Disfunciones del metabolismo del surfactante pulmonar: caso clínico pediátrico / Pulmonary surfactant metabolism dysfunction: A pediatric clinical case report

Las enfermedades pulmonares intersticiales son patologías poco frecuentes en pediatría. Dentro de ellas, se incluyen las disfunciones del metabolismo del surfactante pulmonar, molécula anfipática cuya función es disminuir la tensión superficial y evitar el colapso alveolar. Se presenta el caso de un lactante de 6 meses, en seguimiento por bajo peso, que presentó dificultad respiratoria aguda y cianosis; la radiografía de tórax evidenció infiltrado intersticial, neumomediastino y neumotórax bilateral. Al interrogatorio, surgió antecedente materno de internación al año de vida, con requerimiento de oxigenoterapia prolongada y diagnóstico desconocido; presenta signos de hipoxia crónica. El paciente cursó internación con requerimiento de oxigenoterapia. Se realizaron estudios complementarios en búsqueda de etiología, sin resultados positivos. La tomografía de tórax evidenció opacidades en vidrio esmerilado, engrosamiento del intersticio septal y áreas de atrapamiento aéreo; con resultado de biopsia pulmonar y estudio genético se llegó al diagnóstico de disfunción del metabolismo del surfactante pulmonar.

Interstitial lung diseases are rare in pediatrics. They include dysfunctions in the metabolism of pulmonary surfactant, an amphipathic molecule that reduces surface tension and prevents alveolar collapse. Here we describe the case of a 6-month-old infant controlled for low weight, who presented with acute respiratory distress and cyanosis; his chest X-ray showed interstitial infiltrate, pneumomediastinum, and bilateral pneumothorax. During history-taking, it was noted that his mother had a history of hospitalization at 1 year old with unknown diagnosis, requiring prolonged oxygen therapy; she now shows signs of chronic hypoxia. The patient was hospitalized and required oxygen therapy. Ancillary tests were done to look for the etiology of the condition, with no positive results. A chest computed tomography showed groundglass opacities, thickening of the septal interstitium, and areas of air trapping; based on the results of a lung biopsy and a genetic study, pulmonary surfactant metabolism dysfunction was diagnosed.

Perfil de pacientes evaluados con el Test de Capacidad de Difusión de Monóxido de Carbono: Una experiencia chilena / Profile of patients evaluated with the Carbon Monoxide Diffusion Capacity Test: A Chilean experience

ANTECEDENTES: La prueba de capacidad de difusión de monóxido de carbono (DLCO) es una evaluación de función pulmonar rutinaria y no invasiva clínicamente útil para determinar el estado de la función pulmonar en pacientes con trastornos crónicos como la enfermedad pulmonar intersticial difusa (EPID). OBJETIVO: Describir el perfil sociodemográfico y clínico de usuarios de la prueba DLCO en Valdivia, Chile. Materiales y Métodos: Estudio observacional, retrospectivo, de base documental. A partir de registros de 490 pacientes que se realizaron la prueba DLCO entre 2017 y 2019, se describen características sociodemográficas, clínicas y reporte de consumo de cigarrillo como cigarrillos/d e índice paquetes/año (IPA), comparando por sexo. RESULTADOS: La mayor proporción de evaluados fueron mujeres (61%), con una edad mediana de 65 años, mayor en mujeres (66 vs 64 años; p = 0,0361). La mayoría consultaron por EPID (54,5%). Según estado nutricional, 38% presentó preobesidad y 24,7% obesidad I (24,7%), destacando que 40,5% de las mujeres y 33% de los hombres se encontraron en alguna categoría de obesidad. Entre quienes reportaron información de consumo de cigarrillos (n = 346, 70,6%), 14,7% (n = 51) eran consumidores actuales, con un consumo mediano de 10 cigarrillos/d, sin diferencias por sexo. Entre exfumadores (n = 144; 50% hombres/mujeres) hubo significativamente menor consumo diario (5 vs 15; p = 0,0300) y de IPA (7 vs 18; p = 0,0083) en mujeres. CONCLUSIONES: En usuarios de DLCO el principal diagnóstico de consulta fue EPID. Destacó alta frecuencia de obesidad y tabaquismo, sin diferencia de consumo por sexo en fumadores actuales, pero sí en exfumadores.

BACKGROUND: The carbon monoxide diffusion capacity test (DLCO) is a clinically useful, routine, non-invasive lung function assessment to determine the status of lung function in patients with chronic disorders such as interstitial lung disease (ILD). AIM: To describe the sociodemographic and clinical profile of users of the DLCO test in Valdivia, Chile. MATERIALS AND METHODS: Observational, retrospective, documentary-based study. From the records of 490 patients who underwent the DLCO test between 2017 and 2019, sociodemographic and clinical characteristics and reports of cigarette consumption are described, such as cigarettes/d and pack-year index (PYI), comparing by sex. Results: The highest proportion of those evaluated were women (61%), with a median age of 65 years, higher in women (66 vs. 64 years; p = 0.0361). The majority consulted for ILD (54.5%). According to nutritional status, 38% presented pre-obesity and 24.7% obesity I (24.7%), highlighting that 40.5% of women and 33% of men were in some category of obesity. Among those who reported information on cigarette consumption (n = 346, 70.6%), 14.7% (n = 51) were current consumers, with a median consumption of 10 cigarettes/d, without differences by sex. Among exsmokers (n = 144; 50% men/women) there was significantly less daily (5 vs 15; p = 0.0300) and IPA (7 vs 18; p = 0.0083) consumption in women. CONCLUSIONS: In DLCO users, the main consultation diagnosis was ILD. High frequency of obesity and smoking stood out, with no difference in consumption by sex in current smokers, but yes in ex-smokers.

A concise review of diagnosis and evaluation of interstitial lung abnormalities / 中华劳动卫生职业病杂志

Interstitial lung abnormalities (ILAs) refer to the subtle or mild signs of ILAs pulmonary parenchyma on chest HRCT scans, which are not yet sufficient to diagnose a certain interstitial lung disease, may be potentially compatible an early stage of the diseases. The signs of ILAs usually includes ground-glass opacities, reticular abnormakicies, honeycombing, traction bronchiectasis or non-emphysematous cysts. This article reviews the research progreses in the definition and classification, risk factors, prognosis, comorbidities and management of ILAs in combination with domestic and foreign literatures.

A non-small cell lung carcinoma patient responded to crizotinib therapy after alectinib-induced interstitial lung disease / 浙江大学学报·医学版

A 54-year-old, non-smoking woman was diagnosed as stage ⅣB adenocarcinoma with widespread bone metastasis (cT4N2M1c) in the First Affiliated Hospital, Zhejiang University School of Medicine. Immunohistochemistry result showed the presence of anaplastic lymphoma kinase (ALK) gene rearrangement; next-generation sequencing (NGS) indicated EML4-ALK fusion (E6:A20) with concurrent CCDC148-ALK (C1:A20), PKDCC-ALK (Pintergenic:A20)and VIT-ALK (V15:A20) fusions. After 32 weeks of alectinib treatment, the patient complained cough and exertional chest distress but had no sign of infection. Computed tomography (CT) showed bilateral diffuse ground glass opacities, suggesting a diagnosis of alectinib-related interstitial lung disease (ILD). Following corticosteroid treatment and discontinuation of alectinib, clinical presentations and CT scan gradually improved, but the primary lung lesions enlarged during the regular follow-up. The administration of crizotinib was then initiated and the disease was stable for 25 months without recurrence of primary lung lesions and ILD.

Fisiología respiratoria: fisiología de las enfermedades pulmonares restrictivas / Pathophysiology of pulmonary restrictive diseases

Las enfermedades restrictivas comprenden un grupo heterogéneo de trastornos que se caracterizan por una alteración en la distensibilidad pulmonar, generada por enfermedades del parénquima o intersticio pulmonar o por problemas extrapulmonares (alteraciones de la caja torácica o enfermedades neuromusculares). Presentan un patrón característico en las pruebas de función pulmonar, relación VEF1/ FVC normal o aumentada con CVF disminuida, VEF1 disminuido leve o normal y capacidad pulmonar total disminuida (CPT). Su manejo es complejo debido a la dificultad para establecer el diagnóstico diferencial, por lo que se recomienda una derivación precoz a un especialista en enfermedades respiratorias y el enfrentamiento por un equipo multidisciplinario.

Restrictive diseases comprise a heterogeneous group of disorders characterized by an alteration in lung compliance, generated by diseases of the lung parenchyma or interstitium, as well as by extrapulmonary problems (abnormalities of the rib cage or neuromuscular diseases). They present a characteristic pattern in pulmonary function tests, with decreased FVC (forced vital capacity), slightly decreased or normal FEV1 (forced expiratory volume in 1 second), normal or increased FEV1/FVC ratio, and decreased total lung capacity. Its management is complex due to the difficulty in establishing the differential diagnosis, so early referral to a specialist in respiratory diseases and confrontation by a multidisciplinary team is recommended.

Caracterización clínico-radiológica de pacientes con enfermedad pulmonar intersticial y panel de miositis positivo en hospital Santiago Oriente / Clinical-radiological characterization of patients with interstitial lung disease and positive myositis panel at hospital Santiago Oriente

Introducción: Las Enfermedades Pulmonares Intersticiales (EPI) afectan principalmente al intersticio pulmonar, con importante morbimortalidad asociada. Tienen un espectro de posibles etiologías que es cada vez más amplio. Hay una importante causalidad a partir de Enfermedades del Tejido Conectivo (ETC), describiéndose cada vez más casos asociados a Síndrome Antisintetasa, y con diversos patrones radiológicos según serología obtenida, agrupada en "Panel de Miositis" (PaM). El presente estudio de cohorte retrospectiva reúne PaMs realizados en el Hospital Santiago Oriente, correlacionando resultados con manifestaciones clínicas e imagenológicas. Material y Métodos: Se recuperaron 33 PaMs realizados entre 2017 y 2022, y a través de revisión de fichas de los pacientes de quienes provenían las PaMs se consignaron las principales manifestaciones clínicas, imagenológicas y de la serología reumatológica complementaria, estableciendo correlaciones entre múltiples variables. Resultados: Hubo 15 pacientes PaM positivos (45,4%), 8 de ellos (53%) ya contaban con alguna miopatía inflamatoria diagnosticada. Los principales hallazgos clínicos consignados fueron pápulas de Gottron, artritis, eritema heliotropo, Fenómeno de Raynaud y fiebre. El anticuerpo positivo más frecuente fue Ro-52. Se pudo objetivar ANA positivo en 10 casos (66,7%). Se identificó EPI en 66,7% de aquellos con PaM positivo, siendo la Neumonía Intersticial no específica fibrótica con Neumonía en Organización la manifestación más frecuente. No hubo asociación significativa entre manifestaciones imagenológicas y anticuerpos específicos. Se encontró ANA 1/80 en 66,7% de los casos, lo cual no se asoció a mayor riesgo de EPI. Conclusiones: Existe asociación entre varias ETC y las EPI. Destaca la importancia de los hallazgos clínicos para establecer un adecuado índice de sospecha, para dirigir oportunamente el estudio complementario (ej: PaM), y la eventual terapia específica.

Introduction: Interstitial Lung Diseases (ILD) mainly affect the pulmonary interstitium, with significant associated morbidity and mortality. They have a spectrum of possible etiologies that is increasingly broad. There is an important causality from Connective Tissue Diseases (CTD), describing more and more cases associated with Antisynthetase Syndrome, and with different radiological patterns according to the serology obtained, enclosed into "Panel of Myositis" (PaM). This retrospective cohort study gathers PaMs performed at Hospital Santiago Oriente, PaM results are correlated with clinical and imaging manifestations. Material and Methods: 33 PaMs performed between 2017 and 2022 were saved up and by reviewing the clinical records of the patients from whom the PaMs came, their clinical and radiological manifestations and the results of their complementary rheumatological serology were recorded to establish correlations between multiple variables. Results: There were 15 positive PaMs (45.4%), 8 (53%) of them already had some diagnosed inflammatory myopathy. The main clinical findings reported were Gottron's papules, arthritis, heliotrope erythema, Raynaud's phenomenon, and fever. The most frequent positive antibody detected was Ro-52. Positive ANA could be found in 10 cases (66.7%). PID was identified in 66.7% of those with a positive PaM, being non-specific fibrotic Interstitial Pneumonia with Organizing Pneumonia being the most frequent manifestation. There was no significant association between imaging manifestations and specific antibodies. ANA 1/80 was found in 6.7% of the cases, which was not associated with an increased risk of PID. Conclusions: There is association between several CTEs and EPIs. It is necessary to highlight the importance of the clinical findings to establish an adequate index of suspicion, in order to timely direct the complementary study (eg: PaM), and the eventual specific therapy.

Manifestaciones pulmonares al diagnóstico de 170 pacientes con vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos: cohorte retrospectiva de un centro universitario / Pulmonary manifestations at the diagnosis of 170 patients with vasculitis associated with anticytoplasmic neutrophil antibodies: retrospective cohort of a university center

INTRODUCCIÓN: Las Vasculitis Asociadas a Anticuerpos Anticitoplasma de Neutrófilos (VAA) son infrecuentes, pero de amplio espectro de presentación. Si bien el consenso de clasificación de Chapel Hill del año 2012, sigue vigente, la tendencia actual es clasificarlas de acuerdo al marcador inmunológico: anti-Proteinasa 3 (PR3) o anti-mieloperoxidasa (MPO). Las manifestaciones pulmonares clásicas son la hemorragia alveolar y los nódulos pulmonares. En los últimos 10 años se ha descrito la enfermedad pulmonar difusa (EPD). Los estudios epidemiológicos son escasos, y suelen representar en su mayoría poblaciones norteamericanas o europeas. El objetivo es describir las características del compromiso pulmonar al debut en VAA en un centro universitario. PACIENTES Y MÉTODO: De un total de 190 pacientes con diagnóstico de VAA se incluyeron 170 en seguimiento en nuestro centro. Se revisaron aspectos clínicos, demográficos, laboratorio e imagenológicos de los pacientes incluidos. RESULTADOS: De los 170 pacientes, 112 (65,88%) presentaron compromiso pulmonar. 106 (94,64%) de los pacientes fueron anticuerpos anti citoplasma de neutrófilos (ANCA) positivos; de estos, 56 (53,27%) MPO (+) y 39 (36,45%) PR-3 (+). Un tercio de los pacientes de ambos grupos presentó hemorragia alveolar. En los pacientes MPO (+) predomina la EPD (53,5%) y en PR-3 (+) los nódulos pulmonares (69,23%). Destaca la baja frecuencia de patología obstructiva asociada. CONCLUSIONES: El compromiso pulmonar en las VAA es prevalente y heterogéneo. En nuestra serie, destaca la frecuencia de EPD en VAA MPO (+), lo que releva la importancia del estudio con ANCA en paciente con diagnóstico y seguimiento por EPD.

INTRODUCTION: Antineutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV) are uncommon, but of broad spectrum of presentation. Although the 2012 Chapel Hill classification consensus remains valid, the current trend is to classify them according to the immunological marker: anti-Proteinase 3 antibody (PR-3) or anti-Myeloperoxidase antibody (MPO). The classic pulmonary manifestations are alveolar hemorrhage and pulmonary nodules. Interstitial lung disease (ILD) has been described in the last 10 years. Epidemiological studies are scarce, and they usually represent mostly North American or European populations. The objective is to describe the characteristics of lung involvement upon debut in AAV in a university center. PATIENTS AND METHODS: Of a total of 190 patients diagnosed with AAV, 170 were included in follow-up at our center. Clinical, demographic, laboratory and imaging aspects of the included patients were reviewed. RESULTS: Of the 170 patients, 112 (65.88%) had lung involvement. 106 (94.64%) of the patients were ANCA (+); of these, 56 (53.27%) MPO (+) and 39 (36.45%) PR-3 (+). One third of the patients in both groups had alveolar hemorrhage. In MPO (+) patients, ILD predominates (53.5%) and in PR-3 (+) pulmonary nodules (69.23%). The low frequency of associated obstructive pathology stands out. CONCLUSIONS: Pulmonary manifestations in AAVs are frequent and heterogeneous. Locally, the association of ILD and AAV MPO (+) stands out, which highlights the importance of ANCA study in patients with diagnosis and follow-up by ILD.

Prevalencia y letalidad de enfermedades pulmonares intersticiales en la Región de Los Ríos, Chile / Prevalence and lethality of interstitial pulmonary diseases in the Region of Los Ríos, Chile

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a subtype of interstitial lung disease (ILD) that significantly affects people's quality of life, whose prevalence and mortality has increased. AIM: To determine the prevalence and lethality of ILD in the Los Ríos Region between the years 2018 and 2019. MATERIAL AND METHODS: Review of a database of all patients attended at an outpatient clinic of the regional hospital. Those patients with the diagnosis of ILD and seen between 2018 and 2019 were selected. Mortality and its causes were verified with death certificates. RESULTS: In the study period, 339 cases with ILD, aged 71 ± 10 years (64% women) were identified. The calculated ILD prevalence was 84 cases per 100,000 inhabitants, with a higher predominancy in Futrono and Paillaco communes. IPF and Connective Tissue Diseases were the predominant subtypes. Overall lethality was 18%, with more deaths among patients with IPF (n = 31). CONCLUSIONS: In the Los Ríos Region, ILDs have a relevant prevalence and lethality.

Expert consensus on the diagnosis and treatment of anticancer drug-induced interstitial lung disease / 中华肿瘤杂志

Drug-induced interstitial lung disease (DILD) is the most common pulmonary adverse events caused by anti-cancer treatment. In recent years, with the development of clinical oncology, a large amount of novel anti-cancer drugs have been approved and widely used in clinical practice, and the incidence of anti-cancer drug related DILD is gradually increasing. DILD lacks specific clinical manifestations or diagnostic criteria. If not treated properly, it may leads to interruption or discontinuation of anti-cancer treatment, or even become life threat in severe cases. Therefore, the Anti-cancer Drug-induced Interstitial Lung Disease Management Group have reached a consensus on the diagnosis and management of anti-cancer DILD after several rounds of discussion. This consensus aims to improve clinicians' awareness of anti-cancer drug related-DILD and proposes an algorithm for the diagnosis and treatment of this disease, and to improve patients' prognosis and quality of life.

Taquipnea persistente de la infancia: hiperplasia de células neuroendocrinas, una revisión / Persistent tachypnea of infancy: neuroendocrine cell hyperplasia, a review

La hiperplasia de células neuroendocrinas de la infancia (HCNEI) constituye una de las enfermedades intersticiales más frecuentes en pediatría. Tanto su etiología como los mecanismos fisiopatológicos involucrados son inciertos. Suele presentarse en pacientes por lo demás sanos, durante los primeros meses de vida con taquipnea, retracciones costales, rales e hipoxemia. En la tomografía axial computada de tórax de alta resolución (TACAR) presenta imágenes características en vidrio esmerilado de distribución central y zonas de atrapamiento aéreo. Para el diagnóstico, además de la clínica y la TACAR, podemos recurrir a la biopsia en casos atípicos. Los hallazgos histológicos reflejan una arquitectura pulmonar normal y un aumento en el número de células neuroendocrinas. El manejo global es con medidas de sostén, ya que no se cuenta con un tratamiento específico. La sintomatología suele mejorar con la edad y el pronóstico es favorable.

Neuroendocrine cell hyperplasia of infancy (NEHI) is one of the most common interstitial lung diseases of childhood. The etiology and pathophysiological mechanisms involved are uncertain. It usually presents in otherwise healthy patients during the first months of life with tachypnea, rib retractions, crackles, and hypoxemia. High-resolution chest computed tomography (HRCT) shows ground-glass opacities of central distribution and areas of air trapping. For diagnosis purposes, in addition to clinical and HRCT features, a lung biopsy is indicated for atypical cases. Histological findings reflect normal architecture and an increased number of neuroendocrine cells. The management consists of supportive and preventive care, since there is no specific treatment. Symptoms usually improve with age and the prognosis is favorable.

Acometimento da função ventricular direita em pacientes com esclerose sistêmica e doença pulmonar intersticial: avaliação pelo doppler tecidual / Impairment of right ventricular function in patients with systemic sclerosis and interstitial lung disease: tissue doppler evaluation

Introdução: A esclerose sistêmica (ES) é uma doença autoimune do tecido conjuntivo que cursa com fibrose e disfunção microvascular. O envolvimento dos órgãos viscerais, incluindo os pulmões e o coração, é a principal causa de óbito na ES. Nesse contexto, analisamos a relação entre os parâmetros ventriculares direitos (VD) pela ecocardiografia com Doppler tecidual e o acometimento pulmonar em pacientes com ES. Métodos: Os pacientes que preencheram os Critérios de Classificação da ES de 2013 foram submetidos à ecocardiografia com Doppler tecidual para avaliação da função sistólica (fração de ejeção) ventricular esquerda (VE), enquanto a função sistólica do VD foi avaliada por meio da fração de variação de área do VD (fractional area change ­ FAC), velocidade (sistólica) do Doppler tecidual, índice de desempenho miocárdico (IDM) e excursão sistólica do plano anular tricúspide (TAPSE). A pressão sistólica pulmonar foi estimada por insuficiência tricúspide. A tomografia computadorizada de alta resolução (TCAR) de tórax avaliou a presença de fibrose pulmonar. De acordo com os resultados da TCAR, os pacientes foram divididos em 2 subgrupos: Grupo I, incluindo pacientes com fibrose pulmonar (n=26), e Grupo II sem fibrose (n=17). Resultados: Entre os 43 pacientes com ES, a maioria era do sexo feminino (86%) com idade de 51±12 anos. Todos os pacientes apresentavam função ventricular sistólica normal, avaliada pela FEVE>55% e FAC VD>35%. Não houve diferença significativa em termos de idade ou duração da doença para os grupos. Exceto pela diminuição das velocidades do Doppler tecidual em pacientes com fibrose pulmonar, todos os índices de desempenho do VD foram semelhantes. Conclusão: Em pacientes com ES e fibrose pulmonar, o Doppler tecidual identifica acometimento miocárdico longitudinal precoce do VD, apesar do desempenho sistólico radial preservado do VD.(AU)

Introduction: Systemic sclerosis (SSc) is an autoimmune tissue connective disease that courses with fibrosis and microvascular dysfunction. Involvement of the visceral organs, including the lungs and heart, is the main cause of death among patients with SSc. In this context, here we analyzed the relationship between right ventricle (RV) parameters assessed by tissue Doppler echocardiography and lung involvement in patients with SSc. Methods: Patients fulfilling the 2013 SSc Classification Criteria underwent tissue Doppler echocardiography for the assessment of left ventricular (LV) systolic function (ejection fraction) and RV fractional area change (FAC), tissue Doppler s' (systolic) velocity, myocardial performance index, and tricuspid annular plane systolic excursion for the assessment of RV systolic function. Pulmonary systolic pressure was estimated using tricuspid regurgitation. Chest high-resolution computed tomography was used to evaluate the presence of pulmonary fibrosis. The patients were divided into two subgroups accordingly: Group I, patients with pulmonary fibrosis (n=26); and Group II, those without fibrosis (n=17). Results: Among the 43 patients with SSc, most were female (86%), and the mean age was 51 ± 12 years. All patients had normal systolic ventricular function as evidenced by an LV ejection fraction > 55% and an RV FAC > 35%. No significant intergroup difference was noted in age or disease duration. Except for a decreased tissue Doppler s' velocity in patients with lung fibrosis, all indexes of RV performance were similar. Conclusion: In patients with SSc and pulmonary fibrosis, tissue Doppler identified early RV longitudinal myocardial involvement despite preserved RV radial systolic performance.(AU)

Diagnóstico de las enfermedades pulmonares intersticiales difusas: estudio del BAL - Su utilidad para el diagnóstico / Diagnosis of Diffuse Interstitial Lung Diseases: BAL Study - Its Utility for the Diagnosis

Resumen Introducción: Las enfermedades pulmonares intersticiales difusas son un grupo heterogéneo de enfermedades respiratorias con difícil diagnóstico. El estudio del lavado broncoalvolar mediante citometría de flujo puede definir patrones celulares típicos en diferentes en fermedades, proporcionando algo de ayuda en el diagnóstico diferencial. El objetivo de este estudio ha sido analizar retrospectivamente la utilidad clínica de las subpoblaciones celulares y linfocitarias detectadas en el lavado broncoalveolar por citometría de flujo, con la finalidad de definir patrones celulares típicos que permitan el diagnóstico diferencial de enfermedades granulomatosas pulmonares. Materiales y métodos: En el estudio se han incluido 44 pacientes retrospectivamente. Los sujetos fueron diagnosticados de sar coidosis o neumonitis por hipersensibilidad durante un periodo de 3 años. Se realizó el análisis celular de lavado broncoalveolar por citometría de flujo, pruebas histológicas y de imagen (TACAR), como parte del diagnóstico. Los porcentajes de células T, células B, células NK, CD4, CD8 y CD4 / CD8 se analizaron por citometría de flujo, a través de los marcadores CD3 +, CD19 + CD4 +, CD8 +, CD3 + CD4-CD8- y CD3 + CD16-CD56-. Resultados: Concluimos que los parámetros de mayor utilidad fueron la linfocitosis y sobre todo, el cociente CD4/CD8. Este cociente se presentó alto en patologías como la sarcoidosis y se invirtió en la neumonitis por hipersensibilidad, con respecto a los valores hallados en sangre periférica. Conclusiones: El estudio de BAL es útil para discriminar entre enfermedades pulmonares intersticiales granulomatosas y otras EPID.

Diagnosis of Diffuse Interstitial Lung Diseases: BAL Study - Its Utility for the Diagnosis

Abstract Introduction: Diffuse interstitial lung diseases are a hard-to-diagnose heterogeneous group of respiratory diseases. The study of bronchoalveolar lavage through flow cytometry may define typical cell patterns in different diseases and so help confirm the differential diagnosis. The purpose of this study was to retrospectively analyze the clinical utility of cell and lymphocyte subpopulations detected in the bronchoalveolar lavage by flow cytometry in order to define typical cell patterns that allow for making a differential diagnosis of granulomatous lung diseases. Materials and methods: The retrospective study included 44 patients. The subjects were diagnosed with sarcoidosis or hypersen sitivity pneumonitis during a period of 3 years. We performed the cellular analysis of bronchoalveolar lavage through flow cytometry and histological and imaging testing (HRCAT, High Resolution Computed Axial Tomography) as part of the diagnosis. The percentages of T cells, B cells, NK cells, CD4, CD8 and CD4/CD8 were analyzed by flow cytometry for the following markers: CD3 +, CD19 + CD4 +, CD8 +, CD3 + CD4-CD8- and CD3 + CD16-CD56-. Results: We conclude that the most important parameters were lymphocytosis and especially the CD4/CD8 quotient. This quotient was high for diseases such as sarcoidosis and low for hypersensitivity pneumonitis, in comparison with the values found in the peripheral blood. Conclusions: The BAL (Bronchoalveolar Lavage) study is useful for differentiating between granulomatous interstitial lung diseases and other DILDs (diffuse interstitial lung diseases).

Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury / 北京大学学报(医学版)

OBJECTIVE@#To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection.@*METHODS@#Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn, and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens.@*RESULTS@#A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P < 0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P < 0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P < 0.05).@*CONCLUSION@#The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

Criobiopsia en enfermedades pulmonares intersticiales difusas. Experiencia en un centro de Argentina / Cryobiopsy in interstitial lung disease: a real-life experience from a single center in Argentina

Resumen La criobiopsia transbronquial pulmonar (CBTB) ha sido introducida recientemente para el diagnóstico histológico de las enfermedades pulmonares intersticiales difusas (EPID). Nuestro objetivo fue evaluar el rédito diagnóstico y la seguridad de la CBTB para EPID en un centro de tercer nivel, en Buenos Aires, Argentina. Se efectuó una revisión retrospectiva de sujetos a los que se les realizó una CBTB en este centro desde septiembre de 2016 a noviembre de 2019. Se registró la información referida al paciente, el procedimiento y sus complicaciones, el diagnóstico histológico y multidisciplinario. Se analizaron potenciales factores asociados a diagnóstico y complicaciones por regresión logística. Se incluyeron 52 pacientes. La media de muestras fue 5.7 (DE 1.7) con una mediana de diámetro de 6 mm (rango intercuartil 6-8). Trece (25%) enfermos desarrollaron neumotórax sin encontrarse casos de sangrado grave o muerte. El rédito diagnóstico fue de 73.1% y 84.5% para la histología y la evaluación multidisciplinaria respectivamente. El número de muestras se asoció al rédito diagnóstico en el análisis multivariado (OR 2.15 -IC95% 1.16-3.99). La CBTB parece ser segura y efectiva para la evaluación de las EPID en la práctica al aplicarse en un centro con acceso a evaluación multidisciplinaria.

Abstract Transbronchial lung cryobiopsy (TBLC) has been recently introduced for the histological assessment of interstitial lung diseases. The objectives were to assess the diagnostic yield and safety of TBLC for interstitial lung diseases in our setting. A retrospective review of subjects who underwent TBLC in a tertiary care center from September 2016 to November 2019 was performed. Data regarding subject and procedure characteristics, complications, histopathological and multidisciplinary diagnosis was recorded. Logistic regression was used to analyze potential factors associated to diagnosis and complications. A total of 52 subjects were included. Mean number of samples was 5.7 (SD 1.7) with a median sample diameter of 6 mm (interquartile range 6-8). Pneumothorax developed in 13 (25%) participants, and no cases of severe bleeding or death were registered. A 73.1% and 84.5% diagnostic yield was recorded through histology and added multidisciplinary evaluation respectively. The number of samples was associated to the diagnostic yield in a multivariate analysis (OR 2.15 -CI95% 1.163.99). TBLC appears to be safe and effective for the assessment of interstitial lung diseases in a real life setting when applied in a center with access to multidisciplinary evaluation.

Contribución del panel de miositis en el estudio de pacientes con enfermedades pulmonares intersticiales y sospecha de enfermedad del tejido conectivo / Contribution of myositis panel in the study of patients with interstitial lung disease and suspicion of connective tissue disease

INTRODUCCIÓN: La manifestación extramuscular de las miopatías inflamatorias idiopáticas (MII) es la enfermedad pulmonar intersticial (EPI) y el diagnóstico se basa en autoanticuerpos séricos. Los nuevos anticuerpos específicos y asociados a MII han ayudado a identificar nuevas entidades clínicas en el espectro de MII. El objetivo de este estudio es evaluar la contribución diagnóstica de un panel de anticuerpos de miositis (PM) en una cohorte de pacientes chilenos con EPI sin una enfermedad del tejido conectivo (ETC) definitiva. MATERIALES Y MÉTODOS: A partir de enero de 2017 se realizó un panel de miositis a 111 pacientes consecutivos con EPI y sospecha de ETC, pero sin un diagnóstico definitivo a través de otra herramienta diagnóstica, en el programa de Pulmón-Reumatológico del Instituto Nacional del Tórax, Santiago, Chile. Se compararon las características basales clínicas y serológicas de los pacientes que se asociaban más frecuentemente a la probabilidad de tener un panel positivo. RESULTADOS: El PM fue positivo en 56 de 111 pacientes. El síndrome antisintetasa (SAS) fue el diagnóstico más frecuente. Los anticuerpos más frecuentes fueron Ro-52, PM / Scl-75 y Ku. Las variables más frecuentes en el grupo PM(+) fueron la presencia del Raynaud, miositis, manos de mecánico, los anticuerpos Ro y La positivos, la presencia de un patrón combinado de neumonía intersticial inespecífica y neumonía organizada en la tomografía computarizada de tórax. CONCLUSIONES: la incorporación del PM nos ha ayudado a mejorar nuestra precisión diagnóstica en pacientes con EPI / ETC. Presentamos elementos clínicos y serológicos que perfeccionan el rendimiento de la prueba.

INTRODUCTION: The most common extramuscular manifestation of the idiopathic inflammatory myopathies (IIM) is interstitial lung disease (ILD) and the diagnosis is based on serum autoantibodies. The new specific and associated antibodies to IIM have helped to identify new clinical entities in the spectrum of IIM. The objective of this study is to evaluate the diagnostic contribution of a myositis antibodies panel (MP) in a cohort of Chilean patients with ILD without a definitive connective tissue disease (CTD). MATERIALS AND METHODS: Starting on January 2017 we performed a MP to 111 consecutive patients with ILD and suspected CTD but without a definitive diagnosis through another diagnostic tools in the Lung-Rheumatological Program at the "Instituto Nacional del Tórax", Santiago, Chile. The clinical and serological baseline characteristics of the patients that were most frequently associated with the probability of having a positive panel were compared. RESULTS: The MP was positive in 56 of 111 patients. Anti synthetase syndrome (ASS) was the most prevalent diagnosis. The most frequent antibodies were Ro-52, PM/Scl-75 and Ku. The most frequent variables in the positive MP group were the presence of Raynaud's phenomenon, myositis, mechanic's hands, positive Ro and La antibodies and the presence of combined pattern of nonspecific interstitial pneumonia and organizing pneumonia in chest computed tomography scan. CONCLUSIONS: The incorporation of the MP has helped us to improve our diagnostic precision of patients with CTD/ILD. We present clinical and serological elements that refine the performance of the test.

Hiperplasia de células neuroendocrinas: reporte de caso / Neuroendocrine cell hyperplasia: case report

A clinical case of Neuroendocrine Cell Hyperplasia is presented with a bibliographic review. An infant patient with respiratory distress syndrome, characterized by nasal flaring, retractions, and tachypnea with temporary resolution with the use of bronchodilators. However, the patient requires oxygen. With complementary examinations (negative viral panel twice) and epidemiology it is classified as a viral Bronchiolitis. Without improvement, extrapulmonar pathologies were suspected, discarding hearth disease, epilepsy, pathological gastroesophageal reflux. New tests were performed to rule out other pathologies, including immunological disorders. Those results were normal, so a high-resolution chest tomography was done which allowed the diagnosis of Neuroendocrine Cell Hyperplasia. During the follow up the child had improved and required oxygen until he was two years old. Neuroendocrine Cell Hyperplasia belongs to a huge group of less common interstitial disorders, which diagnosis is clinical and radiological. It can easily be confused with common respiratory disorders. For this reason, it is important to know about this disease to make an early diagnosis. Most of the cases had a gradual (months to years) improvement.

Se presenta un caso clínico de Hiperplasia de Células Neuroendocrinas y la revisión de la literatura. Paciente lactante menor con cuadro de dificultad respiratoria, caracterizado por aleteo nasal, retracciones y taquipnea persistente acompañada de desaturación. Sin adecuada respuesta al uso de broncodilatadores. Por exámenes complementarios, panel viral negativo en dos ocasiones y epidemiología, se le diagnostica una bronquiolitis viral. Por no presentar mejoría se completan estudios, descartándose neumonía atípica, cardiopatía, epilepsia, reflujo gastroesofágico patológico y compromiso inmunológico. El diagnóstico fue determinado en base a la clínica, junto con imágenes en vidrio esmerilado característicos en lóbulo medio y língula. En su seguimiento mejora paulatinamente, requiriendo soporte de oxígeno hasta los dos años. La Hiperplasia de Células Neuroendocrinas es una patología intersticial pulmonar poco frecuente, cuyo diagnóstico es clínico y radiológico. Puede ser fácilmente confundida con desórdenes respiratorios comunes, por lo que es importante sospecharla para realizar un diagnóstico precoz. La mayor parte de los casos evolucionan con declinación de los síntomas, mejorando espontáneamente en meses o en los primeros años de vida.

El intersticio pulmonar y sus enfermedades en la infancia. Deficiencia de ABCA3. Seguimiento durante doce años. Perspectivas ¿Un nuevo paradigma genético? / The pulmonary interstitium and its diseases in childhood. ABCA3 deficiency. Follow-up for 12 years. Perspectives. A new genetic paradigm?

Introducción. Sobre la base de un caso clínico, se presenta la descripción del cuadro intersticial por deficiencia de ABCA3, de una paciente de catorce años de edad, en seguimiento durante doce años. Método. Evaluación clínica con extensos estudios para descartar otras patologías semejantes. El diagnóstico definitivo fue determinado por el estudio genético para deficiencias de ABCA3 y otros defectos genéticos realizados por el Dr. Larry Nogee, Hospital Johns Hopkins, EE. UU. Objetivos. Describir detalladamente la evolución de la paciente durante doce años, con énfasis en los estudios anteriormente mencionados. Sugerir la presencia de un cambio de paradigma pronóstico en lo que se conocía sobre la evolución de esta enfermedad intersticial pulmonar grave, tratar de mejorar la calidad de vida y posiblemente el pronóstico. Presentar los hallazgos de genética, anatomía patológica y radiología en consultas y evaluaciones por centros de referencia. Resultados. Realizado su diagnóstico de deficiencia genética de ABCA3, presentamos su seguimiento actualizado hasta el año 2020. Esta debe ser sospechada en niños pequeños desde el nacimiento y durante los primeros años ante la persistencia de cuadros pulmonares crónicos con desaturación de oxígeno e imágenes tomográficas que sugieren cuadro intersticial. Se decidió tratar el cuadro en los años 2019-2020, durante seis meses, según bibliografía y consultas con centros de referencia en los Estados Unidos, con la finalidad de determinar la posible mejoría de su patología y decidir la continuación o suspensión de la medicación. Se usaron pulsos con metilprednisolona- hidroxicloroquina y azitromicina. Se logró mantener estable su función pulmonar y mejorar notablemente su calidad de vida. (AU)

Introduction. A clinical case diagnosed with ABCA3 deficiency is described. Patient is now fourteen years old. She´s being followed up since she was two years old. Methodology. clinical follow ­ up with extensive studies to rule out other similar pathologies. Final diagnosis was done through genetic studies done at Johns Hopkins Hospital by Nogee LM. Objective. To present a detailed evolution description of twelve years' follow-up with the support of the aforementioned studies, to suggest a change in diagnostic ­ prognostic paradigm on what was known of mortality in this severe pulmonary interstitial pathology to improve life quality and possibly prognosis. Present the findings of genetics, pathological anatomy and radiology in consultations and evaluations by reference centers. Results. Having made her diagnosis of genetic ABCA3 deficiency, we present her up dated follow-up until 2020. This should be suspected in young children from birth and during the first years due to the persistence of chronic pulmonary symptoms with oxygen desaturation and tomographic images that suggest interstitial symptoms. It was decided to treat the condition in the years 2019-2020, for six months, according to the bibliography and consultations with reference centers in the United States, in order to determine the possible improvement of her pathology and decide to continue or suspend the medication. Pulses with methylprednisolone hydroxychloroquine and azithromycin were used. Her lung function was stable and her quality of life significantly improved. (AU)

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.