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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">SpO<span class="elsevierStyleInf">2</span> value at rest and during the 6MWT in the three chronic pulmonary diseases explored here&#46; For further explanations&#44; see text&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Exercise limitation is common in many respiratory diseases like chronic obstructive pulmonary disease &#40;COPD&#41;&#44; interstitial lung diseases &#40;ILD&#41;&#44; and pulmonary arterial hypertension &#40;PAH&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#8211;3</span></a> The six-minute walking test &#40;6MWT&#41; is widely used to assess exercise response in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> Also&#44; previous studies have shown that 6MWT reflects equally well to the conventional constant-load test on the cycle ergometer the degree of impairment in hemodynamic response to exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> The desaturation distance ratio &#40;DDR&#41; has recently been proposed as a potential integrative marker of exercise response that considers the distance walked during the test &#40;6MWD&#41; and the oxygen desaturation area estimated from the difference between the transcutaneous oxygen saturation value &#40;SpO<span class="elsevierStyleInf">2</span>&#41; measured every minute <span class="elsevierStyleItalic">vs&#46;</span> a theoretical maximum of 100&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a> We hypothesized that the difference between SpO<span class="elsevierStyleInf">2</span> and the SpO<span class="elsevierStyleInf">2</span> value determined at rest would better reflect the response to exercise in different diseases&#46; This study tests this hypothesis by comparing the DDR values obtained using the original and the new method in patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>308&#41; with three prevalent chronic respiratory diseases &#40;COPD&#44; ILD&#44; and PAH&#41;&#46; Besides&#44; we sought to investigate the correlation of DDR with resting lung function measurements in these three diseases&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this retrospective analysis&#44; we included 104 patients with COPD&#44; 104 with ILD&#44; and 100 with PAH&#44; all diagnosed according to international guidelines&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">8&#8211;10</span></a> who performed a 6MWT between October 2014 and May 2015&#46; All patients were clinically stable&#44; and none was participating in any rehabilitation program or clinical trial&#46; We excluded patients on long-term oxygen therapy&#44; mechanical ventilation&#44; and&#47;or tracheostomized&#46; The study was approved by the Ethics Committee of our hospital &#40;HCB&#47;2017&#47;0469&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Demographic and anthropometric parameters were recorded and resting lung function was measured following international standards&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">11&#44;12</span></a> Reference values were those of Roca et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">13&#44;14</span></a> In patients with PAH&#44; pulmonary hemodynamics were determined by right heart catheterization&#44; also following standard procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> All participants performed a 6MWT according to the international guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> Reference values were those of Enright et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> During the test&#44; SpO<span class="elsevierStyleInf">2</span> and heart rate &#40;HR&#41; were monitored continuously by Pulsox&#174;-300 &#40;Minolta Co&#46;&#44; Tokyo&#44; Japan&#41;&#46; Absolute changes in SpO<span class="elsevierStyleInf">2</span> &#40;&#916;SpO<span class="elsevierStyleInf">2</span>&#41; were calculated by subtracting the values at baseline from those determined immediately after 6MWT was finished&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> DDR was calculated as the desaturation area &#40;DA&#41; over the 6MWD&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> DA was calculated using two different methods&#44; the one proposed originally by Ijiri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> &#40;<span class="elsevierStyleItalic">vs&#46;</span> a theoretical maximal SpO<span class="elsevierStyleInf">2</span> value of 100&#37;&#41;&#44; and the one tested in this study &#40;<span class="elsevierStyleItalic">vs&#46;</span> the actual SpO<span class="elsevierStyleInf">2</span> value determined in each patient at rest&#44; before the 6MWT starts&#41;&#46; Results are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation for those distributed normally and as median and &#40;25&#8211;75&#37; percentile&#41; for those non-normally distributed&#46; Categorical variables are presented as proportions&#46; ANOVA was used to compared groups&#46; Correlations were assessed using Spearman&#39;s correlation test&#44; and multivariable linear regression was used to explore the relationship of DDR with resting lung function variables&#44; adjusted by age and BMI&#44; in each of the three diseases studied here&#46; A <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; most COPD patients were male&#44; with a mean age of 66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8 years&#44; and had moderate-severe airflow limitation and moderately decreased carbon monoxide diffusing capacity &#40;DL<span class="elsevierStyleInf">CO</span>&#41;&#46; ILD patients were of similar age &#40;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; but they included a higher proportion of females &#40;45&#37;&#41; and showed a mild restrictive pattern with a moderate DL<span class="elsevierStyleInf">CO</span> reduction&#46; PAH patients were younger and mainly females&#44; with normal spirometry and lung volumes but a moderately reduced DL<span class="elsevierStyleInf">CO</span>&#59; their mean pulmonary arterial pressure was 47 &#40;39&#8211;54&#41; mmHg &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The 6MWD was similar in all patients and generally well preserved&#46; SpO<span class="elsevierStyleInf">2</span> at rest was lower in COPD and decreased during exercise in all diseases &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Using the calculation method initially proposed by Ijiri<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a> neither the DA nor DDR was significantly different across diseases &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; By contrast&#44; considering the resting SpO<span class="elsevierStyleInf">2</span> value in each individual as its own reference to calculate DA &#40;and&#44; therefore&#44; DDR&#41;&#46; Multivariable linear regression analysis showed that DL<span class="elsevierStyleInf">CO</span> &#37;pred&#46; and resting SpO<span class="elsevierStyleInf">2</span> were independent determinants of DDR in all three diseases&#46; Besides&#44; we observed that&#44; in COPD&#44; the severity of airflow limitation &#40;FEV<span class="elsevierStyleInf">1</span>&#37;ref&#41; was also an independent DDR predictor&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The main findings of this study are that&#58; &#40;1&#41; the calculation of DDR considering the resting SpO<span class="elsevierStyleInf">2</span> is more sensitive than the initially proposed method &#40;that considered a theoretical reference value of 100&#37; SpO<span class="elsevierStyleInf">2</span><a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a>&#41;&#59; and &#40;2&#41; DL<span class="elsevierStyleInf">CO</span> and resting SpO<span class="elsevierStyleInf">2</span> were independent determinants of DDR shared by the three diseases studied here&#44; plus the severity of airflow limitation in patients with COPD&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A few previous studies have investigated DDR &#40;using the original method <a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a>&#41; in patients with ILD<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> or COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> Like in these previous studies&#44; we found that the new DDR calculation in patients with ILD and COPD was significantly related to DLco and&#44; to a lesser extent&#44; to FEV<span class="elsevierStyleInf">1</span>&#46; To our knowledge&#44; this is the first study to investigate DDR in patients with PAH&#44; to contrast it with patients with ILD and COPD&#44; and to investigate potential DDR correlations with lung function at rest in these three diseases&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We could not explore the potential prognostic value of DDR in these diseases because this study was retrospective&#46; However&#44; DL<span class="elsevierStyleInf">CO</span> is a well-established prognostic factor in different chronic respiratory diseases&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">10&#44;18</span></a> so its significant and independent relationship with DDR suggests that DDR may also be a good prognostic factor&#46; This will have to be tested prospectively&#44; but it is of note that Hsieh et al&#46; have recently reported that the distance-desaturation product&#44; an index similar to DDR&#44; predicted 6-year mortality in a prospective study of 69 patients with stable non-CF bronchiectasis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Also&#44; In 81 patients with IPF&#44; Lettieri et al&#46; found that each component of the 6MWT independently predicted mortality in IPF with greater accuracy than spirometry&#46; However&#44; a composite of both parameters&#44; the distance-saturation product&#44; provides slightly greater accuracy and represents a novel measure for assessing survival in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> On the other hand&#44; DDR can be useful to assess the effects of a therapeutic intervention&#44; such as the impact of supplementary oxygen during exercise or other&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Our study has strengths and limitations&#46; Among the former&#44; the description of a new method to calculate DDR in a large number of well-characterized patients with COPD&#44; ILD&#44; and PAH&#46; Among the latter&#44; its retrospective design&#46; Additionally&#44; we did not have information about the patient&#39;s exacerbations&#44; which would have allowed a better characterization of the sample&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study describes a new and more sensitive method to calculate DDR in patients with COPD&#44; ILD&#44; and PAH and shows that DL<span class="elsevierStyleInf">CO</span> and resting SpO<span class="elsevierStyleInf">2</span> &#40;plus airflow limitation in patients with COPD&#41; were independent determinants of the new DDR&#46; In terms of clinical implication&#44; being new DDR a more sensitive method&#44; it could offer information about response to drug&#39;s treatment and to rehabilitation programs&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors&#8217; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">X&#46; Alsina-Restoy&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#46; F&#46; Burgos&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#46; R&#46; Torres-Castro&#58; Formal analysis&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; Y&#46; Torralba-Garc&#237;a&#58; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; E&#46; Arismendi&#58; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; J&#46;A&#46; Barber&#224;&#58; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; A&#46; Agust&#237;&#58; Formal analysis&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; I&#46; Blanco&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest directly or indirectly related to the manuscript contents except FB &#40;which declares them in his COI&#41;&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">SpO<span class="elsevierStyleInf">2</span> value at rest and during the 6MWT in the three chronic pulmonary diseases explored here&#46; For further explanations&#44; see text&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; BMI&#44; body mass index&#59; FVC&#44; forced vital capacity&#59; FEV<span class="elsevierStyleInf">1</span>&#44; forced expiratory volume in the first second&#59; TLC&#44; total lung capacity&#59; DL<span class="elsevierStyleInf">CO</span>&#44; diffusion capacity for carbon monoxide&#59; mPAP&#44; mean pulmonary arterial pressure&#59; 6MWD&#44; six-minute walking distance&#59; SpO<span class="elsevierStyleInf">2</span>&#44; peripheral capillary oxygen saturation&#59; DA&#44; desaturation area&#59; DDR&#44; desaturation distance ratio&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">COPD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>104&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ILD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>104&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Age&#44; years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Gender&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37; males&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">85 &#40;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">57 &#40;55&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;26&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smoking exposure&#44; pack-years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46 &#40;35&#8211;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;0&#8211;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0 &#40;0&#8211;14&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FVC&#44; &#37; predicted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV<span class="elsevierStyleInf">1</span>&#44; &#37; predicted&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#44; ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TLC&#44; &#37;predicted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;94&#8211;121&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;55&#8211;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;82&#8211;100&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Original DA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Original DDR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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Scientific Letter
A New and More Sensitive Method to Integrate the Desaturation Distance Ratio During a 6-Minute Walking Test in Chronic Respiratory Diseases: Physiological Correlates
Un método nuevo y más sensible para integrar la relación entre distancia y desaturación durante la prueba de la marcha de seis minutos en las enfermedades respiratorias crónicas: correlaciones fisiológicas
Xavier Alsina-Restoya,b, Felip Burgosa,b,c, Rodrigo Torres-Castroa,d, Yolanda Torralba-Garcíaa,b,c, Ebymar Arismendia,c, Joan Albert Barberàa,b,c, Àlvar Agustía,b,c,1, Isabel Blancoa,b,c,1,
Corresponding author
iblanco2@clinic.cat

Corresponding author.
a Servei de Pneumologia, Institut Clínic Respiratori, Hospital Clinic de Barcelona, Universitat de Barcelona, Spain
b Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
c Biomedical Research Network in Respiratory Diseases (CIBERES), Madrid, Spain
d Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile
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        "titulo" => "Un m&#233;todo nuevo y m&#225;s sensible para integrar la relaci&#243;n entre distancia y desaturaci&#243;n durante la prueba de la marcha de seis minutos en las enfermedades respiratorias cr&#243;nicas&#58; correlaciones fisiol&#243;gicas"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">SpO<span class="elsevierStyleInf">2</span> value at rest and during the 6MWT in the three chronic pulmonary diseases explored here&#46; For further explanations&#44; see text&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Exercise limitation is common in many respiratory diseases like chronic obstructive pulmonary disease &#40;COPD&#41;&#44; interstitial lung diseases &#40;ILD&#41;&#44; and pulmonary arterial hypertension &#40;PAH&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#8211;3</span></a> The six-minute walking test &#40;6MWT&#41; is widely used to assess exercise response in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> Also&#44; previous studies have shown that 6MWT reflects equally well to the conventional constant-load test on the cycle ergometer the degree of impairment in hemodynamic response to exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> The desaturation distance ratio &#40;DDR&#41; has recently been proposed as a potential integrative marker of exercise response that considers the distance walked during the test &#40;6MWD&#41; and the oxygen desaturation area estimated from the difference between the transcutaneous oxygen saturation value &#40;SpO<span class="elsevierStyleInf">2</span>&#41; measured every minute <span class="elsevierStyleItalic">vs&#46;</span> a theoretical maximum of 100&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a> We hypothesized that the difference between SpO<span class="elsevierStyleInf">2</span> and the SpO<span class="elsevierStyleInf">2</span> value determined at rest would better reflect the response to exercise in different diseases&#46; This study tests this hypothesis by comparing the DDR values obtained using the original and the new method in patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>308&#41; with three prevalent chronic respiratory diseases &#40;COPD&#44; ILD&#44; and PAH&#41;&#46; Besides&#44; we sought to investigate the correlation of DDR with resting lung function measurements in these three diseases&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this retrospective analysis&#44; we included 104 patients with COPD&#44; 104 with ILD&#44; and 100 with PAH&#44; all diagnosed according to international guidelines&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">8&#8211;10</span></a> who performed a 6MWT between October 2014 and May 2015&#46; All patients were clinically stable&#44; and none was participating in any rehabilitation program or clinical trial&#46; We excluded patients on long-term oxygen therapy&#44; mechanical ventilation&#44; and&#47;or tracheostomized&#46; The study was approved by the Ethics Committee of our hospital &#40;HCB&#47;2017&#47;0469&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Demographic and anthropometric parameters were recorded and resting lung function was measured following international standards&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">11&#44;12</span></a> Reference values were those of Roca et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">13&#44;14</span></a> In patients with PAH&#44; pulmonary hemodynamics were determined by right heart catheterization&#44; also following standard procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> All participants performed a 6MWT according to the international guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> Reference values were those of Enright et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> During the test&#44; SpO<span class="elsevierStyleInf">2</span> and heart rate &#40;HR&#41; were monitored continuously by Pulsox&#174;-300 &#40;Minolta Co&#46;&#44; Tokyo&#44; Japan&#41;&#46; Absolute changes in SpO<span class="elsevierStyleInf">2</span> &#40;&#916;SpO<span class="elsevierStyleInf">2</span>&#41; were calculated by subtracting the values at baseline from those determined immediately after 6MWT was finished&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> DDR was calculated as the desaturation area &#40;DA&#41; over the 6MWD&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> DA was calculated using two different methods&#44; the one proposed originally by Ijiri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> &#40;<span class="elsevierStyleItalic">vs&#46;</span> a theoretical maximal SpO<span class="elsevierStyleInf">2</span> value of 100&#37;&#41;&#44; and the one tested in this study &#40;<span class="elsevierStyleItalic">vs&#46;</span> the actual SpO<span class="elsevierStyleInf">2</span> value determined in each patient at rest&#44; before the 6MWT starts&#41;&#46; Results are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation for those distributed normally and as median and &#40;25&#8211;75&#37; percentile&#41; for those non-normally distributed&#46; Categorical variables are presented as proportions&#46; ANOVA was used to compared groups&#46; Correlations were assessed using Spearman&#39;s correlation test&#44; and multivariable linear regression was used to explore the relationship of DDR with resting lung function variables&#44; adjusted by age and BMI&#44; in each of the three diseases studied here&#46; A <span class="elsevierStyleItalic">p</span> value<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; most COPD patients were male&#44; with a mean age of 66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8 years&#44; and had moderate-severe airflow limitation and moderately decreased carbon monoxide diffusing capacity &#40;DL<span class="elsevierStyleInf">CO</span>&#41;&#46; ILD patients were of similar age &#40;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#41;&#44; but they included a higher proportion of females &#40;45&#37;&#41; and showed a mild restrictive pattern with a moderate DL<span class="elsevierStyleInf">CO</span> reduction&#46; PAH patients were younger and mainly females&#44; with normal spirometry and lung volumes but a moderately reduced DL<span class="elsevierStyleInf">CO</span>&#59; their mean pulmonary arterial pressure was 47 &#40;39&#8211;54&#41; mmHg &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The 6MWD was similar in all patients and generally well preserved&#46; SpO<span class="elsevierStyleInf">2</span> at rest was lower in COPD and decreased during exercise in all diseases &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Using the calculation method initially proposed by Ijiri<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a> neither the DA nor DDR was significantly different across diseases &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; By contrast&#44; considering the resting SpO<span class="elsevierStyleInf">2</span> value in each individual as its own reference to calculate DA &#40;and&#44; therefore&#44; DDR&#41;&#46; Multivariable linear regression analysis showed that DL<span class="elsevierStyleInf">CO</span> &#37;pred&#46; and resting SpO<span class="elsevierStyleInf">2</span> were independent determinants of DDR in all three diseases&#46; Besides&#44; we observed that&#44; in COPD&#44; the severity of airflow limitation &#40;FEV<span class="elsevierStyleInf">1</span>&#37;ref&#41; was also an independent DDR predictor&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The main findings of this study are that&#58; &#40;1&#41; the calculation of DDR considering the resting SpO<span class="elsevierStyleInf">2</span> is more sensitive than the initially proposed method &#40;that considered a theoretical reference value of 100&#37; SpO<span class="elsevierStyleInf">2</span><a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a>&#41;&#59; and &#40;2&#41; DL<span class="elsevierStyleInf">CO</span> and resting SpO<span class="elsevierStyleInf">2</span> were independent determinants of DDR shared by the three diseases studied here&#44; plus the severity of airflow limitation in patients with COPD&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A few previous studies have investigated DDR &#40;using the original method <a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;7</span></a>&#41; in patients with ILD<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> or COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> Like in these previous studies&#44; we found that the new DDR calculation in patients with ILD and COPD was significantly related to DLco and&#44; to a lesser extent&#44; to FEV<span class="elsevierStyleInf">1</span>&#46; To our knowledge&#44; this is the first study to investigate DDR in patients with PAH&#44; to contrast it with patients with ILD and COPD&#44; and to investigate potential DDR correlations with lung function at rest in these three diseases&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We could not explore the potential prognostic value of DDR in these diseases because this study was retrospective&#46; However&#44; DL<span class="elsevierStyleInf">CO</span> is a well-established prognostic factor in different chronic respiratory diseases&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">10&#44;18</span></a> so its significant and independent relationship with DDR suggests that DDR may also be a good prognostic factor&#46; This will have to be tested prospectively&#44; but it is of note that Hsieh et al&#46; have recently reported that the distance-desaturation product&#44; an index similar to DDR&#44; predicted 6-year mortality in a prospective study of 69 patients with stable non-CF bronchiectasis&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Also&#44; In 81 patients with IPF&#44; Lettieri et al&#46; found that each component of the 6MWT independently predicted mortality in IPF with greater accuracy than spirometry&#46; However&#44; a composite of both parameters&#44; the distance-saturation product&#44; provides slightly greater accuracy and represents a novel measure for assessing survival in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> On the other hand&#44; DDR can be useful to assess the effects of a therapeutic intervention&#44; such as the impact of supplementary oxygen during exercise or other&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Our study has strengths and limitations&#46; Among the former&#44; the description of a new method to calculate DDR in a large number of well-characterized patients with COPD&#44; ILD&#44; and PAH&#46; Among the latter&#44; its retrospective design&#46; Additionally&#44; we did not have information about the patient&#39;s exacerbations&#44; which would have allowed a better characterization of the sample&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study describes a new and more sensitive method to calculate DDR in patients with COPD&#44; ILD&#44; and PAH and shows that DL<span class="elsevierStyleInf">CO</span> and resting SpO<span class="elsevierStyleInf">2</span> &#40;plus airflow limitation in patients with COPD&#41; were independent determinants of the new DDR&#46; In terms of clinical implication&#44; being new DDR a more sensitive method&#44; it could offer information about response to drug&#39;s treatment and to rehabilitation programs&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors&#8217; contributions</span><p id="par0050" class="elsevierStylePara elsevierViewall">X&#46; Alsina-Restoy&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#46; F&#46; Burgos&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#46; R&#46; Torres-Castro&#58; Formal analysis&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; Y&#46; Torralba-Garc&#237;a&#58; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; E&#46; Arismendi&#58; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; J&#46;A&#46; Barber&#224;&#58; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; A&#46; Agust&#237;&#58; Formal analysis&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#59; I&#46; Blanco&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#44; Writing &#8211; review &#38; editing&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest directly or indirectly related to the manuscript contents except FB &#40;which declares them in his COI&#41;&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">SpO<span class="elsevierStyleInf">2</span> value at rest and during the 6MWT in the three chronic pulmonary diseases explored here&#46; For further explanations&#44; see text&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; BMI&#44; body mass index&#59; FVC&#44; forced vital capacity&#59; FEV<span class="elsevierStyleInf">1</span>&#44; forced expiratory volume in the first second&#59; TLC&#44; total lung capacity&#59; DL<span class="elsevierStyleInf">CO</span>&#44; diffusion capacity for carbon monoxide&#59; mPAP&#44; mean pulmonary arterial pressure&#59; 6MWD&#44; six-minute walking distance&#59; SpO<span class="elsevierStyleInf">2</span>&#44; peripheral capillary oxygen saturation&#59; DA&#44; desaturation area&#59; DDR&#44; desaturation distance ratio&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">COPD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>104&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ILD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>104&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Age&#44; years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Gender&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37; males&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">85 &#40;82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">57 &#40;55&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;26&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Smoking exposure&#44; pack-years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46 &#40;35&#8211;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;0&#8211;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0 &#40;0&#8211;14&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FVC&#44; &#37; predicted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV<span class="elsevierStyleInf">1</span>&#44; &#37; predicted&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#44; ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">TLC&#44; &#37;predicted&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">106 &#40;94&#8211;121&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Original DA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Original DDR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;133 &#40;0&#46;10&#8211;0&#46;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">New DA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">New DDR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;075 &#40;0&#46;044&#8211;0&#46;133&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                            0 => "M&#46;W&#46; Dodson"
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                        "tituloSerie" => "Heart Fail Clin"
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                        "volumen" => "14"
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                        "paginaFinal" => "269"
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Article information
ISSN: 03002896
Original language: English
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