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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristics &#40;ROC&#41; curve to identify&#58; a&#41; functional impairment&#44; based on the cut-offs of the 6MWT&#60;70&#37; predicted and 1-minSTS&#60;70&#37; predicted&#59; and&#44; b&#41; chance of survival &#40;cut-offs of 6MWT&#60;250 m&#44; &#60;330 m and &#60;350 m&#41; in the Chester step test in people with interstitial lung disease&#46; Legend&#58; 1-minSTSpp&#44; 1-minute sit-to-stand test&#44; percentage predicted&#59; 6MWT&#44; 6-minute walk test&#59; 6MWTpp&#44; 6-minute walk test percentage predicted&#59; AUC&#44; area under the curve&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="para0002" class="elsevierStylePara elsevierViewall">Interstitial lung diseases &#40;ILD&#41; encompass a heterogeneous group of lung diseases with more than 300 subtypes&#44; with the most common being sarcoidosis&#44; idiopathic pulmonary fibrosis &#40;IPF&#41;&#44; hypersensitivity pneumonitis&#44; connective tissue disease-associated ILD&#44; pneumoconiosis and drug-induced ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> Although these subtypes present different aetiology and prognosis&#44;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> all share common clinical features such as disabling symptoms and impaired functional capacity&#44; which accelerate disease progression and mortality risk&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> Assessing functional capacity&#44; a highly meaningful health-domain for the daily life of people with ILD&#44; is therefore crucial&#46; The 6-minute walk test &#40;6MWT&#41; has been the most widely used test to assess it and to predict survival in ILD&#44;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> however its applicability across settings &#40;e&#46;g&#46;&#44; patients&#8217; homes&#41; is limited&#46; Alternative tests such as the 1-minute sit-to-stand test &#40;1-minSTS&#41;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> and the Chester step test &#40;CST&#41;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> have emerged&#46; Both are simple and low-cost field tests which require minimal physical space to assess functional capacity&#44; however&#44; the CST also enables exercise prescription&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> The CST has shown to be valid and reliable in people with ILD&#44;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> however its suitability for use as a first-line screening tool is still unknown&#46; Thus&#44; we explored the discriminative ability of the CST in distinguishing people with ILD with&#47;without functional capacity impairment and low&#47;higher chance of survival&#46;</p><p id="para0003" class="elsevierStylePara elsevierViewall">A cross-sectional study was conducted with ethical approval from three ethic committees &#91;Administra&#231;&#227;o Regional de Sa&#250;de do Centro &#40;Ref&#46; 16&#47;2020&#41;&#44; Centro Hospitalar do Baixo Vouga &#40;N&#47;ref&#46;15-04-2019&#59; 15-05-2019&#41; and UICISA&#58;E &#40;P&#47;N&#176;P619-10&#47;2019&#59; P620-10&#47;2019&#41;&#93;&#46; Data protection followed the European regulation &#40;EU 2016&#47;679&#41;&#46; Adult individuals diagnosed with ILD and clinically stable for 1 month prior the study were included&#46; Individuals with other lung diseases and&#47;or a clinical condition that may limit their participation in data collection were excluded&#46; Informed consent was obtained from each participant prior to data collection&#46;</p><p id="para0004" class="elsevierStylePara elsevierViewall">Sociodemographic&#44; anthropometric and clinical data &#40;lung function&#44; ILD subtype&#44; comorbidities and medication&#41; were collected with a questionnaire and medical records&#46; Participants were classified according ILD-GAP model&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> Additionally&#44; dyspnoea was assessed with modified British Medical Research Council&#8211;dyspnoea scale&#44; physical activity with Brief-Physical Activity Assessment Tool and functional capacity with the CST&#44; the 6MWT and the 1-minSTS test&#46; The CST is a 5-stage incremental step test lasting for a maximum of 10 min&#44; where participants step according to a timed metronome&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> More steps indicate better functional capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> Further details on monitoring and criteria to interrupt the CST can be found in supplementary material 1&#46; The 6MWT and the 1-minSTS were performed as recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a></p><p id="para0005" class="elsevierStylePara elsevierViewall">A receiver operating characteristics &#40;ROC&#41; curve analysis was performed&#46; We determined the thresholds for the CST to identify&#58; i&#41; functional impairment&#44; based on cut-offs of the 70&#37; predicted of the 6MWT and the 1-minSTS&#59;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> and&#44; ii&#41; higher chance of survival&#44; based on published mortality-associated ILD cut-offs of the 6MWT &#40;250 m&#44; 330 m and 350 m&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> The optimal cut-off points were identified by the highest Youden index &#91;the point where the sensitivity &#40;SN&#41; and specificity &#40;SP&#41; were simultaneously maximized&#93;&#46; The area under the curve &#40;AUC&#41; and the SN&#44; SP and accuracy were also calculated&#46; The AUC was interpreted as&#58; &#60;0&#46;5-no discrimination&#44; 0&#46;5&#8211;0&#46;69-poor discrimination&#44; 0&#46;7&#8211;0&#46;79-acceptable discrimination&#44; 0&#46;8&#8211;0&#46;89-excellent discrimination&#44; &#8805;0&#46;9-outstanding discrimination&#46; People with ILD below or above the cut-off point of the CST or with&#47;without comorbidities or amongst ILD subtypes were compared using independent <span class="elsevierStyleItalic">t</span>-test&#47;Mann-Whitney U&#47;chi-square tests&#46; The impact of SpO<span class="elsevierStyleInf">2</span> levels during the performance of the CST on the prognosis was computed using a linear mixed model&#46; The level of significance was set at 0&#46;05&#46;</p><p id="para0006" class="elsevierStylePara elsevierViewall">Ninety-four people with ILD &#40;64&#177;13 years&#44; DL<span class="elsevierStyleInf">CO</span>&#61;51&#177;21&#37; predicted&#41; were included &#40;Supplementary material 2 and <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46; During the CST performance&#44; a significant decrease in SpO<span class="elsevierStyleInf">2</span> &#40;&#8722;3&#46;5 &#177; 3&#46;8&#37;&#44; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41; was observed similarly between ILD severity &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41; &#40;Supplementary material 3&#41;&#46; Number of steps in the CST was not influenced by comorbidities or ILD subtype &#40;<span class="elsevierStyleItalic">p</span>&#62;0&#46;05&#41; &#40;Supplementary material 4 and 5&#41;&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0007" class="elsevierStylePara elsevierViewall">Cut-offs of 41 and 40 steps in the CST were determined to differentiate participants with and without functional impairment using 6MWT&#60;70&#37; predicted and 1-minSTS&#60;70&#37; predicted&#44; respectively&#46; The 6MWT&#60;70&#37; predicted cut-off demonstrated better discriminative ability &#40;AUC&#61;0&#46;92 &#91;0&#46;86&#8211;0&#46;99&#93;&#59; SN&#61;87&#37;&#44; SP&#61;88&#37;&#41; compared to the 1-minSTS&#60;70&#37; predicted cut-off &#40;AUC&#61;0&#46;72 &#91;0&#46;62&#8211;0&#46;82&#93;&#59; SN&#61;87&#37;&#44; SP&#61;58&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a> and Supplementary material 6&#41;&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0008" class="elsevierStylePara elsevierViewall">Except for the 6MWT&#60;250 m cut-off&#44; the other two cut-offs of the 6MWT identified a cut-off of 41 steps in the CST&#44; to potentially reflect higher chance of survival in people with ILD&#46; The cut-offs of the 6MWT&#60;330 m and &#60;350 m showed best discriminative ability&#44; with an outstanding discrimination &#40;AUC&#61;0&#46;96&#59; 0&#46;91&#8211;1 and AUC&#61;0&#46;95&#59; 0&#46;90&#8211;1&#41; and higher balanced SN and SP &#40;89&#37;&#47;94&#37; and 92&#37;&#47;90&#37;&#44; respectively&#41; compared with the cut-off of 6MWT&#60;250 m &#40;AUC&#61;0&#46;89&#59; 0&#46;81&#8211;0&#46;97&#59; SN&#61;83&#37;&#44; SP&#61;90&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a> and Supplementary material 6&#41;&#46;</p><p id="para0009" class="elsevierStylePara elsevierViewall">People below the cut-off of 41 steps in the CST were older&#44; predominantly diagnosed with IPF&#44; &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41;&#44; at severe disease stages &#40;according ILD-GAP model&#41; and had worse lung function &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#41;&#44; dyspnoea &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41; and functional capacity in all measures &#40;CST&#44; 1-minSTS and 6MWT&#59; <span class="elsevierStyleItalic">p</span>&#60;0&#46;001&#41; than those above the cut-off &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">A cut-off of 41 steps in the CST can effectively identify functional capacity impairment and chance of survival in ILD&#46; This is the first study analysing the CST ability to detect health-related impairments&#46; These findings have significant clinical implications&#44; offering a meaningful and person-centred test&#44;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> representative of daily activities &#40;stair climbing&#41; and which can be conducted in any setting&#44; even in limited-spaces&#46; Using our 41 steps cut-off&#44; health professionals may now personalise interventions to enhance functional capacity in ILD&#46;</p><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Funding</span><p id="para0011" class="elsevierStylePara elsevierViewall">This project was funded by Programa Operacional de Competitividade e Internacionaliza&#231;&#227;o &#8211; POCI&#44; through <span class="elsevierStyleGrantSponsor" id="gs0001">Fundo Europeu de Desenvolvimento Regional - FEDER</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0001">POCI-01-0145-FEDER- 007628</span>&#41;&#44; by <span class="elsevierStyleGrantSponsor" id="gs0002">Funda&#231;&#227;o para a Ci&#234;ncia e a Tecnologia</span> &#40;PhD grant <span class="elsevierStyleGrantNumber" refid="gs0002">SFRH&#47;BD&#47;148741&#47;2019</span> and <span class="elsevierStyleGrantNumber" refid="gs0002">COVID&#47;BD&#47;153477&#47;2023</span>&#41; and under the project UIDB&#47;04501&#47;2020&#46;</p></span></span>"
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristics &#40;ROC&#41; curve to identify&#58; a&#41; functional impairment&#44; based on the cut-offs of the 6MWT&#60;70&#37; predicted and 1-minSTS&#60;70&#37; predicted&#59; and&#44; b&#41; chance of survival &#40;cut-offs of 6MWT&#60;250 m&#44; &#60;330 m and &#60;350 m&#41; in the Chester step test in people with interstitial lung disease&#46; Legend&#58; 1-minSTSpp&#44; 1-minute sit-to-stand test&#44; percentage predicted&#59; 6MWT&#44; 6-minute walk test&#59; 6MWTpp&#44; 6-minute walk test percentage predicted&#59; AUC&#44; area under the curve&#46;</p>"
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          "leyenda" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Values are presented as frequencies &#40;percentages&#41;&#44; mean&#177;standard deviation or median &#91;IQR&#93;&#46;</p><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Legend&#58; 1-minSTS&#44; 1-minute Sit-To-Stand test&#59; 6MWT&#44; 6-minute walk test&#59; BMI&#44; body mass index&#59; BPAAT&#44; Brief Physical Activity Assessment Tool&#59; CHP&#44; Chronic Hypersensitivity Pneumonitis&#59; CST&#44; Chester step test&#59; CTD-ILD&#44; Connective Tissue Disease-associated ILD&#59; DL<span class="elsevierStyleInf">CO</span>&#44; Diffusing Capacity for Carbon Monoxide&#59; FEV<span class="elsevierStyleInf">1</span>&#44; Forced Expiratory Volume in 1 second&#59; FVC&#44; Forced Vital Capacity&#59; GORD&#44; gastro-oesophageal reflux disease&#59; ILD&#44; Interstitial Lung Disease&#59; ILD-GAP model&#44; Interstitial Lung Disease-Gender&#44; Age and Physiology model&#59; IPF&#44; Idiopathic Pulmonary Fibrosis&#59; LTOT&#44; long-term oxygen therapy&#59; mMRC&#44; modified Medical British Research Council&#59; OSA&#44; obstructive sleep apnoea&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Total sample &#40;<span class="elsevierStyleItalic">n</span> &#61; 94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">CST&#60;41 steps &#40;<span class="elsevierStyleItalic">n</span> &#61; 40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">CST&#8805;41 steps &#40;<span class="elsevierStyleItalic">n</span> &#61; 54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0006"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0007"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">64&#177;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">73&#177;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">60&#177;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">&#60;0&#46;001&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Sex &#40;female&#41;&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">51 &#40;54&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22 &#40;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">29 &#40;53&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&#46;2 &#91;25&#46;5&#8211;31&#46;4&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&#46;1 &#91;25&#46;9&#8211;31&#46;5&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&#46;6 &#91;25&#8211;31&#46;4&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;884&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Lung function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span>&#44; L &#40;<span class="elsevierStyleItalic">n</span> &#61; 82&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#91;1&#46;4&#8211;2&#46;5&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;7 &#91;1&#46;3&#8211;2&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;2 &#91;1&#46;7&#8211;2&#46;7&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;002&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span>&#44;&#37; predicted &#40;<span class="elsevierStyleItalic">n</span> &#61; 93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">82&#46;3 &#177; 20&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">79&#177;18&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">78&#46;5 &#177; 22&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;202&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>FVC&#44; L &#40;<span class="elsevierStyleItalic">n</span> &#61; 85&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;4 &#177; 0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#177; 0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;7 &#177; 0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">&#60;0&#46;001&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>FVC&#44;&#37; predicted &#40;<span class="elsevierStyleItalic">n</span> &#61; 94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">79&#46;4 &#177; 18&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">79&#177;16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">83&#46;3 &#177; 19&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;017&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV1&#47;FVC&#44;&#37; &#40;<span class="elsevierStyleItalic">n</span> &#61; 94&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">78&#46;1 &#177; 4&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">81&#46;6 &#177; 16&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">80&#46;4 &#177; 11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;685&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>DL<span class="elsevierStyleInf">CO</span>&#44;&#37; predicted &#40;<span class="elsevierStyleItalic">n</span> &#61; 92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50&#46;5 &#177; 21&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">38&#46;5 &#177; 19&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">59&#46;8 &#177; 18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">&#60;0&#46;001&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Exacerbations&#47;year&#44; median &#91;IQR&#93; &#40;<span class="elsevierStyleItalic">n</span> &#61; 93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#91;0&#8211;0&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#91;0&#8211;0&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#91;0&#8211;1&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;487&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ILD subtypes&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>CHP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">40 &#40;42&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19 &#40;47&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;38&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;527&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>IPF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;22&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;32&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;14&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;049&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>CTD-ILD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;18&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;572&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>DR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;506&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;24&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;051&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0091"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ILD-GAP model&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41; &#40;<span class="elsevierStyleItalic">n</span> &#61; 93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>0&#8211;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">53 &#40;56&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39 &#40;73&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">&#60;0&#46;001&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>2&#8211;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">25 &#40;26&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;20&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;158&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>4&#8211;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;12&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9 &#40;22&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;026&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0111"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>&#62;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;076&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Smoking status&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;157&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Never&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">57 &#40;60&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0123"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27 &#40;67&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30 &#40;55&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0126"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Former&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33 &#40;35&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;32&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20 &#40;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0131"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Current&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0136"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Pack&#47;years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20 &#91;3&#46;5&#8211;50&#46;5&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0138"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19 &#91;0&#8211;58&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20 &#91;4&#46;9&#8211;48&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;722&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0141"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Comorbidities&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0144"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0146"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50 &#40;53&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0148"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26 &#40;65&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">24 &#40;24&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;061&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0151"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0153"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;454&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0156"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>GORD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0158"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0159"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0160"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0161"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Pulmonary hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0162"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0163"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0164"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0165"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;178&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0166"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">34 &#40;36&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0168"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0169"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0170"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;523&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0171"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>OSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0172"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0174"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0175"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0176"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Depression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0177"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;14&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0178"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0179"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;14&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0180"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0181"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Pharmacological treatment for ILD&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41; &#40;<span class="elsevierStyleItalic">n</span> &#61; 93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0182"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0183"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0184"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0185"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0186"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Antifibrotic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0187"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0188"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0189"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0190"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;031&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0191"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0192"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">35 &#40;37&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0193"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0194"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;32&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0195"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;280&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0196"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Immunosuppressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0197"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26 &#40;29&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0198"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0199"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;26&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0200"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;494&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0201"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>LTOT&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0202"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">44 &#40;46&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0203"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">29 &#40;72&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0204"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;27&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0205"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">&#60;0&#46;001&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0206"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">mMRC&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0207"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0208"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0209"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0210"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0211"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Grade 0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0212"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;13&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0213"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0214"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;20&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0215"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;038&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0216"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Grade 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0217"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22 &#40;23&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0218"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0219"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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Vol. 30. Issue 3.
Pages 313-316 (May - June 2024)
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Vol. 30. Issue 3.
Pages 313-316 (May - June 2024)
Letter to the Editor
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Chester step test to identify functional impairment in interstitial lung disease
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C. Paixãoa,b, A. Alvesc, A.S. Gravea,b, P.G. Ferreirad,e, D. Brooksf,g, A. Marquesa,b,
Corresponding author
amarques@ua.pt

Corresponding author at: Lab3R – Respiratory Research and Rehabilitation Laboratory, School of Health Sciences, University of Aveiro (ESSUA), Aveiro, Portugal and iBiMED – Institute of Biomedicine, University of Aveiro, Aveiro, Portugal, Agras do Crasto - Campus Universitário de Santiago, Edifício 30, 3810-193, Aveiro, Portugal.
a Respiratory Research and Rehabilitation Laboratory (Lab3R), School of Health Sciences (ESSUA), University of Aveiro, Aveiro, Portugal
b iBiMED – Institute of Biomedicine, Department of Medical Sciences, University Aveiro, Aveiro, Portugal
c REMEO Home Department, Linde Healthcare, Porto, Portugal
d ILD Outpatient Clinic, Pulmonology Department – Centro Hospitalar Universitário de Coimbra (CHUC), Coimbra, Portugal
e Faculty of Medicine of University of Coimbra (FMUC), Coimbra, Portugal
f School of Rehabilitation Science, McMaster University, Hamilton, Canada
g West Park Healthcare Centre, Toronto, Canada
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Table 1. Sample characterisation (n = 94) and comparison of people below (n = 40) and above (n = 54) the cut-off point (41 steps).
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Dear Editor,

Interstitial lung diseases (ILD) encompass a heterogeneous group of lung diseases with more than 300 subtypes, with the most common being sarcoidosis, idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, connective tissue disease-associated ILD, pneumoconiosis and drug-induced ILD.1 Although these subtypes present different aetiology and prognosis,1 all share common clinical features such as disabling symptoms and impaired functional capacity, which accelerate disease progression and mortality risk.2 Assessing functional capacity, a highly meaningful health-domain for the daily life of people with ILD, is therefore crucial. The 6-minute walk test (6MWT) has been the most widely used test to assess it and to predict survival in ILD,3 however its applicability across settings (e.g., patients’ homes) is limited. Alternative tests such as the 1-minute sit-to-stand test (1-minSTS)4 and the Chester step test (CST)5 have emerged. Both are simple and low-cost field tests which require minimal physical space to assess functional capacity, however, the CST also enables exercise prescription.5,6 The CST has shown to be valid and reliable in people with ILD,7 however its suitability for use as a first-line screening tool is still unknown. Thus, we explored the discriminative ability of the CST in distinguishing people with ILD with/without functional capacity impairment and low/higher chance of survival.

A cross-sectional study was conducted with ethical approval from three ethic committees [Administração Regional de Saúde do Centro (Ref. 16/2020), Centro Hospitalar do Baixo Vouga (N/ref.15-04-2019; 15-05-2019) and UICISA:E (P/N°P619-10/2019; P620-10/2019)]. Data protection followed the European regulation (EU 2016/679). Adult individuals diagnosed with ILD and clinically stable for 1 month prior the study were included. Individuals with other lung diseases and/or a clinical condition that may limit their participation in data collection were excluded. Informed consent was obtained from each participant prior to data collection.

Sociodemographic, anthropometric and clinical data (lung function, ILD subtype, comorbidities and medication) were collected with a questionnaire and medical records. Participants were classified according ILD-GAP model.8 Additionally, dyspnoea was assessed with modified British Medical Research Council–dyspnoea scale, physical activity with Brief-Physical Activity Assessment Tool and functional capacity with the CST, the 6MWT and the 1-minSTS test. The CST is a 5-stage incremental step test lasting for a maximum of 10 min, where participants step according to a timed metronome.5,7 More steps indicate better functional capacity.5,7 Further details on monitoring and criteria to interrupt the CST can be found in supplementary material 1. The 6MWT and the 1-minSTS were performed as recommended.4,9

A receiver operating characteristics (ROC) curve analysis was performed. We determined the thresholds for the CST to identify: i) functional impairment, based on cut-offs of the 70% predicted of the 6MWT and the 1-minSTS;10 and, ii) higher chance of survival, based on published mortality-associated ILD cut-offs of the 6MWT (250 m, 330 m and 350 m).3,11 The optimal cut-off points were identified by the highest Youden index [the point where the sensitivity (SN) and specificity (SP) were simultaneously maximized]. The area under the curve (AUC) and the SN, SP and accuracy were also calculated. The AUC was interpreted as: <0.5-no discrimination, 0.5–0.69-poor discrimination, 0.7–0.79-acceptable discrimination, 0.8–0.89-excellent discrimination, ≥0.9-outstanding discrimination. People with ILD below or above the cut-off point of the CST or with/without comorbidities or amongst ILD subtypes were compared using independent t-test/Mann-Whitney U/chi-square tests. The impact of SpO2 levels during the performance of the CST on the prognosis was computed using a linear mixed model. The level of significance was set at 0.05.

Ninety-four people with ILD (64±13 years, DLCO=51±21% predicted) were included (Supplementary material 2 and Table 1). During the CST performance, a significant decrease in SpO2 (−3.5 ± 3.8%, p<0.001) was observed similarly between ILD severity (p>0.05) (Supplementary material 3). Number of steps in the CST was not influenced by comorbidities or ILD subtype (p>0.05) (Supplementary material 4 and 5).

Table 1.

Sample characterisation (n = 94) and comparison of people below (n = 40) and above (n = 54) the cut-off point (41 steps).

Characteristics  Total sample (n = 94)  CST<41 steps (n = 40)  CST≥41 steps (n = 54)  p 
Age, years  64±13  73±10  60±13  <0.001* 
Sex (female), n (%)  51 (54.3)  22 (55)  29 (53.7)  1.000 
BMI, kg/m2  28.2 [25.5–31.4]  28.1 [25.9–31.5]  28.6 [25–31.4]  0.884 
Lung function         
FEV1, L (n = 82)  2 [1.4–2.5]  1.7 [1.3–2]  2.2 [1.7–2.7]  0.002* 
FEV1,% predicted (n = 93)  82.3 ± 20.9  79±18.1  78.5 ± 22.5  0.202 
FVC, L (n = 85)  2.4 ± 0.8  2 ± 0.7  2.7 ± 0.8  <0.001* 
FVC,% predicted (n = 94)  79.4 ± 18.9  79±16.7  83.3 ± 19.6  0.017* 
FEV1/FVC,% (n = 94)  78.1 ± 4.1  81.6 ± 16.3  80.4 ± 11.5  0.685 
DLCO,% predicted (n = 92)  50.5 ± 21.4  38.5 ± 19.7  59.8 ± 18  <0.001* 
Exacerbations/year, median [IQR] (n = 93)  0 [0–0]  0 [0–0]  0 [0–1]  0.487 
ILD subtypes, n (%)         
CHP  40 (42.6)  19 (47.5)  21 (38.9)  0.527 
IPF  21 (22.3)  13 (32.5)  8 (14.8)  0.049* 
CTD-ILD  15 (16)  5 (12.5)  10 (18.5)  0.572 
DR  2 (2.1)  0 (0)  2 (3.7)  0.506 
Other  16 (17)  3 (7.5)  13 (24.1)  0.051 
ILD-GAP model, n (%) (n = 93)         
0–1  53 (56.4)  14 (35)  39 (73.6)  <0.001* 
2–3  25 (26.6)  14 (35)  11 (20.8)  0.158 
4–5  12 (12.8)  9 (22.5)  3 (5.7)  0.026* 
>5  3 (3.2)  3 (7.5)  0 (0)  0.076 
Smoking status, n (%)        0.157 
Never  57 (60.6)  27 (67.5)  30 (55.6)   
Former  33 (35.1)  13 (32.5)  20 (37)   
Current  4 (4.3)  0 (0)  4 (7.4)   
Pack/years  20 [3.5–50.5]  19 [0–58]  20 [4.9–48]  0.722 
Comorbidities, n (%)         
Yes  50 (53.2)  26 (65)  24 (24.4)  0.061 
Chronic infections  7 (7.4)  4 (10)  3 (5.6)  0.454 
GORD  0 (0)  0 (0)  0 (0)  – 
Pulmonary hypertension  2 (2.1)  2 (5)  0 (0)  0.178 
Heart disease  34 (36.2)  16 (40)  18 (33.3)  0.523 
OSA  4 (4.3)  2 (5)  2 (3.7)  1.000 
Depression  14 (14.9)  8 (15)  8 (14.8)  1.000 
Pharmacological treatment for ILD, n (%) (n = 93)         
Antifibrotic  4 (4.3)  4 (10)  0 (0)  0.031* 
Oral corticosteroids  35 (37.2)  18 (45)  17 (32.1)  0.280 
Immunosuppressants  26 (29.8)  14 (35)  14 (26.4)  0.494 
LTOT, n (%)  44 (46.8)  29 (72.5)  15 (27.8)  <0.001* 
mMRC, n (%)         
Grade 0  13 (13.8)  2 (5)  11 (20.4)  0.038* 
Grade 1  22 (23.4)  6 (15)  16 (29.6)  0.139 
Grade 2  37 (39.4)  15 (37.5)  22 (40.7)  0.832 
Grade 3  17 (18.1)  12 (30)  5 (9.3)  0.014* 
Grade 4  5 (5.3)  5 (12.5)  0 (0)  0.012* 
BPAAT, total score (n = 56)  0 [0–2]  0 [0–2]  1 [0–4]  0.216 
CST, no steps  52 [28–54]  23.5 [15.5–35]  86.5 [70–125]  <0.001* 
1-minSTS, repetitions  22.4 ± 8.1  17.1 ± 6.2  26.4 ± 7.1  <0.001* 
6MWT, meters (n = 70)  416.8 ± 134.9  270.1 ± 96  479.7 ± 94.1  <0.001* 

Values are presented as frequencies (percentages), mean±standard deviation or median [IQR].

Legend: 1-minSTS, 1-minute Sit-To-Stand test; 6MWT, 6-minute walk test; BMI, body mass index; BPAAT, Brief Physical Activity Assessment Tool; CHP, Chronic Hypersensitivity Pneumonitis; CST, Chester step test; CTD-ILD, Connective Tissue Disease-associated ILD; DLCO, Diffusing Capacity for Carbon Monoxide; FEV1, Forced Expiratory Volume in 1 second; FVC, Forced Vital Capacity; GORD, gastro-oesophageal reflux disease; ILD, Interstitial Lung Disease; ILD-GAP model, Interstitial Lung Disease-Gender, Age and Physiology model; IPF, Idiopathic Pulmonary Fibrosis; LTOT, long-term oxygen therapy; mMRC, modified Medical British Research Council; OSA, obstructive sleep apnoea.

Cut-offs of 41 and 40 steps in the CST were determined to differentiate participants with and without functional impairment using 6MWT<70% predicted and 1-minSTS<70% predicted, respectively. The 6MWT<70% predicted cut-off demonstrated better discriminative ability (AUC=0.92 [0.86–0.99]; SN=87%, SP=88%) compared to the 1-minSTS<70% predicted cut-off (AUC=0.72 [0.62–0.82]; SN=87%, SP=58%) (Fig. 1 and Supplementary material 6).

Fig. 1.

Receiver operating characteristics (ROC) curve to identify: a) functional impairment, based on the cut-offs of the 6MWT<70% predicted and 1-minSTS<70% predicted; and, b) chance of survival (cut-offs of 6MWT<250 m, <330 m and <350 m) in the Chester step test in people with interstitial lung disease. Legend: 1-minSTSpp, 1-minute sit-to-stand test, percentage predicted; 6MWT, 6-minute walk test; 6MWTpp, 6-minute walk test percentage predicted; AUC, area under the curve.

(0.16MB).

Except for the 6MWT<250 m cut-off, the other two cut-offs of the 6MWT identified a cut-off of 41 steps in the CST, to potentially reflect higher chance of survival in people with ILD. The cut-offs of the 6MWT<330 m and <350 m showed best discriminative ability, with an outstanding discrimination (AUC=0.96; 0.91–1 and AUC=0.95; 0.90–1) and higher balanced SN and SP (89%/94% and 92%/90%, respectively) compared with the cut-off of 6MWT<250 m (AUC=0.89; 0.81–0.97; SN=83%, SP=90%) (Fig. 1 and Supplementary material 6).

People below the cut-off of 41 steps in the CST were older, predominantly diagnosed with IPF, (p<0.001), at severe disease stages (according ILD-GAP model) and had worse lung function (p<0.05), dyspnoea (p<0.001) and functional capacity in all measures (CST, 1-minSTS and 6MWT; p<0.001) than those above the cut-off (Table 1).

A cut-off of 41 steps in the CST can effectively identify functional capacity impairment and chance of survival in ILD. This is the first study analysing the CST ability to detect health-related impairments. These findings have significant clinical implications, offering a meaningful and person-centred test,12 representative of daily activities (stair climbing) and which can be conducted in any setting, even in limited-spaces. Using our 41 steps cut-off, health professionals may now personalise interventions to enhance functional capacity in ILD.

Funding

This project was funded by Programa Operacional de Competitividade e Internacionalização – POCI, through Fundo Europeu de Desenvolvimento Regional - FEDER (POCI-01-0145-FEDER- 007628), by Fundação para a Ciência e a Tecnologia (PhD grant SFRH/BD/148741/2019 and COVID/BD/153477/2023) and under the project UIDB/04501/2020.

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