{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T15:01:12Z","timestamp":1784386872247,"version":"3.55.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["19K08624, 16K09536, 25461156, 21590964, 16390234, JP22K11391 and JP22H04411"],"award-info":[{"award-number":["19K08624, 16K09536, 25461156, 21590964, 16390234, JP22K11391 and JP22H04411"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["JPMH20FC1027, JPMH23FC1031"],"award-info":[{"award-number":["JPMH20FC1027, JPMH23FC1031"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Chronic respiratory failure (CRF) is a critical complication in patients with chronic obstructive pulmonary disease (COPD) and is characterized by an increase in the arterial-alveolar oxygen gradient (A-aDO<jats:sub>2<\/jats:sub>). The long-term trajectory and prognostic significance remain unclear. This study aimed to assess the prognostic impact of A-aDO<jats:sub>2<\/jats:sub> and elucidate its trajectory over ten years.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We enrolled 170 outpatients with COPD from a prospective cohort study. Arterial blood gas (ABG) analyses were conducted annually for ten years while monitoring the development of CRF.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>157 patients completed the observation period, of whom 21 developed CRF (CRF group) and 136 did not (non-CRF group). In the CRF group, there was a gradual increase in A-aDO<jats:sub>2<\/jats:sub> along with decreases in partial pressure of oxygen (PaO<jats:sub>2<\/jats:sub>) and partial pressure of carbon dioxide (PaCO<jats:sub>2<\/jats:sub>) over ten years, although there were no changes in the non-CRF group. The CRF group had higher baseline A-aDO<jats:sub>2<\/jats:sub> and higher \u0394A-aDO<jats:sub>2<\/jats:sub> in the first year than the non-CRF group (3.76 vs. 0.42 Torr\/year, p = 0.030). Kaplan-Meier analyses, and multivariate Cox proportional hazards analysis revealed that both baseline A-aDO<jats:sub>2<\/jats:sub> and \u0394A-aDO<jats:sub>2<\/jats:sub> were significantly associated with the development of CRF. Retrospective tracking from the initiation of long-term oxygen therapy (LTOT) revealed significant increases in A-aDO<jats:sub>2<\/jats:sub> from 5 years prior to LTOT initiation in the CRF group when compared to the non-CRF group.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>An increasing trend in A-aDO<jats:sub>2<\/jats:sub> may be a significant sign for the future development of CRF. A transition of the annual change of A-aDO<jats:sub>2<\/jats:sub> from a stable state to a deterioration phase can serve as a prognostic factor for developing CRF within 5 years.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0318377","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T18:27:53Z","timestamp":1738175273000},"page":"e0318377","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Trajectory of the arterial-alveolar oxygen gradient in COPD for a decade"],"prefix":"10.1371","volume":"20","author":[{"given":"Kazuma","family":"Nagata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-1090","authenticated-orcid":true,"given":"Susumu","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Uemasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Tanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuyasu","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Muro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7431-9044","authenticated-orcid":true,"given":"Toyohiro","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"issue":"4","key":"pone.0318377.ref001","doi-asserted-by":"crossref","first-page":"2300239","DOI":"10.1183\/13993003.00239-2023","article-title":"Global 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Uemasu","year":"2019","journal-title":"Respirology."},{"issue":"3","key":"pone.0318377.ref005","first-page":"214","article-title":"Role of Alveolar-Arterial Gradient in Partial Pressure of Oxygen and PaO(2)\/Fraction of Inspired Oxygen Ratio Measurements in Assessment of Pulmonary Dysfunction.","volume":"87","author":"DE Harris","year":"2019","journal-title":"AANA J."},{"issue":"9","key":"pone.0318377.ref006","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/j.1440-1681.2008.04971.x","article-title":"Alveolar-arterial oxygen gradient, pneumonia severity index and outcomes in patients hospitalized with community acquired pneumonia.","volume":"35","author":"MQ Moammar","year":"2008","journal-title":"Clin Exp Pharmacol Physiol"},{"issue":"9","key":"pone.0318377.ref007","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1016\/j.ajem.2020.05.048","article-title":"The alveolar-arterial gradient, pneumonia severity scores and inflammatory markers to predict 30-day 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Novel Chest Computed Tomography-derived Index for Prognosis","volume":"13","author":"K Tanimura","year":"2016","journal-title":"Ann Am Thorac Soc."},{"issue":"12","key":"pone.0318377.ref027","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1164\/rccm.201009-1535OC","article-title":"Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease","volume":"183","author":"N Tanabe","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"pone.0318377.ref028","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.21037\/jtd-20-2263","article-title":"Narrative review of current COPD status in Japan.","volume":"13","author":"N Tanabe","year":"2021","journal-title":"J Thorac Dis"},{"issue":"8","key":"pone.0318377.ref029","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/resp.12367","article-title":"Obesity hypoventilation syndrome in Japan and independent determinants of arterial carbon dioxide levels.","volume":"19","author":"Y Harada","year":"2014","journal-title":"Respirology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T18:28:04Z","timestamp":1738175284000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318377"}},"subtitle":[],"editor":[{"given":"Alonso","family":"Soto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0318377","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,29]]}}}