.","DOI":"10.1136\/thorax.57.3.192"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"907","DOI":"10.4187\/respcare.05936","article-title":"Accuracy of Transcutaneous CO2 Values Compared With Arterial and Capillary Blood Gases","volume":"63","author":"Lambert","year":"2018","journal-title":"Respir. Care"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/9\/1814\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:50:53Z","timestamp":1760161853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/9\/1814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,21]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["jcm10091814"],"URL":"https:\/\/doi.org\/10.3390\/jcm10091814","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,21]]}}}