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The current study examined if low resting DL<jats:sub>CO<\/jats:sub> and higher exercise ventilatory requirements were associated with earlier critical dynamic mechanical constraints, dyspnoea and exercise limitation in patients with mild COPD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective analysis, we compared <jats:italic>V\u02d9<\/jats:italic><jats:sub>E<\/jats:sub>\/<jats:italic>V\u02d9<\/jats:italic>CO<jats:sub>2<\/jats:sub>, dynamic inspiratory reserve volume (IRV), dyspnoea and exercise capacity in groups of patients with Global Initiative for Chronic Obstructive Lung Disease stage 1 COPD with (1) a resting DL<jats:sub>CO<\/jats:sub> at or greater than the lower limit of normal (\u2265LLN; Global Lung Function Initiative reference equations [<jats:italic>n<\/jats:italic>\u00a0=\u00a044]) or (2) below the &lt;LLN (<jats:italic>n<\/jats:italic>\u00a0=\u00a033), and age\u2010 and sex\u2010matched healthy controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a081).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Spirometry and resting lung volumes were similar in the two COPD groups. During exercise, <jats:italic>V\u02d9<\/jats:italic><jats:sub>E<\/jats:sub>\/<jats:italic>V\u02d9<\/jats:italic>CO<jats:sub>2<\/jats:sub> (nadir and slope) was consistently higher in the DL<jats:sub>CO<\/jats:sub>\u2009&lt;\u2009LLN compared with the other groups (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The DL<jats:sub>CO<\/jats:sub>\u2009&lt;\u2009LLN group had lower IRV and greater dyspnoea intensity at standardized submaximal work rates and lower peak work rate and oxygen uptake than the other two groups (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reduced exercise capacity in patients with DL<jats:sub>CO<\/jats:sub>\u2009&lt;\u2009LLN was related to higher ventilatory requirements, a faster rate of decline in dynamic IRV and greater dyspnoea during exercise. These simple measurements should be considered for the clinical evaluation of unexplained exercise intolerance in individuals with ostensibly mild COPD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.14045","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T03:00:53Z","timestamp":1617850853000},"page":"786-795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Reduced exercise tolerance in mild chronic obstructive pulmonary disease: The contribution of combined abnormalities of diffusing capacity for carbon monoxide and ventilatory efficiency"],"prefix":"10.1111","volume":"26","author":[{"given":"Devin B.","family":"Phillips","sequence":"first","affiliation":[{"name":"Respiratory Investigation Unit, Department of Medicine Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"James","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Department of Medicine Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-519X","authenticated-orcid":false,"given":"Amany F.","family":"Elbehairy","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Department of Medicine Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus  Kingston Ontario Canada"},{"name":"Department of Chest Diseases, Faculty of Medicine Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Milne","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Department of Medicine Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus  Kingston Ontario Canada"},{"name":"Department of Medicine Clinician Investigator Program University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra G.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Department of Medicine Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-4720","authenticated-orcid":false,"given":"Nicolle J.","family":"Domnik","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Department of Medicine Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"de\u2010Torres","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Department of Medicine Queen's University and Kingston Health Sciences Centre, Kingston General Hospital Campus  Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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