Initial results with [18F]FAPI-74 PET/CT in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. 68Ga-labeled FAP ligands exhibited highly promising results due to the crucial role of activated fibroblasts in fibrosis imaging of the lung. However, 18F-labeled FAP ligands might provide qualitatively much higher imaging results with accompanying economic benefits due to large-scale production. Thus, we sought to investigate the potential of [18F]FAPI-74 prospectively in a small patient cohort. METHODS: Eight patients underwent both [18F]FAPI-74-PET/CT and HRCT scans and were then compared with a control group without any fibrosing pulmonary disease. The tracer uptake of fibrotic lung areas was analyzed in synopsis with radiological and clinical parameters. RESULTS: We observed a positive correlation between the fibrotic active volume, the Hounsfield scale, as well as the vital and diffusing capacity of the lung. CONCLUSION: The initial results confirm our assumption that [18F]FAPI-74 offers a viable non-invasive assessment method for pulmonary fibrotic changes in patients with IPF.

Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement.

Background: The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema (CPFE). The lack of consensus over definitions and diagnostic criteria has limited CPFE research. Goals: The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome. Methods: This research statement was developed by a committee including 19 pulmonologists, 5 radiologists, 3 pathologists, 2 methodologists, and 2 patient representatives. The final document was supported by a focused systematic review that identified and summarized all recent publications related to CPFE. Results: This task force identified that patients with CPFE are predominantly male, with a history of smoking, severe dyspnea, relatively preserved airflow rates and lung volumes on spirometry, severely impaired DlCO, exertional hypoxemia, frequent pulmonary hypertension, and a dismal prognosis. The committee proposes to identify CPFE as a syndrome, given the clustering of pulmonary fibrosis and emphysema, shared pathogenetic pathways, unique considerations related to disease progression, increased risk of complications (pulmonary hypertension, lung cancer, and/or mortality), and implications for clinical trial design. There are varying features of interstitial lung disease and emphysema in CPFE. The committee offers a research definition and classification criteria and proposes that studies on CPFE include a comprehensive description of radiologic and, when available, pathological patterns, including some recently described patterns such as smoking-related interstitial fibrosis. Conclusions: This statement delineates the syndrome of CPFE and highlights research priorities.

Latin American Registry of Idiopathic Pulmonary Fibrosis (REFIPI): Clinical Characteristics, Evolution and Treatment.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and frequently fatal disease. Currently there are national and multinational registries in Europe, United States, Australia and China to better understand the magnitude of the problem and the characteristics of the IPF patients. However, there are no national or regional registries in Latin America, so the objective of this study was to carry out a Latin American registry that would allow the identification of IPF patients in our region. METHODOLOGY: A system consisting of 3 levels of control was designed, ensuring that patients met the diagnostic criteria for IPF according to international guidelines ATS/ERS/ALAT/JRS 2011. Demographic, clinical, serological, functional, tomographic, histological and treatment variables were recorded through a digital platform. RESULTS: 761 IPF patients from 14 Latin American countries were included for analysis, 74.7% were male, with a mean age of 71.9+8.3 years. In general there was a long period of symptoms before definitive diagnosis (median 1 year). In functional tests, an average reduction of FVC (70.9%) and DLCO (53.7%) was detected. 72% received at least one antifibrotic drug (pirfenidone or nintedanib) and 11.2% of the patients had an acute exacerbation, of which 38 (45.2%) died from this cause. CONCLUSIONS: Like other registries, we found that there is difficulty in the recognition and excessive delay in the diagnosis of IPF in Latin America. Most of the patients in REFIPI received antifibrotics; these were well tolerated and associated with fewer adverse events than those reported in clinical trials.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study / Enfermedad pulmonar intersticial asociada con miositis: Características clínicas y factores relacionados con la mejoría de la función pulmonar. Estudio latinoamericano multicéntrico de cohorte

Background and objectives: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. Methods: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. Results: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. Conclusions: Worse baseline PF could be related to the absence of extra-thoracic symptoms and “classic” antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.(AU)

Antecedentes y objetivos: Los pacientes con enfermedad pulmonar intersticial (EPI) pueden presentar positividad para autoanticuerpos específicos de enfermedades autoinmunes, como los anticuerpos mioespecíficos (AME) o mioasociados (AMA). Existe escasa información disponible sobre pronóstico y respuesta al tratamiento de estos pacientes. Nuestro objetivo fue describir las características clínicas, radiológicas, funcionales y pronósticas de una cohorte latinoamericana de pacientes con EPI y AME/AMA. Métodos: Estudio retrospectivo multicéntrico de una cohorte pacientes con EPI y AME/AMA, evaluados en tres centros latinoamericanos entre 2016 y 2018. Describimos variables clínicas, tomográficas y funcionales. Analizamos variables asociadas con valores funcionales bajos al inicio y mejoría funcional mediante regresión logística. Resultados: Incluimos 211 pacientes, 77,4% mujeres, con una media de edad de 57 años. Los anticuerpos más frecuentes fueron Ro-52 y Jo-1. Valores funcionales bajos al inicio se asociaron con la presencia de EPI desde el debut y con un patrón de neumonía intersticial no específica (NINE)/neumonía organizativa (NO) en la tomografía computarizada de alta resolución (TACAR). Se analizó la evolución funcional en 121 pacientes: 48% permanecieron estables y 33% presentaron mejoría. El patrón de NO en TACAR, se asoció significativamente con mejoría funcional, mientras que la presencia de EPI desde el debut y la ausencia de esclerodactilia mostraron una tendencia en el análisis multivariado. Conclusiones: Valores funcionales bajos al debut podrían asociarse con la ausencia de síntomas extratorácicos al inicio, por llevar a un diagnóstico y tratamiento tardíos. Por el contrario, la presencia de síntomas sistémicos al debut, junto con formas más agudas de EPI como NINE/NO podrían asociarse con mejoría funcional por permitir un diagnóstico y tratamiento precoz.(AU)

Myositis-associated Interstitial Lung Disease: Clinical Characteristics and Factors Related to Pulmonary Function Improvement: A Latin-American Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: ILD patients can be positive to highly specific autoantibodies of connective tissue diseases (CTD). Among them stand out myositis-specific and associated autoantibodies (MSA/MAA). There is limited knowledge about treatment response and prognosis of ILD patients positive to MSA/MAA (MSA/MAA-ILD). Our aim was to describe clinical, radiological and pulmonary function (PF) of MSA/MAA-ILD Latin-American patients and risk factors associated to PF at onset and long term follow up. METHODS: Multicentric retrospective study of MSA/MAA-ILD patients evaluated between 2016 and 2018 in 3 ILD clinics in Latin America. Clinical, functional and tomographic variables were described. Variables associated with poor baseline PF and associated with functional improvement (FI) were analyzed in a multivariate logistic regression model. RESULTS: We included 211 patients, 77.4% female, mean age 57 years old. Most frequent MSA/MAA were Ro-52 and Jo-1. Poor baseline PF was associated to ILD as initial diagnosis and NSIP/OP HRCT pattern. 121 patients were included in the follow up PF analysis: 48.8% remained stable and 33% had a significant FI. In multivariate analysis, OP pattern on HRCT was associated with FI. Systemic symptoms from the beginning and the absence of sclerodactyly showed a trend to be associated with FI. CONCLUSIONS: Worse baseline PF could be related to the absence of extra-thoracic symptoms and "classic" antibodies in CTD (ANA), which causes delay in diagnosis and treatment. In contrast, FI could be related to the presence of extra-thoracic signs that allow timely diagnosis and therapy, and more acute and subacute forms of ILD, such as OP pattern.

Cuadro clínico del COVID-19 / Clinical presentation of COVID-19

El Coronavirus SARS-CoV-2 produce la enfermedad COVID-19, cuya manifestación más grave y potencialmente letal es la neumonía. En este artículo revisaremos las manifestaciones clínicas del COVID-19, la fisiopatología de la neumonía, el manejo intrahospitalario previo al ingreso a Unidades de Cuidados Intensivos, la embolia pulmonar que es una complicación muy frecuente de esta enfermedad y el seguimiento de los pacientes posterior al alta. Para esta publicación nos hemos basado en publicaciones médicas y en estudios que hemos hecho durante esta pandemia en nuestro Centro de Enfermedades Respiratorias. i:es

The SARS-CoV-2 Coronavirus causes the COVID-19 disease, the most severe and potentially fatal manifestation of which is pneumonia. In this article, we will review the clinical manifestations of COVID-19, the pathophysiology of pneumonia, in-hospital management prior to admission to Intensive Care Units, pulmonary embolism, which is a very frequent complication of this disease, and the follow-up of patients after hospitalization. For this publication we have relied on medical publications and studies that we have done during this pandemic at our Center for Respiratory Diseases. i:en

Enfermedades pulmonares intersticiales. Una perspectiva actual / Update on interstitial lung diseases

Interstitial lung diseases are a broad, diverse, challenging group of diseases, most of them chronic whose prognosis is not good. In the last two decades there have been considerable advances in the knowledge of the epidemiology, pathological and genetic bases and treatment of several of these diseases. This article summarizes and presents updated information about their classification, new knowledge on genetics and treatments in idiopathic pulmonary fibrosis, advances in the diagnosis and management of hypersensitivity pneumonitis and a review of the broad spectrum of interstitial diseases associated with connective tissue diseases. Several clinical trials are currently underway whose results will be available in the coming years and will provide more information and tools to improve the treatment of these patients.

[Update on interstitial lung diseases]. / Enfermedades pulmonares intersticiales. Una perspectiva actual.

Interstitial lung diseases are a broad, diverse, challenging group of diseases, most of them chronic whose prognosis is not good. In the last two decades there have been considerable advances in the knowledge of the epidemiology, pathological and genetic bases and treatment of several of these diseases. This article summarizes and presents updated information about their classification, new knowledge on genetics and treatments in idiopathic pulmonary fibrosis, advances in the diagnosis and management of hypersensitivity pneumonitis and a review of the broad spectrum of interstitial diseases associated with connective tissue diseases. Several clinical trials are currently underway whose results will be available in the coming years and will provide more information and tools to improve the treatment of these patients.

[Acute pulmonary fibrosis associated with Paraquat poisoning. Report of one case]. / Fibrosis pulmonar aguda asociada a intoxicación por Paraquat: caso clínico.

Paraquat, a non-selective bipyridyl pesticide, is one of the leading causes of death from intoxication in many parts of Asia and America. It is the second most sold herbicide worldwide, being widely used in Chile. Its ingestion generates toxicity due to the release of superoxide radicals, mainly affecting kidneys, lungs and liver. There is no antidote available. We report a 31 years old male who ingested Paraquat for suicidal purposes. He developed an acute renal and hepatic failure and a rapidly progressive severe respiratory failure with images compatible with acute pulmonary fibrosis. No response to immunosuppressive treatment was observed. He died eight days after admission. The use of cyclophosphamide associated with glucocorticoids could lower risk of death the in these patients, although the pathophysiology of respiratory failure is still under study.

Fibrosis pulmonar aguda asociada a intoxicación por Paraquat: caso clínico / Acute pulmonary fibrosis associated with Paraquat poisoning: report of one case

Paraquat, a non-selective bipyridyl pesticide, is one of the leading causes of death from intoxication in many parts of Asia and America. It is the second most sold herbicide worldwide, being widely used in Chile. Its ingestion generates toxicity due to the release of superoxide radicals, mainly affecting kidneys, lungs and liver. There is no antidote available. We report a 31 years old male who ingested Paraquat for suicidal purposes. He developed an acute renal and hepatic failure and a rapidly progressive severe respiratory failure with images compatible with acute pulmonary fibrosis. No response to immunosuppressive treatment was observed. He died eight days after admission. The use of cyclophosphamide associated with glucocorticoids could lower risk of death the in these patients, although the pathophysiology of respiratory failure is still under study.

Neumonía por Pneumocystis jiroveci post inicio de tratamiento con infliximab en paciente con enfermedad de Crohn / Pneumocystis jiroveci pneumonia following infliximab therapy in patient with Crohn's disease

There are no evidence-based guidelines about prophylaxis against Pneumocystis jiroveci pneumonia in inflammatory bowel disease. We report a case of P. jiroveci pneumonia in patient with Crohn's disease receiving infliximab and methotrexate. This case emphasizes the importance of considering the possibility of this infection in inflammatory bowel disease patients treated on biological therapy.

[Pneumocystis jiroveci pneumonia following infliximab therapy in patient with Crohn's disease]. / Neumonía por Pneumocystis jiroveci post inicio de tratamiento con infliximab en paciente con enfermedad de Crohn.

There are no evidence-based guidelines about prophylaxis against Pneumocystis jiroveci pneumonia in inflammatory bowel disease. We report a case of P. jiroveci pneumonia in patient with Crohn's disease receiving infliximab and methotrexate. This case emphasizes the importance of considering the possibility of this infection in inflammatory bowel disease patients treated on biological therapy.

A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus.

BACKGROUND: In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. METHODS: We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. RESULTS: From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. CONCLUSIONS: Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.

[Survival of patients with biopsy-proven idiopathic pulmonary fibrosis: Chilean National Thorax Institute experience]. / Supervivencia de pacientes con fibrosis pulmonar idiopática diagnosticados por biopsia quirúrgica de pulmón: experiencia del Instituto Nacional del Tórax.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is the most prevalent of all interstitial lung diseases. The usual underlying pathological picture is an interstitial pneumonia (UIP). AIM: To describe the evolution of a Chilean cohort of patients with IPF. MATERIAL AND METHODS: Patients with the disease were identified at the pathology registry of National Institute of Thoracic Diseases, Santiago, Chile. Patients were included if they had surgical biopsy of UIP and compatible clinical and radiological characteristics. The medical records of included patients were reviewed, recording clinical information and lung function test results. Survival was analyzed obtaining death records from the Chilean National Identification Service. RESULTS: Data from 142 patients with a mean age of 58 years (42% men), were analyzed. Mean initial lung function showed a forced vital capacity (FVC) of 73%, carbon monoxide diffusing capacity (DLCO) of 57% and a distance covered in 6-minute walk (6MWT) of 95% of expected normal values. The median survival was 80 months. Predictors of survival were a DLCO of less than 40% and an oxygen saturation at the end of the 6MWT of less than 89%. CONCLUSIONS: Survival in this group of patients was higher than the figures reported elsewhere. DLCO and the fall of oxygen saturation after walking were predictors of mortality, as previously described in other populations.

Supervivencia de pacientes con fibrosis pulmonar idiopática diagnosticados por biopsia quirúrgica de pulmón: experiencia del Instituto Nacional del Tórax / Survival of patients with biopsy-proven idiopathic pulmonary fibrosis: Chilean National Thorax Institute experience

Background: Idiopathic Pulmonary Fibrosis (IPF) is the most prevalent of all interstitial lung diseases. The usual underlying pathological picture is an interstitial pneumonia (UIP). Aim: To describe the evolution of a Chilean cohort of patients with IPF. Material and Methods: Patients with the disease were identified at the pathology registry of National Institute of Thoracic Diseases, Santiago, Chile. Patients were included if they had surgical biopsy of UIP and compatible clinical and radiological characteristics. The medical records of included patients were reviewed, recording clinical information and lung function test results. Survival was analyzed obtaining death records from the Chilean National Identification Service. Results: Data from 142 patients with a mean age of 58 years (42% men), were analyzed. Mean initial lung function showed a forced vital capacity (FVC) of 73%, carbon monoxide diffusing capacity (DLCO) of 57% and a distance covered in 6-minute walk (6MWT) of 95% of expected normal values. The median survival was 80 months. Predictors of survival were a DLCO of less than 40% and an oxygen saturation at the end of the 6MWT of less than 89%. Conclusions: Survival in this group of patients was higher than the figures reported elsewhere. DLCO and the fall of oxygen saturation after walking were predictors of mortality, as previously described in other populations.

[Bridge to lung transplantation with a novel pumpless lung assist device. Report of one case]. / Uso del dispositivo de asistencia respiratoria Novalung como puente a trasplante pulmonar: Caso clínico.

Devices such as Novalung can be used as a bridge to lung transplantation while waiting for a suitable donor. We report a 50 year-old male with a terminal pulmonary fibrosis and candidate for lung transplantation. He was admitted to the hospital due to a severe deterioration of his respiratory condition, with the presence of severe respiratory acidosis despite conventional invasive respiratory support. Respiratory support with Novalung was started, resulting in a progressive reduction of pCO2 that became normal ten hours after the installation of the device. Five days later a successful lung transplantation was performed.

Uso del dispositivo de asistencia respiratoria Novalung® como puente a trasplante pulmonar: Caso clínico / Bridge to lung transplantation with a novel pumpless lung assist device: Report of one case

Devices such as Novalung® can be used as a bridge to lung transplantation while waiting for a suitable donor. We report a 50 year-old male with a terminal pulmonary fibrosis and candidate for lung transplantation. He was admitted to the hospital due to a severe deterioration of his respiratory condition, with the presence of severe respiratory acidosis despite conventional invasive respiratory support. Respiratory support with Novalung® was started, resulting in a progressive reduction ofpCOz that became normal ten hours after the installation of the device. Five days later a successful lung transplantation wasperformed.

Correlatos psicosociales de las farmacodependencias: resultados de un estudio en Santiago de Chile / Psychosocial reports of drug dependence: results of a study in Santiago de Chile

Este estudio examina la influencia relativa de diversos factores psicosociales en el uso de substancias químicas en una muestra de adolescentes de Santiago de Chile. Estos incluyen variables de tipo sociodemográfico, del grupo de pares, de la familia destrezas aprendidas y de personalidad. Todas éstas se incorporaron en un modelo predictivo de la aparición de conductas de riesgo especificas. Entre los resultados dignos de mención están que la edad, los modelos de rol de los pares y de la familia tuvieron el papel más importante. Además, hicieron contribuciones importantes destrezas aprendidas tales como rechazo de drogas y empatía. Finalmente, el autoconcepto y la ansiedad fueron variables de personalidad que predijeron significativamente tanto el uso de marihuana como de alcohol. Es interesante constatar que hay características psicosociales similares en Chile y en los Estados Unidos tendientes a predecir el uso adolescente de substancias. Investigaciones futuras debieran determinar hasta que grado factores psicosociales como los examinados aquí predicen universalmente el consumo de substancias