Original Article
Interstitial Lung Disease Related to Rheumatoid Arthritis: Evolution After Treatment
La enfermedad pulmonar intersticial relacionada con la artritis reumatoide: evolución después del tratamiento
Jorge Rojas-Serranoa,
, Edilzar González-Velásquezb, Mayra Mejíac, Alain Sánchez-Rodríguezd, Guillermo Carrilloc
Corresponding author
a Servicio Clínico de Enfermedades Intersticiales del Pulmón, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico
b Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México DF, Mexico
c Servicio Clínico de Enfermedades Intersticiales del Pulmón, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México DF, Mexico
d Universidad Veracruzana, Campus Minatitlan, Veracruz, Mexico
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(A) Cystic lesions of subpleural and baseline distribution resembling those seen in usual interstitial pneumonia, associated with areas of ground glass. (B) Ground glass with central distribution, respecting subpleural areas and discrete reticulation, resembling the pattern observed in the nonspecific interstitial pneumonia. (C) Reticulation and ground glass diffusely distributed, broncocentric, being an indeterminate pattern of interstitial lung disease.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that can cause interstitial lung and airway disease.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Lung involvement confers a poor prognosis and it is an important cause of death in RA patients.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> A cohort study described that the cumulative incidence for interstitial lung disease (ILD) in RA is 7.8%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Nowadays, there is no consensus of how patients should be treated. It has been proposed that the American Thoracic Society/European Respiratory Society (ATS/ERS) classification for idiopathic interstitial pneumonias should be used to classify RA patients with interstitial lung disease, and there is evidence that the tomographic pattern of lung disease may be an important prognostic factor.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–8</span></a> This study was done with the aim of describing the evolution of lung function at 6 months of follow-up in a cohort of RA patients with ILD, treated according to the medical judgment of the attending physician and to describe if there is a difference in the response to treatment according to the tomography findings.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">This is a retrospective cohort of RA patients classified according to the ACR/87 criteria,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> all with ILD defined by a restrictive pattern in lung function tests (TLC <80%, normal FEV1/FVC and FVC <80%) and with evidence of ILD in high resolution computed tomography (HRCT) and a low diffusing capacity for carbon monoxide (DLCO). Patients were evaluated and treated in the interstitial lung diseases unit at the Instituto Nacional de Enfermedades Respiratorias, a national referral center for respiratory diseases. Attending physicians (pulmonologists and rheumatologists) have experience in the medical assessment of ILD. At baseline patients have an evaluation of lung function including spirometry, DLCO, and HRCT. Then, at a minimum of 4 months of follow-up, a second assessment of lung function was done.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A complete description of baseline HRCT findings was done. HRCT findings were classified according the ATS/ERS criteria. The HRCT reader was blinded to clinical data. A Kazerooni scale for fibrosis and inflammation was also calculated.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Our reader has a high intraobserver concordance in the Kazerooni score, with an intraclass correlation coefficient of 0.90 (95% CI: 0.84–0.94). HRCT was performed with 1.0 or 1.5<span class="elsevierStyleHsp" style=""></span>mm thick axial section taken at 1<span class="elsevierStyleHsp" style=""></span>cm intervals throughout the entire thorax and were reconstructed using a high-spatial frequency algorithm. Between 20 and 25 CT scans images were acquired in each patient. The study was approved by the Institutional Review Board of our institute. As this is a retrospective study, no written informed consent from patients was taken.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analysis</span><p id="par0020" class="elsevierStylePara elsevierViewall">Pulmonary function tests values were compared at a 6-month of follow-up with baseline values using the Wilcoxon signed-rank test or the <span class="elsevierStyleItalic">t</span>-test for paired data. <span class="elsevierStyleItalic">α</span> was set at 5%, all analyses are two sided.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0025" class="elsevierStylePara elsevierViewall">Forty patients with ILD related to RA were identified, 90% were female with a mean age of 58.5±9.86 years. Respiratory symptoms at diagnosis had a mean time since onset of 13 months. The majority of patients had a longstanding RA, with a mean time with joint symptoms of 64 months (IQR 12–150); only 40.6% of patients used disease modifying antirheumatic drugs (DMARDs) before the diagnosis of ILD related to RA. The rest of demographic data and the clinical characteristics of the patients are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Medical treatment was decided by the attending physician. A myriad of treatments were used, nevertheless all patients received a high dose of prednisone (1<span class="elsevierStyleHsp" style=""></span>mg/kg/day) scheme for 6 weeks with a reduction scheme ending with a dose of 10<span class="elsevierStyleHsp" style=""></span>mg/day of prednisone at about the 6–8 months of follow-up. DMARDs used are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Methotrexate was used in 18/40 (45%) patients and leflunomide or azathioprine or both were indicated in 22/40 (55%). At a minimum of 4 months of follow-up (mean of 10.5 months of follow-up, IQR: 6–18 months of follow-up) an improvement in baseline FVC values was observed (mean (IQR) 1.47 Lts. (0.99–1.91) vs 1.66 Lts. (1.37–2.1)), <span class="elsevierStyleItalic">P</span><.004 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). No differences were found between the DMARDs used. Patients had a mean 22.5 months of follow-up after the baseline evaluation. Four patients died, one of right heart failure, two of acute exacerbations and one died in an outpatient setting, possibly of respiratory failure. The mean survival was 64 months. No differences were found between DMARDs and survival.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">High Resolution CT Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">We had the initial HRCT of 33 patients; of these, 4 (12%) had a usual interstitial pneumonia (UIP) pattern, 12 (38%) had nonspecific interstitial pneumonia (NSIP) pattern and 17 (50%) had an indeterminate pattern with diffuse ground glass and reticulation images (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). The mean of the Kazerooni fibrosis scales was 0.47 and the mean of the Kazerooni ground glass scale score was 2.33 (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). We compared the response in the FVC at 6 months of follow-up between patients with a value <0.47 of the fibrosis Kazerooni scale and those who had higher values. Those with lower Kazerooni scores (<0.47) were the ones who had a significant improvement in the FVC values (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">The results in this study show that patients with RA and ILD may have an improvement in the FVC after treatment with high doses of corticosteroids and DMARDs. This improvement is related to the degree of fibrosis present at the beginning of the medical treatment, because patients with lower Kazerooni fibrosis scores were the ones who showed improvement in the FVC values.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The general characteristics of the patients deserve some comment. First, although patients had a mean duration of RA symptoms of 64 months, only 40% of the patients had a history of previous use of DMARDs. So, the majority of EPI-RA patients described in this cohort had not been treated according to current guidelines. Although male sex has been described as a risk factor for EPI-AR, in our cohort we only had 4 male patients. The mean age of our patients, is very similar to what has been described in other cohorts.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Nowadays, there is no consensus about the medical treatment in ILD related to RA. Although the prognosis in RA has improved in recent years and DMARDs, especially methotrexate has shown its efficacy and safety in the treatment of RA,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> the use of several DMARDs in the case of ILD related to RA is controversial. Some authors have suggested that methotrexate should not be used in a patient with ILD related to RA because of the risk of acute pneumonitis.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Nevertheless, some recent data questions that recommendation. Park et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> have shown that RA patients with a usual ILD pattern are a high risk group for acute exacerbations defined by the Akira criteria.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In this report, RA patients with a usual ILD pattern had a higher incidence of acute exacerbations compared to idiopathic pulmonary fibrosis patients. More importantly, no RA patient in this report was treated with methotrexate or other DMARDs previously described as a possible cause of acute pneumonitis. Kim et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> have reported that methotrexate and anti TNF-α treatment are not associated with worse prognosis in a cohort of ILD related to RA patients. Analyses of large data sets have not shown any evidence of association between rheumatoid arthritis treatment and the risk of severe interstitial lung disease.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In conclusion, the results of this study and that of previous studies suggest that the recommendation of not giving methotrexate or other DMARDs to ILD related to RA patients is not accurate.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Another interesting finding in this study is the frequency of HRCT scans patterns. As Kim et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> reported, the most prevalent HRCT pattern was an indeterminate pattern with diffuse ground glass and reticulation in 50% of those patients with a baseline HRCT scan, followed by a NSIP in 38% and a usual pattern in 12% of the patients. The usual pattern is associated with a worse prognosis. We found no difference in survival according to the type of pattern, but our sample size and time of follow-up do not allow having firm conclusions in this regard. Nevertheless, patients with less than 0.47 fibrosis Kazerooni score had a better improvement of the FVC baseline values. The cut of value was selected arbitrarily because it was the mean of the Kazerooni scale for fibrosis in our patients.</p><p id="par0065" class="elsevierStylePara elsevierViewall">There are several limitations in the present study, first its retrospective nature and that the treatments that patients received were selected by the treating physicians. This fact does not allow having a valid comparison of different DMARDs used in this cohort, and also, no conclusions about the long term prognosis should be made. Another limitation is the short follow-up of the patients, so we cannot estimate even if the improvement in FVC is sustained in time. We believe that clinical trials must be done to answer which DMARD is the best option to treat patients with ILD related to RA. These clinical trials ideally should compare the effect of traditional DMARDs and new biological therapeutic agents. Other important limitation is that no measurement of RA disease activity was taken.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In conclusion, patients with RA and ILD may have an improvement in the FVC after a treatment with high doses of corticosteroids and DMARDs. The improvement is seen in the patients with lower Kazerooni fibrosis scores.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres125727" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec113018" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres125728" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusion" ] ] 3 => array:2 [ "identificador" => "xpalclavsec113019" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical Analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "High Resolution CT Results" ] ] ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-08-26" "fechaAceptado" => "2011-12-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec113018" "palabras" => array:4 [ 0 => "Rheumatoid arthritis" 1 => "Interstitial lung disease" 2 => "Methotrexate" 3 => "Pulmonary function tests" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec113019" "palabras" => array:4 [ 0 => "Artritis reumatoide" 1 => "Enfermedad pulmonar intersticial" 2 => "Metotrexato" 3 => "Pruebas de función pulmonar" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe the evolution of lung function in a cohort of rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) treated according to the medical judgment of attending physicians.</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective cohort of RA patients with ILD, defined by a restrictive pattern in lung function tests and evidence of ILD in high resolution computed tomography (HRCT). Patients had an assessment of lung function including spirometry, diffusing capacity for carbon monoxide (DLCO), and HRCT. At a minimum of 4 months of follow-up, a second assessment of lung function was done. All patients received a high dose of prednisone (1<span class="elsevierStyleHsp" style=""></span>mg/kg/day) scheme for 6 weeks with a reduction scheme ending with a dose of 10<span class="elsevierStyleHsp" style=""></span>mg/day of prednisone at about 6–8 months of follow-up. Methotrexate was used in 18/40 (45%) patients and leflunomide or azathioprine or both were indicated in 22/40 (55%).</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Forty patients were identified. An indeterminate pattern with diffuse ground glass and reticulation images (50%) was the most prevalent pattern on HRCT scans. At a minimum of 4 months of follow-up, an improvement in basal FVC values was observed (median (IQR)) 1.47 Lts. (0.99–1.91) vs 1.66 Lts. (1.37–2.1)), <span class="elsevierStyleItalic">P</span><.004. Patients with lower Kazerooni scores for fibrosis (<0.47) had a better improvement in the FVC values.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Patients with RA and ILD may have an improvement in the FVC after a treatment with high doses of corticosteroids and disease modifying antirheumatic drugs (DMARDs).</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir la evolución de la función pulmonar en una cohorte de pacientes con enfermedad pulmonar intersticial asociada a la artritis reumatoide (EPI-AR), tratados de acuerdo al juicio de sus médicos tratantes.</p> <span class="elsevierStyleSectionTitle">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohorte retrospectivo de pacientes con EPI-AR, demostrada con un patrón restrictivo en las pruebas de función pulmonar, y de enfermedad pulmonar intersticial en las tomografía de alta resolución (HRCT). Los pacientes tuvieron una evaluación basal de la función pulmonar que incluyó espirometría, DLCO y HRCT. En un mínimo de 4 meses, una segunda evaluación de la función pulmonar fue realizada. Todos los pacientes recibieron una dosis alta de prednisona (1<span class="elsevierStyleHsp" style=""></span>mg/kg/día) por 6 semanas con un esquema de reducción, con una dosis de prednisona de 10<span class="elsevierStyleHsp" style=""></span>mg/día a los 6 u 8 meses de seguimiento. Se prescribió metotrexate en 18/40 (45%) pacientes, leflunamida o azatioprina, o ambas en 22/40 (55%) pacientes.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se identificaron 40 pacientes con EPI-AR, El patrón más frecuente en la HRCT fue el indeterminado, con imágenes reticulares y de vidrio despulido en un 50% de los casos. A los 4 meses de seguimiento se observó una mejoría de los valores de la capacidad vital forzada (CVF), mediana basal de 1.47 Lts, intervalo inter cuartil (IIC): 0.99-1.91 Lts., Vs. Mediana de 1.66 Lts., IIC:1.37-2.1 Lts., p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.004. Los pacientes con los puntajes menores de la escala de Kazerooni para fibrosis pulmonar, (< 0.47) fueron los que presentaron una mejoría en los valores de la CVF.</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con EPI-AR pueden tener una mejoría en la CVF después del tratamiento con dosis altas de corticosteroides y fármacos modificadores de la enfermedad. (FARMES).</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please, cite this article as: Rojas-Serrano J, et al. Interstitial Lung Disease Related to Rheumatoid Arthritis: Evolution After Treatment. Reumatol Clin. 2012;<span class="elsevierStyleBold">8(2)</span>:68–71.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 500 "Ancho" => 1751 "Tamanyo" => 134835 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Representative CT images of RA-ILD patients. (A) Cystic lesions of subpleural and baseline distribution resembling those seen in usual interstitial pneumonia, associated with areas of ground glass. (B) Ground glass with central distribution, respecting subpleural areas and discrete reticulation, resembling the pattern observed in the nonspecific interstitial pneumonia. (C) Reticulation and ground glass diffusely distributed, broncocentric, being an indeterminate pattern of interstitial lung disease.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1002 "Ancho" => 1901 "Tamanyo" => 299108 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Baseline CT images of a patient with ILD related to RA. (A) Multiple cystic images with perivascular and random distribution, and diffuse ground glass opacities and patchy areas of lung consolidations with broncocentric interstitium thickening. (B) One year follow-up CT images after treatment with prednisone and methotrexate, showing less ground glass opacities, resolution of the consolidation areas and broncocentric interstitium thickening.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>=40 \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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"><span class="elsevierStyleItalic">Female sex</span> \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">36 (90) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Age (year old, mean±SD)</span> \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">58.5±9.86 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Years of formal education (mean, IQR)</span> \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">3 (0–9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Duration of respiratory symptoms at baseline in months (mean, IQR)</span> \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">14 (3–36) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Rheumatoid arthritis symptoms at baseline in months (mean, IQR)</span> \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">64 (12–150) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Previous use of DMARDs</span> \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">13/32 (40.6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Previous use of methotrexate</span> \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">11/32 (34.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Previous use of leflunomide</span> \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">3/32 (9.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Patients treated with methotrexate in our institute</span> \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">18/40 (45%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Methotrexate+leflunomide \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">3/18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Methotrexate+azathioprine \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">6/18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><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"><span class="elsevierStyleItalic">Patients treated with azathioprine or leflunomide without methotrexate</span> \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">22/40 (55%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Leflunomide \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">12/22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Azathioprine \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">10/22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Azathioprine+leflunomide \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">6/22 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212212.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Patients Included in The Study.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">First Evaluation, <span class="elsevierStyleItalic">n</span>=40 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Six Months Follow-Up, <span class="elsevierStyleItalic">n</span>=40 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">FVC (l)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.47 (0.99–1.91) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.66 (1.37–2.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">FVC (%)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.62 (0.42–0.77) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.73 (0.56–0.91) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212211.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">Mean (IQR).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Comparison of Forced Vital Capacities (FVC) at Baseline and After 6 Months Follow-Up.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">ATS/ERS: American Thoracic Society/European Respiratory Society; HRCT: high resolution computed tomography; UIP: usual interstitial pneumonia; NSIP: nonspecific interstitial pneumonia.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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">HRCT Pattern, <span class="elsevierStyleItalic">n</span>=33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Kazerooni Score (Mean, IQR)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Ground Glass \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Fibrosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">UIP, <span class="elsevierStyleItalic">n</span>=4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.49 (0.99–1.83) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.91 (1.41–2.33) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">NSIP, <span class="elsevierStyleItalic">n</span>=12 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.49 (1.83–3) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.49 (0.99–1.83) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Inflammatory indeterminate, <span class="elsevierStyleItalic">n</span>17 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5 (2–3) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0–0.33) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212214.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">HRCT Findings According to The ATS/ERS Criteria and The Kazerooni Scale Score for Fibrosis and Ground Glass (Mean, IQR).</p>" ] ] 5 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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">Variable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Forced Vital Capacity (% of Predicted)</td><td 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"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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">At Baseline \t\t\t\t\t\t\n \t\t\t\t</td><td 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">At a Minimum of 6 Months of Follow-Up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>=33 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>=33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Kazerooni fibrosis scale score <0.47, <span class="elsevierStyleItalic">n</span>=15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.65 (0.42–0.80) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.83 (0.71–0.89)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><.025 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Kazerooni fibrosis scale score ≥0.47, <span class="elsevierStyleItalic">n</span>=18 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.62 (0.42–0.74) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.66 (0.51–0.87)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212213.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">The comparison of the FVC (% of predicted) at a minimum of 6 months of follow-up between patients with Kazerooni scale score values <0.47 vs >0.47 was of <span class="elsevierStyleItalic">P</span><.065.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Comparison of FVC Values at Baseline and at a Minimum of 6 Months of Follow-Up According to The Mean of The Kazerooni Fibrosis Scale Score of The Sample, Patients With Less of 0.47 Had a Statistically Significant Improvement of the FVC Baseline Values.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rheumatoid arthritis, the clinical picture" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.A. Isenberg" 1 => "P.J. Maddison" 2 => "P.G.D. Woo" 3 => "C. Breedveld Ferdinand" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "edicion" => "3rd ed." "titulo" => "Oxford textbook of rheumatology" "fecha" => "2010" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Koduri" 1 => "S. Norton" 2 => "A. Young" 3 => "N. Cox" 4 => "P. Davies" 5 => "J. Devlin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/keq035" "Revista" => array:6 [ "tituloSerie" => "Rheumatology" "fecha" => "2010" "volumen" => "49" "paginaInicial" => "1483" "paginaFinal" => "1489" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20223814" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mortality and cause of death in Japanese patients with rheumatoid arthritis based on a large observational cohort, IORRA" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Nakajima" 1 => "E. Inoue" 2 => "E. Tanaka" 3 => "G. Singh" 4 => "E. Sato" 5 => "D. Hoshi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/03009741003604542" "Revista" => array:6 [ "tituloSerie" => "Scandinavian Journal of Rheumatology" "fecha" => "2010" "volumen" => "39" "paginaInicial" => "360" "paginaFinal" => "367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20476859" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence and mortality of interstitial lung disease in rheumatoid arthritis: a population-based study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Bongartz" 1 => "C. Nannini" 2 => "Y.F. Medina-Velasquez" 3 => "S.J. Achenbach" 4 => "C.S. Crowson" 5 => "J.H. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 18 | 28 |
| 2024 October | 55 | 22 | 77 |
| 2024 September | 53 | 22 | 75 |
| 2024 August | 65 | 35 | 100 |
| 2024 July | 59 | 37 | 96 |
| 2024 June | 88 | 38 | 126 |
| 2024 May | 55 | 22 | 77 |
| 2024 April | 61 | 32 | 93 |
| 2024 March | 87 | 31 | 118 |
| 2024 February | 53 | 29 | 82 |
| 2024 January | 52 | 17 | 69 |
| 2023 December | 69 | 31 | 100 |
| 2023 November | 51 | 49 | 100 |
| 2023 October | 43 | 39 | 82 |
| 2023 September | 98 | 36 | 134 |
| 2023 August | 51 | 17 | 68 |
| 2023 July | 31 | 24 | 55 |
| 2023 June | 38 | 27 | 65 |
| 2023 May | 41 | 21 | 62 |
| 2023 April | 38 | 12 | 50 |
| 2023 March | 63 | 30 | 93 |
| 2023 February | 56 | 34 | 90 |
| 2023 January | 41 | 18 | 59 |
| 2022 December | 69 | 46 | 115 |
| 2022 November | 49 | 35 | 84 |
| 2022 October | 68 | 34 | 102 |
| 2022 September | 33 | 46 | 79 |
| 2022 August | 40 | 42 | 82 |
| 2022 July | 46 | 45 | 91 |
| 2022 June | 45 | 48 | 93 |
| 2022 May | 53 | 39 | 92 |
| 2022 April | 59 | 41 | 100 |
| 2022 March | 109 | 87 | 196 |
| 2022 February | 92 | 39 | 131 |
| 2022 January | 77 | 46 | 123 |
| 2021 December | 34 | 40 | 74 |
| 2021 November | 52 | 43 | 95 |
| 2021 October | 96 | 64 | 160 |
| 2021 September | 61 | 42 | 103 |
| 2021 August | 48 | 37 | 85 |
| 2021 July | 31 | 24 | 55 |
| 2021 June | 62 | 42 | 104 |
| 2021 May | 47 | 57 | 104 |
| 2021 April | 108 | 97 | 205 |
| 2021 March | 114 | 56 | 170 |
| 2021 February | 60 | 40 | 100 |
| 2021 January | 46 | 23 | 69 |
| 2020 December | 36 | 34 | 70 |
| 2020 November | 35 | 20 | 55 |
| 2020 October | 30 | 29 | 59 |
| 2020 September | 100 | 34 | 134 |
| 2020 August | 98 | 24 | 122 |
| 2020 July | 103 | 17 | 120 |
| 2020 June | 40 | 17 | 57 |
| 2020 May | 49 | 18 | 67 |
| 2020 April | 60 | 20 | 80 |
| 2020 March | 21 | 12 | 33 |
| 2020 February | 3 | 2 | 5 |
| 2020 January | 4 | 0 | 4 |
| 2019 September | 6 | 0 | 6 |
| 2019 June | 2 | 0 | 2 |
| 2019 April | 1 | 0 | 1 |
| 2019 March | 3 | 2 | 5 |
| 2019 January | 1 | 0 | 1 |
| 2018 May | 4 | 1 | 5 |
| 2018 April | 38 | 12 | 50 |
| 2018 March | 56 | 13 | 69 |
| 2018 February | 37 | 8 | 45 |
| 2018 January | 30 | 6 | 36 |
| 2017 December | 29 | 11 | 40 |
| 2017 November | 25 | 9 | 34 |
| 2017 October | 28 | 10 | 38 |
| 2017 September | 25 | 11 | 36 |
| 2017 August | 21 | 10 | 31 |
| 2017 July | 28 | 26 | 54 |
| 2017 June | 34 | 13 | 47 |
| 2017 May | 35 | 19 | 54 |
| 2017 April | 27 | 9 | 36 |
| 2017 March | 21 | 8 | 29 |
| 2017 February | 14 | 4 | 18 |
| 2017 January | 21 | 7 | 28 |
| 2016 December | 49 | 15 | 64 |
| 2016 November | 53 | 11 | 64 |
| 2016 October | 65 | 14 | 79 |
| 2016 September | 68 | 7 | 75 |
| 2016 August | 45 | 3 | 48 |
| 2016 July | 29 | 3 | 32 |
| 2015 December | 2 | 0 | 2 |
| 2015 September | 2 | 20 | 22 |
| 2015 August | 5 | 12 | 17 |
| 2015 July | 23 | 9 | 32 |
| 2015 June | 34 | 7 | 41 |
| 2015 May | 56 | 6 | 62 |
| 2015 April | 44 | 10 | 54 |
| 2015 March | 41 | 2 | 43 |
| 2015 February | 59 | 4 | 63 |
| 2015 January | 59 | 12 | 71 |
| 2014 December | 54 | 6 | 60 |
| 2014 November | 56 | 6 | 62 |
| 2014 October | 44 | 8 | 52 |
| 2014 September | 41 | 4 | 45 |
| 2014 August | 44 | 6 | 50 |
| 2014 July | 50 | 11 | 61 |
| 2014 June | 42 | 10 | 52 |
| 2014 May | 46 | 11 | 57 |
| 2014 April | 35 | 11 | 46 |
| 2014 March | 56 | 14 | 70 |
| 2014 February | 50 | 10 | 60 |
| 2014 January | 46 | 9 | 55 |
| 2013 December | 38 | 3 | 41 |
| 2013 November | 35 | 6 | 41 |
| 2013 October | 33 | 12 | 45 |
| 2013 September | 41 | 4 | 45 |
| 2013 August | 49 | 13 | 62 |
| 2013 July | 33 | 5 | 38 |
| 2013 June | 44 | 10 | 54 |
| 2013 May | 39 | 10 | 49 |
| 2013 April | 31 | 6 | 37 |
| 2013 March | 33 | 9 | 42 |
| 2013 February | 27 | 7 | 34 |
| 2013 January | 29 | 9 | 38 |
| 2012 December | 26 | 13 | 39 |
| 2012 November | 45 | 6 | 51 |
| 2012 October | 23 | 6 | 29 |
| 2012 September | 12 | 4 | 16 |
| 2012 July | 4 | 0 | 4 |
| 2012 June | 9 | 0 | 9 |
| 2012 May | 10 | 0 | 10 |
| 2012 April | 11 | 0 | 11 |
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