Silicoproteinosis en paciente minero en Colombia. Reporte de caso / Silicoproteinosis in a mining patient in Colombia. Case report

La silicosis pulmonar es una enfermedad ocupacional que continúa ocasionando morbilidad en el mundo. Debido a que el sílice es el mineral más abundante en la tierra y en las rocas, son numerosas las fuentes de exposición laboral a la inhalación del polvo de sílice en varios sectores industriales. Por su parte, la silicoproteinosis pulmonar es una forma aguda muy rara de silicosis, que puede desarrollarse con un período de latencia más corto en comparación con la silicosis, luego de la primera exposición al sílice, y se caracteriza por un rápido deterioro de la función pulmonar, sin respuesta efectiva a ningún tratamiento. Por su forma de presentación tan atípica, reportamos el caso de un hombre de 58 años, con antecedente laboral de trabajo en mina de extracción de oro en socavón

Pulmonary silicosis is an occupational disease that continues to cause morbidity in the world. Because silica is the most abundant mineral in soil and rock, sources of occupational exposure to inhalation of silica dust are numerous in various industrial sectors. Alternately, pulmonary silicoproteinosis is a very rare acute form of silicosis, which can develop with a shorter latency period compared to silicosis after the first exposure to silica, and is characterized by a rapid deterioration of lung function, without effective response to any treatment. Due to its atypical form of presentation, we report the case of a 58-year-old man, with a history of working in a gold mine

Proteinosis alveolar pulmonar: reporte de caso en paciente con linfoma no hodgkin mesentérico / Pulmonary alveolar proteinosis: report of a case in patient with history of mesenteric non-hodgkin lymphoma

Objetivos: Exponer en base a un caso clínico una revisión de literatura reciente sobre Proteinosis alveolar pulmonar (PAP). Presentación del caso: Revisión de ficha clínica electrónica de paciente de sexo masculino de 76 años con antecedente de linfoma no Hodgkin (LNH) mesentérico, estirpe B de tipo folicular, quien acude en forma reiterada a servicios de urgencia por cuadro de dos meses de evolución de fiebre, compromiso del estado general y tos. Al examen físico destaca crépitos en hemitórax derecho. Se realizó Tomografía computada (TC) de tórax que mostró opacidades pulmonares en vidrio esmerilado periféricas, con engrosamiento septal liso y algunas bandas retráctiles subpleurales. Se manejó ambulatoriamente con Azitromicina por una semana. Sin respuesta, evoluciona con baja de peso y diaforesis nocturna. Nueva TC de tórax en enero 2021, muestra nuevos focos de "empedrado" periféricos extensos, descrito como "crazy paving", focos de vidrio esmerilado difusos extensos, sin condensación y con resolución de bandas retráctiles. Estudio infeccioso negativo. Se realiza lavado broncoalveolar (LBA) con estudio histológico de líquido que muestra proceso inflamatorio crónico con abundantes macrófagos y material proteináceo. Discusión: Tras el descarte de patología infecciosa, se orientó el estudio hacia otras causas de enfermedad parenquimatosa pulmonar. Así, resulta fundamental la descripción correcta del patrón imagenológico tomográfico y el LBA que resultaron compatibles con PAP. Conclusión: La PAP es una patología infrecuente, pero una historia clínica adecuada, el planteamiento de diagnósticos diferenciales de neumonía de lenta resolución, asociado el reconocimiento del patrón radiológico característico y el estudio histológico con LBA permiten realizar un diagnóstico certero, con gran implicancia terapéutica.

Objective: To present a review of recent literature on pulmonary alveolar proteinosis (PAP) based on a clinical case. Presentation of the case: Review of electronic clinical record of a 76 years-old masculine patient with history of mesenteric Non-Hodgkin Lymphoma (NHL) follicular-type lineage B, who repeatedly attended the emergency services due to a two-month history of symptoms of fever, compromised general condition and cough. Physical examination revealed crepitus in the right hemithorax. Chest computed tomography (CT) was performed, which showed peripheral ground-glass pulmonary opacities, with smooth septal thickening and some subpleural retractile bands. He was managed on an outpatient basis with Azithromycin for one week. No response; evolves with weight loss and night diaphoresis. New chest CT in January 2021, shows new extensive peripheral "cobblestone" foci, described as "crazy paving", extensive diffuse ground glass foci, without condensation and with resolution of retractile bands. Negative infectious study. Bronchoalveolar lavage (BAL) was performed with a histological study of the fluid showing a chronic inflammatory process with abundant macrophages and proteinaceous material. Discussion: After ruling out infectious pathology, the study was oriented towards other causes of pulmonary parenchymal disease. Thus, the correct description of the tomographic imaging pattern and the BAL that were compatible with PAP are essential. Conclusion: PAP is an infrequent pathology, but an adequate clinical history, the approach to differential diagnoses of slowly resolving pneumonia, associated with the recognition of the characteristic radiological pattern and the histological study with BAL allow an accurate diagnosis to be made, with great therapeutic implications.

Proteinosis alveolar pulmonar / Pulmonary alveolar proteinosis

Resumen La proteinosis alveolar pulmonar (PAP) es una enfermedad pulmonar difusa, infrecuente, secundaria a una alteración en la homeostasis del surfactante. Se presenta el caso de una mujer de 69 años que ingresó a sala de internación por disnea progresiva hasta clase funcional III, de tres meses de evolución, asociada a tos no productiva. Se constató insuficiencia respiratoria tipo I. Como hallazgos en tomografía de tórax se evidenció engrosamiento del intersticio pulmonar intra e interlobulillar, opacidades en vidrio esmerilado y áreas con tendencia a la consolidación bilateral. Se realizó biopsia pulmonar con diagnóstico histológico de PAP y se efectuó tratamiento con lavado pulmonar total, logrando mejoría clínica. Se destaca la necesidad de tener presente diagnósticos diferenciales de insuficiencia respiratoria e infiltrados pulmonares en el contexto de la pandemia por COVID-19, incluidas las entidades muy poco prevalentes como lo es la PAP.

Abstract Pulmonary alveolar proteinosis (PAP) is a rare, diffuse pulmonary disease due to abnormal surfactant homeostasis. We present the case of a 69-year-old woman who was admitted to the hospital for progressive dyspnea with marked limitation in activity, and non-productive cough, of three months of evolution. Type I respiratory failure was confirmed. Chest tomography findings were interlobular and intralobular septal thickening, ground glass opacities and bilateral consolidation. Histological diagnosis was made and whole-lung lavage was performed with clinical improvement. We highlight the need to keep in mind differential diagnoses of respiratory failure and pulmonary infiltrates during COVID-19 pandemic, even rare entities such as PAP.

Clinical characteristics of pulmonary alveolar proteinosis / 中南大学学报(医学版)

OBJECTIVES@#Pulmonary alveolar proteinosis (PAP) is a rare disease with non-specific and various clinical manifestations, often leading to misdiagnosis. This study aims to raise the awareness of this disease via summarizing the clinical characteristics, diagnosis, and therapy of PAP.@*METHODS@#We retrospectively analyzed clinical data of 25 hospitalized cases of PAP during 2008 and 2019 in the Department of Respiratory and Critical Care Medicine of the Second Xiangya Hospital of Central South University.@*RESULTS@#Cough with unkown reason and dyspnea were common clinical manifastations of PAP. Five patients had a history of occupational inhalational exposure. Sixteen patients had typical image features including ground-glass opacification of alveolar spaces and thickening of the interlobular and intralobular septa, in typical shapes called crazy-paving and geographic pattern. Fourteen patients underwent pulmonary function tests, revealing a reduction in the diffusing capacity for carbon monoxide. The positive rate of transbronchial biopsy was 95%. Five patients received the whole lung lavage and the symptoms and imaging fcauters significantly relieved after five-years follow-up.@*CONCLUSIONS@#PAP is characterized by radiographic pattern and pathology. Transbronchial lung biopsy is effective to make diagnosis of PAP. The whole lung lavage remains a efficient therapy.

Proteinose alveolar pulmonar: Relato de caso / Pulmonary alveolar proteinosis: Case report

A proteinose alveolar pulmonar (PAP) é rara e caracterizada por preenchimento alveolar com material lipoproteináceo. A proteinose alveolar é caracterizada por um alvéolo com material eosinofílico, acelular, finamente granular, com fendas de colesterol. Este relato de caso descreve um paciente do sexo masculino, 2 anos, portador de hipogamaglobulinemia. O paciente foi internado com quadro compatível com Stevens- Johnson após uso de amoxicilina e clavulanato para quadro de otite média aguda. Posteriormente, foi encaminhado à unidade de terapia intensiva devido à piora respiratória clínica e radiológica. Biópsia pulmonar: proteinose alveolar com alvéolos distendidos por material proteináceo, eosinofílico e grumoso com infiltrado linfo- histiocitário local. A proteinose alveolar pulmonar é rara e o diagnóstico correto deve ser realizado para que seja realizado tratamento adequado e acompanhamento da evolução. Deve-se atentar para complicações, especialmente infecções oportunistas.

Pulmonary alveolar proteinosis (PAP) is rare and it is characterized by alveolar filling with lipoproteinaceous material. Alveolar proteinosis is characterized by an alveolus with eosinophilic, acellular, finely granular material, with cholesterol cracks. This case report describes a 2-yearold male patient with hypogammaglobulinemia. The patient was hospitalized with Stevens-Johnson-compatible condition after use of amoxicillin and clavulanate for acute otitis media. Subsequently, he was referred to the intensive care unit due to worsening clinical and radiological breathing. Lung biopsy: alveolar proteinosis with alveoli distended by proteinaceous, eosinophilic and lumpy material with local lymphohistiocytic infiltrate. Pulmonary alveolar proteinosis is rare and the correct diagnosis must be made in order to carry out an appropriate treatment and follow-up of the evolution. Attention should be paid to complications, especially opportunistic infections.

Lavado pulmonar bilateral terapéutico en una adolescente con proteinosis alveolar pulmonar. A propósito de un caso / Therapeutic bilateral lung lavage in an adolescent with pulmonary alveolar proteinosis. Case report

La proteinosis alveolar pulmonar es una enfermedad pulmonar difusa caracterizada por la acumulación anormal de surfactante y lipoproteínas en el espacio alveolar, lo cual empeora el intercambio gaseoso y lleva a un curso variable desde una presentación clínica asintomática hasta una falla respiratoria grave.Se presenta a una adolescente de 16 años con este diagnóstico que fue remitida a nuestro Hospital para la realización de un lavado pulmonar total luego de una historia de disnea progresiva, dificultad respiratoria, caída de la función pulmonar y anormalidades radiológicas. Se le realizaron estudios de función pulmonar y mediciones de laboratorio antes y después del lavado pulmonar terapéutico.Luego, la paciente presentó una inmediata mejoría tanto de los síntomas, radiografía de tórax y mediciones de estudios de función pulmonar como en el intercambio gaseoso. El lavado pulmonar total continúa siendo el estándar de oro para el tratamiento de la proteinosis alveolar pulmonar en casos graves

Pulmonary alveolar proteinosis is an unusual diffuse lung disease characterized by abnormal accumulation of pulmonary surfactant and lipoproteins in the alveolar space, which impairs gas exchange with a variable clinical course, ranging from an asymptomatic clinical presentation to severely affected respiratory failure.A 16-year-old girl with diagnosis of pulmonary alveolar proteinosis presented to our hospital for therapeutic lung lavage after a recent history of progressive dyspnea, respiratory distress, declining lung function measurements, and worsening radiographic abnormalities. We obtained baseline pulmonary function tests and laboratory measurements before and after therapeutic bilateral lung lavage. After the lavage, the patient demonstrated an immediate improvement in symptoms, chest radiograph appearance, pulmonary function test measurements, as well as in gas exchange. Whole lung lavage is still the gold standard for treatment of pulmonary alveolar proteinosis in severe cases.

Proteinosis alveolar secundaria: reporte de un caso / Proteinosis alveolar secundaria: case report

La proteinosis alveolar es un enfermedad caracterizada por el acúmulo anormal de surfactante en el espacio alveolar lo que conlleva a disrupción en el intercambio gaseoso. Su fisiopatogenia es variada y en los adultos la forma secundaria es la más frecuente. Presentamos el caso de una paciente con leucemia mieloide aguda en tratamiento compasivo con gemtuzumab ozogamicina, e infecciones respiratorias a repetición que se presenta con disnea progresiva y tos seca. Luego de descartar causa embólica y cardíaca, se realiza tomografía que evidencia opacidades en vidrio esmerilado de distribución difusa y engrosamiento de septos, por lo que ante la sospecha de infección se realiza lavado broncoalveolar que revela líquido blanquecino evidenciando en la citología inclusiones en macrógrafos PAS positivo. Con el diagnóstico de proteinosis alveolar secundaria a enfermedad de base, se reinició tratamiento quimioterápico. Presentó progresión de infiltrados y mayor requerimiento de oxígeno falleciendo pocos días después. (AU)

Patrón crazy paving en una mujer joven: hallazgo inesperado y tratamiento no tradicional en un caso de proteinosis alveolar pulmonar / Crazy paving computed tomography pattern in a young woman: unexpected findings and non-traditional treatment in a pulmonary alveolar proteinosis case

El patrón llamado 'crazy paving' en tomografia computada de tórax (TAC) puede deberse a diferentes condiciones siendo una de ellas la Proteinosis Alveolar Pulmonar (PAP), rara condición que puede llevar a insuficiencia respiratoria y a menudo, a la muerte. Presentamos el caso de una mujer joven con una historia de un año de evolución de disnea progresiva y tos seca que consultó por un cuadro de aparición brusca de fiebre, calofríos, malestar general y falla respiratoria hipoxémica severa (PaO2 = 51,9 mmHg con FiO2 = 0,50) en la cual la TAC de tórax mostraba un patrón de empedrado o 'crazy paving' que significó un desafío diagnóstico resuelto finalmente con una biopsia pulmonar quirúrgica que mostró una PAP. Ante el fracaso del tratamiento tradicional de Lavado Pulmonar Total (LPT) se usó una aproximación terapéutica novedosa consistente en una serie de 4 lavados lobares con un perfluorocarbono, Perflubron (PFC) bajo anestesia local seguido por 5 sesiones de Plasmaféresis. Casi inmediatamente después de este tratamiento la paciente evidenció mejoría radiológica y funcional. La PaO2 fue de 89,9 mmHg respirando aire ambiental y la CVF y el VEF1 aumentaron alcanzado respectivamente el 77 y el 75% de sus valores normales de referencia. Dadas las características químicas y físicas del PFC, pensamos que es una alternativa válida al LPT en estos casos.

Crazy paving computed tomography pattern may be due to a number of causes, one of them being Pulmonary Alveolar Proteinosis, a rare condition leading to respiratory failure and often to death. We present the case of a young woman with a one-year history of progressive dyspnea and dry cough, who consulted for an acute onset of fever, chills, malaise and severe hypoxemic respiratory failure (PaO2 = 51.9 mmHg; FiO2 = 0.50) with a 'crazy paving' pattern on chest CT. This diagnostic challenge was resolved by a surgical lung biopsy that showed a pulmonary alveolar proteinosis. Taking into account that the traditional treatment using whole lung lavage had already failed in this patient, a novel therapeutic approach was settled. A series of 4 lobar lavages with a perfluorocarbon (Perflubron) under local anesthesia followed by 5 plasmapheresis sessions were carried out. The patient showed radiographic and functional improvement almost immediately after this treatment. PaO2 was 89.9 mmHg breathing room air and FVC and FEV1 increased to reach 77 and 75% respectively of their normal reference values. Because of its chemical and physical properties we think this novel therapeutic approach should be a valuable alternative to saline solution for whole lung lavage in these cases.

Proteinosis alveolar pulmonar / Pulmonary alveolar proteinosis an update

La Proteinosis Alveolar Pulmonar (PAP) es una enfermedad poco frecuente, caracterizada por la acumulación de material lipoproteico derivado del surfactante pulmonar al interior de los alvéolos por una falla de depuración de este material por los macrófagos alveolares, siendo la causa más frecuente de esta disfunción la acción bloqueadora producida por anticuerpos anti factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) lo que lleva a un deterioro del intercambio gaseoso. La evolución es variable abarcando desde la resolución espontánea hasta la insuficiencia respiratoria grave y la muerte. Se describen tres formas de PAP: Genética, secundaria y autoinmune (antes primaria o idiopática) siendo esta última la más frecuente en adultos. Clínicamente, se manifiesta por disnea, tos seca e hipoxemia que pueden ser progresivas. En la radiografía de tórax se encuentran opacidades bilaterales y la tomografía computarizada de tórax de alta resolución (TACAR) muestra vidrio esmerilado con sobre posición de engrosamiento septal intra e interlobulillar, patrón conocido como "crazy paving". El diagnóstico se basa en la clínica y en el lavado broncoalveolar con material PAS positivo. La biopsia quirúrgica es confirmatoria. El tratamiento clásico es el lavado pulmonar total (LPT) para remover el contenido alveolar. Otras alternativas son la administración de GM-CSF subcutáneo o inhalado, plasmaferesis y rituximab, cuyos resultados son variables. Diferentes autores han modificado la forma del LPT y combinado los diferentes métodos de tratamiento con el fin de obtener resultados más rápidos y efectivos.

Pulmonary Alveolar Proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant derived lipoproteinaceous material filling the alveoli, secondary to failure of its clearance by macrophages. Most of the patients are adults that have auto antibodies directed to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). The evolution is towards disturbed gaseous exchange with a wide spectrum of disease from spontaneous recovery to death. There are three forms of PAP: genetic, secondary and autoimmune. Symptoms are scarce and patients may present with dyspnea, dry cough and hypoxemia. Chest X ray shows bilateral opacities and thorax CT depicts ground glass opacities surrounded by septal widening, the so called "crazy paving" pattern. Diagnosis is made on clinical and radiological grounds and confirmed by PAS positive staining of bronchoalveolar lavage material or surgical lung biopsy. Accepted treatment is whole lung lavage (WLL) with saline. Alternatives are subcutaneous or inhaled GM-CSF, Plasmapheresis or Rituximab, and even modification of the method of WLL and combination of different manner of treatment.

Characterization and outcomes of pulmonary alveolar proteinosis in Brazil: a case series / Proteinose alveolar pulmonar: caracterização e desfechos em uma série de casos no Brasil

ABSTRACT Objective: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by the alveolar accumulation of surfactant, which is composed of proteins and lipids. PAP is caused by a deficit of macrophage activity, for which the main treatment is whole-lung lavage (WLL). We report the experience at a referral center for PAP in Brazil. Methods: This was a retrospective study involving patients with PAP followed between 2002 and 2016. We analyzed information regarding clinical history, diagnostic methods, treatments, and outcomes, as well as data on lung function, survival, and complications. Results: We evaluated 12 patients (8 of whom were women). The mean age was 41 ± 15 years. Most of the patients were diagnosed by means of BAL and transbronchial biopsy. The mean number of WLLs performed per patient was 2.8 ± 2.5. One third of the patients never underwent WLL. Four patients (33.3%) had associated infections (cryptococcosis, in 2; nocardiosis, in 1; and tuberculosis, in 1), and 2 (16.6%) died: 1 due to lepidic adenocarcinoma and 1 due to complications during anesthesia prior to WLL. When we compared baseline data with those obtained at the end of the follow-up period, there were no significant differences in the functional data, although there was a trend toward an increase in SpO2. The median follow-up period was 45 months (range, 1-184 months). The 5-year survival rate was 82%. Conclusions: To our knowledge, this is the largest case series of patients with PAP ever conducted in Brazil. The survival rate was similar to that found at other centers. For symptomatic, hypoxemic patients, the treatment of choice is still WLL. Precautions should be taken in order to avoid complications, especially opportunistic infections.

RESUMO Objetivo: A proteinose alveolar pulmonar (PAP) é uma doença rara, caracterizada pelo acúmulo alveolar de substância surfactante, composta por proteínas e lipídios. É causada por um déficit de atividade macrofágica, cujo principal tratamento é a lavagem pulmonar total (LPT). Relatamos a seguir a experiência de um centro de referência brasileiro em PAP. Métodos: Estudo retrospectivo com a avaliação de pacientes com PAP acompanhados entre 2002 e 2016. Informações sobre história clínica, métodos diagnósticos, tratamentos realizados e desfechos, incluindo dados de função pulmonar, sobrevida e presença de complicações, foram analisados. Resultados: Foram incluídos 12 pacientes (8 mulheres), com média de idade de 41 ± 15 anos. A maioria dos pacientes foi diagnosticada por LBA e biópsia transbrônquica. A média do número de LPT realizadas por paciente foi de 2,8 ± 2,5. Um terço dos pacientes não foi submetido à LPT. Quatro pacientes (33,3%) apresentaram infecções associadas (criptococose, em 2; nocardiose, em 1; e tuberculose, em 1) e houve 2 óbitos (16,6%): 1 por adenocarcinoma lepídico e 1 por complicações na indução anestésica pré-LPT. Não houve diferença significativa entre os dados funcionais; porém houve uma tendência de aumento da SpO2 ao se comparar os dados iniciais aos do final do seguimento. A mediana de seguimento foi de 45 meses (1-184 meses), com taxa de sobrevida em 5 anos de 82%. Conclusões: Pelo que sabemos, esta é a maior série de casos de PAP no Brasil. A taxa de sobrevida foi semelhante à encontrada em outros centros. A LPT ainda é o tratamento de escolha para pacientes sintomáticos e hipoxêmicos. Deve-se atentar para complicações, especialmente infecções oportunistas.

A pediatric case of relapsed pulmonary alveolar proteinosis despite successful whole lung lavage / 소아과

Pulmonary alveolar proteinosis (PAP) is a rare disease in children characterized by intra-alveolar accumulation of surfactant proteins, which severely reduces gaseous exchange. Whole lung lavage (WLL) is the preferred technique for the treatment of severe PAP. Herein, we present a pediatric case of PAP treated with WLL. An 11-year-old boy was admitted with the chief complaint of a dry cough lasting 6 months. He developed symptoms of dyspnea on exertion and had difficulty in climbing stairs. He was ultimately diagnosed with PAP through video-assisted thoracoscopic lung biopsy. As first-line of treatment for PAP, he underwent therapeutic WLL for each of his lungs on separate days. After a brief recovery, his symptoms gradually worsened; therefore, he underwent a second WLL. This is the first pediatric case of PAP relapse despite successful WLL in Korea.

Whole-lung lavage complicated with pneumothorax: a case report / 대한마취과학회지

A patient with pulmonary alveolar proteinosis underwent whole lung lavage of the right lung. Lavage of the left lung was not immediately possible because of severe hypoxemia. Three days later, after correction of hypoxemia, we re-attempted the left lung lavage. However, the patient had severe hypoxemia (SpO₂< 80%) within a few minutes of performing right one lung ventilation (OLV). On bronchoscopic examination, proper tube location was confirmed. Bronchodilator nebulization and steroid injection were attempted with no effect. While searching for the cause of the hypoxemia, we found that the breath sound from the right lung had become very weak and distant compared with that from initial auscultation. Right pneumothorax was diagnosed on chest X-ray and a chest tube was inserted. After confirming pneumothorax resolution, we re-tried right OLV and were able to proceed with the left lung lavage without signs of aggravating air leak, loss of tidal volume, or severe hypoxemia.

Déficit congénito de proteína de surfactante: caso clínico / Deficiency of surfactant protein: Case report

Introducción: El déficit congénito de surfactante es una entidad de diagnóstico inhabitual en recién nacidos. Se reporta un caso clínico de déficit de proteína B del surfactante, se revisa el estudio, tratamiento y diagnóstico diferencial de los déficit de proteínas del surfactante y enfermedad crónica intersticial de la infancia. Caso clínico: Recién nacido de término que cursa dificultad respiratoria, con velamiento pulmonar recurrente y respuesta transitoria a administración de surfactante. El estudio inmunohistoquímico y genético confirmaron diagnóstico de déficit de proteína B de surfactante. Conclusiones: La enfermedad pulmonar congénita requiere un alto índice de sospecha. El déficit de proteína B de surfactante genera un cuadro clínico progresivo y mortal en la mayoría de los casos, al igual que el déficit de transportador ATP binding cassette, sub-family A member 3 (ABCA3). El déficit de proteína C es insidioso y puede presentarse con un patrón radiológico pulmonar intersticial. Debido a la similitud en el patrón histológico, el estudio genético permite una mayor certeza en el pronóstico y la posibilidad de entregar un adecuado consejo genético.

Introduction: Congenital surfactant deficiency is a condition infrequently diagnosed in newborns. A clinical case is presented of surfactant protein B deficiency. A review is performed on the study, treatment and differential diagnosis of surfactant protein deficiencies and infant chronic interstitial lung disease. Case report: The case is presented of a term newborn that developed respiratory distress, recurrent pulmonary opacification, and a transient response to the administration of surfactant. Immunohistochemical and genetic studies confirmed the diagnosis of surfactant protein B deficiency. Conclusions: Pulmonary congenital anomalies require a high index of suspicion. Surfactant protein B deficiency is clinically progressive and fatal in the majority of the cases, similar to that of ATP binding cassette subfamily A member 3 (ABCA3) deficiency. Protein C deficiency is insidious and may present with a radiological pulmonary interstitial pattern. Due to the similarity in the histological pattern, genetic studies help to achieve greater certainty in the prognosis and the possibility of providing adequate genetic counselling.

Tos e hipoxemia como manifestación clínica de la proteinosis alveolar: Reporte de caso clínico / Cough and hypoxemia as clinical manifestation of pulmonary alveolar proteinosis: Clinical case report

La proteinosis alveolar es una enfermedad pulmonar crónica poco frecuente, especialmente en pediatría, caracterizada por la acumulación anormal de lipoproteínas y derivados del surfactante en el espacio intraalveolar, que genera una grave reducción del intercambio gaseoso. La forma de presentación idiopática constituye más del 90% de los casos relacionados con un fenómeno de autoinmunidad, con producción de anticuerpos dirigidos contra el receptor del factor estimulante de colonias de granulocitos y macrófagos. Se presenta un caso clínico de una niña de 4 años de edad tratada por neumonía atípica con evolución desfavorable por hipoxemia persistente. El diagnóstico se obtuvo a través del estudio anatomopatológico de la biopsia pulmonar por toracotomía. Se llevaron a cabo 17 lavados broncopulmonares mediante endoscopía respiratoria y la paciente evidenció franca mejoría clínica.

Alveolar proteinosis is a rare chronic lung disease, especially in children, characterized by abnormal accumulation of lipoproteins and derived surfactant in the intra-alveolar space that generates a severe reduction of gas exchange. Idiopathic presentation form constitutes over 90% of cases, a phenomenon associated with production of autoimmune antibodies directed at the receptor for granulocyte-macrophage colony-stimulating factor. A case of a girl of 5 years of age treated because of atypical pneumonia with unfavorable evolution due to persistent hypoxemia is presented. The diagnosis is obtained through pathologic examination of lung biopsy by thoracotomy, as treatment is carried out by 17bronchopulmonary bronchoscopy lavages and the patient evidences marked clinical improvement.

The clinical features of indium-related lung diseases / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To discuss the clinical features of Indium-related lung diseases.</p><p><b>METHODS</b>We searched database of Chinese and Pubmed, Embase, Web of Science to collect research data of indium-related lung diseases from Jan. 1998 to Aprl. 2014. Case reports, exposure histories and lab results were analysed and summarized.</p><p><b>RESULTS</b>1998 to Mar 2010, ten cases of indium-related lung diseases were published. Seven cases of interstitial pneumonia were reported in Japan, two cases of pulmonary alveolar proteinosis (PAP) were reported in the USA and one case of PAP reported in China. Chest computer tomography (CT) showed diffuse or local ground glass appearance (GGA) in 8 cases, 3 of which also showed centrilobular nodules; Pulmonary function test were normal only in one out of 8 cases. Cholesterol clefts were found in 4 cases of interstitial pneumonia. 3 cases died among 6 cases who were followed-up.</p><p><b>CONCLUSIONS</b>Occupational exposure to indium compounds are contributory to different pulmonary diseases, which are composed of interstitial pneumonia and pulmonary alveolar proteinosis. The relationships between In-C, In-S and these pulmonary diseases are unclear.</p>

Whole Lung Lavage Treatment of Chinese Patients with Autoimmune Pulmonary Alveolar Proteinosis: A Retrospective Long-term Follow-up Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulmonary alveolar proteinosis (PAP) is a rare lung disease, the most common type of which is autoimmune PAP. The gold standard therapy for PAP is whole lung lavage (WLL). Few studies have reported the optimal technique with which to evaluate the response to WLL. In this study, we aimed to identify parameters with which to assess the need for repeat WLL during a long-term 8-year follow-up.</p><p><b>METHODS</b>We conducted a retrospective analysis of 120 patients with autoimmune PAP with 80 of whom underwent WLL. Physiologic, serologic, and radiologic features of the patients were analyzed during an 8-year follow-up after the first WLL treatment.</p><p><b>RESULTS</b>Of the 40 patients without any intervention, 39 patients either achieved remission or remained stable and only one died of pulmonary infection. Of the 56 patients who underwent WLL for 1 time, 55 remained free from a second WLL and 1 patient died of cancer. Twenty-four required additional treatments after their first WLL. The baseline PaO 2 (P = 0.000), PA-aO 2 (P = 0.000), shunt fraction rate (P = 0.001), percent of predicted normal diffusing capacity of the lung for carbon monoxide (DLCO%Pred) (P = 0.016), 6-min walk test (P = 0.013), carcinoembryonic antigen (CEA) (P = 0.007), and neuron-specific enolase (NSE) (P = 0.003) showed significant differences among the three groups. The need for a second WLL was significantly associated with PaO 2 (P = 0.000), CEA (P = 0.050) , the 6-minute walk test (P = 0.026), and DLCO%Pred (P = 0.041). The DLCO%Pred on admission with a cut-off value of 42.1% (P = 0.001) may help to distinguish whether patients with PAP require a second WLL.</p><p><b>CONCLUSIONS</b>WLL is the optimal treatment method for PAP and provides remarkable improvements for affected patients. The DLCO%Pred on admission with a cut-off value of 42.1% may distinguish whether patients with PAP require a second WLL.</p>

Pulmonary alveolar proteinosis in a 15-year-old girl

Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease characterized by the accumulation of lipoproteins derived from surfactants in the distal air space. The lack of granulocyte macrophage colony-stimulating factor is believed to contribute to macrophage dysfunction and the impaired processing of surfactants. Because the prevalence of PAP in the general population is less than 1 in 200,000, and the typical age at presentation is 35 to 50 years, PAP is a very rare disease in children. To the best of our knowledge, there has been no Korean report on PAP in children. We describe here a patient who was diagnosed with PAP at the aged 15 years.

Diagnostic value of transbronchial lung biopsy in pulmonary alveolar proteinosis / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the diagnostic value and limits of transbronchial lung biopsy (TBLB) in pulmonary alveolar proteinosis (PAP).@*METHODS@#The complete hospital data from Second Xiangya Hospital, Central South University, between June, 2006 and December, 2012, were analyzed retrospectively in 25 patients with PAP (who were diagnosed pathologically by TBLB or not by TBLB) and in 4 patients with other disease (who were misdiagnosed by TBLB).@*RESULTS@#Among the 25 patients with PAP, 14 patients were confirmed by TBLB in the fi rst time [TBLB positive rate in the first time was 56% (14/25)]; 6 patients who were misdiagnosed by TBLB in the fi rst time were confirmed by TBLB in the second time [the positive rate in the second time was 24% (6/25)]. Th e total positive rate was 80% (20/25). Th e total negative rate was 20% (5/25). Five patients with PAP, who showed negative results in TBLB analysis, were confirmed by the typical CT as well as the whole lung lavage. In addition, 4 patients with other diseases were misdiagnosed as PAP by TBLB.@*CONCLUSION@#TBLB is a very good diagnosis method. But the negative results in the first time cannot exclude PAP. TBLB should be repeated if conditions allow. If clinical manifestation and CT results are typical, it can be used for diagnosis of PAP combined with the positive results from bronchoalveolar lavage fluid check. However, for non-typical cases, it needs TBLB pathological diagnosis.

Proteinosis alveolar pulmonar: Una puesta al día / Pulmonary Alveolar Proteinosis: Up to Date

La Proteinosis Alveolar Pulmonar (PAP) es una enfermedad rara, caracterizada por la acumulación de surfactante en el interior del espacio alveolar, resultando en una alteración del intercambio gaseoso. El curso clínico es variable, abarcando desde la resolución espontánea hasta el fallo respiratorio y muerte. Se han descripto tres formas de PAP: genética, secundaria y primaria o idiopática, siendo esta última la más frecuente en la población adulta. Avances en el conocimiento de la fisiopatología de la PAP han demostrado que la forma idiopática es el resultado de la generación de autoanticuerpos anti factor estimulante de colonias granulocito-macrófago (GM-CSF). Todas las formas de PAP resultan en disfunción macrofágica con la acumulación del material lipoproteináceo en el espacio alveolar. La PAP se caracteriza por disnea progresiva, tos seca e hipoxemia. Se encuentran opacidades bilaterales en la radiografía de tórax y la tomografía computada de alta resolución pone de manifiesto vidrio esmerilado con engrosamiento de los septos inter e intralobulillar, conformando el patrón típico en empedrado. Si bien la biopsia quirúrgica es el método de referencia para el diagnóstico definitivo, la combinación de las manifestaciones clínicas características y el lavado broncoalveolar (LBA) con material PAS positivo a menudo son suficientes para establecer el diagnóstico. El tratamiento de elección en primera medida sigue siendo el lavado pulmonar total bajo anestesia general con el objeto de remover el material proteináceo del espacio alveolar y mejorar el intercambio gaseoso. Recientemente, estudios han demostrado que el tratamiento inhalatorio o subcutáneo con GM-CSF podría beneficiar a algunos pacientes con formas idiopáticas de PAP.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of surfactant lipids and protein in the alveolar spaces, resulting in impairment in gas exchange. The clinical course can be variable, ranging from spontaneous resolution to respiratory failure and death. There are three forms of PAP: congenital, acquired and idiopathic, being the latter the most prevalent form in the adult population. Advances in the understanding of the pathophysiology of PAP demonstrate that the idiopathic form is due to antigranulocyte macrophage-colony stimulating factor (GM-CSF) antibodies. All the forms of PAP cause macrophage dysfunction leading to accumulation of the proteinaceous material. PAP is characterized by progressive exertional dyspnea and nonproductive cough with hypoxemia. Bilateral infiltrates are typically present on chest radiograph; high-resolution computed tomography reveals diffuse ground-glass opacities and airspace consolidation with interlobular septal thickening in a characteristic “crazy paving” pattern. Although surgical lung biopsy will provide a definitive diagnosis, a combination of typical clinical and imaging features with periodic acid-Schiff (PAS)-positive material on bronchoalveolar lavage and transbronchial biopsies is usually sufficient. The current standard of care is to perform whole lung lavage under anesthesia on these patients to clear the alveolar space to help improving respiratory physiology. Recent studies have demonstrated that GM-CSF (inhalation or subcutaneous) can result in improvement in some patients with idiopathic PAP.

Characteristics of serum lipid metabolism in patients with autoimmune pulmonary alveolar proteinosis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the serum lipid panels in consecutive autoimmune pulmonary alveolar proteinosis(APAP)patients and analyze their relationship with anti-granulocyte macrophage-colony stimulating factor(GM-CSF)antibody and other markers.</p><p><b>METHODS</b>Thirty-two non-diabetic APAP patients were enrolled in the study. Serum lipids of these patients and 100 healthy volunteers were tested after an overnight fasting. Anti-GM-CSF antibody levels were measured with enzyme-linked immunosorbent assay. The correlation of serum lipids with lactate dehydrogenase,carcinoembryonic antigen,pulmonary function,and artery blood gas parameters were analyzed.</p><p><b>RESULTS</b>Total cholesterol and low-density lipoprotein cholesterol levels [(5.54±0.99)and(3.73±0.83)mmol/L respectively] were significantly higher in APAP patients than in healthy volunteers [(5.05±0.97)and(3.17±0.89)mmol/L respectively](all P<0.05). High-density lipoprotein cholesterol(HDL-C)level of the APAP group [(1.10±0.18)mmol/L ]was significantly lower than that of the healthy group(P<0.05). Low-density lipoprotein/HDL and total cholesterol/HDL ratios in the APAP group(3.47±0.90 and 5.14±1.12 respectively)were significantly higher than those in the healthy group[(2.63±0.87)and(4.18±1.12)](all P<0.05). There was no significant difference in triglyceride level between the two groups(P>0.05). HDL-C level was negatively correlated with alveolar-arterial oxygen pressure difference(r=-0.436,P<0.05)and positively correlated with arterial oxygen saturation(r=0.459,P<0.05). None of the lipid markers correlated with serum anti-GM-CSF antibody levels(all P>0.05).</p><p><b>CONCLUSIONS</b>APAP patients were likely to suffer from disturbed lipid metabolism,which was correlated with disease severity to some degree. Lipid markers deserved more attention in the management of APAP patients.</p>