Approach to interstitial lung disease associated with systemic sclerosis-A survey to pulmonologists and rheumatologists in Colombia.

INTRODUCTION: Interstitial lung disease is a leading cause of mortality in patients with systemic sclerosis. Currently, there is a lack of consensus regarding screening, rescreening, diagnosis, and follow-up practices in interstitial lung disease associated with systemic sclerosis (SSc-ILD) in Colombia. METHODS: A structured survey focused on clinical practices in patients with SSc-ILD was conducted. Members of the Asociación Colombiana de Neumología y Cirugía de Tórax (Asoneumocito) and the Asociación Colombiana de Reumatología (Asoreuma) were invited to participate from March 2023 to May 2023. RESULTS: We surveyed 51 pulmonologists and 44 rheumatologists. Overall, 51.6% reported having access to multidisciplinary team discussion in ILD. Among the 95 participants, 78.9% would routinely perform a high-resolution computed tomography scan of the chest once a diagnosis of systemic sclerosis was established. This practice is more frequent among rheumatologists (84.1%) than among pulmonologists (74.5%). Approximately half of the participants would rescreen patients annually with computed tomography scan (56.8%) if baseline images were negative. Spirometry (81.1%), diffusing capacity of the lung for carbon monoxide (80.0%), and 6-min walk test (55.8%) were the most frequently performed tests upon diagnosis of systemic sclerosis. During follow-up, participants would consider repeating pulmonary function tests mostly every 6 months. CONCLUSIONS: Screening of SSc-ILD is high among pulmonologists and rheumatologists. Decision-making on diagnosis and follow-up is similar between specialties, but there are variations in their frequency and indications. Further research is needed to evaluate how to adapt recommendations for assessing SSc-ILD in different settings.

Patrón de neumonía organizativa en TC de tórax: prevalencia y asociación con resultados clínicos en una cohorte de pacientes con COVID-19 grave/crítico / Organizing Pneumonia Pattern on Chest CT: Prevalence and Association with Clinical Outcomes in a Cohort of Patients with Severe/Critical COVID-19

Introducción: La neumonía por COVID-19 puede presentarse con dos patrones radio-lógicos: daño alveolar difuso o neumonía organizativa. Estos patrones tienen diferente evolución y pronóstico en pacientes sin infección por COVID-19. Nuestro objetivo fue evaluar la prevalencia del patrón radiológico de neumonía organizativa y su asociación con los desenlaces clínicos.Métodos: Se realizó un estudio de cohorte retrospectivo que incluyó a pacientes adultos hospitalizados por COVID-19 grave/crítica a los que se les realizó una tomografía computarizada de tórax en los 21 días posteriores al diagnóstico. Los patrones radiológicos fueron revisados y clasificados por dos radiólogos expertos. Resultados: De los 80 pacientes incluidos, el 89% (n=71) presentaron un patrón compatible con neumonía organizativa. Los principales hallazgos radiológicos fueron la distribución multilobar (98,7%) y bilateral (97,6%) con opacidades en vidrio esmerilado (97,6%). El 44% (n=33) de los sujetos requirió ingreso en cuidados intensivos, de los cuales el 24% (n=19) recibió ventilación mecánica. La presencia de neumonía organizativa se asoció de forma independiente con una disminución de las probabilidades de ventilación mecánica o muerte (Odds ratio 0,14; intervalo de confianza del 95%: 0,02 - 0,96; valor de p 0,045) en un modelo multivariado que incluía la edad, el sexo, el IMC y la afectación pulmonar en la TC.Conclusiones: Un patrón radiológico de neumonía organizativa es altamente prevalen-te en pacientes con COVID-19 grave/crítico y se asocia con mejores resultados clínico

Introduction: COVID-19 pneumonia can present with two distinct radiologic patterns: diffuse alveolar damage or organizing pneumonia. These patterns have been linked to different outcomes in non-COVID-19 settings. We sought to assess the prevalence of organizing pneumonia radiologic pattern and its association with clinical outcomes. Methods: We performed a retrospective cohort study including adult patients hospita- lized for severe/critical COVID-19 who underwent chest computed tomography within 21 days of diagnosis. Radiologic patterns were reviewed and classified by two expert radiologists. Results: Among 80 patients included, 89% (n=71) presented a pattern consistent with organizing pneumonia. The main radiologic findings were multilobar (98.7%) and bilateral (97.6%) distribution with ground glass opacities (97.6%). Intensive care admission was required for 44% (n=33) of subjects, of which 24% (n=19) received mechanical ventilation. The presence of organizing pneumonia was independently associated with a decreased odds of mechanical ventilation or death (Odds ratio 0.14; 95% confidence interval 0.02 - 0.96; p value 0.045) in a multivariate model including age, gender, BMI and lung involvement on CT. Conclusion: A radiologic pattern of organizing pneumonia is highly prevalent in patients with severe/critical COVID-19 and is associated with improved clinical outcomes.

Prevalencia de la enfermedad pulmonar esclerodermia-intersticial limitada frente a la extensa en el momento del diagnóstico de SSc-EPID según los criterios de Goh et al. Revisión sistemática y metaanálisis / Prevalence of the limited vs. extensive scleroderma-related interstitial lung disease at the time of diagnosis of SSc-ILD based on Goh et al. criteria. Systematic review and meta-analysis

Introducción: Goh et al. propusieron en 2008 un algoritmo clasificatorio de SSc-EPID limitada o extensa. La prevalencia de ambos en el momento del diagnóstico de SSc-EPID no se conoce con exactitud. Métodos: La revisión se realizó mediante MEDLINE y SCOPUS desde 2008 hasta 2023 y utilizando los términos: «sistémica», «esclerodermia» o «enfermedad pulmonar intersticial» [MesH]. Se utilizó la escala de Newcastle-Ottawa para la evaluación de la calificación de los estudios observacionales y la escala de Jadad para los ensayos clínicos. Se realizó el método inverso ponderado por la varianza. Resultados: Se incluyeron inicialmente 27 estudios en la revisión sistemática y metaanálisis (SRMA). De ellos, 17 estudios no tenían datos coincidentes. Comunicaron datos de 2.149 pacientes, 1.369 (81,2%) eran mujeres. La edad media era de 52,4 (DE 6,6) años. El 45,2% de los pacientes presentaban el subtipo difuso y el 54,8% el subtipo limitado o esclerodermia sinusal. El 38,7% de los pacientes presentaban anticuerpos antitopoisomerasa positivos y el 14,2% anticuerpos anticentrómero positivos. El porcentaje medio de capacidad vital forzada al inicio del estudio fue del 80,5% (DE 6,9) y de capacidad de difusión pulmonar para el monóxido de carbono fue del 59,1% (DE 9,6). Doce estudios presentaron datos de extensión de SSc-EPID ajustados por PFR y se incluyeron en el metaanálisis. Los 10 estudios observacionales de cohortes se analizaron por separado. El porcentaje global de afectación limitada se estimó en un 63,5% (IC del 95%: 55,3-73; p<0,001) utilizando el modelo de efectos aleatorios. La heterogeneidad entre estudios (I2) fue del 9,8% (IC del 95%: 0-68,2%). La afectación pulmonar extensa se estimó en 34,3% (IC del 95%: 26-45,4; p<0,001). La heterogeneidad entre estudios (I2) fue del 0% (IC del 95%: 0-61,6%) con el modelo de efectos aleatorios.(AU)

Introduction: Goh et al. proposed in 2008 a classificatory algorithm of limited or extensive SSc-ILD. The prevalence of both at the time of diagnosis of SSc-ILD is not known with exactitude. Methods: The review was undertaken by means of MEDLINE and SCOPUS from 2008 to 2023 and using the terms: “systemic”, “scleroderma” or “interstitial lung disease” [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment for observational studies and the Jadad scale for clinical trials. The inverse variance-weighted method was performed. Results: Twenty-seven studies were initially included in the systematic review and meta-analysis (SRMA). Of these, 17 studies had no overlapping data. They reported data from 2,149 patients, 1,369 (81.2%) were female. The mean age was 52.4 (SD 6.6) years. 45.2% of the patients had the diffuse subtype and 54.8% had the limited or sine scleroderma subtype. A total of 38.7% of the patients showed positive antitopoisomerase antibodies and 14.2% positive anticentromere antibodies. The mean percentage of forced vital capacity at baseline was 80.5% (SD 6.9) and of diffusing capacity of the lungs for carbon monoxide was 59.1% (SD 9.6). Twelve studies presented SSc-ILD extension data adjusted for PFTs and were included in the meta-analysis. The 10 observational cohort studies were analyzed separately. The overall percentage of limited extension was estimated at 63.5% (95%CI 55.3–73; p<0.001) using the random-effects model. Heterogeneity between studies (I2) was 9.8% (95%CI 0–68.2%) with the random-effects model. Extensive pulmonary involvement was estimated at 34.3% (95%CI 26–45.4; p<0.001). Heterogeneity between studies (I2) was 0% (95%CI 0–61.6%) with the random-effects model. Conclusion: The overall percentage of limited SSc-ILD at the time of diagnosis of SSc-ILD was estimated at 63.5% and extensive at 34.3%.(AU)

Pulmonary manifestations and prognosis of a cohort of patients with interstitial lung disease and positive to anti-Th/To autoantibodies / Manifestaciones pulmonares y pronóstico de una cohorte de pacientes con enfermedad pulmonar intersticial y autoanticuerpos anti-Th/To positivos

Introduction: Th/To autoantibody may be relevant in evaluating patients with interstitial lung disease (ILD) because the clinical diagnosis of systemic sclerosis (SSc) may not be evident. The study's objective was to describe manifestations and evolution of pulmonary function in a cohort of ILD patients positive for Th/To autoantibodies. Methods: ILD patients positive for anti-Th/To autoantibody were enrolled in this protocol. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. Results: Fifty-two patients positive for anti-Th/To autoantibodies with ILD were included. Only 21% of the patients fulfilled the ACR/EULAR 2013 systemic sclerosis classification criteria, and 63.4% fulfilled the IPAF ATS/ERS 2015 criteria. Twenty-five percent of the patients died during follow-up. Respiratory failure was the principal cause of death. Twenty-nine patients (56%) were positive for other hallmark SSc autoantibodies. The most frequent HRCT pattern was nonspecific interstitial pneumonia (NISP). Survival was strongly associated to the systolic pulmonary arterial pressure (sPAP), male sex and the extent of fibrosis in HRCT; besides, patients positive for other hallmark SSc autoantibodies had worse survival compared to those positive only to anti-Th/To. Seventy-six percent of them behaved as fibrotic progressive pulmonary disease, with an absolute decline of the FVC of at least 5%. Conclusions: Only a small proportion of ILD patients positive for Th/To meet the criteria to be classified as SSc; however, most met criteria for IPAF. A high proportion of patients behave as progressive fibrotic pulmonary disease. Survival is associated with sPAP, the extent of lung disease, and the presence of other hallmark SSc autoantibodies. (AU)

Introducción: El autoanticuerpo Th/To puede ser relevante en la evaluación de pacientes con enfermedad pulmonar intersticial (EPI) debido a que el diagnóstico clínico de esclerosis sistémica (ES) puede no ser evidente. El objetivo del estudio fue describir las manifestaciones clínicas y la evolución de la función pulmonar en una cohorte de pacientes con EPI positivos para autoanticuerpos Th/To. Métodos: En este protocolo se inscribieron pacientes con EPI positivos para autoanticuerpos anti-Th/To. Se registraron las características clínicas iniciales y se realizó un análisis de supervivencia para identificar los factores de riesgo asociados con una peor supervivencia. Resultados: Se incluyeron 52 pacientes positivos para autoanticuerpos anti-Th/To con EPI. Solo el 21% de los pacientes cumplió los criterios de clasificación para esclerosis sistémica ACR/EULAR 2013 y el 63,4% cumplió los criterios de neumonía con características autoinmunes ATS/ERS 2015. El 25% de los pacientes falleció durante el seguimiento. La insuficiencia respiratoria fue la principal causa de muerte. Veintinueve pacientes (56%) dieron positivo para otros autoanticuerpos distintivos de ES. El patrón más frecuente en la tomografía computarizada de alta resolución (TCAR) fue la neumonía intersticial inespecífica. La supervivencia estuvo estrechamente asociada con la presión arterial pulmonar sistólica (PAPs), el sexo masculino y la extensión de fibrosis en la TCAR. Además, los pacientes positivos para otros autoanticuerpos distintivos de ES tuvieron una peor supervivencia en comparación con aquellos positivos solo para anti-Th/To. El 66% de ellos se comportaron como enfermedad pulmonar fibrótica progresiva, con una disminución absoluta de la capacidad vital forzada de al menos el 5%. Conclusiones: Solo una pequeña proporción de pacientes con EPI positivos para Th/To cumplieron con los criterios para ser clasificados como ES... (AU)

Prevalence of the limited vs. extensive scleroderma-related interstitial lung disease at the time of diagnosis of SSc-ILD based on Goh et al. criteria. Systematic review and meta-analysis.

INTRODUCTION: Goh et al. proposed in 2008 a classificatory algorithm of limited or extensive SSc-ILD. The prevalence of both at the time of diagnosis of SSc-ILD is not known with exactitude. METHODS: The review was undertaken by means of MEDLINE and SCOPUS from 2008 to 2023 and using the terms: "systemic", "scleroderma" or "interstitial lung disease" [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment for observational studies and the Jadad scale for clinical trials. The inverse variance-weighted method was performed. RESULTS: Twenty-seven studies were initially included in the systematic review and meta-analysis (SRMA). Of these, 17 studies had no overlapping data. They reported data from 2,149 patients, 1,369 (81.2%) were female. The mean age was 52.4 (SD 6.6) years. 45.2% of the patients had the diffuse subtype and 54.8% had the limited or sine scleroderma subtype. A total of 38.7% of the patients showed positive antitopoisomerase antibodies (ATA) and 14.2% positive anticentromere antibodies (ACA). The mean percentage of forced vital capacity (FVC) at baseline was 80.5% (SD 6.9) and of diffusing capacity of the lungs for carbon monoxide (DLco) was 59.1% (SD 9.6). Twelve studies presented SSc-ILD extension data adjusted for PFTs and were included in the meta-analysis. The 10 observational cohort studies were analyzed separately. The overall percentage of limited extension was estimated at 63.5% (95%CI 55.3-73; p < 0.001) using the random-effects model. Heterogeneity between studies (I2) was 9.8% (95%CI 0-68.2%) with the random-effects model. Extensive pulmonary involvement was estimated at 34.3% (95%CI 26-45.4; p < 0.001). Heterogeneity between studies (I2) was 0% (95%CI 0-61.6%) with the random-effects model. CONCLUSION: The overall percentage of limited SSc-ILD at the time of diagnosis of SSc-ILD was estimated at 63.5% and extensive at 34.3%.

CXCL10 as a biomarker of interstitial lung disease in patients with rheumatoid arthritis.

INTRODUCTION: Pulmonary involvement is a frequent and serious rheumatoid arthritis (RA) manifestation that affects 60%-80% of patients. CXCL10 is an inflammatory chemokine that regulates different biological responses, such as chemotaxis, angiogenesis, and inflammation. AIM: This study aimed to identify the role of CXCL10 as a peripheral blood marker of RA-ILD and its correlation with disease activity. PATIENTS AND METHODS: This cross-sectional study included 73 patients with RA (33 with ILD and 40 without ILD). Pulmonary function tests and high-resolution computed tomography were performed. Blood samples were taken for complete blood count and blood chemistry analysis, and human interferon-inducible protein 10 (IP-10/CXCL10) level. Statistical Package for the Social Sciences (version 22) was used for all statistical calculations. RESULTS: The serum CXCL10 level and patient age (r=.393, p=.024), disease duration (r=.756, p<0.001), erythrocyte sedimentation rate (r=.516, p=.002), C-reactive protein (r=.539, p=.001), and rheumatoid factor (r=.663, p<.001) revealed a significant positive correlation. Furthermore, the Modified Health Assessment Questionnaire (r=-.418, p=.015) revealed a significant negative correlation. Patients with RA-ILD show significantly higher CXCL10 than those without ILD (p<.001). CONCLUSION: CXCL10 is a useful RA disease activity biomarker and is an RA-ILD-sensitive biomarker, also CXCL10 is a significant predictor for development of RA-ILD.

Pulmonary manifestations and prognosis of a cohort of patients with interstitial lung disease and positive to anti-Th/To autoantibodies.

INTRODUCTION: Th/To autoantibody may be relevant in evaluating patients with interstitial lung disease (ILD) because the clinical diagnosis of systemic sclerosis (SSc) may not be evident. The study's objective was to describe manifestations and evolution of pulmonary function in a cohort of ILD patients positive for Th/To autoantibodies. METHODS: ILD patients positive for anti-Th/To autoantibody were enrolled in this protocol. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. RESULTS: Fifty-two patients positive for anti-Th/To autoantibodies with ILD were included. Only 21% of the patients fulfilled the ACR/EULAR 2013 systemic sclerosis classification criteria, and 63.4% fulfilled the IPAF ATS/ERS 2015 criteria. Twenty-five percent of the patients died during follow-up. Respiratory failure was the principal cause of death. Twenty-nine patients (56%) were positive for other hallmark SSc autoantibodies. The most frequent HRCT pattern was nonspecific interstitial pneumonia (NISP). Survival was strongly associated to the systolic pulmonary arterial pressure (sPAP), male sex and the extent of fibrosis in HRCT; besides, patients positive for other hallmark SSc autoantibodies had worse survival compared to those positive only to anti-Th/To. Seventy-six percent of them behaved as fibrotic progressive pulmonary disease, with an absolute decline of the FVC of at least 5%. CONCLUSIONS: Only a small proportion of ILD patients positive for Th/To meet the criteria to be classified as SSc; however, most met criteria for IPAF. A high proportion of patients behave as progressive fibrotic pulmonary disease. Survival is associated with sPAP, the extent of lung disease, and the presence of other hallmark SSc autoantibodies.

CXCL10 as a biomarker of interstitial lung disease in patients with rheumatoid arthritis / CXCL10 como biomarcador de enfermedad pulmonar intersticial en pacientes con artritis reumatoide

Introduction: Pulmonary involvement is a frequent and serious rheumatoid arthritis (RA) manifestation that affects 60%–80% of patients. CXCL10 is an inflammatory chemokine that regulates different biological responses, such as chemotaxis, angiogenesis, and inflammation. Aim: This study aimed to identify the role of CXCL10 as a peripheral blood marker of RA-ILD and its correlation with disease activity. Patients and methods: This cross-sectional study included 73 patients with RA (33 with ILD and 40 without ILD). Pulmonary function tests and high-resolution computed tomography were performed. Blood samples were taken for complete blood count and blood chemistry analysis, and human interferon-inducible protein 10 (IP-10/CXCL10) level. Statistical Package for the Social Sciences (version 22) was used for all statistical calculations. Results: The serum CXCL10 level and patient age (r=.393, p=.024), disease duration (r=.756, p<0.001), erythrocyte sedimentation rate (r=.516, p=.002), C-reactive protein (r=.539, p=.001), and rheumatoid factor (r=.663, p<.001) revealed a significant positive correlation. Furthermore, the Modified Health Assessment Questionnaire (r=−.418, p=.015) revealed a significant negative correlation. Patients with RA-ILD show significantly higher CXCL10 than those without ILD (p<.001). Conclusion: CXCL10 is a useful RA disease activity biomarker and is an RA-ILD-sensitive biomarker, also CXCL10 is a significant predictor for development of RA-ILD.(AU)

Introducción: La afección pulmonar es una manifestación frecuente y grave de la artritis reumatoide (AR) que afecta al 60-80% de los pacientes. CXCL10 es una quimiocina inflamatoria que regula diferentes respuestas biológicas, como la quimiotaxis, la angiogénesis y la inflamación. Propósito: Este estudio tuvo como objetivo identificar el papel de CXCL10 como marcador en sangre periférica de RA-ILD y su correlación con la actividad de la enfermedad. Pacientes y métodos: Estudio transversal que incluyó a 73 pacientes con AR (33 con EPI y 40 sin EPI). Se realizaron pruebas de función pulmonar y tomografía computarizada de alta resolución. Se tomaron muestras de sangre para hemograma completo y análisis de química sanguínea y el nivel de proteína 10 inducible por interferón humano (IP-10/CXCL10). Se utilizó el paquete estadístico para las ciencias sociales (versión 22) para todos los cálculos estadísticos. Resultados: El nivel sérico de CXCL10 y la edad del paciente (r=0,393, p=0,024), la duración de la enfermedad (r=0,756, p<0,001), la velocidad de sedimentación globular (r=0,516, p=0,002), la proteína C reactiva (r=0,539, p=0,001) y el factor reumatoide (r=0,663, p<0,001) revelaron una correlación positiva significativa. Además, el Cuestionario de Evaluación de la Salud Modificado (r=−0,418, p=0,015) reveló una correlación negativa significativa. Los pacientes con RA-ILD muestran un CXCL10 significativamente mayor que aquellos sin ILD (p<0,001). Conclusión: CXCL10 es un biomarcador útil de la actividad de la enfermedad de AR y es un biomarcador sensible a AR-ILD, también CXCL10 es un predictor significativo para el desarrollo de AR-ILD.(AU)

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome / Anticuerpos contra las células parietales como biomarcadores potenciales de enfermedad pulmonar intersticial relacionada con el síndrome de Sjögren primario

Background ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. Methods Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. Results A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). Conclusion APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS (AU)

Antecedentes La enfermedad pulmonar intersticial (EPI) es una manifestación común del síndrome de Sjögren primario (SSp) y está relacionada con un mayor riesgo de muerte. Los anticuerpos anticélulas parietales (AACP) están fuertemente expresados por células epiteliales alveolares proliferantes en los pulmones fibróticos y están relacionados con la disminución acelerada de la función pulmonar en la gibrosis pulmonar idiopática. En este estudio, pretendemos evaluar la aplicación clínica de la AACP en pacientes con EPI con SSp. Método Se revisaron los datos clínicos, de laboratorio, de función pulmonar e imágenes de los pacientes con SSp y se utilizó la ESSDAI para evaluar la actividad de la enfermedad en general. Se registraron 5 características principales de imagen pulmonar de la EPI y 2 radiólogos ciegos experimentados realizaron una puntuación semicuantitativa de HRCT de forma independiente. Comparamos las características clínicas de los pacientes con y sin EPI con SSp y realizamos un análisis de regresión logística de los factores de riesgo de EPI en SSp. Resultados Un total de 74 pacientes con SSp y 40 controles sanos fueron incluidos en el estudio. La EPI es más común en el grupo positivo de AACP que en el grupo negativo de APCA. El nivel cuantitativo de AACP, está positivamente relacionado con la puntuación de imagen. El análisis multifactorial encontró que la larga duración, el aumento de los niveles de AACP y el aumento de los niveles de KL-6 fueron factores de riesgo independientes para la EPI en pacientes con SSp. El área bajo la curva ROC de AACP es de 0,6618 y la concentración umbral fue de 153,82 ng/ml (sensibilidad 45,24% y especificidad 87,50%). Conclusiones Los niveles de AACP son un factor de riesgo independiente y pueden ser biomarcadores potenciales de EPI en pacientes con SSp (AU)

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome.

BACKGROUND: ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. METHODS: Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. RESULTS: A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). CONCLUSION: APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS.

Enfermedad pulmonar intersticial en colangitis biliar primaria / Interstitial Lung Disease in Primary Biliary Cholangitis

RESUMEN Durante el transcurso de la colangitis biliar primaria se puede desarrollar compromiso intersticial pulmonar: neumonía organizada, fibrosis intersticial, neumonía intersticial linfoide, neumonía intersticial no específica. A pesar de que el diagnóstico de colangitis biliar primaria usualmente precede a las manifestaciones pulmonares, puede ocurrir lo inverso. La frecuencia de enfermedad intersticial en pacientes con colangitis biliar primaria no es conocida con exactitud. Puede estar o no asociada a otras enfermeda des del tejido conectivo; por lo tanto, es necesario realizar una búsqueda sistemática de estas y de las manifestaciones pulmonares de dicha entidad. Presentamos el caso de una paciente con diagnóstico previo de colangitis biliar primaria, la cual desarrolla durante el curso de su enfermedad, afectación pulmonar intersticial.

ABSTRACT During the course of PBC, interstitial lung involvement may develop: organizing pneu monia, interstitial fibrosis, lymphoid interstitial pneumonia, or non-specific interstitial pneumonia. Although the diagnosis of PBC usually precedes pulmonary manifestations, the opposite can occur. The frequency of interstitial disease in patients with PBC is not exactly known. It may or may not be associated with other connective tissue diseases; therefore, it is necessary to carry out a systematic search of these diseases and the pulmonary manifestations of this entity. We present the case of a patient with a previ ous diagnosis of PBC, who developed interstitial lung involvement during the course of the disease.

Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies / Factores de riesgo clínicos en pacientes con enfermedad pulmonar intersticial con anticuerpos anti-MDA5

Introduction The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. Methods This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. Results Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02–13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. Conclusion Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD (AU)

Introducción La enfermedad autoinmune asociada a los anticuerpos anti-MDA5 es una entidad poco estudiada. Los objetivos de este estudio son describir una cohorte de sujetos con enfermedad pulmonar intersticial (EPI) positivos al anticuerpo anti-MDA5 e identificar los factores clínicos de riesgo asociados con la supervivencia. Métodos Estudio de cohorte de un solo centro de pacientes con EPI y positivos al anticuerpo anti-MDA5. Se registraron las características clínicas basales y se realizó un análisis de supervivencia para identificar los factores de riesgo asociados con la supervivencia. Resultados Se incluyeron 53 pacientes con EPI y positivos a anti-MDA5; 12 pacientes fallecieron por una enfermedad intersticial rápidamente progresiva (EPI-RP). Los signos dermatológicos asociados a anti-MDA5 (pápulas de Gottron, signo de Gottron, pápulas palmares, signo de la V del escote, eritema facial de dermatomiositis y úlceras cutáneas) se asociaron fuertemente con la EPI-RP (HR: 3,7, IC 95%: 1,02-13,35). Los pacientes con manifestaciones dermatológicas eran más jóvenes, tenían mayores títulos de anticuerpos anti-MDA5, tenían mayor frecuencia de patrones inflamatorios en la tomografía de tórax de alta resolución y menor extensión de la fibrosis en la TCAR. Conclusión Las manifestaciones dermatológicas en los pacientes con EPI positivos a anticuerpos anti-MDA5 están asociados a EPI-RP y a desenlaces fatales al corto plazo. Los signos dermatológicos pueden identificar un subgrupo de pacientes positivos a anti-MDA5 con mayor riesgo de EPI-RP (AU)

Lista de comprobación para la atención farmacéutica del paciente con enfermedad pulmonar intersticial (CheckEPID): un consenso basado en el método Delphi / Checklist for Pharmaceutical Care of the Patient with interstitial lung disease (CheckEPID): A Delphi-based consensus

Objetivo desarrollar una lista de comprobación para facilitar la atención farmacéutica al paciente con enfermedad pulmonar intersticial que requieren o están en tratamiento con antifibróticos. Método 5 especialistas en farmacia hospitalaria desarrollaron un listado inicial de 37 ítems divididos en 4 bloques: 1) primera visita del paciente, que incluía datos generales del paciente y datos del primer tratamiento; 2) visitas de seguimiento, valorando aspectos del seguimiento del tratamiento con nintedanib o pirfenidona; 3) telefarmacia, consistente en la evaluación de la inclusión de pacientes en un programa de este tipo, evolución de la enfermedad e identificación del contacto con el servicio de farmacia y 4) tratamiento no farmacológico e información al paciente. Para decidir su potencial inclusión en el listado de comprobación se realizaron 2 rondas del Delphi en las que los panelistas tenían que valorar de cada ítem propuesto su grado de acuerdo con su «utilidad», que fue el criterio determinante para su inclusión y su «aplicabilidad». Resultados se contactó con 48 farmacéuticos hospitalarios, 30 (63%) aceptaron por escrito participar, 28 (58%) completaron la primera ronda del Delphi y 27 (56%) completaron la segunda ronda. Después de la primera ronda el cuestionario se modificó y quedó constituido por 40 ítems. De los 40 ítems evaluados tras las 2 rondas del Delphi, hubo 2 que, basados en la utilidad, los participantes del Delphi no alcanzaron el consenso para su inclusión en el listado: el referido a «Antecedentes de intervención quirúrgica, específicamente cirugía abdominal en las últimas 4 semanas» (finalmente mantenido en el listado por su implicación en la indicación de nintedanib) y el de realizar recomendaciones sobre «Relajación». En 2 de los ítems no se alcanzó consenso sobre su aplicabilidad: «Estratificación del paciente según el modelo del paciente crónico de la SEFH» y «Recogida de resultados comunicados por el paciente». Conclusiones... (AU)

Objective To develop a checklist to facilitate pharmaceutical care for patients with interstitial lung disease who require or are undergoing treatment with antifibrotic drugs. Method Five hospital pharmacists developed an initial list of 37 items divided into 4 blocks: 1) First visit, which included general patient data and data from the first treatment; 2) Follow-up visits, assessing aspects of the follow-up of the treatment with nintedanib or pirfenidone; 3) Telepharmacy, consisting of the evaluation of the inclusion of patients in a program of this type, course of the disease, and identification of the contact with the pharmacy service; 4) Non-pharmacological treatment and patient information. To decide its potential inclusion in the checklist, two rounds of the Delphi were carried out in which the panelists had to assess the degree of agreement of each proposed item according to its “utility”, which was the determining criterion for its inclusion, and its “applicability”. Results 48 hospital pharmacists were contacted, 30 (63%) agreed in writing to participate, 28 (58%) completed the first round of the Delphi, and 27 (56%) completed the second round. After the first round of the Delphi the questionnaire was amended and comprised 40 items. Of the 40 items evaluated after the two rounds of the Delphi, there were two that, based on utility, the participants did not reach consensus for inclusion in the checklist: The one referring to “History of surgical intervention, specifically abdominal surgery in the last 4 weeks” (finally kept on the checklist due to its involvement in the indication of nintedanib) and to make recommendations on “Relaxation”. No consensus was reached on their applicability for two of the items: “Patient stratification according to the Spanish Society of Hospital Pharmacy (SEFH) chronic patient model” and “Collection of Results Reported by the Patient”. Conclusions ... (AU)

Abordaje paliativo en enfermedades respiratorias avanzadas / Palliative Approach in Advanced Respiratory Diseases

Las enfermedades respiratorias crónicas avanzadas son prevalentes y producen deterioro de la calidad de vida, en particular la enfermedad pulmonar obstructiva crónica (EPOC), las enfermedades pulmonares intersticiales difusas (EPID) y las enfermedades neuromusculares progresivas con compromiso diafragmático (ENM). Quienes las padecen presentan síntomas persistentes que no son siempre adecuada-mente controlados por los tratamientos recomendados por las guías clínicas de mane-jo. El tratamiento paliativo de los síntomas persistentes es un punto relevante y suelen presentarse barreras para su implementación.Este artículo ofrece una revisión narrativa sobre una perspectiva latinoamericana acerca del rol de los cuidados paliativos en enfermedades respiratorias avanzadas.

Advanced chronic respiratory diseases are prevalent and cause deterioration in qual-ity of life, particularly chronic obstructive pulmonary disease (COPD), diffuse intersti-tial lung diseases (ILD) and progressive neuromuscular diseases with diaphragmatic involvement (NMD). Those who suffer from them usually present persistent symptoms that are not always adequately controlled by the treatments recommended by the clinical management guidelines. Palliative treatment of persistent symptoms is a relevant point, but the pal-liative approach usually presents barriers to its implementation.This article offers a narrative review over Latin American perspective on the role of pal-liative care in advanced respiratory diseases.

[Translated article] Checklist for the pharmaceutical care of patients with interstitial lung disease (CheckEPID): A Delphi-based consensus.

OBJECTIVE: To develop a checklist to facilitate pharmaceutical care for patients with interstitial lung disease who require or are undergoing treatment with antifibrotic drugs. METHOD: Five hospital pharmacists developed an initial list of 37 items divided into 4 blocks: (1) First visit, which included general patient data and data from the first treatment; (2) follow-up visits, assessing aspects of the follow-up of the treatment with nintedanib or pirfenidone; (3) telepharmacy, consisting of the evaluation of the inclusion of patients in a program of this type, course of the disease, and identification of the contact with the pharmacy service; (4) non-pharmacological treatment and patient information. To decide its potential inclusion in the checklist, 2 rounds of the Delphi were carried out in which the panelists had to assess the degree of agreement of each proposed item according to its "utility", which was the determining criterion for its inclusion, and its "applicability". RESULTS: Forty-eight hospital pharmacists were contacted, 30 (63%) agreed in writing to participate, 28 (58%) completed the first round of the Delphi, and 27 (56%) completed the second round. After the first round of the Delphi, the questionnaire was amended and comprised 40 items. Of the 40 items evaluated after the 2 rounds of the Delphi, there were 2 that, based on utility, the participants did not reach consensus for inclusion in the checklist: the one referring to "History of surgical intervention, specifically abdominal surgery in the last 4 weeks" (finally kept on the checklist due to its involvement in the indication of nintedanib) and to make recommendations on "Relaxation". No consensus was reached on their applicability for 2 of the items: "Patient stratification according to the Spanish Society of Hospital Pharmacy (SEFH) chronic patient model" and "Collection of Results Reported by the Patient". CONCLUSIONS: The management of patients with ILD and/or pulmonary fibrosis is complex and requires a multidisciplinary approach where the hospital pharmacist plays a key role, especially, although not only, in monitoring drug treatment. We believe that this checklist can contribute from pharmaceutical care to improving the integrated care of patients with ILD who require or are undergoing treatment with antifibrotic drugs.

Utilidad del ultrasonido para el diagnóstico de enfermedad pulmonar intersticial en enfermedades difusas del tejido conectivo / Ultrasound for diagnosis of interstitial lung disease in diffuse connective tissue diseases

Las enfermedades difusas del tejido conectivo con frecuencia desarrollan enfermedad pulmonar intersticial, lo que conlleva peor pronóstico y acorta la supervivencia. La tomografía axial computarizada de alta resolución es la prueba diagnóstica de elección, ya que esta es muy competitiva con la histopatología; sin embargo, el costo y la radiación pueden limitar su empleo, particularmente como escrutinio. El ultrasonido pulmonar, estudio rápido, de acceso fácil, reproducible y de menor costo, resulta muy atractivo para determinar la existencia de enfermedad pulmonar intersticial. Adicionalmente, se requiere de poca experiencia para determinar las alteraciones correlacionables con estos padecimientos pulmonares. Las líneas B y las irregularidades pleurales conforman el denominado síndrome intersticial ultrasonográfico, aunque debemos tener en mente que no es específico y estamos obligados a considerar anormalidades hemodinámicas, cardiovasculares e infecciosas. En esta revisión, exponemos la alta prevalencia de esta enfermedad pulmonar en los principales padecimientos reumatológicos, con énfasis en la utilidad del ultrasonido pulmonar, su facilidad de realización y alto desempeño diagnóstico. (AU)

Patients with diffuse connective tissue diseases frequently develop interstitial lung disease, which carries a worse prognosis and shortens survival. High-resolution computed tomography is the first-choice test, and is competitive with histopathology, however, the cost and radiation may limit its use, particularly for screening. Lung ultrasound is a rapid, accessible, reproducible, and inexpensive study that is useful for diagnosis of interstitial lung disease. Furthermore, extensive training is not required to identify the alterations associated with these lung diseases. B lines and pleural irregularities compose the ultrasonographic interstitial syndrome, although it must be kept in mind that it is not specific, and it is necessary to rule out haemodynamic, cardiovascular, and infectious abnormalities. This review highlights the elevated prevalence of this lung condition in the main rheumatological diseases, with emphasis on the usefulness of pulmonary ultrasound. (AU)

Description of a single centre cohort of patients with systemic sclerosis from the University Hospital of Buenos Aires and factors associated with lung function deterioration. A retrospective study.

INTRODUCTION: Given the paucity of data in Latin America and especially in Argentina regarding the epidemiology of SSc, the prevalence of ILD, its course, and particularly the response to treatment, our objective was to evaluate a cohort of SSc patients evaluated in a single University Hospital in Buenos Aires. PATIENTS/METHODS: We included 152 patients with SSc, followed from disease onset to last pulmonary function test and with at least two PFT and up to 30 months between each. RESULTS: Sixty-one percent had diffuse SSc (DSSc) and 32% limited SSc (LSSc). The only significant clinical differences between these groups were a higher initial mRodnan score and prevalence of ILD in the DSSc. These also had significantly more anti Scl-70 (Topoisomerase 1) antibodies compared to the LSSC group who had significantly more anti centromere antibodies. The DSSc group also had significantly more extensive damage on HRCT with no differences in terms of imaging patterns. Comparing patients with and without ILD by HRCT, those with ILD had significantly more extensive damage, significantly more anti Scl-70 antibodies, and significantly fewer anti centromere antibodies than those without ILD. Patients whose ILD progressed had a smoking history (OR 4.97) and prior immunosuppressive treatment (OR 15.6) (multivariate analysis). Overall disease duration was significantly shorter in those who progressed. CONCLUSIONS: Our SSc population had similar characteristics to those described elsewhere as well as prevalence of ILD and its progression. We found a shorter disease duration, smoking, and prior immunosuppressive treatment to be associated with ILD progression.

Description of a single centre cohort of patients with systemic sclerosis from the University Hospital of Buenos Aires and factors associated with lung function deterioration. A retrospective study / Descripción de una cohorte de pacientes con esclerosis sistémica del Hospital de la Universidad de Buenos Aires y factores asociados al deterioro de la función pulmonar. Un estudio retrospectivo

Introduction: Given the paucity of data in Latin America and especially in Argentina regarding the epidemiology of SSc, the prevalence of ILD, its course, and particularly the response to treatment, our objective was to evaluate a cohort of SSc patients evaluated in a single University Hospital in Buenos Aires. Patients/Methods: We included 152 patients with SSc, followed from disease onset to last pulmonary function test and with at least two PFT and up to 30 months between each. Results: Sixty-one percent had diffuse SSc (DSSc) and 32% limited SSc (LSSc). The only significant clinical differences between these groups were a higher initial mRodnan score and prevalence of ILD in the DSSc. These also had significantly more anti Scl-70 (Topoisomerase 1) antibodies compared to the LSSC group who had significantly more anti centromere antibodies. The DSSc group also had significantly more extensive damage on HRCT with no differences in terms of imaging patterns. Comparing patients with and without ILD by HRCT, those with ILD had significantly more extensive damage, significantly more anti Scl-70 antibodies, and significantly fewer anti centromere antibodies than those without ILD. Patients whose ILD progressed had a smoking history (OR 4.97) and prior immunosuppressive treatment (OR 15.6) (multivariate analysis). Overall disease duration was significantly shorter in those who progressed. Conclusions: Our SSc population had similar characteristics to those described elsewhere as well as prevalence of ILD and its progression. We found a shorter disease duration, smoking, and prior immunosuppressive treatment to be associated with ILD progression.(AU)

Introducción: La escasez de datos en Latinoamérica, y especialmente en Argentina, sobre la epidemiología de la esclerosis sistémica (SSc), la prevalencia de enfermedad pulmonar intersticial (EPID) y su progresión, llevó a evaluar una cohorte de pacientes con SSc atendidos en un hospital universitario de Buenos Aires, Argentina. Pacientes/Métodos: Incluimos 152 pacientes con SSc, seguidos desde el inicio de la enfermedad hasta el último examen funcional respiratorio (EFR) y con por lo menos dos EFR separados por un mínimo de 30 meses. Resultados: El 61% tenían enfermedad difusa (DSSc) y el 32%, limitada (LSSc). Aquellos con DSSc tuvieron significativamente un mayor índice modificado de Rodnan y prevalencia de EPID. Estos también tuvieron significativamente más anticuerpos anti-Scl-70 (topoisomerasa 1) comparados con LSSc, quienes tuvieron significativamente más anticuerpos anti-centrómero. Aquellos con DSSc mostraron significativamente más daño en la tomografía computada de alta resolución (TACAR), pero sin diferencias respecto a patrón de imágenes. Aquellos con EPID por TACAR tuvieron significativamente más daño, más anticuerpos anti Scl-70 y menos anticuerpos anti-centrómero que aquellos sin EPID. La progresión de EPID (análisis multivariado) se relacionó con consumo de tabaco (OR: 4,97) y uso previo de inmunosupresores (OR: 15,6). La duración de la enfermedad fue menor en los que progresaron. Conclusiones:Nuestra población de SSc tuvo características similares a lo descripto en el resto del mundo, así como la prevalencia y la progresión de EPID. Encontramos una menor duración de enfermedad, el consumo de tabaco y el uso previo de inmunosupresores asociados a la progresión de EPID.(AU)

Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies.

INTRODUCTION: The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. METHODS: This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. RESULTS: Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02-13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. CONCLUSION: Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD.

Checklist for Pharmaceutical Care of the Patient with interstitial lung disease (CheckEPID): A Delphi-based consensus. / Lista de comprobación para la atención farmacéutica del paciente con enfermedad pulmonar intersticial (CheckEPID): un consenso basado en el método Delphi.

OBJECTIVE: To develop a checklist to facilitate pharmaceutical care for patients with interstitial lung disease who require or are undergoing treatment with antifibrotic drugs. METHOD: Five hospital pharmacists developed an initial list of 37 items divided into 4 blocks: 1) First visit, which included general patient data and data from the first treatment; 2) Follow-up visits, assessing aspects of the follow-up of the treatment with nintedanib or pirfenidone; 3) Telepharmacy, consisting of the evaluation of the inclusion of patients in a program of this type, course of the disease, and identification of the contact with the pharmacy service; 4) Non-pharmacological treatment and patient information. To decide its potential inclusion in the checklist, two rounds of the Delphi were carried out in which the panelists had to assess the degree of agreement of each proposed item according to its "utility", which was the determining criterion for its inclusion, and its "applicability". RESULTS: 48 hospital pharmacists were contacted, 30 (63%) agreed in writing to participate, 28 (58%) completed the first round of the Delphi, and 27 (56%) completed the second round. After the first round of the Delphi the questionnaire was amended and comprised 40 items. Of the 40 items evaluated after the two rounds of the Delphi, there were two that, based on utility, the participants did not reach consensus for inclusion in the checklist: The one referring to "History of surgical intervention, specifically abdominal surgery in the last 4 weeks" (finally kept on the checklist due to its involvement in the indication of nintedanib) and to make recommendations on "Relaxation". No consensus was reached on their applicability for two of the items: "Patient stratification according to the Spanish Society of Hospital Pharmacy (SEFH) chronic patient model" and "Collection of Results Reported by the Patient". CONCLUSIONS: The management of patients with ILD and/or pulmonary fibrosis is complex and requires a multidisciplinary approach where the hospital pharmacist plays a key role, especially, although not only, in monitoring drug treatment. We believe that this checklist can contribute from pharmaceutical care to improving the integrated care of patients with ILD who require or are undergoing treatment with antifibrotic drugs.