{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:10:42Z","timestamp":1791727842618,"version":"4.3.4"},"reference-count":89,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NHLBI\u2010RO1 HL173987"],"award-info":[{"award-number":["NHLBI\u2010RO1 HL173987"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The biological effects of hypercapnia on the lungs have been controversial. Earlier publications suggesting that hypercapnia was beneficial for mechanically ventilated patients with acute lung injury led to the clinical paradigm of \u201cpermissive hypercapnia\u201d. However, more recent studies have challenged this paradigm by reporting that hypercapnia activates signaling pathways with deleterious effects. This review focuses on the effects of elevated CO\n                    <jats:sub>2<\/jats:sub>\n                    as a signaling molecule, highlighting the pathways and processes contributing to the detrimental effects of hypercapnia on the alveolar epithelium, the airways and immune system.\n                  <\/jats:p>","DOI":"10.1002\/cph4.70104","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T06:46:46Z","timestamp":1769237206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hypercapnia Effects on Lung Function"],"prefix":"10.1002","volume":"16","author":[{"given":"Seungseo","family":"Choi","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Dada","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob I.","family":"Sznajder","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/emj.2004.018309"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-021-00860-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-209753"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68782"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200410-1369OC"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0291"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1999.276.1.L20"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2019-0354OC"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.5.F633"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00025-06"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001238"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.1.79"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000085"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.170316"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500150"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32008-x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040550"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1251120"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094133"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000222418.99976.1d"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000057895.22008.EC"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00813-15"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159331"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12930"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.010908.163250"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200909-096JS"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1139\/y11-052"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.10.006"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.150.6.7952641"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.070326"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.11.001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.689983"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0487OC"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00591"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3311"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501708"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905925106"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.07.012"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2021_521"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.625715"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2015.04.051"},{"key":"e_1_2_9_43_1","first-page":"567","article-title":"Hypercapnia: Permissive and Therapeutic","volume":"72","author":"Kavanagh B.","year":"2006","journal-title":"Minerva Anestesiologica"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70153-5"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.735580"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-021-00184-z"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0114OC"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)02388-0"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-003-2051-1"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.6.2003066"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.12-0576"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.046953"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0373OC"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091416"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201701164R"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201410-1900OC"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.15326\/jcopdf.7.4.2020.0176"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl8716"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20984"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200202000-00034"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam6603"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.01.09"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-016-4611-1"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401957200"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2008.110304"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1595103"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.22.2.153"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.15-0681"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201008-1280CI"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.4046\/trd.2018.0030"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0800353"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat1662"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273781"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.598122"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2004.10.014"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.118232"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00022.2002"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.6.ed1801d"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002332"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2024"},{"key":"e_1_2_9_81_1","first-page":"752","article-title":"AMP\u2010Activated Protein Kinase Regulates CO2\u2010Induced Alveolar Epithelial Dysfunction in Rats and Human Cells by Promoting Na, K\u2010ATPase Endocytosis","volume":"118","author":"Vad\u00e1sz I.","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0395PS"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00456.2011"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.290056"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-136895"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.08.002"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0356OC"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.1220"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1995.268.4.L642"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611329200"}],"container-title":["Comprehensive Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cph4.70104","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cph4.70104","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cph4.70104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:07:26Z","timestamp":1772971646000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cph4.70104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":89,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/cph4.70104"],"URL":"https:\/\/doi.org\/10.1002\/cph4.70104","archive":["Portico"],"relation":{},"ISSN":["2040-4603","2040-4603"],"issn-type":[{"value":"2040-4603","type":"print"},{"value":"2040-4603","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]},"assertion":[{"value":"2025-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70104"}}