Criterios de cribado de la enfermedad pulmonar intersticial difusa asociada a la artritis reumatoide: propuesta de expertos basada en metodología Delphi / Screening criteria for interstitial lung disease associated to rheumatoid arthritis: Expert proposal based on Delphi methodology

Objetivo: Elaborar una propuesta multidisciplinar de criterios de cribado de enfermedad pulmonar intersticial difusa (EPID) en pacientes con artritis reumatoide (AR) y, a la inversa, que sirvan de referencia en la derivación entre los servicios de Reumatología y Neumología para la detección precoz de estos pacientes. Métodos: Se revisó de forma sistemática la literatura sobre factores de riesgo para el desarrollo de EPID en la AR, la utilidad de los distintos métodos diagnósticos para su identificación en pacientes con AR y las diferentes propuestas de criterios de derivación a Reumatología por sospecha de AR precoz. Basándose en la evidencia disponible y en su experiencia clínica, un comité científico formado por dos reumatólogos y dos neumólogos propuso unos criterios de cribado que fueron evaluados mediante el método Delphi por un panel de siete neumólogos y siete reumatólogos. Todos los participantes eran expertos en esta patología. Resultados: Se han elaborado unos criterios para el cribado de EPID en pacientes diagnosticados de AR, y unos criterios para la detección precoz de AR en casos de EPID de causa no filiada. Se incluyen también propuestas sobre las pruebas complementarias a realizar en los diferentes escenarios clínicos considerados y sobre la periodicidad con la que debe repetirse el cribado. Conclusiones: Se propone por primera vez una estrategia de cribado selectivo para el diagnóstico precoz de los pacientes con EPID-AR. Esta propuesta pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones. Los criterios propuestos deben ser evaluados en futuros estudios de validación.(AU)

Objective: To develop a joint proposal for screening criteria of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and vice versa, which serves as a guidelines in patient referral between the Rheumatology and Pneumology departments to early detection of these patients. Methods: A systematic literature review was carried out on the risk factors for the development of ILD in RA patients, and for the referral criteria to Rheumatology for suspected early RA. Based on the available evidence, screening criteria were agreed using the Delphi method by a panel of pneumologists and rheumatologists with expertise in these pathologies. Results: Screening criteria for ILD in patients with RA and for the early detection of RA in cases with ILD of unknown etiology have been developed. In both cases, a detection strategy was based on clinical risk factors. Recommendations also included the complementary tests to be carried out in the different clinical scenarios and on the periodicity that screening should be repeated. Conclusion: A selective screening strategy is recommended for the first time in the early diagnosis of patients with ILD-RA. This multidisciplinary proposal aims to solve some common clinical questions and help decision-making, although its usefulness to identify these patients with good sensitivity must be confirmed in a validation study.(AU)

Screening criteria for interstitial lung disease associated to rheumatoid arthritis: Expert proposal based on Delphi methodology.

OBJECTIVE: To develop a joint proposal for screening criteria of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and vice versa, which serves as a guidelines in patient referral between the Rheumatology and Pneumology departments to early detection of these patients. METHODS: A systematic literature review was carried out on the risk factors for the development of ILD in RA patients, and for the referral criteria to Rheumatology for suspected early RA. Based on the available evidence, screening criteria were agreed using the Delphi method by a panel of pneumologists and rheumatologists with expertise in these pathologies. RESULTS: Screening criteria for ILD in patients with RA and for the early detection of RA in cases with ILD of unknown etiology have been developed. In both cases, a detection strategy was based on clinical risk factors. Recommendations also included the complementary tests to be carried out in the different clinical scenarios and on the periodicity that screening should be repeated. CONCLUSION: A selective screening strategy is recommended for the first time in the early diagnosis of patients with ILD-RA. This multidisciplinary proposal aims to solve some common clinical questions and help decision-making, although its usefulness to identify these patients with good sensitivity must be confirmed in a validation study.

Recomendaciones SER-SEPAR para el manejo de la enfermedad pulmonar intersticial difusa asociada a la artritis reumatoide. Parte 2: tratamiento / SER-SEPAR recommendations for the the management of rheumatoid arthritis-related interstitial lung disease. Part 2: Treatment

Objetivo: Elaborar unas recomendaciones multidisciplinares para mejorar el manejo de la enfermedad pulmonar intersticial difusa asociada a la artritis reumatoide (EPID-AR). Métodos: Un panel de reumatólogos y neumólogos expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Se realizaron revisiones sistemáticas de la evidencia, que se graduó de acuerdo con los criterios del SIGN. Tras ello, se formularon las recomendaciones. Resultados: Se seleccionaron seis preguntas PICO, tres de las cuales específicamente evaluaron la seguridad y la eficacia de los glucocorticoides, fármacos de acción lenta moduladores de la enfermedad (FAME) sintéticos clásicos e inmunosupresores, FAME biológicos, FAME sintéticos dirigidos y antifibróticos en el tratamiento de los pacientes con EPID-AR. Se formularon un total de 12 recomendaciones específicas sobre este tema con base en la evidencia encontrada y/o consenso de expertos. Conclusiones: Se presenta el primer documento oficial SER-SEPAR de recomendaciones específicas para el abordaje terapéutico de la EPID-AR con el fin de ayudar en la toma de decisiones a los clínicos directamente implicados en su manejo.(AU)

Objective: To develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). Methods: Clinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. Results: Six PICO questions were selected, three of which analysed the safety and effectiveness of glucocorticoids, classical synthetic disease-modifying anti-rheumatic drugs (DMARDs) and other immunosuppressants, biological agents, targeted synthetic DMARDs, and antifibrotic therapies in the treatment of this complication. A total specific of 12 recommendations on this topic were formulated based on the evidence found and/or expert consensus. Conclusions: We present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions, reduce clinical healthcare variability, and facilitate decision-making for patients.(AU)

Recomendaciones SER-SEPAR para el manejo de la enfermedad pulmonar intersticial difusa asociada a la artritis reumatoide. Parte 1: epidemiología, factores de riesgo y pronóstico / SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 1: Epidemiology, risk factors and prognosis

Objetivo: Elaborar unas recomendaciones multidisciplinares para mejorar el manejo de la enfermedad pulmonar intersticial difusa asociada a la artritis reumatoide (EPID-AR). Métodos: Un panel de reumatólogos y neumólogos expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Se realizaron revisiones sistemáticas de la evidencia, que se graduó de acuerdo con los criterios del Scottish Intercollegiate Guidelines Network (SIGN). Tras ello, se formularon las recomendaciones. Resultados: Se seleccionaron seis preguntas PICO, tres de las cuales específicamente evaluaron la incidencia y la prevalencia de esta complicación, los factores de riesgo para su desarrollo, y los factores pronósticos de mortalidad y de progresión de la EPID-AR. Se formularon un total de 6 recomendaciones específicas sobre estos aspectos, estructuradas por pregunta, con base en la evidencia encontrada y/o consenso de expertos. Conclusiones: Se presenta el primer documento oficial SER-SEPAR de recomendaciones específicas para el abordaje la EPID-AR, con el fin de ayudar en la toma de decisiones a los clínicos directamente implicados en su manejo y aproximar la práctica asistencial a la mejor evidencia posible.(AU)

Objective: To develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). Methods: Clinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. Results: Six PICO questions were selected, three of which analysed the incidence and prevalence of RA-ILD, associated risk factors, and predictors of progression and mortality. A total of 6 specific recommendations on these topics, structured by question, were formulated based on the evidence found and/or expert consensus. Conclusions: We present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions and facilitate decision-making for patients.(AU)

SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 2: Treatment.

OBJECTIVE: To develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. RESULTS: Six PICO questions were selected, three of which analysed the safety and effectiveness of glucocorticoids, classical synthetic disease-modifying anti-rheumatic drugs (DMARDs) and other immunosuppressants, biological agents, targeted synthetic DMARDs, and antifibrotic therapies in the treatment of this complication. A total of 12 recommendations were formulated based on the evidence found and/or expert consensus. CONCLUSIONS: We present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions, reduce clinical healthcare variability, and facilitate decision-making for patients.

SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 1: Epidemiology, risk factors and prognosis.

OBJECTIVE: To develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). METHODS: Clinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. RESULTS: Six PICO questions were selected, three of which analysed the incidence and prevalence of RA-ILD, associated risk factors, and predictors of progression and mortality. A total of 6 specific recommendations on these topics, structured by question, were formulated based on the evidence found and/or expert consensus. CONCLUSIONS: We present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions and facilitate decision-making for patients.

Prevalencia y características clínicas de la enfermedad pulmonar intersticial difusa sintomática en la artritis reumatoide en una población española / Prevalence and clinical characteristics of symptomatic diffuse interstitial lung disease in rheumatoid arthritis in a Spanish population

Antecedentes y objetivos: En España, los estudios epidemiológicos de prevalencia de enfermedad pulmonar intersticial difusa (EPID) en artritis reumatoide (AR) son escasos y limitados. Nuestro objetivo fue estimar la prevalencia de EPID sintomática en AR y sus características en nuestra área. Materiales y métodos: Se diseñó un estudio observacional longitudinal prospectivo en la consulta interdisciplinar de Reumatología y Neumología, en el que incluimos AR con síntomas respiratorios y EPID confirmada por tomografía computarizada de alta resolución. Resultados: De las 2.729 personas con AR de nuestra área, 47 presentaban EPID sintomática, estimándose una prevalencia de EPID sintomática en AR del 1,72% (intervalo de confianza del 95%: 1,26-2,29) con una edad al diagnóstico de AR de 57,3±13,3 años. Fue más frecuente en hombres, el 60,6% tenía antecedente de tabaquismo y el 84,3 y el 84,7% factor reumatoide y anticuerpos antipéptidos cíclicos citrulinados, respectivamente. El patrón más frecuente fue neumonía intersticial usual (NIU) en 28 (31,1%), la neumonía intersticial no específica (NINE) fue más frecuente en mujeres y el síndrome combinado enfisema-fibrosis (SCEF) exclusivamente en hombres. Conclusiones: En este estudio hemos analizado la prevalencia de AR-EPID sintomática en nuestra área, la cual está por debajo de lo esperado, probablemente en relación con las definiciones utilizadas. Así mismo, hemos descrito que el patrón NIU es el más frecuente en la AR, seguido del NINE y analizado por primera vez la prevalencia de SCEF en la AR, que alcanza el 13% (AU)

Background and objectives: In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. Materials and methods: In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. Results: Of the 2,729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26 - 2.29) with an age at diagnosis of RA of 57.3±13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. Conclusions: We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time (AU)

Different Faces of Idiopathic Pulmonary Fibrosis With Preserved Forced Vital Capacity / Diferentes caras de la fibrosis pulmonar idiopática con capacidad vital forzada preservada

Introduction Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. Methods Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. Results 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern. Conclusions Patients with preserved FVC but presenting UIP radiological pattern and moderate–severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Introducción La fibrosis pulmonar idiopática (FPI) es progresiva e irreversible. Existen algunas discrepancias sobre la estadificación de la FPI, especialmente en las fases leves. La capacidad vital forzada (FVC) superior al 80% se ha considerado una FPI temprana o leve incluso para el diseño de ensayos clínicos. Métodos Estudio español multicéntrico, observacional, retrospectivo de pacientes con FPI diagnosticados entre 2012-2016, en función de los criterios ATS/ERS, que presentaban FVC mayor o igual al 80% al diagnóstico. Se analizaron características clínicas y demográficas, función pulmonar, patrón radiológico, tratamiento y seguimiento. Resultados Se incluyeron 225 pacientes con FPI, el 72,9% eran varones. La edad media fue de 69,5 años. El patrón predominante en la tomografía computarizada de alta resolución (TCAR) fue compatible con neumonía intersticial usual (NIU) (51,6%). El 84,7% de los pacientes presentó síntomas respiratorios (disnea de esfuerzo o tos) y el 33,33% mostró desaturación con una saturación de oxígeno inferior al 90% en la prueba de la marcha de los 6min (PM6M). El tratamiento antifibrótico se inició en el momento del diagnóstico en el 55,11% de los pacientes. La mediana de la CVF fue del 89,6% (RIC 17) y el 58,7% de los pacientes presentó una disminución de la capacidad pulmonar de difusión del monóxido de carbono (DLCO) por debajo del 60% del valor teórico; la mayoría presentó progresión funcional (61,4%) y una mayor mortalidad a los 3 años (20,45%). Se observó una correlación estadísticamente significativa de la mortalidad a los 3 años entre una DLCO<60% y el patrón radiológico compatible con UIP. Conclusiones Los pacientes con FVC conservada pero que presentan patrón radiológico de NIU y disminución moderada-grave de la de DLCO en el momento del diagnóstico se asociaron a un mayor riesgo de progresión, fallecimiento o tener que recibir un trasplante de pulmón. Por lo tanto, en estos casos, una FVC preservada no sería representativa de una FPI temprana o leve

Smoking-related interstitial lung disease.

Exposure to smoke is associated with the development of diseases of the airways and lung parenchyma. Apart from chronic obstructive pulmonary disease (COPD), in some individuals, tobacco smoke can also trigger mechanisms of interstitial damage that result in various pathological changes and pulmonary fibrosis. A causal relation has been established between tobacco smoke and a group of entities that includes respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell histiocytosis (LCH), and acute eosinophilic pneumonia (AEP). Smoking is considered a risk factor for idiopathic pulmonary fibrosis (IPF); however, the role and impact of smoking in the development of this differentiated clinical entity, which has also been called combined pulmonary fibrosis and emphysema (CPFE) as well as nonspecific interstitial pneumonia (NIP), remains to be determined. The definition of smoking-related interstitial fibrosis (SRIF) is relatively recent, with differentiated histological characteristics. The likely interconnection between the mechanisms involved in inflammation and pulmonary fibrosis in all these processes often results in an overlapping of clinical, radiological, and histological features in the same patient that can sometimes lead to radiological patterns of interstitial lung disease that are impossible to classify. For this reason, a combined approach to diagnosis is recommendable. This combined approach should be based on the joint interpretation of the histological and radiological findings while taking the clinical context into consideration. This paper aims to describe the high-resolution computed tomography (HRCT) findings in this group of disease entities in correlation with the clinical manifestations and histological changes underlying the radiological pattern.

Different Faces of Idiopathic Pulmonary Fibrosis With Preserved Forced Vital Capacity.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. METHODS: Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. RESULTS: 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern. CONCLUSIONS: Patients with preserved FVC but presenting UIP radiological pattern and moderate-severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Prevalence and clinical characteristics of symptomatic diffuse interstitial lung disease in rheumatoid arthritis in a Spanish population.

BACKGROUND AND OBJECTIVES: In Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. MATERIALS AND METHODS: In our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. RESULTS: Of the 2729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26-2.29) with an age at diagnosis of RA of 57.3 ±â€¯13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. CONCLUSIONS: We have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.

Systematic review of the impact of drugs on diffuse interstitial lung disease associated with rheumatoid arthritis.

OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such us TNFi, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.

Revisión sistemática sobre el impacto de los fármacos en la enfermedad pulmonar intersticial difusa asociada a Artritis Reumatoide / Systematic Review of the Impact of Drugs on Diffuse Interstitial Lung Disease Associated with Rheumatoid Arthritis

Objetivo: Revisar la evidencia disponible sobre la repercusión de los tratamientos de la artritis reumatoide (AR) en la enfermedad pulmonar intersticial difusa (EPID) asociada. Métodos: Revisión sistemática de estudios que evalúan el impacto del tratamiento farmacológico en pacientes con AR y EPID. Se realizó una búsqueda bibliográfica en MEDLINE, EMBASE y Cochrane, selección de artículos y evaluación de la calidad metodológica (FLC 3.0 OSTEBA) y graduación del nivel de evidencia (SING). Resultados: Se identificaron 1.720 referencias en búsqueda primaria y 7 en manual o indirecta. Se incluyeron 43 artículos: 7 revisiones sistemáticas, 2 ensayos clínicos aleatorizados, 5 estudios de cohortes, 8 estudios de casos-controles y 21 series de casos. Metotrexato (MTX) y leflunomida (LEF) no aumentan la incidencia, complicaciones ni mortalidad por EPID. Aunque los resultados no son uniformes, los anti-TNF han tenido con frecuencia peores resultados en incidencia, progresión y mortalidad por EPID que MTX, LEF, abatacept (ABA) y rituximab (RTX). La evidencia encontrada es escasa para los inhibidores de JAK quinasas y antifibróticos, y controvertida para los inhibidores de la IL-6. Conclusiones: No existe evidencia de que MTX o LEF empeoren el pronóstico de los pacientes con AR-EPID. RTX y ABA parecen tener mejores resultados que otros biológicos, como anti-TNF, consiguiendo con frecuencia la estabilización y, en algunos casos, la mejoría de la EPID en pacientes con AR.(AU)

Objective: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). Methods: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. Results: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. Conclusions: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such as anti-TNF, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.(AU)

Detection of autoantibodies in bronchoalveolar lavage in patients with diffuse interstitial lung disease / Detección de autoanticuerpos en el lavado broncoalveolar en pacientes con enfermedad pulmonar intersticial difusa

Introduction: Serum autoantibodies support the diagnosis of interstitial lung disease (ILD) related to systemic autoimmune diseases (SAD-ILD). Nevertheless, their presence in the bronchoalveolar lavage (BAL) has not been explored.Objectives: To demonstrate the presence of autoantibodies in the BAL of ILD patients at onset of clinical evaluation, its relation with serum autoantibodies and to analyze clinical features of patients with autoantibodies in BAL.Methods: Autoantibodies against extractable nuclear antigens (ENAs) were analyzed by immunoblot in the BAL of 155 patient with suspected diagnosis of ILD and 10 controls.Results: Seven ENAs were detected in the BAL of 19 patients (Anti-Ro52, Anti-Ro60, CENP-B, Anti-La, Jo-1, Sm/RNP and Anti-SL70). The most frequent ENA was anti-Ro52 (13 patients; 68,4% of positives ones). Seven patients presented more than one ENAs. Fourteen were diagnosed of SAD-ILD, 3 of interstitial pneumonia with autoimmune features, one of non-specific idiopathic pneumonia and other of silicosis. In 10 cases (52%) IgA autoantibodies were also detected. The autoantibodies observed in BAL were also detected in the serum of 17 patients (90%). There were no significant clinical differences with the patients with SAD-ILD or interstitial pneumonia with autoimmune features with patients with negative BAL.Conclusion: The study of ENAs in BAL is feasible and can be a useful tool in the ILD initial algorithm, specifically sustaining the suspected diagnosis of SAD-ILD. (AU)

Introducción: Los autoanticuerpos séricos apoyan el diagnóstico de sospecha en la enfermedad intersticial difusa (EPID) asociada a enfermedades autoinmunes sistémicas (EPID-EAS). Su presencia en el lavado broncoalveolar (LBA) no ha sido estudiada.Objetivos: Demostrar la presencia de autoanticuerpos en el LBA de pacientes con EPID de inicio, compararlos con los resultados del suero y analizar los aspectos clínicos de los pacientes con autoanticuerpos en el LBA.Métodos: Se analizaron autoanticuerpos contra antígenos extraíbles del núcleo (ENA) mediante inmunoblot en el LBA de 155 pacientes con sospecha diagnóstica de EPID y 10 controles.Resultados: Se detectaron 7 especificidades ENA en el LBA de 19 pacientes (anti-Ro52, anti-Ro60, CENP-B, anti-La, Jo-1, Sm/RNP y anti-SL70), siendo el anti-Ro52 el más frecuente (13 pacientes; 68,4% de los positivos). Siete pacientes presentaron más de una especificidad. Catorce fueron diagnosticados de EPID-EAS, 3 de neumonía intersticial con rasgos autoinmunes, uno de neumonía intersticial no específica idiopática y otro de silicosis. En 10 casos (52%) se detectaron autoanticuerpos de clase IgA en el LBA. Los autoanticuerpos detectados en LBA también se hallaron en el suero de 17 pacientes (90%). No hubo diferencias clínicas significativas entre los pacientes con autoanticuerpos en LBA con respecto a aquellos con EPID-EAS o neumonía intersticial con rasgos autoinmunes con LBA negativo.Conclusión: El estudio de ENA en LBA es factible y puede ser una herramienta útil en el algoritmo inicial en la EPID, concretamente, para apoyar el diagnóstico de sospecha de la EPID-EAS. (AU)

Utilidad de la ecografía extraarticular aplicada a las enfermedades inflamatorias sistémicas en la práctica clínica / Usefulness of extra-articular ultrasound applied to systemic inflammatory diseases in clinical practice

La ecografía es una técnica de imagen no invasiva, inocua, reproducible y coste-eficiente, que aporta información inmediata al poder realizarla en nuestras consultas. El buen perfil de la técnica y los avances tecnológicos acontecidos en los últimos años, que han permitido una mejora sustancial en la resolución de la imagen hasta hacerla casi anatómica, han impulsado la investigación sobre su aplicación al estudio integral de las enfermedades inflamatorias sistémicas. En la actualidad, se ha traspasado el umbral de utilizar la ecografía para investigar exclusivamente las manifestaciones músculo-esqueléticas, para aplicarla también al estudio de las manifestaciones extraarticulares y las comorbilidades asociadas a las enfermedades reumáticas. En la presente revisión repasaremos su utilidad para el diagnóstico de la afectación glandular en el síndrome de Sjögren, la enfermedad pulmonar intersticial o la arteritis de células gigantes y para la estratificación del riesgo cardiovascular en pacientes con enfermedades reumáticas inflamatorias crónicas.(AU)

Ultrasound is a non-invasive, innocuous, reproducible, cost-efficient imaging technique that provides immediate information, as it can be performed in our consultations. The good profile of ultrasound and the technological advances that have taken place in recent years, which have allowed a substantial improvement in the resolution of the image to make it almost anatomical, have promoted research on its application in the comprehensive study of systemic inflammatory diseases. At present, the threshold of using ultrasound to exclusively investigate musculoskeletal manifestations has been crossed, to also apply it to the study of extra-articular manifestations and comorbidities associated with rheumatic diseases. In this review we will revise its usefulness for the diagnosis of glandular involvement in Sjögren's syndrome, interstitial lung disease or giant cell arteritis and for stratification of cardiovascular risk in patients with chronic inflammatory rheumatic diseases.(AU)

Detection of Autoantibodies in Bronchoalveolar Lavage in Patients with Diffuse Interstitial Lung Disease. / Detección de autoanticuerpos en el lavado broncoalveolar en pacientes con enfermedad pulmonar intersticial difusa.

INTRODUCTION: Serum autoantibodies support the diagnosis of interstitial lung disease (ILD) related to systemic autoimmune diseases (SAD-ILD). Nevertheless, their presence in the bronchoalveolar lavage (BAL) has not been explored. OBJECTIVES: To demonstrate the presence of autoantibodies in the BAL of ILD patients at onset of clinical evaluation, its relation with serum autoantibodies and to analyze clinical features of patients with autoantibodies in BAL. METHODS: Autoantibodies against extractable nuclear antigens (ENAs) were analyzed by immunoblot in the BAL of 155 patient with suspected diagnosis of ILD and 10 controls. RESULTS: Seven ENAs were detected in the BAL of 19 patients (Anti-Ro52, Anti-Ro60, CENP-B, Anti-La, Jo-1, Sm/RNP and Anti-SL70). The most frequent ENA was anti-Ro52 (13 patients; 68,4% of positives ones). Seven patients presented more than one ENAs. Fourteen were diagnosed of SAD-ILD, 3 of interstitial pneumonia with autoimmune features, one of non-specific idiopathic pneumonia and other of silicosis. In 10 cases (52%) IgA autoantibodies were also detected. The autoantibodies observed in BAL were also detected in the serum of 17 patients (90%). There were no significant clinical differences with the patients with SAD-ILD or interstitial pneumonia with autoimmune features with patients with negative BAL. CONCLUSION: The study of ENAs in BAL is feasible and can be a useful tool in the ILD initial algorithm, specifically sustaining the suspected diagnosis of SAD-ILD.

Usefulness of extra-articular ultrasound applied to systemic inflammatory diseases in clinical practice. / Utilidad de la ecografía extraarticular aplicada a las enfermedades inflamatorias sistémicas en la práctica clínica.

Ultrasound is a non-invasive, innocuous, reproducible, cost-efficient imaging technique that provides immediate information, as it can be performed in our consultations. The good profile of ultrasound and the technological advances that have taken place in recent years, which have allowed a substantial improvement in the resolution of the image to make it almost anatomical, have promoted research on its application in the comprehensive study of systemic inflammatory diseases. At present, the threshold of using ultrasound to exclusively investigate musculoskeletal manifestations has been crossed, to also apply it to the study of extra-articular manifestations and comorbidities associated with rheumatic diseases. In this review we will revise its usefulness for the diagnosis of glandular involvement in Sjögren's syndrome, interstitial lung disease or giant cell arteritis and for stratification of cardiovascular risk in patients with chronic inflammatory rheumatic diseases.

Systematic Review of the Impact of Drugs on Diffuse Interstitial Lung Disease Associated with Rheumatoid Arthritis. / Revisión sistemática sobre el impacto de los fármacos en la enfermedad pulmonar intersticial difusa asociada a Artritis Reumatoide.

OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such as anti-TNF, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.

A Multidisciplinary Proposal for a Diagnostic Algorithm in Idiopathic Pulmonary Fibrosis: The Role of Transbronchial Cryobiopsy. / Propuesta multidisciplinar respecto al algoritmo diagnóstico de la fibrosis pulmonar idiopática: papel de la criobiopsia transbronquial.

The diagnosis of idiopathic pulmonary fibrosis (IPF) is a complex process that requires the multidisciplinary integration of clinical, radiological, and histological variables. Due to its diagnostic yield, surgical lung biopsy has been the recommended procedure for obtaining samples of lung parenchyma, when required. However, given the morbidity and mortality of this technique, alternative techniques which carry a lower risk have been explored. The most important of these is transbronchial cryobiopsy -transbronchial biopsy with a cryoprobe- which is useful for obtaining lung tissue with less comorbidity. Yield may be lower than surgical biopsy, but it is higher than with transbronchial biopsy with standard forceps. This option has been discussed in the recent clinical guidelines for the diagnosis of IPF, but the authors do not go so far as recommend it. The aim of this article, the result of a multidisciplinary discussion forum, is to review current evidence and make proposals for the use of transbronchial cryobiopsy in the diagnosis of IPF.

Questions and Answers on Smoking in Patients With Diffuse ILD. Use of PICO Methodology. / Preguntas y respuestas relacionadas con tabaquismo en pacientes con EPID. Aplicación de metodología con formato PICO.

INTRODUCTION: The Smoking and the Diffuse Interstitial Lung Diseases (ILD) groups of ALAT and SEPAR collaborated in the preparation of this document. MATERIALS AND METHODS: This document uses PICO methodology to answer various questions on the relationship between tobacco use and diffuse ILD. RESULTS AND CONCLUSIONS: The main recommendations are: a) moderate level of evidence and strong recommendation to consider smoking as a risk factor for the development and/or modification of the progression of diffuse ILD; b) moderate level of evidence to identify an increase in mortality in diffuse ILD, irrespective of histologic pattern. Low evidence for ascribing it to smoking and strong recommendation for the early identification of patients with diffuse ILD. Further studies are needed to evaluate the effect of smoking cessation in patients with diffuse ILD; c) low level of evidence and weak recommendation for defining the impact of passive smoking in diffuse ILD; d) low level of evidence to demonstrate that smoking cessation improves the outcomes of patients diagnosed with diffuse ILD and strong recommendation to advise smoking cessation in smokers with diffuse ILD, and e) low level of evidence to support the clinical or epidemiological usefulness of active case finding for diffuse ILD in smoking cessation programs, and strong recommendation justifying the performance of spirometry in active case finding, based not on current smoking status, but on previous accumulated consumption, even in asymptomatic cases.