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"copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Reumatol Clin. 2022;18:597-602" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Study the Relationship of MDCT Staging in Disease Extent with the Systemic Sclerosis Disease Parameters" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "597" "paginaFinal" => "602" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudiar la relación de la estadificación de la TCMD en la extensión de la enfermedad con los parámetros de la enfermedad de esclerosis sistémica" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1061 "Ancho" => 1305 "Tamanyo" => 257733 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Axial HRCT images at level 3 and 4 in a 38 year-old female show mixed reticular and GGO patterns as septal thickening in lung bases and limited patchy areas of GGO. This patient had FVC 61% of predicted value (mild restriction pulmonary impairment). A predominant reticular pattern and a coarseness grade of 3 were assigned.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Abeer M. Ghandour, Rania M. Gamal, Gehan Seif Eldein, Aya M. Gamal, Eman El-Hakeim, Marwa A.A. Galal, Fatma H. El-Nouby, Yasmine S. Makarem, Ahmed Abdellatif Awad, Ahmed A. Hafez, Hanan Sayed M. Abozaid" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Abeer M." "apellidos" => "Ghandour" ] 1 => array:2 [ "nombre" => "Rania M." "apellidos" => "Gamal" ] 2 => array:2 [ "nombre" => "Gehan Seif" "apellidos" => "Eldein" ] 3 => array:2 [ "nombre" => "Aya M." "apellidos" => "Gamal" ] 4 => array:2 [ "nombre" => "Eman" "apellidos" => "El-Hakeim" ] 5 => array:2 [ "nombre" => "Marwa A.A." "apellidos" => "Galal" ] 6 => array:2 [ "nombre" => "Fatma H." "apellidos" => "El-Nouby" ] 7 => array:2 [ "nombre" => "Yasmine S." 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"apellidos" => "Abozaid" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1699258X21001200" "doi" => "10.1016/j.reuma.2021.04.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X21001200?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574322001605?idApp=UINPBA00004M" "url" => "/21735743/0000001800000010/v1_202211240657/S2173574322001605/v1_202211240657/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173574322000636" "issn" => "21735743" "doi" => "10.1016/j.reumae.2021.09.004" "estado" => "S300" "fechaPublicacion" => "2022-12-01" "aid" => "1578" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Reumatol Clin. 2022;18:580-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Proposals for the incorporation of the nursing role in the certification of axial spondyloarthritis units. 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Revisión bibliográfica y consenso entre expertas" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2407 "Ancho" => 2500 "Tamanyo" => 289474 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">PRISMA Flow chart. Graphical representation of the search and study selection process, from the number of records identified in the search to the number of studies finally included in the review.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Irene Carrillo, Adriana López-Pineda, Silvia García-Díaz, Amparo López, Lídia Valencia Muntalà, Xavier Juanola, Pedro Zarco, Emilio Ignacio, José Joaquín Mira" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Irene" "apellidos" => "Carrillo" ] 1 => array:2 [ "nombre" => "Adriana" "apellidos" => "López-Pineda" ] 2 => array:2 [ "nombre" => "Silvia" "apellidos" => "García-Díaz" ] 3 => array:2 [ "nombre" => "Amparo" "apellidos" => "López" ] 4 => array:2 [ "nombre" => "Lídia" "apellidos" => "Valencia Muntalà" ] 5 => array:2 [ "nombre" => "Xavier" "apellidos" => "Juanola" ] 6 => array:2 [ "nombre" => "Pedro" "apellidos" => "Zarco" ] 7 => array:2 [ "nombre" => "Emilio" "apellidos" => "Ignacio" ] 8 => array:2 [ "nombre" => "José Joaquín" "apellidos" => "Mira" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X21002321" "doi" => "10.1016/j.reuma.2021.09.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X21002321?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574322000636?idApp=UINPBA00004M" "url" => "/21735743/0000001800000010/v1_202211240657/S2173574322000636/v1_202211240657/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Screening of interstitial lung disease in patients with rheumatoid arthritis: A systematic review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "587" "paginaFinal" => "596" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Sandra Garrote-Corral, Lucía Silva-Fernández, Daniel Seoane-Mato, Mercedes Guerra-Rodríguez, Myriam Aburto, Santos Castañeda, Claudia Valenzuela, Javier Narváez" "autores" => array:8 [ 0 => array:3 [ "nombre" => "Sandra" "apellidos" => "Garrote-Corral" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Lucía" "apellidos" => "Silva-Fernández" "email" => array:1 [ 0 => "luciasilva@ser.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Daniel" "apellidos" => "Seoane-Mato" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ 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class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Reumatología, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Investigación, Sociedad Española de Reumatología, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario de Galdakao, Galdakao, Bizkaia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Cátedra UAM-Roche, EPID-Futuro, Departamento de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario de La Princesa, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cribado de enfermedad pulmonar intersticial difusa en pacientes con artritis reumatoide: una revisión sistemática" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1978 "Ancho" => 2505 "Tamanyo" => 208105 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flow chart of the selection of studies.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Lung involvement is a common extra-articular manifestation in rheumatoid arthritis (RA), which can occur in 60%–80% of patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Different types of pulmonary involvement have been described, including interstitial lung disease (ILD), pleural disease, rheumatoid nodules, bronchiectasis and vasculitis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Different studies have estimated the prevalence of ILD in RA to be between 1% and 58% depending on the methodology used.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The cumulative incidence of clinically significant ILD (abnormal pulmonary function tests [PFT]: decrease in forced vital capacity [FVC] or diffusing capacity of the lungs for carbon monoxide [DLCO] of 15% of normal) in RA patients has been found to be 5% at 10 years<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and 6.8% after 30 years of follow-up.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> ILD is a major cause of morbidity and mortality. Mortality at 5 years after diagnosis was 35.9% in a US study.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Underdiagnosis poses a major difficulty in determining the incidence and prevalence of ILD. A high prevalence of subclinical ILD (19%–57%) has been observed,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> defined as that incidentally detected on high-resolution computed tomography (HRCT) and without symptoms. These radiological findings are progressive in half the patients<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and are associated with subsequent onset of respiratory symptoms and PFT abnormalities.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The exact relationship between RA and ILD is not known, but genetic and environmental mechanisms are thought to be involved.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Two pathways of connection between joint and lung disease have been proposed. On the one hand, it is possible that the disease starts in the synovial tissue following an immune response against citrullinated proteins, which would subsequently cross-react with tissue antigens in the lung.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> This theory is supported by the fact that joint disease appears before lung disease in most patients. Another possibility is that immune tolerance is initially lost in the lung, and that ILD generates an immune response against citrullinated proteins that secondarily spreads to the joints.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> This idea is supported by the observation that ILD may precede other extrapulmonary manifestations and by the existence of a high number of citrullinated peptides in the lung parenchyma of patients with RA-ILD.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The temporal relationship between joint disease and ILD is therefore highly variable. Furthermore, the severity of lung involvement does not correlate with the severity of RA, although some features of RA, such as elevated rheumatoid factor, are risk factors for ILD. Some patients may be asymptomatic even though they show significant radiological involvement.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Given the significant morbidity and mortality associated with RA-ILD, screening methods to diagnose asymptomatic cases and provide prompt treatment are essential. To help in the development of criteria for screening patients with RA-ILD, we conducted a systematic review to identify the different methods of screening for interstitial lung disease used in patients with RA.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The recommendations of the PRISMA guidelines were followed for this review.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Search strategy</span><p id="par0035" class="elsevierStylePara elsevierViewall">A health sciences librarian (MGR) designed a systematic search strategy in the databases PubMed (Medline), Embase (Elsevier), and Cochrane Library (Wiley). The search included MeSH terms and free text with their different combinations referring to “rheumatoid arthritis”, “interstitial lung disease” and “screening” until April 2020 (Appendix <a class="elsevierStyleCrossRef" href="#sec0090">B</a>, Annex 1 of the supplementary material). The search was limited to human studies and articles published in English, French, or Spanish. A hand search of the references of the articles retrieved was also performed.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Selection of studies</span><p id="par0040" class="elsevierStylePara elsevierViewall">The Covidence systematic review tool (<a href="http://www.covidence.org">www.covidence.org</a>) was used to screen studies. Studies of any design using screening methods for interstitial lung disease in patients with RA were selected. As per protocol, studies were included in which: (a) the study population was adult patients with RA; (b) the intervention consisted of any method of screening for ILD (questionnaire, examination, complementary tests…); and (c) the validity or reliability of the screening method was assessed, or screening criteria were described. Two reviewers (SGC and LSF) first independently screened by title and abstract. Any discrepancies were resolved by consensus. The selected articles were then evaluated in detail to select those for final inclusion based on the above criteria. A third reviewer (DSM) resolved any disagreement on inclusion between the two reviewers. The reason for excluding all the rejected studies was recorded.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data extraction</span><p id="par0045" class="elsevierStylePara elsevierViewall">The two reviewers extracted information from the articles independently using specific templates. The retrieved articles were classified according to the screening method studied (HRCT, PFT, ultrasound, etc). Study characteristics were extracted in terms of design, population included, screening method, gold standard used, and results of comparison. A synthesis of the collected information was made in a narrative form with tabulation of the characteristics and results of each included study. Study quality was assessed using the scale for levels of scientific evidence and formulating recommendations for diagnostic questions (NICE [National Institute for Health and Care Excellence]<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> adaptation of the levels of evidence of the Oxford Centre for Evidence Based Medicine and Centre for Reviews and Dissemination<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>).</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">The diagram in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> details the results of the search. The search strategy identified 849 studies, of which 35 were duplicates. Initial screening by title and abstract discarded 757. Nineteen of the 54 articles reviewed in detail met the inclusion criteria. In addition, 6 articles found by hand search of the references of retrieved articles were selected. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the characteristics of the 25 included articles. The most relevant results of the studies are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The excluded articles and the reasons for exclusion are detailed in Appendix <a class="elsevierStyleCrossRef" href="#sec0090">B</a>, Annex 2 of the supplementary material.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">A total of 2593 RA patients without a known diagnosis of ILD were included. The included population was mainly female (70%), with a mean age of 46–68 years, and a mean disease duration of between 1 and 12 years.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Most of the included studies were of cross-sectional design, except for the study by Gochuico et al.,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> which is a prospective cohort. After quality assessment, 2 studies were of high quality,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> 12 of medium quality,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8,18–27</span></a> and 11 of low quality.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28–38</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Apart from 2 studies,<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,38</span></a> lung HRCT was the most frequently used tool for screening for ILD. Some studies also used other tools such as digital auscultation, biochemical markers, bronchoalveolar lavage (BAL), pulmonary function tests (PFTs), or lung ultrasound, as detailed below.</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Digital auscultation</span><p id="par0070" class="elsevierStylePara elsevierViewall">Studies by Pancaldi et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and Manfredi et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> compare the use of a digital stethoscope to automatically detect velcro-type lung crackles with HRCT findings. The digital audio collected was analysed using an algorithm for the binary classification of the findings (VECTOR). The target population comprised patients diagnosed with RA who had undergone HRCT for respiratory symptoms, velcro crackles, pathological lung function, or lung nodule study. Digital auscultation achieved diagnostic accuracy of 84%–90%, specificity of 77%–88%, sensitivity of 93%, positive predictive value (PPV) 75%–83%, and negative predictive value (NPV) 94%–95% in detecting ILD, and the accuracy obtained by auscultation by a rheumatologist was 67.2%.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Biochemical markers</span><p id="par0075" class="elsevierStylePara elsevierViewall">The study by Abdel-Wahab et al. established a significant association between serum levels of interleukin-33 (IL-33) and the presence of DIDP in patients with RA.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Castellanos-Moreira et al.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> assessed the presence of autoantibodies against 3 carbamylated antigens: foetal calf serum (FCS), fibrinogen (Fib), and chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) in RA patients. Included patients without a previous diagnosis of ILD were screened with HRCT. It was found that all anti-carbamylated protein antibodies studied were more frequent and with higher mean titres in the ILD group. In addition, logistic regression adjusted for age, RA duration, anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), sex and cumulative tobacco dose showed that anti-FCS, anti-CFFHP and anti-FCS-IgA were independently associated with ILD. Another study<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> that evaluated different serum biomarkers in a Chinese cohort (later confirmed in a US cohort) showed an association between levels of extracellular matrix metalloproteinases 7 (MMP-7) and IFNγ-inducible protein-10 (IP-10) and the presence of (HRCT-diagnosed) ILD in RA patients. This finding was confirmed in patients with clinical and subclinical ILD. Biomarker levels were correlated with the severity of the ILD. The area under the ROC curve (Receiver Operating Characteristic curve) of these markers for the diagnosis of ILD reached values between 0.68 and 0.86. In a study<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> with fewer RA patients who underwent lung HRCT, higher levels of CA15-3 and CA125 were laboratory determined in patients with ILD than in those without ILD. Finally, the study by Doyle et al.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> showed a significant increase in MMP-7, PARC, and surfactant protein D in patients with subclinical ILD in two different cohorts.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Bronchoalveolar lavage</span><p id="par0080" class="elsevierStylePara elsevierViewall">The search yielded 2 studies conducted in the late 1980s<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,38</span></a> in which BAL was used to screen for ILD in RA patients. The diagnosis of ILD was established by plain chest X-ray and patients underwent BAL for cellular and biochemical analysis. The study by Tishler et al.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> showed that patients with radiological abnormalities had a higher percentage of lymphocytes in the BAL than patients with normal X-rays. Gilligan et al.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> detected subclinical ILD in 15% of patients by chest X-ray and PFT. In the BAL of patients with established ILD, there was a significant difference in the number of neutrophils compared to controls, as well as an increase in collagenase and N-terminal procollagen type III. Gochuico et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> compared BAL findings between RA patients with biopsy-confirmed pulmonary fibrosis, RA and subclinical ILD diagnosed by HRCT and RA patients without lung disease. Platelet-derived growth factor (PDGF)-AB and PDGF-BB levels were higher in patients with ILD versus those with RA without ILD. Moreover, significantly higher levels of interferon gamma and transforming growth factor beta 1 (TFG-β1) were detected in patients with ILD with progression of lung damage versus those without.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Pulmonary function test</span><p id="par0085" class="elsevierStylePara elsevierViewall">PFTs have been assessed in several studies for the diagnosis of ILD. The study by Mohd Noor et al.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> estimated that PFT abnormalities exist in 95% of patients with RA of more than 5 years’ disease duration, 66.6% of them with restrictive pattern. Zhang et al.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> observed that patients with ILD had significantly more PFT abnormalities consisting of restrictive pattern and decreased diffusion. Mori et al.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> found that patients with ILD had significantly lower DLCO and DLCO/VA (DLCO corrected for alveolar volume) values than patients without ILD. Wang et al.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> proposed a DLCO cut-off point of less than 52.95% for the detection of HRCT-confirmed ILD. This DLCO screening method achieved sensitivity of 100% and specificity of 61%. Yilmazer et al.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> found a significant association between DLCO values <75% and respiratory symptoms with the presence of ILD in multivariate analysis. In the study by Leonel et al.,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> PFT was statistically significant as a predictor of HRCT abnormalities in patients with RA. Manfredi et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> studied the accuracy of PFT for the diagnosis of ILD with FVC cut-off points below 70% and DLCO below 47%. They reported an accuracy of 52.8% and 54.9%, sensitivity of 20% and 30.8%, and specificity of 82.1% and 80%, respectively.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Lung ultrasound</span><p id="par0090" class="elsevierStylePara elsevierViewall">Three studies assessed the usefulness of transthoracic lung ultrasound in screening for ILD.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17,20</span></a> Cogliati et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> evaluated the presence of B-lines in 72 lung segments (28 anterior and 44 posterior) following anatomical lines. The presence of more than 10 B-lines in a single segment was considered diagnostic of ILD. In this study, the sensitivity of ultrasound compared to HRCT was 92% and specificity 56% in a population of RA patients with suspected ILD. The group of Moazedi-Fuerst et al.,<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,20</span></a> in addition to B-lines (pathological if more than two lines), considered pleural thickening (pathological if more than 3 mm), and the presence of subpleural nodules (pathological if at least one nodule). Ultrasound was estimated to have a sensitivity of 92%–97%, specificity of 56%–97%, PPV of 94%, and NPV of 99% for the diagnosis of HRCT-confirmed ILD in consecutive RA patients without respiratory symptoms.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,20</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">High-resolution computed tomography</span><p id="par0095" class="elsevierStylePara elsevierViewall">HRCT was the most sensitive technique for the diagnosis of ILD compared to chest X-ray or PFT in several studies, although a relationship between HRCT findings and respiratory symptoms could not be established.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31,32</span></a> In the series of Hassan et al.,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> HRCT detected 5% of ILD in respiratory asymptomatic RA patients. In the study by Gabbay et al.,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> 33% of RA patients with RA of less than 2 years' duration had ILD on HRCT, clinically insignificant in 3 out of 4 patients. In the paper by Gochuico et al.,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> 33% of patients had subclinical ILD on inclusion in the study. After a mean follow-up of 1.5 years, 57% of these patients were found to have progression of lung damage as assessed by HRCT.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Combination of several tests</span><p id="par0100" class="elsevierStylePara elsevierViewall">The combination of HRCT and PFT detected subclinical ILD in 17%–55% of RA patients in the different studies.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8,21,23</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27,33</span></a> Gabbay et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> found that 58% of patients with RA of less than 2 years’ duration had some abnormality suggestive of ILD in the tests performed (HRCT, chest X-ray,PFT, BAL, scintigraphy). Forty-four percent had subclinical ILD (mild abnormalities on HRCT, FFP and BAL).</p><p id="par0105" class="elsevierStylePara elsevierViewall">The studies by Gabbay et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and Dawson et al.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> concluded that plain X-ray is not a highly sensitive technique for the diagnosis of ILD in RA.</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">ILD is a common extra-articular manifestation in patients with RA. It accounts for 7%–20% of deaths, making it the second leading cause of death after cardiovascular disease.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39,40</span></a> The prevalence varies depending on the cohort studied and method used, ranging from 5%-61%. Between 5% and 55% of patients are thought to be asymptomatic.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8,21,23</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25,27,33</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The temporal relationship between joint involvement and ILD is variable, although the diagnosis of RA usually precedes the diagnosis of lung involvement. Several risk factors have been described in patients with RA for the development of ILD. The main associations have been found to be with older age, male sex, smoking history, and the presence of RF and anti-CCP2 antibodies. The importance of screening for ILD in RA patients lies in the morbidity and mortality associated with it. However, the presence of ILD influences treatments for control of joint activity and progression of radiological damage.</p><p id="par0120" class="elsevierStylePara elsevierViewall">The studies included in this review evaluated the use of different diagnostic techniques to screen for ILD in patients with RA.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Digital auscultation is one of the most recently developed techniques. Considering that lung auscultation, together with specific history taking, is the most useful clinical tool to establish a suspicion of ILD, the INSPIRATE study<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,24</span></a> explored the usefulness of a digital stethoscope to detect velcro-like crackles. Digital auscultation achieved an accuracy of 84%–90% in the diagnosis of ILD compared to HRCT. As it is a non-invasive technique, these results could make it a useful tool in screening for ILD.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Regarding the use of serum biochemical markers, an association between the presence of subclinical ILD in RA patients has been observed with markers such as IL-33,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> MMP-7,<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,29</span></a> IP-10,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> PARC, surfactant protein D,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and antibodies to the carbamylated antigens FCS, Fib and CFFHP<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>; however, cut-off points for the application of these markers in clinical practice have not yet been established. Apart from their use as a screening technique, biomarkers could be of interest to assess the progression and prognosis of patients already diagnosed with ILD.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Two low-quality studies have failed to demonstrate the usefulness of BAL in screening for ILD.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,38</span></a> Since the widespread use of HRCT, BAL has fallen into disuse for the diagnosis of ILD and is now reserved for excluding other diseases (cancer, infections, etc.). Several studies have explored the usefulness of PFT in screening for ILD with very different results. The most frequent abnormalities were decreased DLCO and restrictive pattern.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,33–35</span></a> An association has been found between decreased DLCO and the presence of ILD on HRCT. The sensitivity of PFT for diagnosing ILD was between 59% and 100%, and the specificity between 61% and 83%. Decreased DLCO was found to be the most sensitive abnormality.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,36,37</span></a> As a non-invasive technique, PFT is useful for complementary screening.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Three studies on the use of transthoracic lung ultrasound for screening for ILD were included.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17,20</span></a> A good association was found between ultrasound and HRCT findings, with ultrasound achieving sensitivities of over 90%.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,17</span></a> Given that ultrasound is a fast, non-invasive technique that costs less than HRCT and avoids subjecting the patient to additional radiation, it can be considered a key tool in screening for ILD during follow-up of RA patients.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> However, the need for specialist training may limit its accessibility.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Lung HRCT was found to be the most sensitive technique for early detection in asymptomatic patients.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31,32</span></a> It is currently considered the gold standard test for the diagnosis and classification of the type of ILD in RA patients and is the gold standard used in most validity studies of other techniques. A single study prospectively followed up patients with ILD diagnosed by HRCT.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Radiological progression was found in 57% of patients with ILD after a mean follow-up of one and a half years.</p><p id="par0150" class="elsevierStylePara elsevierViewall">One of the limitations of this review is that most of the studies included were not specifically designed for screening for ILD and the methodological quality was generally poor. The populations were also very heterogeneous, as they included both respiratory asymptomatic and highly symptomatic patients in the same cohorts. This heterogeneity in both the populations included and the methodology of the studies did not allow for a meta-analysis.</p><p id="par0155" class="elsevierStylePara elsevierViewall">In conclusion, ILD is a common manifestation in patients with RA. Given the high morbidity and mortality associated with the condition, techniques that allow early detection are important. In our review, HRCT proved the most sensitive technique and plain X-ray the least sensitive. In PFT, decreased DLCO was the most sensitive parameter for detecting ILD. Other methods such as digital auscultation, biomarkers, and lung ultrasound could be emerging methods for screening for ILD, but more studies are needed to establish their real value in larger and unselected RA patient populations.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This review was funded by the <span class="elsevierStyleGrantSponsor" id="gs0005">Spanish Society of Rheumatology</span>.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of interests</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1806267" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aims" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1578417" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1806266" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1578418" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Search strategy" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Selection of studies" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Data extraction" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Digital auscultation" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Biochemical markers" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Bronchoalveolar lavage" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "Pulmonary function test" ] 4 => array:2 [ "identificador" => "sec0055" "titulo" => "Lung ultrasound" ] 5 => array:2 [ "identificador" => "sec0060" "titulo" => "High-resolution computed tomography" ] 6 => array:2 [ "identificador" => "sec0065" "titulo" => "Combination of several tests" ] ] ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-01-22" "fechaAceptado" => "2021-07-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1578417" "palabras" => array:4 [ 0 => "Rheumatoid arthritis" 1 => "Interstitial lung disease" 2 => "Screening" 3 => "Systematic review" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1578418" "palabras" => array:4 [ 0 => "Artritis reumatoide" 1 => "Enfermedad pulmonar intersticial" 2 => "Cribado" 3 => "Revisión sistemática" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Aims</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Interstitial lung disease (ILD) is frequent in patients with rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. The aim of this review was to identify the different screening methods for ILD in patients with RA.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">We ran a systematic search in Pubmed, Embase and Cochrane Library up to April 2020 and did a hand search of the references of the retrieved articles. The search was limited to humans and articles published in English, Spanish or French. We selected studies with any design where: (a) the population included adult patients with RA; (b) the intervention was any screening method for ILD; and (c) validity or reliability of the screening method were evaluated, or a screening method was described. Two reviewers independently screened the articles by title and abstract and subsequently extracted the information using a specific data extraction form.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">25 studies were included with a total of 2593 patients. The most frequently used tool for ILD screening was high resolution computed tomography (HRCT) of the lung. Electronic auscultation, biochemical markers, bronchoalveolar lavage (BAL), pulmonary function tests (PFTs) and lung ultrasonography were also evaluated. Across the different studies, electronic auscultation and lung ultrasonography achieved higher accuracy than PFTs, BAL and biochemical markers.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">HRCT resulted as the most sensitive tool for ILD screening in patients with RA. Given its harmlessness and high sensitivity, lung ultrasonography may become the first-choice tool in the future.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aims" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La enfermedad pulmonar intersticial difusa (EPID) es una manifestación frecuente en pacientes con artritis reumatoide (AR) y asocia una gran morbimortalidad. El objetivo de esta revisión fue identificar los distintos métodos de cribado de EPID en pacientes con AR.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Se realizó una búsqueda sistemática en Pubmed, Embase y Cochrane Library hasta abril de 2020 y una búsqueda manual en la bibliografía de los artículos recuperados. Se limitó a estudios en humanos y artículos publicados en inglés, francés o español. Se seleccionaron estudios de cualquier diseño en los que: (a) la población a estudiar fuesen pacientes adultos con AR; (b) la intervención consistiese en cualquier método de cribado de EPID; y (c) se evaluase la validez o fiabilidad del método de cribado, o se describiesen criterios de cribado. Dos revisoras realizaron la selección por título y abstract de forma independiente y posteriormente extrajeron la información utilizando plantillas específicas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 25 estudios con un total de 2.593 pacientes. La herramienta más frecuentemente utilizada para el cribado de EPID fue la tomografía computarizada de alta resolución (TCAR) pulmonar. También se evaluaron la auscultación electrónica, los marcadores bioquímicos, el lavado broncoalveolar (LBA), las pruebas de función respiratoria (PFR) y la ecografía pulmonar. En los diferentes estudios, la auscultación electrónica y la ecografía pulmonar alcanzaron mayor precisión que las PFR, el LBA y los marcadores bioquímicos.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La TCAR ha demostrado ser la técnica más sensible para el cribado de EPID en pacientes con AR. Dada su inocuidad y su alta sensibilidad, es posible que la ecografía pulmonar se posicione como técnica de elección en un futuro.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Garrote-Corral S, Silva-Fernández L, Seoane-Mato D, Guerra-Rodríguez M, Aburto M, Castañeda S, et al. Cribado de enfermedad pulmonar intersticial difusa en pacientes con artritis reumatoide: una revisión sistemática. Reumatol Clín. 2022;18:587–596.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0175" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0090" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1978 "Ancho" => 2505 "Tamanyo" => 208105 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flow chart of the selection of studies.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Anti-CFFHP: antibodies against fibrin/filaggrin homocitrullinated peptide; Anti-FCS: antibodies against foetal calf serum; Anti-Fib: anti-fibrinogen antibodies; AUC: area under the curve; BAL: Bronchoalveolar lavage; CA125: Carbohydrate antigen 125; CA19-9: Carbohydrate antigen 19-9; CA15-3: Carbohydrate antigen 15-3; CEA: carcinoembryonic antigen; DLCO: diffusing capacity for carbon monoxide; DLCO/VA: DLCO corrected for alveolar volume; FVC: forced vital capacity; HRCT: high-resolution computed tomography; IFN: interferon; IL: interleukin; ILD: interstitial lung disease; IP-10: interferon-gamma-inducible protein 10; MMP-7: matrix metalloproteinase-7; NPV: negative predictive value; PPV: positive predictive value; PFT: pulmonary function tests; RA: rheumatoid arthritis; TLC: total lung capacity; VC: vital capacity.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervention \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Links assessed \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Quality of evidence<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> (NICE) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pancaldi (2018)<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 70 patients with RA (with and without respiratory symptoms for whom an HRCT was requested) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Auscultation with digital stethoscope (analysis with VECTOR algorithm) lung HRCT</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Accuracy, sensitivity, specificity, PPV and NPV of the VECTOR algorithm in the diagnosis of ILD</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-RA-no ILD: 43, women 17, mean age: 66.8 ± 10.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-RA-ILD: 27, women 23, mean age: 69.8 ± 8.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Manfredi (2019)<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 137 consecutive patients with RA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Auscultation with digital stethoscope (analysis with VECTOR algorithm) lung HRCT</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Accuracy, sensitivity, specificity, PPV and NPV of the VECTOR algorithm for the diagnosis of ILD</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">for whom an HRCT was requested (respiratory symptoms, X-ray abnormalities, infection, monitoring of lung nodules) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-RA-no ILD: 78, women 31, mean age: 66.5 ± 10.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-RA-ILD: 59, women 45, mean age: 69.8 ± 9.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abdel-Wahab (2016)<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 50 patients with RA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Analysis of IL-33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Correlation between IL-33 and ILD</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Women: 41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lung HRCT</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean age: 51.1 ± 9.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 30 controls \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Women: 23 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean age: 51 ± 9.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Castellanos-Moreira (2020)<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 179 patients with RA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-CarP antibody test: anti-FCS, anti-Fib, anti-CFFHP and anti-FCS-IgA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Correlation between levels of Anti-carP antibodies and ILD</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous diagnosis of ILD: 31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HRCT patients with no previous diagnosis of ILD</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-non-ILD RA: 142, women 116, mean age: 57.7 ± 12.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-RA-ILD: 37, women 25, mean age: 67.3 ± 10.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chen (2015)<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 133 consecutive patients with RA (identification cohort, China) regardless of respiratory symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HRCT and PFT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Correlation between biomarkers (MMP-7 and IP-10) and ILD and its severity</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RA-no ILD: 50, women 41, mean age: 43.4 ± 15.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biomarker assay by ELISA MMP-7, IP-10, IFNγ, IL-8, IL-10, IL-15, IL-22, and α IL-2 receptor chain</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RA-indeterminate ILD: 34, women 34, mean age: 57.07 ± 9.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RA moderate-severe ILD: 41, women 29, mean age: 53.02 ± 14.20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 86 patients with RA (US replication cohort, previous diagnosis of ILD: 44%). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RA-no ILD: 22, women 16, mean age: 50.32 ± 7.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RA-indeterminate ILD: 15, women 15, mean age: 54.33 ± 12.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RA moderate-severe ILD: 49, women 18, mean age: 65.27 ± 10.80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Wang (2015)<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 41 patients with RA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HRCT, PFT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Correlation between lung function variables associated with ILD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross- sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">irrespective of respiratory symptoms for whom an HRCT was requested \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blood test: tumour markers (CEA, CA125, CA19-9 and CA15-3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Association between analytical variables and presence of ILD</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-RA without ILD: 16, women 10, mean age: 56.19 ± 12.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-CCP, ESR, CRP</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- RA-ILD: 25, women 11, mean age: 63.56 ± 11.90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doyle (2015)<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 113 patients with RA with HRCT performed for clinical reasons (BRASS cohort) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HRCT performed previously \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Correlation between biomarkers and ILD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- RA without ILD: 29, women 28, mean age: 53 ± 12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum biomarker assay (MMP-7, PARC, surfactant protein D) RF, anti-CCP</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Development of an index to identify subclinical ILD in RA</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Subclinical RA-ILD: 29, women 23, mean age: 68 ± 10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Clinical RA-ILD: 17, women 13, mean age: 65 ± 10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Indeterminate RA- ILD: 38 n = 76 patients with RA (ACR cohort) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- RA without ILD: 22, women 16, mean age: 50 ± 8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Subclinical RA-ILD: 18, women 13, mean age 65 ± 8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Clinical RA-ILD: 21, women 12, mean age: 64 ± 14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Indeterminate RA- ILD: 15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tishler<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> (1986)<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n = 12 patients with RA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chest X-ray \t\t\t\t\t\t\n \t\t\t\t</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cell distribution in patients with RA according to whether they had chest X-ray abnormalities</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cross-sectional</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">with no respiratory symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n