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Quantitative assessment of interstitial lung disease in Sjögren’s syndrome

Identifieur interne : 000B86 ( Ncbi/Merge ); précédent : 000B85; suivant : 000B87

Quantitative assessment of interstitial lung disease in Sjögren’s syndrome

Auteurs : Pablo Guisado-Vasco [Espagne] ; Mario Silva [Italie] ; Miguel Angel Duarte-Millán [Espagne] ; Gianluca Sambataro [Italie] ; Chiara Bertolazzi [Mexique] ; Mauro Pavone [Italie] ; Isabel Martín-Garrido [Espagne] ; Oriol Martín-Segarra [Espagne] ; José Manuel Luque-Pinilla [Espagne] ; Daniele Santilli [Italie] ; Domenico Sambataro [Italie] ; Sebastiano E. Torrisi [Italie] ; Ada Vancheri [Italie] ; Marwin Gutiérrez [Mexique] ; Mayra Mejia [Mexique] ; Stefano Palmucci [Italie] ; Flavio Mozzani [Italie] ; Jorge Rojas-Serrano [Mexique] ; Carlo Vanchieri [Italie] ; Nicola Sverzellati [Italie] ; Alarico Ariani [Italie]

Source :

RBID : PMC:6839858

Abstract

Background

Interstitial lung disease (ILD) is a frequent manifestation of Sjögren’s syndrome (SS), an autoimmune disease of salivary and lacrimal glands, and affects approximately 20% of patients. No clinical or serological features appear to be useful to predict its presence, severity or progression, and chest high-resolution computed tomography (CT) remains the gold standard for diagnosis. Semiquantitative CT (SQCT) based on visual assessment (Goh and Taouli scoring) can estimate ILD extent, although it is burdened by relevant intra- and interobserver variability. Quantitative chest CT (QCT) is a promising alternative modality to assess ILD severity.

Aim

To determine whether QCT assessment can identify extensive or limited lung disease in patients with SS and ILD.

Methods

This multi-center, cross-sectional and retrospective study enrolled patients with SS and a chest CT scan. SQCT assessment was carried out in a blinded and centralized manner to calculate both Goh and Taouli scores. An operator-independent analysis of all CT scans with the open-source software platform Horos was used to evaluate the QCT indices. Patients were classified according to the extent of ILD and differences in QCT index distribution were investigated with non-parametric tests.

Results

From a total of 102 consecutive patients with SS, the prevalence of ILD was 35.3% (36/102). There was a statistically significant difference in QCT index distribution between the SS with ILD and SS without ILD groups (p<0.001). Moreover, SS-ILD patients with ILD >20% (by Goh score) had a QCT index statistically different from those with limited ILD extent (p<0.001). Finally, QCT indices showed a moderate-to-good correlation with the Goh and Taouli scores (from 0.44 to 0.65; p<0.001).

Conclusions

QCT indices can identify patients with SS and ILD and discriminate those with lesser or greater lung disease.


Url:
DOI: 10.1371/journal.pone.0224772
PubMed: 31703067
PubMed Central: 6839858

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PMC:6839858

Le document en format XML

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<name sortKey="Gutierrez, Marwin" sort="Gutierrez, Marwin" uniqKey="Gutierrez M" first="Marwin" last="Gutiérrez">Marwin Gutiérrez</name>
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<name sortKey="Mozzani, Flavio" sort="Mozzani, Flavio" uniqKey="Mozzani F" first="Flavio" last="Mozzani">Flavio Mozzani</name>
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<name sortKey="Rojas Serrano, Jorge" sort="Rojas Serrano, Jorge" uniqKey="Rojas Serrano J" first="Jorge" last="Rojas-Serrano">Jorge Rojas-Serrano</name>
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<nlm:aff id="aff001">
<addr-line>Internal Medicine, Complejo hospitalario Ruber Juan Bravo, Universidad Europea (Madrid), Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Internal Medicine, Complejo hospitalario Ruber Juan Bravo, Universidad Europea (Madrid), Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Luque Pinilla, Jose Manuel" sort="Luque Pinilla, Jose Manuel" uniqKey="Luque Pinilla J" first="José Manuel" last="Luque-Pinilla">José Manuel Luque-Pinilla</name>
<affiliation wicri:level="3">
<nlm:aff id="aff001">
<addr-line>Internal Medicine, Complejo hospitalario Ruber Juan Bravo, Universidad Europea (Madrid), Madrid, Spain</addr-line>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Internal Medicine, Complejo hospitalario Ruber Juan Bravo, Universidad Europea (Madrid), Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Santilli, Daniele" sort="Santilli, Daniele" uniqKey="Santilli D" first="Daniele" last="Santilli">Daniele Santilli</name>
<affiliation wicri:level="1">
<nlm:aff id="aff006">
<addr-line>Internal Medicine and Rheumatoloy Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Internal Medicine and Rheumatoloy Unit, Azienda Ospedaliero-Universitaria di Parma, Parma</wicri:regionArea>
<wicri:noRegion>Parma</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sambataro, Domenico" sort="Sambataro, Domenico" uniqKey="Sambataro D" first="Domenico" last="Sambataro">Domenico Sambataro</name>
<affiliation wicri:level="1">
<nlm:aff id="aff007">
<addr-line>Department of Clinical and Experimental Medicine, Internal Medicine Unit, Cannizaro Hospital, University of Catania, Catania, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Clinical and Experimental Medicine, Internal Medicine Unit, Cannizaro Hospital, University of Catania, Catania</wicri:regionArea>
<wicri:noRegion>Catania</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Torrisi, Sebastiano E" sort="Torrisi, Sebastiano E" uniqKey="Torrisi S" first="Sebastiano E." last="Torrisi">Sebastiano E. Torrisi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff004">
<addr-line>Regional Referral Center for Rare Lung Diseases, A. O. U. "Policlinico-Vittorio Emanuele" Dpt. of Clinical and Experimental Medicine, University of Catania, Catania, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Regional Referral Center for Rare Lung Diseases, A. O. U. "Policlinico-Vittorio Emanuele" Dpt. of Clinical and Experimental Medicine, University of Catania, Catania</wicri:regionArea>
<wicri:noRegion>Catania</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vancheri, Ada" sort="Vancheri, Ada" uniqKey="Vancheri A" first="Ada" last="Vancheri">Ada Vancheri</name>
<affiliation wicri:level="1">
<nlm:aff id="aff004">
<addr-line>Regional Referral Center for Rare Lung Diseases, A. O. U. "Policlinico-Vittorio Emanuele" Dpt. of Clinical and Experimental Medicine, University of Catania, Catania, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Regional Referral Center for Rare Lung Diseases, A. O. U. "Policlinico-Vittorio Emanuele" Dpt. of Clinical and Experimental Medicine, University of Catania, Catania</wicri:regionArea>
<wicri:noRegion>Catania</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gutierrez, Marwin" sort="Gutierrez, Marwin" uniqKey="Gutierrez M" first="Marwin" last="Gutiérrez">Marwin Gutiérrez</name>
<affiliation wicri:level="1">
<nlm:aff id="aff005">
<addr-line>Division of Musculoskeletal and Rheumatic Disorders, Instituto Nacional de Rehabilitación—“Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico</addr-line>
</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Division of Musculoskeletal and Rheumatic Disorders, Instituto Nacional de Rehabilitación—“Luis Guillermo Ibarra Ibarra”, Mexico City</wicri:regionArea>
<wicri:noRegion>Mexico City</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Mejia, Mayra" sort="Mejia, Mayra" uniqKey="Mejia M" first="Mayra" last="Mejia">Mayra Mejia</name>
<affiliation wicri:level="1">
<nlm:aff id="aff008">
<addr-line>Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Mexico City, Mexico</addr-line>
</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Mexico City</wicri:regionArea>
<wicri:noRegion>Mexico City</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Palmucci, Stefano" sort="Palmucci, Stefano" uniqKey="Palmucci S" first="Stefano" last="Palmucci">Stefano Palmucci</name>
<affiliation wicri:level="1">
<nlm:aff id="aff009">
<addr-line>Department of Medica Surgical Sciences and Advanced Technologies "GR Ingrassia", Radiology I unit, University of Catania, Catania, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Medica Surgical Sciences and Advanced Technologies "GR Ingrassia", Radiology I unit, University of Catania, Catania</wicri:regionArea>
<wicri:noRegion>Catania</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Mozzani, Flavio" sort="Mozzani, Flavio" uniqKey="Mozzani F" first="Flavio" last="Mozzani">Flavio Mozzani</name>
<affiliation wicri:level="1">
<nlm:aff id="aff006">
<addr-line>Internal Medicine and Rheumatoloy Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Internal Medicine and Rheumatoloy Unit, Azienda Ospedaliero-Universitaria di Parma, Parma</wicri:regionArea>
<wicri:noRegion>Parma</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Rojas Serrano, Jorge" sort="Rojas Serrano, Jorge" uniqKey="Rojas Serrano J" first="Jorge" last="Rojas-Serrano">Jorge Rojas-Serrano</name>
<affiliation wicri:level="1">
<nlm:aff id="aff008">
<addr-line>Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Mexico City, Mexico</addr-line>
</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Mexico City</wicri:regionArea>
<wicri:noRegion>Mexico City</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vanchieri, Carlo" sort="Vanchieri, Carlo" uniqKey="Vanchieri C" first="Carlo" last="Vanchieri">Carlo Vanchieri</name>
<affiliation wicri:level="1">
<nlm:aff id="aff004">
<addr-line>Regional Referral Center for Rare Lung Diseases, A. O. U. "Policlinico-Vittorio Emanuele" Dpt. of Clinical and Experimental Medicine, University of Catania, Catania, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Regional Referral Center for Rare Lung Diseases, A. O. U. "Policlinico-Vittorio Emanuele" Dpt. of Clinical and Experimental Medicine, University of Catania, Catania</wicri:regionArea>
<wicri:noRegion>Catania</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sverzellati, Nicola" sort="Sverzellati, Nicola" uniqKey="Sverzellati N" first="Nicola" last="Sverzellati">Nicola Sverzellati</name>
<affiliation wicri:level="1">
<nlm:aff id="aff002">
<addr-line>Scienze Radiologiche, Dipartimento di Medicina e Chirurgia (DiMeC), University of Parma, Parma, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Scienze Radiologiche, Dipartimento di Medicina e Chirurgia (DiMeC), University of Parma, Parma</wicri:regionArea>
<wicri:noRegion>Parma</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Ariani, Alarico" sort="Ariani, Alarico" uniqKey="Ariani A" first="Alarico" last="Ariani">Alarico Ariani</name>
<affiliation wicri:level="1">
<nlm:aff id="aff006">
<addr-line>Internal Medicine and Rheumatoloy Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Internal Medicine and Rheumatoloy Unit, Azienda Ospedaliero-Universitaria di Parma, Parma</wicri:regionArea>
<wicri:noRegion>Parma</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="sec001">
<title>Background</title>
<p>Interstitial lung disease (ILD) is a frequent manifestation of Sjögren’s syndrome (SS), an autoimmune disease of salivary and lacrimal glands, and affects approximately 20% of patients. No clinical or serological features appear to be useful to predict its presence, severity or progression, and chest high-resolution computed tomography (CT) remains the gold standard for diagnosis. Semiquantitative CT (SQCT) based on visual assessment (Goh and Taouli scoring) can estimate ILD extent, although it is burdened by relevant intra- and interobserver variability. Quantitative chest CT (QCT) is a promising alternative modality to assess ILD severity.</p>
</sec>
<sec id="sec002">
<title>Aim</title>
<p>To determine whether QCT assessment can identify extensive or limited lung disease in patients with SS and ILD.</p>
</sec>
<sec id="sec003">
<title>Methods</title>
<p>This multi-center, cross-sectional and retrospective study enrolled patients with SS and a chest CT scan. SQCT assessment was carried out in a blinded and centralized manner to calculate both Goh and Taouli scores. An operator-independent analysis of all CT scans with the open-source software platform Horos was used to evaluate the QCT indices. Patients were classified according to the extent of ILD and differences in QCT index distribution were investigated with non-parametric tests.</p>
</sec>
<sec id="sec004">
<title>Results</title>
<p>From a total of 102 consecutive patients with SS, the prevalence of ILD was 35.3% (36/102). There was a statistically significant difference in QCT index distribution between the SS with ILD and SS without ILD groups (p<0.001). Moreover, SS-ILD patients with ILD >20% (by Goh score) had a QCT index statistically different from those with limited ILD extent (p<0.001). Finally, QCT indices showed a moderate-to-good correlation with the Goh and Taouli scores (from 0.44 to 0.65; p<0.001).</p>
</sec>
<sec id="sec005">
<title>Conclusions</title>
<p>QCT indices can identify patients with SS and ILD and discriminate those with lesser or greater lung disease.</p>
</sec>
</div>
</front>
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<name>
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<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
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<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Silva</surname>
<given-names>Mario</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Duarte-Millán</surname>
<given-names>Miguel Angel</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff003">
<sup>3</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
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<name>
<surname>Sambataro</surname>
<given-names>Gianluca</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bertolazzi</surname>
<given-names>Chiara</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pavone</surname>
<given-names>Mauro</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Martín-Garrido</surname>
<given-names>Isabel</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Martín-Segarra</surname>
<given-names>Oriol</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Luque-Pinilla</surname>
<given-names>José Manuel</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Santilli</surname>
<given-names>Daniele</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sambataro</surname>
<given-names>Domenico</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff007">
<sup>7</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Torrisi</surname>
<given-names>Sebastiano E.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vancheri</surname>
<given-names>Ada</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gutiérrez</surname>
<given-names>Marwin</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mejia</surname>
<given-names>Mayra</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff008">
<sup>8</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Palmucci</surname>
<given-names>Stefano</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff009">
<sup>9</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mozzani</surname>
<given-names>Flavio</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rojas-Serrano</surname>
<given-names>Jorge</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff008">
<sup>8</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vanchieri</surname>
<given-names>Carlo</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Sverzellati</surname>
<given-names>Nicola</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Ariani</surname>
<given-names>Alarico</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Validation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>Internal Medicine, Complejo hospitalario Ruber Juan Bravo, Universidad Europea (Madrid), Madrid, Spain</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Scienze Radiologiche, Dipartimento di Medicina e Chirurgia (DiMeC), University of Parma, Parma, Italy</addr-line>
</aff>
<aff id="aff003">
<label>3</label>
<addr-line>Internal Medicine, Hospital universitario Fuenlabrada, Fuenlabrada, Spain</addr-line>
</aff>
<aff id="aff004">
<label>4</label>
<addr-line>Regional Referral Center for Rare Lung Diseases, A. O. U. "Policlinico-Vittorio Emanuele" Dpt. of Clinical and Experimental Medicine, University of Catania, Catania, Italy</addr-line>
</aff>
<aff id="aff005">
<label>5</label>
<addr-line>Division of Musculoskeletal and Rheumatic Disorders, Instituto Nacional de Rehabilitación—“Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico</addr-line>
</aff>
<aff id="aff006">
<label>6</label>
<addr-line>Internal Medicine and Rheumatoloy Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy</addr-line>
</aff>
<aff id="aff007">
<label>7</label>
<addr-line>Department of Clinical and Experimental Medicine, Internal Medicine Unit, Cannizaro Hospital, University of Catania, Catania, Italy</addr-line>
</aff>
<aff id="aff008">
<label>8</label>
<addr-line>Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Mexico City, Mexico</addr-line>
</aff>
<aff id="aff009">
<label>9</label>
<addr-line>Department of Medica Surgical Sciences and Advanced Technologies "GR Ingrassia", Radiology I unit, University of Catania, Catania, Italy</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Kuwana</surname>
<given-names>Masataka</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>Nippon Medical School, JAPAN</addr-line>
</aff>
<author-notes>
<fn fn-type="COI-statement" id="coi001">
<p>
<bold>Competing Interests: </bold>
Prof. Carlo Vanchieri is part of F. Hoffmann-La Roche Ltd. Scientific Board. He has received consulting fees and/or speaker fees from Astrazeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd and Menarini. Prof. Stefano Palmucci has reveived personal fees and honoraria for lectures from Boehringer Ingelheim, Delphi International srl and F. Hoffmann-La Roche Ltd. He has been included in the scientific board for Boehringer Ingelheim. This does not alter our adherence to PLOS ONE policies on sharing data and materials. None of the other authors have any potential conflicts of interest to disclose in relation to this work.</p>
</fn>
<fn fn-type="other" id="econtrib001">
<p>‡ These authors also contributed equally to this work.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>pablogvasco@gmail.com</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>8</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<volume>14</volume>
<issue>11</issue>
<elocation-id>e0224772</elocation-id>
<history>
<date date-type="received">
<day>25</day>
<month>7</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>21</day>
<month>10</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>© 2019 Guisado-Vasco et al</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Guisado-Vasco et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pone.0224772.pdf"></self-uri>
<abstract>
<sec id="sec001">
<title>Background</title>
<p>Interstitial lung disease (ILD) is a frequent manifestation of Sjögren’s syndrome (SS), an autoimmune disease of salivary and lacrimal glands, and affects approximately 20% of patients. No clinical or serological features appear to be useful to predict its presence, severity or progression, and chest high-resolution computed tomography (CT) remains the gold standard for diagnosis. Semiquantitative CT (SQCT) based on visual assessment (Goh and Taouli scoring) can estimate ILD extent, although it is burdened by relevant intra- and interobserver variability. Quantitative chest CT (QCT) is a promising alternative modality to assess ILD severity.</p>
</sec>
<sec id="sec002">
<title>Aim</title>
<p>To determine whether QCT assessment can identify extensive or limited lung disease in patients with SS and ILD.</p>
</sec>
<sec id="sec003">
<title>Methods</title>
<p>This multi-center, cross-sectional and retrospective study enrolled patients with SS and a chest CT scan. SQCT assessment was carried out in a blinded and centralized manner to calculate both Goh and Taouli scores. An operator-independent analysis of all CT scans with the open-source software platform Horos was used to evaluate the QCT indices. Patients were classified according to the extent of ILD and differences in QCT index distribution were investigated with non-parametric tests.</p>
</sec>
<sec id="sec004">
<title>Results</title>
<p>From a total of 102 consecutive patients with SS, the prevalence of ILD was 35.3% (36/102). There was a statistically significant difference in QCT index distribution between the SS with ILD and SS without ILD groups (p<0.001). Moreover, SS-ILD patients with ILD >20% (by Goh score) had a QCT index statistically different from those with limited ILD extent (p<0.001). Finally, QCT indices showed a moderate-to-good correlation with the Goh and Taouli scores (from 0.44 to 0.65; p<0.001).</p>
</sec>
<sec id="sec005">
<title>Conclusions</title>
<p>QCT indices can identify patients with SS and ILD and discriminate those with lesser or greater lung disease.</p>
</sec>
</abstract>
<funding-group>
<funding-statement>This work was supported by Internal/own funds of the Complejo Hospitalario Ruber Juan Bravo for clinical research. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<fig-count count="2"></fig-count>
<table-count count="4"></table-count>
<page-count count="13"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>A public repository of the data will be held in:
<ext-link ext-link-type="uri" xlink:href="http://www.datadryad.org/stash/">www.datadryad.org/stash/</ext-link>
(DOI
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5061/dryad.sbcc2fr22">https://doi.org/10.5061/dryad.sbcc2fr22</ext-link>
). Direct download of the data are available from:
<ext-link ext-link-type="uri" xlink:href="https://datadryad.org/stash/share/1HiLI_7GxvhUu2wIAQNCCUK5ScptshXoJuCggR4g9Js">https://datadryad.org/stash/share/1HiLI_7GxvhUu2wIAQNCCUK5ScptshXoJuCggR4g9Js</ext-link>
. An independent researcher could contact with the Ethics Committee (E-Mail:
<email>ceic@fjd.es</email>
), for full access to confidential data, after requesting personal authorization.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>A public repository of the data will be held in:
<ext-link ext-link-type="uri" xlink:href="http://www.datadryad.org/stash/">www.datadryad.org/stash/</ext-link>
(DOI
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5061/dryad.sbcc2fr22">https://doi.org/10.5061/dryad.sbcc2fr22</ext-link>
). Direct download of the data are available from:
<ext-link ext-link-type="uri" xlink:href="https://datadryad.org/stash/share/1HiLI_7GxvhUu2wIAQNCCUK5ScptshXoJuCggR4g9Js">https://datadryad.org/stash/share/1HiLI_7GxvhUu2wIAQNCCUK5ScptshXoJuCggR4g9Js</ext-link>
. An independent researcher could contact with the Ethics Committee (E-Mail:
<email>ceic@fjd.es</email>
), for full access to confidential data, after requesting personal authorization.</p>
</notes>
</front>
<sub-article id="pone.0224772.r001" article-type="aggregated-review-documents">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0224772.r001</article-id>
<title-group>
<article-title>Decision Letter 0</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kuwana</surname>
<given-names>Masataka</given-names>
</name>
<role>Academic Editor</role>
</contrib>
</contrib-group>
<permissions>
<copyright-statement>© 2019 Masataka Kuwana</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Masataka Kuwana</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<related-article id="rel-obj001" ext-link-type="doi" xlink:href="10.1371/journal.pone.0224772" related-article-type="reviewed-article"></related-article>
<custom-meta-group>
<custom-meta>
<meta-name>Submission Version</meta-name>
<meta-value>0</meta-value>
</custom-meta>
</custom-meta-group>
</front-stub>
<body>
<boxed-text id="pone-0224772-box001" position="float" specific-use="prior_peer_review_unavailable" orientation="portrait">
<sec id="sec010">
<title>Transfer Alert</title>
<p>This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.</p>
</sec>
</boxed-text>
<p>
<named-content content-type="letter-date">21 Aug 2019</named-content>
</p>
<p>PONE-D-19-20968</p>
<p>Quantitative assessment of interstitial lung disease in Sjögren’s syndrome.</p>
<p>PLOS ONE</p>
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<p>Prof. Stefano Palmucci has reveived personal fees and honoraria for lectures from Boehringer Ingelheim, Delphi International srl and F. Hoffmann-La Roche Ltd. He has been included in the scientific board for Boehringer Ingelheim.</p>
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<p>The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. </p>
<p>Reviewer #1: Partly</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
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<p>Reviewer #1: No</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
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<p>**********</p>
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<p>**********</p>
<p>5. Review Comments to the Author</p>
<p>Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)</p>
<p>Reviewer #1: The authors reported quantitative assessment of interstitial lung disease in Sjögren’s syndrome. It is interesting to focus the usefulness of quantitative CT in Sjögren’s syndrome-ILD, but I have some major concerns about the data</p>
<p>Major;</p>
<p>1. CTD-ILD and quantitative CT scores have already been studied, but most patients were scleroderma. Therefore, it was very interesting to examine the quantitative CT score for Sjogren's syndrome in a large number of people. However, only association between CT analysis by histogram and ILD type are not appropriate as a paper.</p>
<p>Regarding scleroderma, CT scores and prognosis have already been examined. Did you classify ILD as limited and extensive, but was it related to prognosis as well as scleroderma? You need to consider if CT score affects prognosis in Sjogren's syndrome.</p>
<p>2. The percentage of patients with pSS-ILD is 72% (Table 1).</p>
<p>The secondary SS needs to be described in detail.</p>
<p>3. It seems necessary to create a table of correlation between quantitative CT analysis and clinical findings, respiratory function tests, and semi-quantitative CT analysis.</p>
<p>Minor</p>
<p>1.The figure is difficult to see and should be considered.</p>
<p>2 .In figure1. 2, the statistical differences between the three groups need to be clearly stated.</p>
<p>Reviewer #2: The authors reported the usefulness of quantitative chest computed tomography</p>
<p>(QCT) assessment of interstitial lung disease (ILD) in patients with Sjögren’s syndrome (SS). In this multi-center and retrospective study, QCT indices identified patients with SS and ILD (SS-ILD), and discriminated those with lesser or greater lung disease.</p>
<p>This is an important study that demonstrates that QCT indices can characterize subjects with SS-ILD in comparison to the standard visual, semi-quantitative methods such as Goh and Taouli scoring.</p>
<p>Major</p>
<p>1. This study showed that QCT indices discriminated the severity of ILD in patients with SS. However, optimal cut-off points for each indicator were not determined. How QCT indices can be utilized in future research.</p>
<p>2. With respect to Taouli scores, in their original paper (Eur Radiol 2002; 12:1504-1511), the authors calculated scores including ground-glass attenuation, honeycombing, centrilobular nodules, reticular pattern, mosaic perfusion, and air trapping. In the present study, how were the Taouli scores determined ?</p>
<p>Minor</p>
<p>1. There were no descriptions of the correlation between QCT indices and the Goh and Taouli scores or pulmonary function test findings in Table 1. Please modify the descriptions.</p>
<p>**********</p>
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<p>Reviewer #2: No</p>
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</body>
</sub-article>
<sub-article id="pone.0224772.r002" article-type="author-comment">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0224772.r002</article-id>
<title-group>
<article-title>Author response to Decision Letter 0</article-title>
</title-group>
<related-article id="rel-obj002" ext-link-type="doi" xlink:href="10.1371/journal.pone.0224772" related-article-type="editor-report"></related-article>
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</front-stub>
<body>
<p>
<named-content content-type="author-response-date">26 Sep 2019</named-content>
</p>
<p>Dear Editor, </p>
<p> Thank you for considering our manuscript, ‘Quantitative assessment of interstitial lung disease in Sjögren’s syndrome’ (PONE-D-19-20968), sent to PLOS One.</p>
<p>We really appreciate the opportunity to review our manuscript in order to fully address your concerns and comments of the referee. </p>
<p> Then, we are going to address point by point the reviewer’s recommendations. </p>
<p>Journal Requirements:</p>
<p>1. When submitting your revision, we need you to address these additional requirements.</p>
<p>Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at</p>
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and
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<p>I have reviewed the POLS ONE’s style guidelines, as you pointed out.</p>
<p>First, I have added a title page to the manuscript body, according to the format recommended by your editorial office. </p>
<p>Second, I have done some changes in the body of the template/manuscript according to them -mainly headings, as required. </p>
<p>2. Thank you for stating the following in the Competing Interests section:</p>
<p>Prof. Carlo Vancheri is part of F. Hoffmann-La Roche Ltd. Scientific Board. He has received consulting fees and/or speaker fees from Astrazeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd and Menarini.</p>
<p>Prof. Stefano Palmucci has reveived personal fees and honoraria for lectures from Boehringer Ingelheim, Delphi International srl and F. Hoffmann-La Roche Ltd. He has been included in the scientific board for Boehringer Ingelheim.</p>
<p>None of the other authors have any potential conflicts of interest to disclose in relation to this work.</p>
<p>Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors
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). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.</p>
<p>Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.</p>
<p>Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests:
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<p>I confirm, it does not alter the conflict of interest policy of your journal. I have added the following sentence, as recommended: ‘This does not alter our adherence to PLOS ONE policies on sharing data and materials’.</p>
<p>Reviewer #1: The authors reported quantitative assessment of interstitial lung disease in Sjögren’s syndrome. It is interesting to focus the usefulness of quantitative CT in Sjögren’s syndrome-ILD, but I have some major concerns about the data</p>
<p>Major;</p>
<p>1. CTD-ILD and quantitative CT scores have already been studied, but most patients were scleroderma. Therefore, it was very interesting to examine the quantitative CT score for Sjogren's syndrome in a large number of people. However, only association between CT analysis by histogram and ILD type are not appropriate as a paper.</p>
<p>Regarding scleroderma, CT scores and prognosis have already been examined. Did you classify ILD as limited and extensive, but was it related to prognosis as well as scleroderma? You need to consider if CT score affects prognosis in Sjogren's syndrome.</p>
<p>Before any new diagnostic technique can be used as an outcome measurement instrument, it should be tested its reliability comparing to actual standards. It is the aim of the present research. Later, it could be used as a prognostic tool – it is our next step in the research. In fact, the development of the quantitative indices in systemic sclerosis followed up the same idea of our working group – the count with some members whose developed this scoring system in scleroderma. First, it was release a publication assessing the reliability of these indices (2015), and them, a model of prediction of mortality was developed (2017).</p>
<p>References </p>
<p>Jousse-Joulin S, et al. Video clip assessment of a salivary gland ultrasound scoring system in Sjögren’s syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise. Ann Rheum Dis 2019;78:967–973 </p>
<p>Ariani A et al. Operator-independent quantitative chest computed tomography versus standard assessment of interstitial lung disease related to systemic sclerosis: a multi-center study. Mod Rheumatol 2015; 25(5):724-30.</p>
<p>Ariani A et al. Quantitative chest computed tomography is associated to two prediction models of mortality in interstitial lung disease related to systemic sclerosis. Rheumatology (Oxford), 2017; 56(6): 922-927. </p>
<p>2. The percentage of patients with pSS-ILD is 72% (Table 1). The secondary SS needs to be described in detail.</p>
<p> A paragraph was added at the beginning of the results section, detailing the diseases associated to SS. </p>
<p>The diseases associated to the development of SS, secondary SS, were: rheumatoid arthritis (5,9%), systemic lupus erythematosus (2%), systemic sclerosis (12,7%), and undifferentiated connective tissue disease (9,8%). Not all cases were affected of ILD, of course: just 10 have secondary SS.</p>
<p>3. It seems necessary to create a table of correlation between quantitative CT analysis and clinical findings, respiratory function tests, and semi-quantitative CT analysis.</p>
<p>This table has been inserted in the text – previously it was designed as supplementary material. It has been named as table 2. Hence, the former table 2 as labeled now as table 3. </p>
<p>Minor</p>
<p>1.The figure is difficult to see and should be considered.</p>
<p>The figures have been edited and introduced some changes to maximize its resolution. </p>
<p>2 .In figure1. 2, the statistical differences between the three groups need to be clearly stated.</p>
<p> Thank you very much for this comment. In order to a better understanding and simplified of the images, it has been added a footnote in both set of figures, which explains the differences between every group (0,1,2), and corresponding p-values. </p>
<p>Reviewer #2: The authors reported the usefulness of quantitative chest computed tomography</p>
<p>(QCT) assessment of interstitial lung disease (ILD) in patients with Sjögren’s syndrome (SS). In this multi-center and retrospective study, QCT indices identified patients with SS and ILD (SS-ILD), and discriminated those with lesser or greater lung disease.</p>
<p>This is an important study that demonstrates that QCT indices can characterize subjects with SS-ILD in comparison to the standard visual, semi-quantitative methods such as Goh and Taouli scoring.</p>
<p>Major</p>
<p>1. This study showed that QCT indices discriminated the severity of ILD in patients with SS. However, optimal cut-off points for each indicator were not determined. How QCT indices can be utilized in future research.</p>
<p>It was inserted/added a new table (number 4) to sum up these cut-off points, according to the Youden index applying using the model of area under the curve. A brief comment has been inserted in the results section. </p>
<p>I am agreeing with the point, that these cut-off points could be use in the next step of the research as predictive models of mortality in ILD related to SS. </p>
<p>2. With respect to Taouli scores, in their original paper (Eur Radiol 2002; 12:1504-1511), the authors calculated scores including ground-glass attenuation, honeycombing, centrilobular nodules, reticular pattern, mosaic perfusion, and air trapping. In the present study, how were the Taouli scores determined ?</p>
<p>These scores were calculating by two expert radiologists, properly trainee in semiquantitative scores. Hence, the score was calculated by the sum of all the categories that represent lung fibrosis, namely: honeycombing, reticular pattern, and ground-glass attenuation.</p>
<p>Minor</p>
<p>1. There were no descriptions of the correlation between QCT indices and the Goh and Taouli scores or pulmonary function test findings in Table 1. Please modify the descriptions.</p>
<p> A new table (Table 2) has been inserted where the correlations are described as recommended. It is mentioned in the results paragraph. </p>
<p>We hope that these comments and improvements have fulfilled the referees’ recommendations. </p>
<p>Such way, your editorial office could consider the current version of the manuscript for its final acceptance.</p>
<p>If there are any further questions or comments after this revision, please do not hesitate to contact us. </p>
<p>Sincerely, </p>
<p>Pablo Guisado Vasco</p>
<supplementary-material content-type="local-data" id="pone.0224772.s001">
<label>Attachment</label>
<caption>
<p>Submitted filename:
<named-content content-type="submitted-filename">Response to reviewers v.1.0.docx</named-content>
</p>
</caption>
<media xlink:href="pone.0224772.s001.docx">
<caption>
<p>Click here for additional data file.</p>
</caption>
</media>
</supplementary-material>
</body>
</sub-article>
<sub-article id="pone.0224772.r003" article-type="aggregated-review-documents">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0224772.r003</article-id>
<title-group>
<article-title>Decision Letter 1</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kuwana</surname>
<given-names>Masataka</given-names>
</name>
<role>Academic Editor</role>
</contrib>
</contrib-group>
<permissions>
<copyright-statement>© 2019 Masataka Kuwana</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Masataka Kuwana</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
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</front-stub>
<body>
<p>
<named-content content-type="letter-date">22 Oct 2019</named-content>
</p>
<p>Quantitative assessment of interstitial lung disease in Sjögren’s syndrome.</p>
<p>PONE-D-19-20968R1</p>
<p>Dear Dr. Guisado-Vasco,</p>
<p>We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.</p>
<p>Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.</p>
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<p>With kind regards,</p>
<p>Masataka Kuwana, MD, PhD</p>
<p>Academic Editor</p>
<p>PLOS ONE</p>
<p>Additional Editor Comments (optional):</p>
<p>Reviewers' comments:</p>
<p>Reviewer's Responses to Questions</p>
<p>
<bold>Comments to the Author</bold>
</p>
<p>1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.</p>
<p>Reviewer #2: All comments have been addressed</p>
<p>**********</p>
<p>2. Is the manuscript technically sound, and do the data support the conclusions?</p>
<p>The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. </p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>3. Has the statistical analysis been performed appropriately and rigorously? </p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>4. Have the authors made all data underlying the findings in their manuscript fully available?</p>
<p>The
<ext-link ext-link-type="uri" xlink:href="http://www.plosone.org/static/policies.action#sharing">PLOS Data policy</ext-link>
requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>5. Is the manuscript presented in an intelligible fashion and written in standard English?</p>
<p>PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.</p>
<p>Reviewer #2: Yes</p>
<p>**********</p>
<p>6. Review Comments to the Author</p>
<p>Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)</p>
<p>Reviewer #2: Thank you for addressing my comments from initial review.The data are potentially interesting and worthy of evaluation for SS-ILD.</p>
<p>**********</p>
<p>7. PLOS authors have the option to publish the peer review history of their article (
<ext-link ext-link-type="uri" xlink:href="https://journals.plos.org/plosone/s/editorial-and-peer-review-process#loc-peer-review-history">what does this mean?</ext-link>
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<p>Reviewer #2: No</p>
</body>
</sub-article>
<sub-article id="pone.0224772.r004" article-type="editor-report">
<front-stub>
<article-id pub-id-type="doi">10.1371/journal.pone.0224772.r004</article-id>
<title-group>
<article-title>Acceptance letter</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kuwana</surname>
<given-names>Masataka</given-names>
</name>
<role>Academic Editor</role>
</contrib>
</contrib-group>
<permissions>
<copyright-statement>© 2019 Masataka Kuwana</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Masataka Kuwana</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
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</front-stub>
<body>
<p>
<named-content content-type="letter-date">1 Nov 2019</named-content>
</p>
<p>PONE-D-19-20968R1 </p>
<p>Quantitative assessment of interstitial lung disease in Sjögren’s syndrome </p>
<p>Dear Dr. Guisado-Vasco:</p>
<p>I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. </p>
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<p>Thank you for submitting your work to PLOS ONE.</p>
<p>With kind regards,</p>
<p>PLOS ONE Editorial Office Staff</p>
<p>on behalf of</p>
<p>Prof. Masataka Kuwana </p>
<p>Academic Editor</p>
<p>PLOS ONE</p>
</body>
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<li>Italie</li>
<li>Mexique</li>
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<li>Communauté de Madrid</li>
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<li>Madrid</li>
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<country name="Espagne">
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<name sortKey="Guisado Vasco, Pablo" sort="Guisado Vasco, Pablo" uniqKey="Guisado Vasco P" first="Pablo" last="Guisado-Vasco">Pablo Guisado-Vasco</name>
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<name sortKey="Duarte Millan, Miguel Angel" sort="Duarte Millan, Miguel Angel" uniqKey="Duarte Millan M" first="Miguel Angel" last="Duarte-Millán">Miguel Angel Duarte-Millán</name>
<name sortKey="Luque Pinilla, Jose Manuel" sort="Luque Pinilla, Jose Manuel" uniqKey="Luque Pinilla J" first="José Manuel" last="Luque-Pinilla">José Manuel Luque-Pinilla</name>
<name sortKey="Martin Garrido, Isabel" sort="Martin Garrido, Isabel" uniqKey="Martin Garrido I" first="Isabel" last="Martín-Garrido">Isabel Martín-Garrido</name>
<name sortKey="Martin Segarra, Oriol" sort="Martin Segarra, Oriol" uniqKey="Martin Segarra O" first="Oriol" last="Martín-Segarra">Oriol Martín-Segarra</name>
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<country name="Italie">
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<name sortKey="Silva, Mario" sort="Silva, Mario" uniqKey="Silva M" first="Mario" last="Silva">Mario Silva</name>
</noRegion>
<name sortKey="Ariani, Alarico" sort="Ariani, Alarico" uniqKey="Ariani A" first="Alarico" last="Ariani">Alarico Ariani</name>
<name sortKey="Mozzani, Flavio" sort="Mozzani, Flavio" uniqKey="Mozzani F" first="Flavio" last="Mozzani">Flavio Mozzani</name>
<name sortKey="Palmucci, Stefano" sort="Palmucci, Stefano" uniqKey="Palmucci S" first="Stefano" last="Palmucci">Stefano Palmucci</name>
<name sortKey="Pavone, Mauro" sort="Pavone, Mauro" uniqKey="Pavone M" first="Mauro" last="Pavone">Mauro Pavone</name>
<name sortKey="Sambataro, Domenico" sort="Sambataro, Domenico" uniqKey="Sambataro D" first="Domenico" last="Sambataro">Domenico Sambataro</name>
<name sortKey="Sambataro, Gianluca" sort="Sambataro, Gianluca" uniqKey="Sambataro G" first="Gianluca" last="Sambataro">Gianluca Sambataro</name>
<name sortKey="Santilli, Daniele" sort="Santilli, Daniele" uniqKey="Santilli D" first="Daniele" last="Santilli">Daniele Santilli</name>
<name sortKey="Sverzellati, Nicola" sort="Sverzellati, Nicola" uniqKey="Sverzellati N" first="Nicola" last="Sverzellati">Nicola Sverzellati</name>
<name sortKey="Torrisi, Sebastiano E" sort="Torrisi, Sebastiano E" uniqKey="Torrisi S" first="Sebastiano E." last="Torrisi">Sebastiano E. Torrisi</name>
<name sortKey="Vancheri, Ada" sort="Vancheri, Ada" uniqKey="Vancheri A" first="Ada" last="Vancheri">Ada Vancheri</name>
<name sortKey="Vanchieri, Carlo" sort="Vanchieri, Carlo" uniqKey="Vanchieri C" first="Carlo" last="Vanchieri">Carlo Vanchieri</name>
</country>
<country name="Mexique">
<noRegion>
<name sortKey="Bertolazzi, Chiara" sort="Bertolazzi, Chiara" uniqKey="Bertolazzi C" first="Chiara" last="Bertolazzi">Chiara Bertolazzi</name>
</noRegion>
<name sortKey="Gutierrez, Marwin" sort="Gutierrez, Marwin" uniqKey="Gutierrez M" first="Marwin" last="Gutiérrez">Marwin Gutiérrez</name>
<name sortKey="Mejia, Mayra" sort="Mejia, Mayra" uniqKey="Mejia M" first="Mayra" last="Mejia">Mayra Mejia</name>
<name sortKey="Rojas Serrano, Jorge" sort="Rojas Serrano, Jorge" uniqKey="Rojas Serrano J" first="Jorge" last="Rojas-Serrano">Jorge Rojas-Serrano</name>
</country>
</tree>
</affiliations>
</record>

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